ORCID Profile
0000-0002-9595-3220
Current Organisations
Prince of Wales Hospital
,
University of New South Wales
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Psychology | Stochastic Analysis And Modelling | Central Nervous System | Clinical Sciences | Learning, Memory, Cognition And Language | Sensory Processes, Perception And Performance | Biomedical Engineering | Radiology And Organ Imaging | Geriatrics and Gerontology | Psychiatry (incl. Psychotherapy) | Biomedical Engineering Not Elsewhere Classified | Central Nervous System | Developmental Psychology and Ageing
ANZSRC Socio-Economic Objective (SEO)
Mental health | Nervous system and disorders | Health related to ageing | Families and Family Services | Neurodegenerative Disorders Related to Ageing | Ageing and Older People | Expanding Knowledge in Psychology and Cognitive Sciences | Mental Health |
Related Links
Publications
Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/NN.4228
Schizophrenia-like illness in velo-cardio-facial syndrome: A genetic subsyndrome of schizophrenia?
Publisher: Elsevier BV
Date: 08-2002
DOI: 10.1016/S0022-3999(02)00431-2
Abstract: The study of genetic illnesses that have a behavioral phenotype resembling psychosis can provide important insights into the genetic basis of psychotic disorders and their patho-mechanisms. An important ex le of such a genetic disorder is the velo-cardio-facial syndrome (VCFS) associated with 22q11 microdeletion. The case of a 22-year-old male, who had the typical genotype and phenotype of VCFS and developed a psychotic illness characterized by withdrawal, catatonic posturing, inappropriate affect, stereotyped behavior, negativism and poverty of speech, is described. He had a partial response to an atypical neuroleptic, but developed myoclonus that was controlled with an anticonvulsant. The association of VCFS with schizophrenia-like psychosis is worthy of further study as it may provide insights into the molecular basis of neurodevelopment and its aberrations in psychotic disorders.
Consumption of pomegranates improves synaptic function in a transgenic mice model of Alzheimer's disease
Publisher: Impact Journals, LLC
Date: 28-07-2016
An International Curriculum for Neuropsychiatry and Behavioural Neurology,Un currículo internacional para neuropsiquiatría y neurología conductual
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.RCP.2017.05.001
Abstract: With major advances in neuroscience in the last three decades, there is an emphasis on understanding disturbances in thought, behaviour and emotion in terms of their neuroscientific underpinnings. While psychiatry and neurology, both of which deal with brain diseases, have a historical standing as distinct disciplines, there has been an increasing need to have a combined neuropsychiatric approach to deal with many conditions and disorders. Additionally, there is a body of disorders and conditions that warrants the skills sets and knowledge bases of both disciplines. This is the territory covered by the subspecialty of Neuropsychiatry from a 'mental' health perspective and Behavioural Neurology from a 'brain' health perspective. This paper elaborates the neuropsychiatric approach to dealing with brain diseases, but also argues for the delineation of a neuropsychiatric territory. In the process, it describes a curriculum for the training of a neuropsychiatrist or a behavioural neurologist who is competent in providing a unified approach to the diagnosis and management of this set of conditions and disorders. The paper describes in some detail the objectives of training in neuropsychiatry and the key competencies that should be achieved in such higher training after a foundational training in psychiatry and neurology. While aiming for an internationally relevant training program, the paper acknowledges the local and regional differences in training expertise and requirements. It provides a common framework of training for both Neuropsychiatry and Behavioural Neurology, while accepting the differences in skills and emphasis that basic training in psychiatry or neurology will bring to the subspecialty training. The future of Neuropsychiatry (or Behavioural Neurology) as a discipline will be influenced by the successful adoption of such a unified training curriculum.
Cognitive and memory training in adults at risk of dementia: A systematic review
Publisher: Springer Science and Business Media LLC
Date: 25-09-2011
Sydney Centenarian Study
Publisher: Springer Singapore
Date: 2016
Startle in Tourette's syndrome [2] (multiple letters)
Publisher: Elsevier BV
Date: 11-1998
Supervisory experience at work is linked to low rate of hippocampal atrophy in late life
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.NEUROIMAGE.2012.08.015
Abstract: Cultivation of an active cognitive lifestyle, including erse and challenging educational, occupational and cognitively-loaded leisure activities may be protective against development of dementia but the mechanisms underlying this link are not clear. We used the Lifetime Experiences Questionnaire (LEQ) to assess the structural brain correlates of cognitive lifestyle in the Sydney Memory and Aging Study, a large population-based cohort of originally 1037 non-demented elderly aged over 70 years of age. After excluding those without structural Magnetic Resonance Image data or Mild Cognitive Impairment at their most recent assessment, 151 cognitively intact subjects were studied. Whole-brain voxel based morphometric analysis found that higher total Lifetime Experiences Questionnaire scores are linked with increased grey matter volume in the medial temporal lobe, especially in the hippoc us. Through a series of more specific analyses, we found that supervisory and managerial experience in midlife was the dominant contributor to this effect. Furthermore, in those with longitudinal neuroimaging data (N=91), we measured hippoc al structural changes over a 2-3 year period by gold-standard manual tracing. The rate of hippoc al atrophy in late-life in those with high level supervisory experience in midlife was five-times slower than those with no midlife supervisory experience (p<0.001). In idual differences in intracranial volume, age, gender, physical activity, depressive symptoms, or apolipoprotein ε4 genetic status could not explain these findings, nor could specific lifestyle patterns in late life. For the first time, we reveal that managerial and supervisory experience during our working life is connected to hippoc al integrity after retirement, some 20-30 years later. Our results stimulate several questions about the nature of work-related effects on longterm behaviour, structural neuroplasticity and neuroprotection, and may help explain differences in dementia-risk based on cognitive lifestyle.
Midlife managerial experience is linked to late life hippocampal morphology and function
Publisher: Springer Science and Business Media LLC
Date: 15-11-2017
Cognitive functioning in older twins: The Older Australian Twins Study
Publisher: Wiley
Date: 10-2011
DOI: 10.1111/J.1741-6612.2011.00534.X
Abstract: To examine the concordance rates of common medical conditions and neurocognitive performance in monozygotic (MZ) and dizygotic (DZ) older twins. Twins aged ≥ 65 years and living in the three Eastern states of Australia were recruited through the Australian Twin Registry and underwent detailed neuropsychological and medical assessment. Assessments were conducted on 113 MZ and 96 DZ twin pairs, with a mean age of 70.5 years. MZ twins were more concordant than DZ twins for hypertension and asthma. MZ twins had higher correlations than DZ twins on most neuropsychological tests, with the exception of some tests related to processing speed. The concordance rate for mild cognitive impairment or dementia was 76.2% in MZ twins and 42.9% in DZ twins, a non-significant difference. Except for some aspects of processing speed, most cognitive functions in older in iduals show significant heritability. The heritability of neurocognitive disorders is, however, low.
Vascular Cognitive Disorder
Publisher: Georg Thieme Verlag KG
Date: 29-03-2019
Abstract: The term vascular cognitive disorder (VCD) refers to a heterogeneous group of disorders in which the primary feature is cognitive impairment attributable to cerebrovascular disease (CVD). This includes not only vascular dementia (VaD) but also cognitive impairment of insufficient severity to meet diagnostic criteria for dementia. VCD is recognized as the second most common cause of dementia after Alzheimer's disease (AD), but prevalence rates vary widely according to the diagnostic criteria employed. There have been recent attempts to standardize diagnostic criteria. VCD incorporates a range of neuropathological mechanisms including poststroke impairment, small and large vessel disease, and cases of mixed-pathology, with CVD interacting with AD and other neuropathologies. Recent neuroimaging data have improved our understanding of the etiology of VCD. Symptomatic treatments for VaD have modest benefit and there is increased focus on the primary and secondary preventative benefits of vascular risk factor control.
Brain reserve and dementia: A systematic review
Publisher: Cambridge University Press (CUP)
Date: 06-10-2006
DOI: 10.1017/S0033291705006264
Abstract: Background. Behavioural brain reserve is a property of the central nervous system related to sustained and complex mental activity which can lead to differential expression of brain injury. Behavioural brain reserve has been assessed using autobiographical data such as education levels, occupational complexity and mentally stimulating lifestyle pursuits. So far there have been several epidemiological reports but no systematic review to put conflicting results into context. Our aim was to quantitatively review evidence for the effect of brain reserve on incident dementia. Method. Cohort studies of the effects of education, occupation, premorbid IQ and mental activities on dementia risk were of interest. Abstracts were identified in MEDLINE (1966–September 2004), CURRENT CONTENTS (to September, 2004), PsychINFO (1984–September 2004), Cochrane Library Databases and reference lists from relevant articles. Twenty-two studies met inclusion criteria. Key information was extracted by both reviewers onto a standard template with a high level of agreement. Studies were combined through a quantitative random-effects meta-analysis. Results. Higher brain reserve was associated with a lowered risk for incident dementia (summary odds ratio, 0·54 95% confidence interval, 0·49–0·59). This effect was found over a median of 7·1 years follow-up and resulted from integrating data across more than 29000 in iduals. Notably, increased complex mental activity in late life was associated with lower dementia rates independent of other predictors a dose–response relationship was also evident between extent of complex mental activities in late life and dementia risk. Conclusions. This study demonstrates robust evidence that complex patterns of mental activity in the early, mid- and late-life stages is associated with a significant reduction in dementia incidence. Randomized control trials based on brain-reserve principles are now required.
Why aren't people with young onset dementia and their supporters using formal services? Results from the INSPIRED study
Publisher: Public Library of Science (PLoS)
Date: 19-07-2017
IGEMS: The Consortium on Interplay of Genes and Environment Across Multiple Studies — An Update
Publisher: Cambridge University Press (CUP)
Date: 23-09-2019
DOI: 10.1017/THG.2019.76
Abstract: The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene–environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14–103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with erse outcomes, including mortality, physical functioning and psychological functioning and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.
Quantifying the cellular NAD+ metabolome using a tandem liquid chromatography mass spectrometry approach
Publisher: Springer Science and Business Media LLC
Date: 23-12-2017
Neural precursors from canine skin: A new direction for testing autologous cell replacement in the brain
Publisher: Mary Ann Liebert Inc
Date: 12-2008
Abstract: Recent work indicates that neural progenitors can be isolated from the skin of rodents and humans. The persistence of these cells in accessible adult tissue raises the possibility of their exploitation for research and therapeutic purposes. This study reports on the derivation, culture, and characterization of homogenous canine skin-derived neuroprecursor cells (SKiNPs) from mature animals. Canine tissue was used because naturalistic brain diseases in community-dwelling dogs are emerging as ecologically sound models for a range of neurological conditions. Adult SKiNPs were initially isolated as neurospheres and then cultured for 10-15 passages in an adherent monolayer assay. Serumfree expansion conditions contained B-27, 20 ng/mL EGF, and 40 ng/mL bFGF. Gene expressions by PCR indicated expression of nestin, CD133, NCAM, and FGF2R, but not GFAP. Highly uniform expression of nestin (76 +/- 8.3%), NCAM (84 +/- 3.3%), betaIII-tubulin (96 +/- 4.3%), and CD133 (68 +/- 13.5%) was also observed. Directed differentiation of SKiNPs in the presence of serum induced betaIIItubulin, NSE, NCAM, and MAP2 in >90% of differentiated cells by immunophenotype analysis. Our culture system rapidly induces canine skin cells into neural precursors, maintains nestin expression in more than 75% of proliferating cells, and generates an almost universal neuronal-like phenotype after 7 days of in vitro differentiation. Their biological characteristics are suggestive of transiently lifying fate-restricted neuroprecursors rather than true neural stem cells. This system may be an effective alternative for autologous neurorestorative cell replacement in canine models for further translational research.
Rates of depression at 3 and 15 months poststroke and their relationship with cognitive decline: The Sydney stroke study
Publisher: Elsevier BV
Date: 06-2007
Psychiatric disorders in ageing
Publisher: Springer Berlin Heidelberg
Date: 2011
Abstract: The ageing of the population brings particular challenges to psychiatric practice. Although the clinical presentation of common psychiatric disorders such as mood and psychotic disorders is largely similar to those in younger adults, late life presentations tend to be more complex as co-morbidity with dementia and physical illness is common. Suicide tends to increase with age in most countries. In this chapter we argue that the aetiology of disorders may be best understood within a stress vulnerability model in which neurobiological and psychosocial factors interplay. We further present that management strategies need to be comprehensive, incorporating physical, social, pharmacological, and psychological treatments appropriate to each case. We close with a call for the use of specialised multi-disciplinary services to improve the overall quality of care.
Hippocampus and amygdala volumes in elderly schizophrenic patients as assessed by magnetic resonance imaging
Publisher: Wiley
Date: 02-2000
DOI: 10.1046/J.1440-1819.2000.00644.X
Abstract: Reduced size of the hippoc us and amygdala has been one of the more consistent morphological findings in schizophrenia, but the question of medial temporal abnormalities in elderly schizophrenia patients has been inadequately addressed. We examined 20 elderly subjects with a DSM-III-R diagnosis of schizophrenia, five of whom had a late-onset schizophrenia (LOS), and compared them with 20 healthy volunteers on magnetic resonance imaging (MRI) and neuropsychological parameters. Hippoc us and amygdala volumes were obtained by manual tracing on T1-weighted 1.5 mm thick contiguous coronal slices perpendicular to the long axis of the hippoc us. Patients had smaller left hippoc al and right amygdala volumes than comparison subjects, the mean differences being 9.7 and 11.1%, respectively, but the right amygdala volumes were not significantly different after Bonferroni correction. The hippoc us-amygdala volumes together were smaller in the schizophrenia group bilaterally. In a pilot analysis, the LOS subjects had non-significantly smaller hippoc us-amygdala volumes than did the early-onset schizophrenia (EOS) subjects. For the schizophrenia group, there were significant correlations between amygdala and hippoc us volumes and some neuropsychological performance indices. The findings are consistent with those reported in younger schizophrenics, and are of the same order of magnitude, suggesting that they are not likely to be progressive. This pilot analysis in LOS subjects argues against the condition being secondary to Alzheimer's disease.
Anthropometric indices in a community-dwelling Australian population aged 70–90 years: The Sydney Memory and Ageing Study
Publisher: Wiley
Date: 11-09-2014
Genome-wide significant results identified for plasma apolipoprotein H levels in middle-aged and older adults
Publisher: Springer Science and Business Media LLC
Date: 31-03-2016
DOI: 10.1038/SREP23675
Abstract: Apolipoprotein H (ApoH) is a multi-functional plasma glycoprotein that has been associated with negative health outcomes. ApoH levels have high heritability. We undertook a genome-wide association study of ApoH levels using the largest s le to date and replicated the results in an independent cohort (total N = 1,255). In the discovery phase, a meta-analysis of two cohorts, the Sydney Memory and Ageing Study (Sydney MAS) and the Older Australian Twins Study (OATS) (n = 942) revealed genome-wide significant results in or near the APOH gene on chromosome 17 (top SNP, rs7211380, p = 1 × 10 −11 ). The results were replicated in an independent cohort, the Hunter Community Study (p 0.002) (n = 313). Conditional and joint analysis (COJO) confirmed the association of the chromosomal 17 region with ApoH levels. The set of independent SNPs identified by COJO explained 23% of the variance. The relationships between the top SNPs and cardiovascular/lipid/cognition measures and diabetes were assessed in Sydney MAS, with suggestive results observed for diabetes and cognitive performance. However, replication of these results in the smaller OATS cohort was not found. This work provides impetus for future research to better understand the contribution of genetics to ApoH levels and its possible impacts on health.
Effects of MCI subtype and reversion on progression to dementia in a community sample
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-05-2017
DOI: 10.1212/WNL.0000000000004015
Abstract: We sought to understand the trajectory of mild cognitive impairment (MCI) better by examining longitudinally different MCI subtypes and progression to dementia and reversion to normal cognition in a community s le. We evaluated the stability of MCI subtypes and risk of dementia over 4 biennial assessments as part of an ongoing prospective cohort study, the Sydney Memory and Ageing Study. While prevalence of MCI and different MCI subtypes remains relatively stable across all assessments, reversion from MCI and transitions between different MCI subtypes were common. Up to 46.5% of participants classified with MCI at baseline reverted at some point during follow-up. The majority (83.8%) of participants with incident dementia were diagnosed with MCI 2 years prior to their dementia diagnosis. Both reverters and participants with stable MCI were at an increased risk of progression to dementia compared to those without MCI at baseline (HR 6.4, p = 0.02, and HR 24.7, p 0.001, respectively) however, the risk of dementia in participants with MCI who did not revert was higher than in reverters (HR 2.5, p = 0.01). This effect was specific to amnestic subtypes (MCI reverters vs nonreverters: amnestic MCI HR 3.3, p = 0.006 nonamnestic MCI: HR 1.3, p = 0.67). Our findings indicate that the relevance of reversion for progression risk depends on the MCI subtype. Subtype specificity and longitudinal characterization are required for the reliable identification of in iduals at high risk of developing dementia.
Brains of anorexia nervosa patients process self-images differently from non-self-images: An fMRI study
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2008.02.031
Abstract: The central disturbance in anorexia nervosa (AN) is a distorted body image. This perceptual error does not extend to judging others' body shapes. We used fMRI to examine if the brain processing of an image of self is different in the brains of AN patients. The s le comprised 10 patients with AN and 10 healthy control women. In a controlled epoch design, subjects were presented with images of self and non-self, matched for body mass index (BMI), in a counter-balanced fashion, and echoplanar images with blood oxygenation level dependent (BOLD) contrast were obtained on a 3T Philips scanner. Processing of non-self-images by control subjects activated the inferior and middle frontal gyri, superior and inferior parietal lobules, posterior lobe of the cerebellum and the thalamus. Patients had a similar pattern of activation with greater activation in the medial frontal gyrus. When the two groups were contrasted for the differential activation with self vs. non-self-images, control subjects had greater activation than patients in the middle frontal gyri, insula, precuneus, and occipital regions while the patients did not have greater activation in any region. AN patients had no significant regions of activation with self-images compared to baseline. We conclude that AN patients process non-self-images similarly to control subjects, but their processing of self-images is quite discrepant, with a lack of activation of the attentional system or the insula. Such discrepant emotional and perceptual processing may underlie the distortion of self-images by AN patients.
O4‐02‐02: Mri Markers of Dementia in the Eighth to Eleventh Decades of Life
Publisher: Wiley
Date: 07-2016
When more is less: Associations between corpus callosum size and handedness lateralization
Publisher: Elsevier BV
Date: 08-2010
THE RELATIONSHIP OF HYPERTENSION, DIABETES AND OTHER VASCULAR RISK FACTORS WITH POSTSTROKE COGNITIVE FUNCTION: THE STROKOG (STROKE AND COGNITION) CONSORTIUM
Publisher: Wiley
Date: 07-2017
Age Shall not Weary Them: Mental Health in the Middle-Aged and the Elderly
Publisher: SAGE Publications
Date: 07-2007
DOI: 10.1080/00048670701392817
Abstract: Objective: The prevalence of mental disorders in the elderly is disputed. The debate in this area can be informed by data from large population surveys that contain sufficient elderly participants. The aim of the present paper was to provide the first direct comparison of the prevalence and demographic correlates of ICD-10 anxiety and affective disorders in the middle-aged and the elderly. Method: The 12 month prevalence and demographic correlates of affective and anxiety disorders were compared in a community s le of middle-aged and elderly Australian residents who took part in the Australian National Mental Health and Well-being Survey (NMHWS). Results: One in seven middle-aged participants and one in 16 elderly participants experienced symptoms consistent with any anxiety or affective disorder in the preceding 12 months. Compared to the middle-aged participants, the elderly had lower rates for most affective and anxiety disorders, and for the combined presence of any disorder. Demographic correlates of mental disorder, especially marital status, were different for the two groups. Conclusions: Community-dwelling elderly in Australia have lower rates of mental disorder compared to the middle-aged. Differences in demographic correlates between groups support the notion that the determinants of mental disorder in the elderly differ substantially from those in middle age.
Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-11-2019
DOI: 10.1212/WNL.0000000000008612
Abstract: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and in idual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. In a combined s le of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in in idual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. This study confirms the high prevalence of PSCI in erse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.
Tics Status
Publisher: SAGE Publications
Date: 06-1996
DOI: 10.3109/00048679609065004
Abstract: Objectives: To describe two patients with tics status, propose a definition of this syndrome and draw attention to its clinical significance. Method: Two patients suffering from Tourette's Syndrome who had developed episodes of continual motor tics that lasted from minutes to hours, were non-suppressible and intruded into normal functioning, were treated with an increase in the dose of haloperidol, in one case with the addition of clonazepam. Results: The offset of the episodes was gradual and the tic disorder was worse after the episodes. One patient had further spontaneous episodes of tics status. Conclusions: The recognition of tics status has implications for the management as well as our understanding of the pathobiology of tics and Tourette's Syndrome. The definition of tics status should be standardised.
Psychiatric consequences of small vessel disease
Publisher: Cambridge University Press
Date: 05-2014
Brief psychosis in thrombocytopenia-absent radius syndrome: a case report.
Publisher: SAGE Publications
Date: 09-2005
The canine cognitive dysfunction rating scale (CCDR): A data-driven and ecologically relevant assessment tool
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.TVJL.2010.05.014
Abstract: Canine cognitive dysfunction (CCD) is an age-related neurobehavioural syndrome which, although common, is severely under-diagnosed in community-based dogs. Using data from a large cross-sectional survey of older dogs (n=957), this study aimed to develop a clinical scale for assessing CCD. Data-driven analytical techniques were used to distil 27 significant behavioural items (previously identified as relevant to CCD) into an assessment tool with maximal cognito-behavioural breadth whilst maintaining clinical utility. The resulting CCD rating scale (CCDR) comprised 13 behavioural items, of which three were sensitive to the severity of the disease stage. When tested on an independent survey s le, the CCDR had an overall 98.9% diagnostic accuracy with a 77.8% positive predictive value and a 99.3% negative predictive value. Test-re-test reliability of the CCDR over 2months was also high (r=0.73, P<0.0001). In conjunction with veterinary assessment, the CCDR could be a valuable tool in research and clinical settings for both the assessment and longitudinal tracking of cognitive change.
Inflammatory biomarkers predict depressive, but not anxiety symptoms during aging: the prospective Sydney Memory and Aging Study.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.PSYNEUEN.2012.02.006
Abstract: This study addresses the paucity of research on the prospective relationship between a range of inflammatory markers and symptoms of depression and anxiety during aging. In the Sydney Memory and Aging Study, the relationships between remitted depression, current and first onset of symptoms of depression or anxiety (Geriatric Depression Scale and Goldberg Anxiety Scale (GDS, GAS), and markers of systemic inflammation (C-reactive protein (CRP), interleukins-1β, -6, -8, -10, -12, plasminogen activator inhibitor-1 (PAI-1), serum amyloid A, tumor necrosis factor-α, and vascular adhesion molecule-1) were investigated. The s le consists of N=1037 non-demented community-dwelling elderly participants aged 70-90 years assessed at baseline and after 2-years. All analyses were adjusted for gender, age, years of education, total number of medical disorders diagnosed by a doctor, cardiovascular disorders, endocrine disorders, smoking, body mass index, currently using anti-depressants, NSAIDS or statins and diabetes mellitus. The results show a significant linear relationship between increasing levels of IL-6 and depressive symptoms at baseline only, whereas IL-8 was associated with depressed symptoms at baseline and at 2 years follow-up. In addition, IL-8 was associated with first onset of mild to moderate depressive symptoms over 2 years. Logistic regression analyses showed that PAI-1 (OR=1.37, 95% CI=1.10-1.71, p=0.005) was associated with remitted depression. Results for anxiety symptoms were negative. The findings are suggestive of IL-6 and IL-8 being associated with current symptoms and IL-8 being associated with first onset of depressive symptoms, whereas PAI-1 could be regarded as a marker of remitted depression.
Disseminated intravascular coagulopathy and thrombocytopenia associated with clozapine-induced neuroleptic malignant syndrome.
Publisher: Wiley
Date: 08-1995
DOI: 10.1111/J.1445-5994.1995.TB01907.X
Abstract: Unprecedented and chaotic growth of cities results in reducing open spaces and water bodies, worsening infrastructure facilities and changes in ecological morphology. This unregulated growth of the urban population led to uneven distribution of urban amenities, facilities and healthcare services. Considering this, the study aimed to draw attention to the existing spatial pattern of healthcare facility centres as well as to find out the possible sites for the provision of healthcare facility centres in the municipal ward (micro-scale) of Midnapore town. This prototype study was conducted using Analytical Hierarchy Process (AHP) and Ordinary Least Square (OLS) evaluation model based on various criteria through Arc GIS environment. The findings indicate that the spatial distribution patterns of existing public healthcare centres were significantly dispersed. Weights based on a set of criteria were calculated by AHP and OLS algorithm and generated suitability evaluation maps classified from 1 (poor suitable) to 4 (most suitable). According to the employed criteria in this study unveil those existing hospitals and primary healthcare centres have not been located in the appropriate locations. The model is found to be valid for the given study area and there is no significant difference between AHP and OLS results. Further, it can be used for preparing the suitability map for the other areas with similar geo-environmental conditions for the proviso of healthcare services as well as will be most effective in preventing disease progression and reducing healthcare inequality on a large scale. The online version contains supplementary material available at 10.1007/s10708-021-10528-w.
The association of APOE ε4 allele with retinal layer thickness and microvasculature in older adults
Publisher: MDPI AG
Date: 27-09-2023
DOI: 10.3390/JCM12196219
Behavioural factors affecting physical health of the New Zealand Maori
Publisher: Elsevier BV
Date: 1990
DOI: 10.1016/0277-9536(90)90345-S
Abstract: A major factor in the aetiology of illness is the behaviour of in iduals with regard to certain risks and hazards of the environment. The Maori of New Zealand have been shown to be at greater risk of illness and death than their non-Maori counterparts. It is estimated that a significant proportion of this excess morbidity and mortality can be attributed to at least four behavioural factors: smoking, obesity, alcohol use and accidents. This paper examines the inter-cultural differences in these factors, both from a contemporary and an historical perspective. Some of the reasons for the continuation of these adverse patterns of behaviour are explored, in particular the role of psycho-cultural stress. Some possible mechanisms of effecting behavioural change in modern Maori society are discussed.
DSM-IV major depressive episode in the elderly: The relationship between the number and the type of depressive symptoms and impairment
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.JAD.2008.12.014
Abstract: There is a lack of studies that assess whether the DSM-IV criteria for Major Depressive Episode (MDE) that use a diagnostic threshold are valid for the elderly and whether each symptom of depression contributes equally to impairment in this group. The Australian National Survey of Mental Health and Wellbeing is a population-based epidemiological survey which utilized the Composite International Diagnostic Instrument to diagnose MDE. Analyses were based on the survey respondents who endorsed either (or both) the "depressed mood" or "loss of interest" core MDE symptoms (60+ years, n=278 40+ years, n=1020). A series of multivariate linear regression analyses were run to assess the relationship between the number and the type of depressive symptoms and five measures of impairment. For those aged 60+ years, a linear relationship alone was observed for the relationship between the number of depressive symptoms and each of the five measures but not all symptoms of depression were equal predictors of impairment loss of energy was the most consistent predictor. When the regression analyses were repeated using respondents aged 40+ years, consistent significant interactions between age and in idual symptoms of depression were not observed. The dimensionality of MDE is assessed focusing solely on symptoms. Our data illustrate the apparent dimensional structure of MDE and the differential impact of depressive symptoms on impairment in an elderly sub-s le. There was little support for systematic age-dependent changes. Adjustments to the diagnostic criteria of MDE may not require age-dependent distinctions.
Classifying MCI Subtypes in Community-Dwelling Elderly Using Cross-Sectional and Longitudinal MRI-Based Biomarkers
Publisher: Frontiers Media SA
Date: 26-09-2017
Cognitive screening improves the predictive value of stroke severity scores for functional outcome 3-6 months after mild stroke and transient ischaemic attack: An observational study
Publisher: BMJ
Date: 08-2013
Sydney Centenarian Study
Publisher: Springer Singapore
Date: 2017
Corrigendum to Light to moderate alcohol use is associated with increased cortical gray matter in middle-aged men: A voxel-based morphometric study [Psychiatry Research: Neuroimaging 163(1) (2008) 61-69] (DOI:10.1016/j.pscychresns.2007.08.009)
Publisher: Elsevier BV
Date: 05-2009
Prevalence of mental disorders in the elderly: the Australian National Mental Health and Well-being Survey
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Design and Development of the Brain Training System for the Digital “Maintain Your Brain” Dementia-Prevention Trial
Publisher: JMIR Publications Inc.
Date: 27-02-2019
DOI: 10.2196/13135
Higher fasting plasma glucose is associated with striatal and hippocampal shape differences: The 2sweet project
Publisher: BMJ
Date: 05-2016
Carrier Dynamics and Saturation Effect in (113)B InAs/InP Quantum Dot Lasers
Publisher: Springer Science and Business Media LLC
Date: 03-2006
Citalopram-Clonazepam combination for primary depersonalization disorder: a case report.
Publisher: SAGE Publications
Date: 06-2002
Changes in cerebral hemodynamic and cognitive parameters after external carotid-internal carotid bypass surgery in patients with severe steno-occlusive disease: A pilot study
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.JNS.2012.07.034
Abstract: The direct impact of external carotid-internal carotid (EC-IC) bypass surgery on cognition of patients with severe steno-occlusive disease of internal carotid (ICA) or middle cerebral artery (MCA) is unknown. In this pilot study, we evaluated changes in cerebral hemodynamic and cognition in these patients. Patients with severe steno-occlusive disease and impaired cerebral vasodilatory reserve (CVR) with transcranial Doppler (TCD) breath holding index (BHI) and acetazolamide-challenged HMPAO-Single Photon Emission Tomographic (SPECT) imaging were offered EC-IC bypass surgery. CVR and cognitive performance using a formal neuropsychological battery were evaluated before and 3-6 months after surgery. Nine patients and 9 matched controls were recruited. Significant CVR improvement from TCD-BHI [median 0 (Inter-quartile range IQR 0.45) to 1.10 (IQR 0.73), p<0.001] and SPECT (p<0.001) was observed in surgery patients. EC-IC bypass patients had significant improvement in verbal memory (p=0.037) and executive function (p=0.043) and a trend of improvement in visual memory (p=0.052) compared to controls. EC-IC bypass surgery in carefully selected patients could improve cerebral hemodynamics and verbal memory and executive function.
Mapping Cortical Brain Asymmetry in 17,141 Healthy Individuals Worldwide via the ENIGMA Consortium
Publisher: Cold Spring Harbor Laboratory
Date: 10-2017
DOI: 10.1101/196634
Abstract: Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across in iduals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy in iduals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippoc al gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets ( N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders. Left-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.
Systematic review and meta-analysis of genetic studies of late-life depression
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.NEUBIOREV.2017.01.028
Abstract: Late-life depression (LLD) is thought to be multifactorial in etiology, including a significant genetic component. While a number of candidate gene studies have been carried out, results remain inconclusive. We undertook a systematic review of all genetic association studies of depression or depressive symptoms in late life published before February 2016, and performed meta-analyses on polymorphisms investigated in three or more independent studies. A total of 46 candidate gene studies examining 56 polymorphisms in 23 genes as well as a genome-wide association study (GWAS) were included. Meta-analyses were conducted for four polymorphisms using random effects models, of which three (APOE, BDNF, SLC6A4) were associated with LLD. These genes are implicated in hippoc al plasticity and stress reactivity, suggesting that dysregulation of these pathways may contribute to LLD. Despite using a large s le, the only GWAS published to date identified only one genome-wide significant locus in the 5q21 region. In the future, larger genetic studies specifically examining LLD, including non-hypothesis-driven GWAS, are required to further identify genetic determinants of LLD.
White matter integrity in mild cognitive impairment: A tract-based spatial statistics study
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.NEUROIMAGE.2010.05.068
Abstract: Mild cognitive impairment (MCI) as a clinical diagnosis has limited specificity, and identifying imaging biomarkers may improve its predictive validity as a pre-dementia syndrome. This study used diffusion tensor imaging (DTI) to detect white matter (WM) structural alterations in MCI and its subtypes, and aimed to examine if DTI can serve as a potential imaging marker of MCI. We studied 96 amnestic MCI (aMCI), 69 non-amnestic MCI (naMCI), and 252 cognitively normal (CN) controls. DTI was performed to measure fractional anisotropy (FA), and tract-based spatial statistics (TBSS) were applied to investigate the characteristics of WM changes in aMCI and naMCI. The diagnostic utility of DTI in distinguishing MCI from CN was further evaluated by using a binary logistic regression model. We found that FA was significantly reduced in aMCI and naMCI when compared with CN. For aMCI subjects, decreased FA was seen in the frontal, temporal, parietal, and occipital WM, together with several commissural, association, and projection fibres. The best discrimination between aMCI and controls was achieved by combining FA measures of the splenium of corpus callosum and crus of fornix, with accuracy of 74.8% (sensitivity 71.0%, specificity 76.2%). For naMCI subjects, WM abnormality was more anatomically widespread, but the temporal lobe WM was relatively spared. These results suggest that aMCI is best characterized by pathology consistent with early Alzheimer's disease, whereas underlying pathology in naMCI is more heterogeneous, and DTI analysis of white matter structural integrity can serve as a potential biomarker of MCI and its subtypes.
Clustering and Additive Effects of Nongenetic Risk Factors in Non–Autosomal-Dominant Degenerative and Vascular Young Onset Dementia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-10-2019
Restriction of activities, social isolation, and dementia
Publisher: Cambridge University Press (CUP)
Date: 16-08-2021
Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2015.09.031
Abstract: The variability of episodic memory decline and hippoc al atrophy observed with increasing age may partly be explained by genetic factors. KIBRA (kidney and brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes previously linked to episodic memory performance and volume of the hippoc us, a key memory structure. However, whether polymorphisms in these two genes also influence age-related longitudinal memory decline and hippoc al atrophy is still unknown. Using data from two independent cohorts, the Sydney Memory and Ageing Study and the Older Australian Twins Study, we investigated whether the KIBRA and CLSTN2 genetic polymorphisms (rs17070145 and rs6439886) are associated with episodic memory performance and hippoc al volume in older adults (65-90 years at baseline). We were able to examine these polymorphisms in relation to memory and hippoc al volume using cross-sectional data and, more importantly, also using longitudinal data (2 years between testing occasions). Overall we did not find support for an association of KIBRA either alone or in combination with CLSTN2 with memory performance or hippoc al volume, nor did variation in these genes influence longitudinal memory decline or hippoc al atrophy in two cohorts of older adults.
Hippocampal atrophy is associated with subjective memory decline: The PATH through life study
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.JAGP.2014.07.009
Abstract: To investigate whether subjective memory decline (SMD) in cognitively healthy in iduals is associated with hippoc al atrophy. Multiple regression analyses assessing the relationship between hippoc al atrophy over 4 years and SMD at baseline and follow-up in 305 cognitively healthy in iduals aged 60-64 years free from dementia, mild cognitive impairment, and other neurological disorders. SMD at baseline was not a significant predictor of hippoc al atrophy. However, SMD at follow-up was associated with greater hippoc al atrophy. Associations were reduced but remained significant after controlling for anxiety and depression symptomatology. Hippoc al atrophy was associated with incident ersisting SMD and this association was not, or only partly, explained by anxiety and depression symptomatology. These results are consistent with a biological origin to subjective memory decline. SMD should be included in screening and neuropsychological batteries.
Genetic and environmental influences on obsessive-compulsive disorder
Publisher: Springer Science and Business Media LLC
Date: 23-02-2008
DOI: 10.1007/S00406-007-0789-0
Abstract: It is important to understand how genetic and environmental factors interact in the development of obsessive-compulsive disorder (OCD) in order to provide a cohesive model of the underlying pathogenic mechanisms. In this article, we provide an overview of the current knowledge of possible genetic and environmental contributions to the development of OCD. We consider the significant challenges for identifying risk factors for OCD as well as promising avenues for overcoming these obstacles in future research. In particular, we discuss the value of focusing on certain phenotypes, applying a dimensional approach, and investigating possible endophenotypes. We also describe innovative study designs that may be used in future research to explore the interaction between genetic vulnerability and environmental risk factors for OCD.
Neurosurgical treatment of mood disorders: Traditional psychosurgery and the advent of deep brain stimulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2009
Assessment of complex mental activity across the lifespan: Development of the Lifetime of Experiences Questionnaire (LEQ)
Publisher: Cambridge University Press (CUP)
Date: 20-11-2007
DOI: 10.1017/S003329170600938X
Abstract: Background. Brain reserve is a property of the central nervous system related to complex mental activity which may mediate the course and clinical expression of brain injury. Since there is no instrument that comprehensively assesses complex mental activity through the lifespan, we developed and tested the Lifetime of Experiences Questionnaire (LEQ) in a prospective study of healthy ageing. Method. The LEQ assesses educational, occupational and cognitive lifestyle activities at different stages through life. Test–retest, item analysis and Item Response Theory (IRT) were used to determine reliability. Dimensionality was evaluated using factor analysis. Validity was established through IRT analysis of test performance, correlation with an extant contemporaneous instrument (Cognitive Activities Scale CAS) and prediction of global cognitive change over 18 months controlling for age, baseline cognition and hypertension. Results. In a s le of healthy older in iduals ( n =79) the LEQ was found to be consistent, coherent and discriminate between in iduals with high and low mental activity levels. Factor analysis revealed a dominant factor which loaded heavily on education, occupation and leisure activity. Total LEQ was significantly correlated with the CAS. Furthermore, in iduals with higher LEQ scores showed less cognitive decline over 18 months, independent of covariates ( r =0·37, p =0·003). Conclusions. The LEQ is a reliable and valid instrument for assessing complex lifespan mental activity which is protective against cognitive decline. The LEQ is therefore proposed as a useful tool for estimating brain reserve in older in iduals and further development is anticipated.
Complex mental activity and risk for dementia.
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Study of Mental Activity and Regular Training (SMART) in at risk individuals: A randomised double blind, sham controlled, longitudinal trial
Publisher: Springer Science and Business Media LLC
Date: 21-04-2011
Structural brain network measures are superior to vascular burden scores in predicting early cognitive impairment in post stroke patients with small vessel disease
Publisher: Elsevier BV
Date: 2019
Effect of prolonged treatment with haloperidol on emotional defecation and movement in rats in a well-habituated environment
Publisher: Elsevier BV
Date: 10-1994
DOI: 10.1016/0165-1781(94)90067-1
Abstract: Sixteen adult male Wistar rats were administered either haloperidol (n = 8), 0.5 mg/kg, or saline (placebo) (n = 8) by subcutaneous injection three times per week for 6 weeks, and were again injected after a 6-week drug-free period. The study was conducted in a well-habituated, distinctive environment to which the rats were introduced 1 hour before the injection on each occasion. The fecal bolus counts 1 hour before and 2 hours after drug injection were obtained, as well as movement counts repeatedly in epochs of 90 seconds upon introduction to the cages and after the injections. Haloperidol produced an overall increase in defecation in the 2 hours after drug injection compared with placebo. The post-drug bolus counts for haloperidol-treated rats were lower in week 2 compared with week 1, but the difference from placebo for this reduction was not significant, and it did not persist beyond week 4. The haloperidol-treated group showed a significant increase in the predrug bolus counts from week 5, suggesting a conditioned response to the cage environment. The haloperidol-treated rats were markedly less mobile than the placebo-treated rats, and with repeated exposure to haloperidol, they tended to develop hypomotility earlier. No tolerance to the movement effect was observed. The defecation and movement effects of haloperidol at 12 weeks were no different from those at week 1. This study supports earlier work indicating that haloperidol produces a dysphoric effect in rats, and it suggests that this effect does not habituate over 6 weeks of repeated administration. It does not replicate the motor aspect of akathisia seen in humans.
Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-01-2019
DOI: 10.1212/WNL.0000000000006851
Abstract: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10 −8 and LINC00539/ZDHHC20, p = 5.82 × 10 −9 . Both have been associated with blood pressure (BP)–related phenotypes, but did not replicate in the smaller follow-up s le or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits ( p value for BI, p [BI] = 9.38 × 10 −25 p [SSBI] = 5.23 × 10 −14 for hypertension), smoking ( p [BI] = 4.4 × 10 −10 p [SSBI] = 1.2 × 10 −4 ), diabetes ( p [BI] = 1.7 × 10 −8 p [SSBI] = 2.8 × 10 −3 ), previous cardiovascular disease ( p [BI] = 1.0 × 10 −18 p [SSBI] = 2.3 × 10 −7 ), stroke ( p [BI] = 3.9 × 10 −69 p [SSBI] = 3.2 × 10 −24 ), and MRI-defined white matter hyperintensity burden ( p [BI] = 1.43 × 10 −157 p [SSBI] = 3.16 × 10 −106 ), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI ( p ≤ 0.0022), without indication of directional pleiotropy. In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
Genome-wide association study of white matter lesions in older individuals
Publisher: Wiley
Date: 07-2011
Textbook of stroke medicine - M Brainin, W-D Heiss (Eds), Cambridge, UK, Cambridge University Press, 2010. Hardback: 326. ISBN: 978-0-521-51826-0.
Publisher: Cambridge University Press (CUP)
Date: 08-2011
DSM-5 and Mental Disorders in Older Individuals
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2015
Memory training alters hippocampal neurochemistry in healthy elderly
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2003
Zero valent iron core–iron oxide shell nanoparticles as small magnetic particle imaging tracers
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9CC08972A
Abstract: Zero valent iron core–iron oxide shell nanoparticles coated with a multi-phosphonate brush co-polymer are shown to be small and effective magnetic nanoparticle imaging tracers.
Can cognitive exercise prevent the onset of dementia? systematic review of randomized clinical trials with longitudinal follow-up
Publisher: Elsevier BV
Date: 03-2009
Acute drug-induced akathisia is not associated with low serum iron status
Publisher: Springer Science and Business Media LLC
Date: 1991
DOI: 10.1007/BF02244089
Weekly Alcohol Consumption, Brain Atrophy, and White Matter Hyperintensities in a Community-Based Sample Aged 60 to 64 Years
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2006
DOI: 10.1097/01.PSY.0000237779.56500.AF
Abstract: The objective of this study was to determine the association between weekly alcohol consumption and brain atrophy in adults aged 60 to 64 years. Brain magnetic resonance imaging scans from 385 adults recruited through a community survey were analyzed. Automated segmentation and manual tracing methods were used to obtain brain subvolumes and automated methods were used to obtain quantification and localization of white matter hyperintensities. Visual measures of cortical atrophy were obtained as were data on health and lifestyle factors. Alcohol consumption was assessed with the Alcohol Use Disorders Identification Test. In men, weekly alcohol consumption had a positive linear association with ventricular volume and gray matter and a negative linear association with white matter. In women, weekly alcohol consumption had a nonlinear relationship with cerebrospinal fluid and white matter. Alcohol consumption was not associated with white matter hyperintensities, corpus callosum size, hippoc al or amygdala volumes in analyses adjusting for confounding variables. An association between alcohol consumption and brain atrophy is evident at the population level. In women, detrimental effects of alcohol on the brain appear to occur at lower levels of consumption. It remains possible that low levels of alcohol consumption have neuroprotective benefits but is clear that high levels of consumption are detrimental.
Neuroimaging and neuropathology indices of cerebrovascular disease burden
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-07-2018
DOI: 10.1212/WNL.0000000000005997
Abstract: To systematically review the literature on the use of both neuroimaging and neuropathologic indices of cerebrovascular disease (CVD) burden, as estimation of this burden could have multiple benefits in the diagnosis and prognosis of cognitive impairment and dementia. MEDLINE and EMBASE databases were searched (inception to June 2017) to obtain and then systematically review all pertinent neuroimaging and neuropathology studies, where an index of CVD was developed or tested. Twenty-five neuroimaging articles were obtained, which included 4 unique indices. These utilized a limited range of CVD markers from mainly structural MRI, most commonly white matter hyperintensities (WMH), cerebral microbleeds, and dilated perivascular spaces. Weighting of the constituent markers was often coarse. There were 7 unique neuropathology indices, which were heterogeneous in their regions s led and lesions examined. There is increasing interest in indices of total CVD burden that incorporate multiple lesions, as traditional in idual markers of CVD such as WMH only provide limited information. Neuropathologic indices are needed to validate neuroimaging findings. The studies clearly demonstrated proof of concept that information from multiple imaging measures of CVD provide more information, including a stronger association with cognitive impairment and dementia, than that provided by a single measure. There has been limited exploration of the psychometric properties of published indices and no comparison between indices. Further development of indices is recommended, including the use of data from diffusion tensor and perfusion imaging.
APPROACHES TO HARMONIZE NEUROPSYCHOLOGICAL DATA ACROSS STUDIES
Publisher: Wiley
Date: 07-2018
Optimal weights for local multi-atlas fusion using supervised learning and dynamic information (SuperDyn): Validation on hippocampus segmentation
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.NEUROIMAGE.2011.01.078
Abstract: We developed a novel method for spatially-local selection of atlas-weights in multi-atlas segmentation that combines supervised learning on a training set and dynamic information in the form of local registration accuracy estimates (SuperDyn). Supervised learning was applied using a jackknife learning approach and the methods were evaluated using leave-N-out cross-validation. We applied our segmentation method to hippoc al segmentation in 1.5T and 3T MRI from two datasets: 69 healthy middle-aged subjects (aged 44-49) and 37 healthy and cognitively-impaired elderly subjects (aged 72-84). Mean Dice overlap scores (left hippoc us, right hippoc us) of (83.3, 83.2) and (85.1, 85.3) from the respective datasets were found to be significantly higher than those obtained via equally-weighted fusion, STAPLE, and dynamic fusion. In addition to global surface distance and volume metrics, we also investigated accuracy at a spatially-local scale using a surface-based segmentation performance assessment method (SurfSPA), which generates cohort-specific maps of segmentation accuracy quantified by inward or outward displacement relative to the manual segmentations. These measurements indicated greater agreement with manual segmentation and lower variability for the proposed segmentation method, as compared to equally-weighted fusion.
Interrupting the trajectory of frailty in dementia with Lewy bodies with anabolic exercise, dietary intervention and deprescribing of hazardous medications
Publisher: BMJ
Date: 04-2020
Abstract: An 87-year-old man with dementia with Lewy bodies, living in residential aged care, exhibited rapid functional decline and weight loss associated with injurious falls over 9 months. Independent clinicians (geriatrician and exercise physiologist) assessed him during an extended wait-list period prior to his commencement of a pilot exercise trial. The highly significant role of treatable factors including polypharmacy, sarcopenia and malnutrition as contributors to frailty and rapid functional decline in this patient are described. The results of a targeted intervention of deprescribing, robust exercise and increased caloric intake on his physical and neuropsychological health status are presented. This case highlights the need to aggressively identify and robustly treat reversible contributors to frailty, irrespective of advanced age, progressive ‘untreatable’ neurodegenerative disease and rapidly deteriorating health in such in iduals. Frailty is not a contraindication to robust exercise it is, in fact, one of the most important reasons to prescribe it.
Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex
Publisher: Springer Science and Business Media LLC
Date: 13-10-2016
Degeneration vs. degeneracy: a neural systems approach to functional reorganization.
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Tardive blepharospasm.
Publisher: Wiley
Date: 11-1998
Abstract: I report on five patients with tar e blepharospasm seen in a movement disorders clinic, out of 25 tar e dystonia patients. They were young (aged 25-50 yrs) four were men and three had a schizophrenic disorder. The onset was gradual while on maintenance neuroleptics in four and on withdrawal in the fifth. There were no significant antecedent events precipitating the disorder. The disorder was bilateral but asymmetric in two cases. Dyskinetic blinking was often an initial feature and tended to persist after the resolution of the blepharospasm. Orolingual dyskinesia was present in one case and tar e akathisia in two other cases. The symptoms fluctuated in severity with a number of exacerbating and relieving factors. Reduction of neuroleptic dose led to improvement with complete reversal in one of two patients who could be withdrawn off neuroleptic medication. These reports suggest that TB, although uncommon, can be a disabling disorder that may improve considerably with the cessation or dose reduction of the neuroleptic drugs. Its treatment and longitudinal course should be further examined.
Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study.
Publisher: Public Library of Science (PLoS)
Date: 21-03-2017
The Brain Effects of Laser Acupuncture in Depressed Individuals: An fMRI Investigation
Publisher: Mary Ann Liebert Inc
Date: 09-2012
P2–155: The subclassification of amnestic MCI using MRI‐based cortical thickness measures
Publisher: Wiley
Date: 07-2013
Reply to the Letter to the Editor by O'Caoimh et al
Publisher: Elsevier BV
Date: 11-2015
The clinical features of tourette's disorder: An Australian study using a structured interview schedule
Publisher: SAGE Publications
Date: 06-1994
DOI: 10.1080/00048679409075645
Abstract: The clinical features of an Australian series of patients fulfilling DSM-III-R criteria for Tourette's Syndrome (TS) were examined. Fifty patients, recruited from a hospital-based outpatient clinic and a self-help group, were interviewed using a structured schedule. TS is a complex disorder with wide ranging manifestations. Forty male and ten female TS patients with a mean age of 20.8 years (SD11.2) were assessed. The mean age of onset of tics was 8.3 years (SD 3.3). Simple motor tics occurring in the rostral body regions were more common (eye 86%, face and head 80%) when compared both to simple tics occurring caudally (leg 52%) and complex motor tics (58%). Simple vocal tics were more common (94%) than complex ones (44%). There was a rostrocaudal pattern in the age of onset and severity of simple motor tics. Rates of comorbidity were 32%, 18% and 30% for Attention-Deficit Hyperactivity Disorder, Major Depression and Generalised Anxiety Disorder respectively and this was reflected in the considerable proportion (32%) of the s le who first presented for reasons other than their tics. There were substantial delays between the age of first presentation and diagnosis of TS owing to the insidious onset of the disorder, misdiagnosis and delays in presentation for help. A comparison of the features of the present patients with those of other published studies revealed similarities with some differences. Better clinical recognition of the symptoms and modes of presentation of TS may improve existing delays in diagnosis and treatment.
Quantum dots as a theranostic approach in Alzheimer's disease: a systematic review
Publisher: Future Medicine Ltd
Date: 08-2021
Abstract: Aim: Quantum dots (QDs) are nanoparticles that have an emerging application as theranostic agents in several neurodegenerative diseases. The advantage of QDs as nanomedicine is due to their unique optical properties that provide high sensitivity, stability and selectivity at a nanoscale range. Objective: To offer renewed insight into current QD research and elucidate its promising application in Alzheimer's disease (AD) diagnosis and therapy. Methods: A comprehensive literature search was conducted in PubMed and Google Scholar databases that included the following search terms: ‘quantum dots’, ‘blood–brain barrier’, ‘cytotoxicity’, ‘toxicity’ and ‘Alzheimer's disease’ PRISMA guidelines were adhered to. Results: Thirty-four publications were selected to evaluate the ability of QDs to cross the blood–brain barrier, potential toxicity and current AD diagnostic and therapeutic applications. Conclusion: QD's unique optical properties and versatility to conjugate to various biomolecules, while maintaining a nanoscale size, render them a promising theranostic tool in AD.
Gender Differences in Frontal Activation While Perceiving Pathologically Thin Female Body Forms
Publisher: Scientific Research Publishing, Inc.
Date: 2011
Threat Perception in Mild Cognitive Impairment and Early Dementia
Publisher: Oxford University Press (OUP)
Date: 11-08-2009
Abstract: Mild cognitive impairment (MCI) and dementia affect many aspects of emotion processing. Even though the ability to detect threat is a particularly important aspect of emotion processing, no study to date has assessed threat perception in either of these groups. The purpose of the present study was to test whether in iduals with MCI (n = 38) and mild dementia (n = 34) have difficulty differentiating between faces and situations normatively judged to be either high or low in threat relative to age-matched controls (n = 34). To achieve this aim, all participants completed 2 danger rating tasks that involved viewing and rating high- and low-danger images. It was also assessed whether threat perception was related to cognitive functioning and emotion recognition. The results indicated that all 3 groups were accurately, and comparably, able to differentiate high from low-danger faces. However, the dementia group had difficulties differentiating high from low-danger situations, which reflected a bias to overattribute the level of threat posed by normatively judged nonthreatening situations. This difficulty was related to more general cognitive decline.
Corrigendum: Identification of Cerebral Metal Ion Imbalance in the Brain of Ageing Octodon degus
Publisher: Frontiers Media SA
Date: 2017
Light to moderate alcohol use is associated with increased cortical gray matter in middle-aged men: A voxel-based morphometric study
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.PSCYCHRESNS.2007.08.009
Abstract: We examined the associations of current alcohol consumption with brain morphometric measures in a healthy, community-dwelling cohort. Cranial T1-weighted 3D-structural MRI scans were obtain in 383 adults (men=211) aged 60-64 years, randomly selected form the larger PATH Through Life study. Voxel-based morphometric analyses were applied to detect regional gray matter and white matter volume changes related to reported weekly alcohol consumption (mean 7.04+/-8.15 drinks per week). Alcohol consumption in men had a linear association with greater gray matter in bilateral superior and medial frontal gyrus, bilateral middle occipital gyrus, right inferior parietal gyrus, bilateral precentral gyrus, left paracentral gyrus, left uncus and left inferior occipital gyrus, and with lesser white matter in bilateral superior temporal and left parahippoc al gyrus, after adjustment for age, education, total intracranial volume, smoking, hypertension, diabetes and hyperlipidemia. In women, there was no significant linear association between alcohol consumption and total or regional brain volumes. Our results showed a dose-related, sexually dimorphic impact of alcohol on brain tissue volumes independent of cerebrovascular risk factors. These findings are consistent with an inverse-U association between alcohol use and brain morphometry, while suggesting an increased vulnerability of white matter to alcohol-related brain damage.
Exploring the feasibility of a meta-structure for DSM-V and ICD-11: Could it improve utility and validity?
Publisher: Cambridge University Press (CUP)
Date: 10-2009
DOI: 10.1017/S0033291709990250
Abstract: The organization of mental disorders into 16 DSM-IV and 10 ICD-10 chapters is complex and based on clinical presentation. We explored the feasibility of a more parsimonious meta-structure based on both risk factors and clinical factors. Most DSM-IV disorders were allocated to one of five clusters as a starting premise. Teams of experts then reviewed the literature to determine within-cluster similarities on 11 predetermined validating criteria. Disorders were included and excluded as determined by the available data. These data are intended to inform the grouping of disorders in the DSM-V and ICD-11 processes. The final clusters were neurocognitive (identified principally by neural substrate abnormalities), neurodevelopmental (identified principally by early and continuing cognitive deficits), psychosis (identified principally by clinical features and biomarkers for information processing deficits), emotional (identified principally by the temperamental antecedent of negative emotionality), and externalizing (identified principally by the temperamental antecedent of disinhibition). Large groups of disorders were found to share risk factors and also clinical picture. There could be advantages for clinical practice, public administration and research from the adoption of such an organizing principle.
Challenges of diagnosing dementia in the oldest old population
Publisher: Oxford University Press (OUP)
Date: 17-05-2013
High arterial pulse wave velocity is a risk factor for falls in community-dwelling older people.
Publisher: Wiley
Date: 15-07-2014
DOI: 10.1111/JGS.12931
Abstract: To examine whether arterial stiffness is a risk factor for falls in community-dwelling older people. Prospective cohort study. Community population, Sydney, Australia. Community-dwelling older adults (mean age 79.8±4.4, 52.2% female N=481). Carotid-femoral pulse wave velocity (PWV) was measured in the supine position after lying for 10 minutes. Demographic, medical, and medication characteristics and levels of physical activity were obtained in clinical interviews and questionnaires, and falls were recorded with monthly falls diaries for 12 months. Participants in the top quintile of PWV (high PWV) were more likely to have higher seated systolic blood pressure (SBP) and heart rate, unsatisfactory control of blood pressure, diabetes mellitus, and lower physical activity levels. These participants were also more likely to be male and taking cardiovascular medications. Of the 473 participants available for follow-up, 212 (44.8%) reported one or more falls. In modified Poisson regression analyses, high PWV was a risk factor for falls (relative risk=1.37, 95% confidence interval=1.06-1.78) after adjusting for use of psychotropic and cardiovascular medications, age, sex, body mass index, seated SBP, heart rate, and diabetes status. In community-dwelling older people, high PWV (as a measure of arterial stiffness) was a risk factor for falls after adjusting for potential demographic, anthropometric, disease, and medication confounders. Further research is required to investigate mediators for this association and the effect of lowering arterial stiffness on falls in older people.
The genetics of white matter lesions.
Publisher: Wiley
Date: 07-07-2011
Is Alzheimer's a disease of the white matter?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
Publisher: Springer Science and Business Media LLC
Date: 03-10-2018
DOI: 10.1038/S41380-018-0118-1
Abstract: Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes ( β = −0.71 to −1.37 P 0.0005). In an independent s le, consistent results were obtained, with significant effects in the pallidum ( β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV ( P = 0.0032, 8.9 × 10 −6 , 1.7 × 10 − 9 , 3.5 × 10 −12 and 1.0 × 10 −4 , respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
Enterprise Computing (Editorial)
Publisher: Elsevier BV
Date: 11-2022
Obsessive compulsive disorder: time to decide on a new model?
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Effects of cerebrovascular risk factors on gray matter volume in adults aged 60-64 years: a voxel-based morphometric study.
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.PSCYCHRESNS.2006.01.009
Abstract: The effect of putative cerebrovascular risk factors on gray matter volume in a community-dwelling, non-demented 60- to 64-year-old cohort was investigated. Cranial T1-weighted MRI scans were obtained in 337 adults and voxel-based morphometric analyses were applied to detect regional gray matter volume differences related to hypertension, diabetes, smoking, and hyperlipidemia in men and women, respectively. Hypertension-related gray matter volume reduction was found in right superior, bilateral medial frontal, left superior temporal and left precentral gyri in men. No regional differences in gray matter related to hypertension were seen in women. Conversely, female but not male smokers had more gray matter volume in right fusiform gyrus and right temporal subgyral gray matter. No differences were observed in gray matter volume in association with diabetes or hyperlipidemia for men or women. Our results suggest that there are different patterns of regional effects in gray matter volume in relation to different cerebrovascular risk factors, and sex differences for the same risk factors.
Classification of Mild Cognitive Impairment Subtypes using Neuropsychological Data
Publisher: SCITEPRESS - Science and and Technology Publications
Date: 2016
Differential Effects of Transcranial Magnetic Stimulation of Left and Right Posterior Parietal Cortex on Mental Rotation Tasks
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/S0010-9452(08)70413-1
Abstract: A recently published study used the interference strategy of transcranial magnetic stimulation (TMS) to demonstrate the role of the right posterior parietal cortex (PPC) in the mental rotation of alphanumeric stimuli. We used similar stimulation parameters over the same left and right PPC regions, and examined the ability to rotate more complex 3D Shepard and Metzler (1971) images. There was reduced accuracy of performance with both right and left PPC stimulation for different angles of rotation of the visual stimuli. Right PPC stimulation led to reduced accuracy to rotate stimuli by 1200, whereas left PPC stimulation affected 180 degrees C rotation. We hypothesise that the two hemispheres make different contributions to the processing underlying visuospatial mental imagery: the right PPC is important for spatial rotations through smaller angles the left hemisphere has a unique role when the stimuli to be compared are rotated through 180 degrees C, a task that engages verbal strategies due to the well-documented special nature of enantiomorphs.
Repetitive transcranial magnetic stimulation for the treatment of obsessive compulsive disorder: a double-blind controlled investigation
Publisher: Cambridge University Press (CUP)
Date: 26-07-2007
DOI: 10.1017/S0033291707001092
Abstract: To determine the efficacy and tolerability of repetitive transcranial magnetic stimulation (rTMS) as a treatment for obsessive compulsive disorder (OCD) in a double-blind placebo-controlled study. Subjects with treatment-resistant OCD were randomized to rTMS ( n =10) or sham rTMS ( n =8) for 10 sessions of daily stimulation over the left dorsolateral prefrontal cortex (DLPFC), with subjects and raters being blind to the treatment. Subjects were offered an open extension of up to 20 sessions of rTMS. The two groups did not differ on change in Yale–Brown Obsessive Compulsive Scale (YBOCS) or Maudsley Obsessive-Compulsive Inventory scores over 10 sessions, with or without correction for depression ratings. Over 20 sessions, there was a significant reduction in total YBOCS scores, but not after controlling for depression. rTMS over 20 sessions was well tolerated. Two weeks of rTMS over the left DLPFC is ineffective for treatment-resistant OCD.
Development of a short‐form version of the Reading the Mind in the Eyes Test for assessing theory of mind in older adults
Publisher: Wiley
Date: 30-07-2020
DOI: 10.1002/GPS.5369
Neurocognitive disorders: Cluster 1 of the proposed meta-structure for DSM-V and ICD-11
Publisher: Cambridge University Press (CUP)
Date: 10-2009
DOI: 10.1017/S0033291709990262
Abstract: In an effort to group mental disorders on the basis of aetiology, five clusters have been proposed. In this paper, we consider the validity of the first cluster, neurocognitive disorders, within this proposal. These disorders are categorized as ‘Dementia, Delirium, and Amnestic and Other Cognitive Disorders’ in DSM-IV and ‘Organic, including Symptomatic Mental Disorders’ in ICD-10. We reviewed the literature in relation to 11 validating criteria proposed by a Study Group of the DSM-V Task Force as applied to the cluster of neurocognitive disorders. ‘Neurocognitive’ replaces the previous terms ‘cognitive’ and ‘organic’ used in DSM-IV and ICD-10 respectively as the descriptor for disorders in this cluster. Although cognitive/organic problems are present in other disorders, this cluster distinguishes itself by the demonstrable neural substrate abnormalities and the salience of cognitive symptoms and deficits. Shared biomarkers, co-morbidity and course offer less persuasive evidence for a valid cluster of neurocognitive disorders. The occurrence of these disorders subsequent to normal brain development sets this cluster apart from neurodevelopmental disorders. The aetiology of the disorders is varied, but the neurobiological underpinnings are better understood than for mental disorders in any other cluster. Neurocognitive disorders meet some of the salient criteria proposed by the Study Group of the DSM-V Task Force to suggest a classification cluster. Further developments in the aetiopathogenesis of these disorders will enhance the clinical utility of this cluster.
Editorial introductions
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
Magnetic resonance spectroscopy in cognitive research
Publisher: Elsevier BV
Date: 03-2004
Validation and Normative Data for the Modified Telephone Interview for Cognitive Status: The Sydney Memory and Ageing Study
Publisher: Wiley
Date: 09-07-2019
DOI: 10.1111/JGS.16033
Abstract: Telephone-based cognitive screens, such as the Telephone Interview for Cognitive Status (TICS), can potentially reduce the barriers and costs of assessing older adults. However, validation of clinically relevant psychometric properties is lacking in a large and comprehensively assessed s le of older adults. Furthermore, published normative data may lack sensitivity as they have not used regression-based demographic corrections or accounted for cases with subsequent dementia. We address these gaps using the modified TICS (TICS-M a modified, 13-item, 39-point version) and provide an online norms calculator for clinicians and researchers. Prospective longitudinal study. Sydney, Australia. A total of 617 community-living older adults, aged from 71 to 91 years. The measures used included the TICS-M, the Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination-Revised (ACE-R), and a comprehensive neuropsychological test battery. Descriptive statistics, correlations, area under the curve, and regression analyses were used to determine the validity and normative properties of the TICS-M. TICS-M total scores (mean = 24.20 SD = 3.76) correlated well with the MMSE (0.70) and ACE-R (0.80) and moderately with neuropsychological tests tested noncontemporaneously. A cutoff score of 21 or lower reliably distinguished between those with and without incident dementia after 1 year (sensitivity = 77% specificity = 88%) but was less reliable at distinguishing mild cognitive impairment from normal cognition. TICS-M scores decreased with age and increased with higher education levels. The robust normative s le, which excluded incident dementia cases, scored higher on the TICS-M and with less variability than the whole s le. An online calculator is provided to compute regression-based norms and reliable change statistics. In a large s le of community-dwelling older adults, the TICS-M performed well in terms of construct validity against typical screening tools and neuropsychological measures and diagnostic validity for incident dementia. The comprehensive, regression-based, and robust normative data provided will help improve the sensitivity, accessibility, and cost-effectiveness of cognitive testing with older adults. J Am Geriatr Soc 67:2108-2115, 2019.
Pulmonary Function, Cognitive Impairment and Brain Atrophy in a Middle-Aged Community Sample
Publisher: S. Karger AG
Date: 2006
DOI: 10.1159/000091438
Abstract: i Objective: /i To determine the relationship of lung function to brain anatomical parameters and cognitive function and to examine the mediating factors for any relationships. i Methods: /i A random sub-s le of 469 persons (men = 252) aged 60–64 years from a larger community s le underwent brain magnetic resonance imaging scans and pulmonary function tests (forced vital capacity, FVC, forced expiratory volume in the first second, FEV sub /sub ). Subjects were assessed for global cognitive function, episodic memory, working memory, information processing speed, fine motor dexterity and grip strength. The magnetic resonance imaging scans were analysed for overall brain atrophy, subcortical atrophy (ventricle-to-brain ratio, VBR), hippoc al volume, and white matter hyperintensity (WMH) volume. i Results: /i FEV sub /sub had a significant negative correlation with overall brain atrophy and VBR in men. The FEV sub /sub /FVC ratio had a significant correlation with WMHs in both men and women. In regression models that controlled for sex, age, height, level of activity, smoking, chronic respiratory disease and education, FEV sub /sub and FVC were significant predictors of VBR but no other structural brain measure. Pulmonary function was also significantly related to information processing speed and fine motor dexterity. Male subjects with chronic respiratory disease had more deep WMHs. Path analyses to examine if structural measures mediated between lung function and cognition, and whether markers of inflammation and oxidative stress or cortisol mediated between lung function and brain measures were negative. i Conclusions: /i Decreased lung function is related to poorer cognitive function and increased subcortical atrophy in mid-adult life. Presence of chronic respiratory disease may be related to deep WMHs in men.
Structural brain networks and neuropsychiatric disorders
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
A high-resolution single photon emission computed tomography study of verbal recognition memory in Alzheimer's disease
Publisher: S. Karger AG
Date: 2006
DOI: 10.1159/000091433
Abstract: i Background: /i In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer’s disease (AD) subjects on a verbal recognition memory task. i Methods: /i Eighteen early AD and 10 matched healthy control subjects underwent split-dose sup m /sup Tc-HMPAO (Ceretec sup ® /sup ) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. i Results: /i In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippoc us. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippoc us. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. i Conclusions: /i Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.
Hypomania Induction in a Patient With Bipolar II Disorder by Transcranial Direct Current Stimulation (tDCS)
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2011
Perception of Biological Motion and Emotion in Mild Cognitive Impairment and Dementia
Publisher: Cambridge University Press (CUP)
Date: 12-06-2012
DOI: 10.1017/S1355617712000665
Abstract: Participants diagnosed with mild cognitive impairment (MCI), dementia and controls completed measures that required decoding emotions from point-light displays of bodily motion, and static images of facial affect. Both of these measures tap social cognitive processes that are considered critical for social competency. Consistent with prior literature, both clinical groups were impaired on the static measure of facial affect recognition. The dementia (but not the MCI) group additionally showed difficulties interpreting biological motion cues. However, this did not reflect a specific deficit in decoding emotions, but instead a more generalized difficulty in processing visual motion (both to action and to emotion). These results align with earlier studies showing that visual motion processing is disrupted in dementia, but additionally show for the first time that this extends to the recognition of socially relevant biological motion. The absence of any MCI related impairment on the point-light biological emotion measure (coupled with deficits on the measure of facial affect recognition) also point to a potential disconnect between the processes implicated in the perception of emotion cues from static versus dynamic stimuli. For clinical (but not control) participants, performance on all recognition measures was inversely correlated with level of semantic memory impairment. ( JINS , 2012, 18 , 1–8)
Clinical determinants of dementia and mild cognitive impairment following ischaemic stroke: The Sydney stroke study
Publisher: S. Karger AG
Date: 2006
DOI: 10.1159/000091434
Abstract: i Background: /i Dementia following stroke is common but its determinants are still incompletely understood. i Methods: /i In the Sydney Stroke Study, we performed detailed neuropsychological and medical-psychiatric assessments on 169 patients aged 50–85 years, 3–6 months after a stroke, and 103 controls with a majority of both groups undergoing MRI brain scans. Stroke subjects were diagnosed as having vascular mild cognitive impairment (VaMCI) or vascular dementia (VaD) or no cognitive impairment by consensus. Demographic, functional, cerebrovascular risk factors and neuroimaging parameters were examined as determinants of dementia using planned logistic regression. i Results: /i 21.3% of subjects were diagnosed with VaD, with one case in those aged 50–59 years, 24% in those aged 60–69 years and 23% in those 70–79 years. There was no difference by sex. The prevalence of VaMCI was 36.7%. VaD subjects had lower premorbid intellectual functioning and had 0.9 years less education than controls. The VaD and VaMCI groups did not differ from the no cognitive impairment group on any specific cerebrovascular risk factor, however overall those with impairment had a greater number of risk factors. They did not differ consistently on depression severity, homocysteine levels and neuroimaging parameters (atrophy, infarct volume and number of infarcts) except for an excess of white matter lesions on MRI and greater number of infarcts in the VaD and VaMCI groups. On a series of logistic regression analyses, stroke volume and premorbid function were significant determinants of cognitive impairment in stroke patients. i Conclusion: /i Post-stroke dementia and MCI are common, especially in older in iduals. Cerebrovascular risk factors are not independent risk factors for VaD, but stroke volume is a significant determinant of dementia. Premorbid functioning is a determinant of post- stroke impairment.
Biological determinants of depression following bereavement
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.NEUBIOREV.2014.12.013
Abstract: There is considerable variability among people in their response to bereavement. While most people adapt well to bereavement, some develop exaggerated and/or pathological responses and may meet criteria for a major depressive episode. Many studies have investigated the effect of psychosocial factors on bereavement outcome but biological factors have not received much attention, hence the focus of this paper. The biological factors studied to date in relation to bereavement outcomes include genetic polymorphisms, neuroendocrine factors, and immunologic/inflammatory markers. In addition, animal studies have shown the alterations of brain neurotransmitters as well as changes in the plasma levels of the neurotrophic growth factors under the influence of peer loss. Recent studies have also investigated the biological basis of stress resilience, and have found a few genetic polymorphisms and potential biomarkers as protective factors in the face of adversity. Longitudinal studies that include data collection prior to, and also after, bereavement and which chart both biological and psychological measures are needed to develop profiles for the prediction of response to bereavement and personalised interventions.
Maori Elder-patient relationship as a therapeutic paradigm.
Publisher: Informa UK Limited
Date: 11-1989
DOI: 10.1080/00332747.1989.11024462
Abstract: This paper examines the dynamics of teh psychotherapeutic relationship between a Maori Elder and Maori psychiatric patients. The functioning of an Elder was examined over a period of 9 months in a psychiatric unit. A content analysis was performed on audiovisual records of 10 interviews conducted by the Elder on five psychiatric patients. The results of this analysis were used to construct a theoretical paradigm of the Elder-Patient Transaction and to contrast it with psychodynamic psychotherapy and pastoral counseling. Distinctive features of relationship, content of the sessions and the issues of dominance and dependence are discussed, and possible mechanisms of change are mentioned.
Differential gene expression in brain and peripheral tissues in depression across the life span: A review of replicated findings
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.NEUBIOREV.2016.08.018
Abstract: There is a growing body of research investigating the gene expression signature of depression at the genome-wide level, with potential for the discovery of novel pathophysiological mechanisms of depression. However, heterogeneity of depression, dynamic nature of gene expression patterns and various sources of noise have resulted in inconsistent findings. We systematically review the current state of transcriptome profiling of depression in the brain and peripheral tissues with a particular focus on replicated findings at the single gene level. By examining 16 brain regions and 5 cell types from the periphery, we identified 57 replicated differentially expressed genes in the brain and 21 in peripheral tissues. Functional overlap between brain and periphery strongly implicates shared pathways in a comorbid phenotype of depression and cardiovascular disease. The findings highlight dermal fibroblasts as a promising experimental model for depression biomarker research, provide partial support for all major theories of depression and suggest a novel candidate gene, PXMP2, which plays a critical role in lipid and reactive oxygen species metabolism.
Is DSM-5 defensible?
Publisher: SAGE Publications
Date: 2013
Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.
Publisher: Public Library of Science (PLoS)
Date: 23-07-2019
A sham-controlled trial of the efficacy and safety of twice-daily rTMS in major depression
Publisher: Cambridge University Press (CUP)
Date: 19-12-2006
Quantitation of NAD+: Why do we need to measure it?
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.BBAGEN.2018.07.023
Abstract: Nicotinamide adenine dinucleotide (NAD NAD+ levels can be elevated therapeutically using NAD+ precursors or through lifestyle modifications including exercise and caloric restriction. However, high amounts of NAD+ may be detrimental in cancer progression and may have deleterious immunogenic roles. Standardized quantitation of NAD+ and related metabolites may therefore represent an important component of NAD+ therapy. Quantitation of NAD+ may serve dual roles not only as an ageing biomarker, but also as a diagnostic tool for the prevention of malignant disorders.
Volumetrics of the caudate nucleus: Reliability and validity of a new manual tracing protocol
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.PSCYCHRESNS.2007.07.005
Abstract: Our aim was to develop a reliable and valid manual segmentation protocol for tracing the caudate nucleus in MRI for volumetric and, potentially, shape analysis of the caudate. Using the protocol, two inter- and intra-rater reliability studies were conducted using five different raters on two different image analysis platforms (ANALYZE, Mayo Biomedical Imaging Resource, Rochester MN, USA, and HERMES, Nuclear Diagnostics AB, Stockholm, Sweden). Reference images for the detailed protocol are described. Two studies were performed. In study 1, the intra-rater class correlation ICC(1,1) for an experienced rater (JCLL) using this protocol for caudate nucleus volumes was evaluated by repeating right and left caudate measurements on 10 scans (20 comparisons) and was 0.972. The inter-rater class correlation ICC(1,k) with OL was 0.922 on 5 scans (10 comparisons) and with BL was 0.960 on 5 scans (10 comparisons). In study 2, VT obtained an intra-rater class correlation of 0.9 on 5 scans (involving 10 comparisons, e.g. right and left caudate). The inter-rater class correlation ICC(1,k) was 0.988 on 5 scans (again involving 10 comparisons) with EM. We therefore developed a novel, reliable and reference image-based, method of outlining the caudate nucleus on axial MRI scans, usable in two different image analysis laboratories, across two different sets number of tracers reliably, and across software platforms. This method is therefore potentially usable for any image analysis package capable of displaying and measuring outlined voxels from MRI brain scans.
Tardive oculogyric crisis and obsessional thoughts
Publisher: Royal College of Psychiatrists
Date: 05-1991
Abstract: In the liver, stellate cells play several important (patho)physiological roles. They express a broad but variable spectrum of intermediate filament (IF) proteins. The aim of this study was to investigate the expression and functions of the intermediate filament protein synemin in hepatic stellate cells (HSCs). In isolated and cultured rat HSCs, synemin expression was examined by quantitative reverse transcriptase polymerase chain reaction, western blotting, and immunocytochemistry. Protein-protein interaction between synemin and possible binding partners was investigated by co-immunoprecipitation and confocal microscopy. Expression of synemin was significantly downregulated with increased culture time. In 1-day cultured HSCs, synemin associated with other IF proteins (GFAP, desmin, and vimentin), and with the focal adhesion proteins vinculin and talin, but not with alpha-actinin or paxillin. Synemin IF and focal adhesion proteins co-localised in long slender processes, but not in the lamellipodia. In human and rat liver tissue, the presence of synemin was investigated by immunohistochemistry. In normal rat and human livers, synemin immunoreactivity was found in HSCs, smooth muscle cells of hepatic arterioles, and nerve bundles in portal tracts, but not in portal fibroblasts. In CCl4-intoxicated rat livers and in human cirrhotic livers, immunoreactivity for synemin in the parenchymal tissue was decreased. Thus synemin was expressed in quiescent HSCs but not in portal fibroblasts and synemin expression decreased with HSC activation in vivo during chronic liver damage and with HSC activation in culture. Synemin forms heteropolymeric filaments with type-III IF proteins and acts as a bridging protein between IFs and a specific type of focal adhesions.
Level of cognitive performance as a correlate and predictor of health behaviors that protect against cognitive decline in late life: The path through life study
Publisher: Elsevier BV
Date: 11-2009
Cortical Gyrification And Sulcal Spans In Early Stage Alzheimer'S Disease
Publisher: Public Library of Science (PLoS)
Date: 21-02-2012
Prevalence and characteristics of depressive symptoms in mild cognitive impairment: The Sydney Memory and Ageing Study
Publisher: Wiley
Date: 04-09-2013
DOI: 10.1111/ACPS.12008
Abstract: Depression might be a risk factor for dementia. However, little is known about the prevalence of depressive symptoms in mild cognitive impairment (MCI) and whether mood or motivation-related symptoms are predominant. A total of 767 non-demented community-dwelling adults aged 70-90 years completed a comprehensive assessment, including neuropsychological testing, and a past psychiatric/medical history interview. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS) and Kessler Psychological Distress Scale (K10). Exploratory factor analysis was performed on the GDS and K10 to derive 'mood' and 'motivation' subscales. A total of 290 participants were classified as having MCI and 468 as cognitively normal (CN). Participants with MCI reported more depressive symptoms, and more MCI participants met the cut-off for clinically significant symptoms, relative to CN participants. Those with amnestic MCI (aMCI), but not non-amnestic MCI, had more depressive symptoms and were more likely to meet the cut-off for clinically significant depressive symptoms, relative to CN participants. Participants with MCI reported more mood-related symptoms than CN participants, while there were no differences between groups on motivation-related symptoms. In iduals with MCI, especially aMCI, endorse more depressive symptoms when compared with cognitively intact in iduals. These findings highlight the importance of assessing and treating depressive symptoms in MCI.
Magnetic resonance imaging in clinical psychiatry
Publisher: Wiley
Date: 04-1990
DOI: 10.1111/J.1600-0447.1990.TB05467.X
Abstract: Although psychiatric researchers have been quick to adopt magnetic resonance imaging (MRI) of the brain in their investigations, its clinical application has been slow to develop and most psychiatrists remain unaware of its potential advantages and disadvantages compared with CT scanning. In this article the procedures are compared and the potential advantages of MRI highlighted with the help of neuropsychiatric case histories. Clinical situations are then discussed in which a psychiatrist should consider ordering a MRI scan subsequent to or instead of a CT scan.
Correlates of Gait Speed Among Older Adults From 6 Countries: Findings From the COSMIC Collaboration
Publisher: Oxford University Press (OUP)
Date: 28-03-2023
Abstract: Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries. We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N = 6 472), with s les ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N = 4 cohorts) and rapid gait speed (N = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified. Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women. This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia.
Transcranial Direct Current Stimulation Priming of Therapeutic Repetitive Transcranial Magnetic Stimulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2009
Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-07-2018
DOI: 10.1212/WNL.0000000000006000
Abstract: To investigate the effects of completed pregnancy with childbirth and incomplete pregnancy without childbirth on the late-life cognition and the risk of Alzheimer disease (AD) in women. Using the pooled data of 3,549 women provided by 2 population-based cohort studies, we conducted logistic regression analyses to examine retrospectively the associations of completed and incomplete pregnancy with the risks of mild cognitive impairment and AD. For women without dementia, we also conducted analyses of covariance to examine the associations of completed and incomplete pregnancy with Mini-Mental State Examination (MMSE) score. Grand multiparous women who experienced ≥5 completed pregnancies showed an ≈1.7-fold higher risk of AD than those who experienced 1 to 4 completed pregnancies (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.04–2.72), while those who had incomplete pregnancies showed half the level of AD risk compared with those who never experienced an incomplete pregnancy (OR 0.43, 95% CI 0.24–0.76 for 1 incomplete pregnancy OR 0.56, 95% CI 0.34–0.92 for ≥2 incomplete pregnancies). In women without dementia, the grand multiparous had worse MMSE scores than those with 1 to 4 completed pregnancies ( p 0.001), while those who experienced ≥1 incomplete pregnancies had better MMSE scores than those who never experienced an incomplete pregnancy ( p = 0.008). Grand multiparity was associated with high risk of AD, while incomplete pregnancy was associated with low risk of AD in late life.
Development and clinimetric testing of the Unified Drug-Induced Movement Disorders Scale (UDIMS)
Publisher: Cold Spring Harbor Laboratory
Date: 22-03-2022
DOI: 10.1101/2022.03.21.22272729
Abstract: Objective: Several movement disorders develop secondary to the use of psychotropic drugs, for which multiple symptom rating scales are in common use. We planned to develop the Unified Drug-Induced Movement Scale (UDIMS) to assess the severity and impact of drug-induced dyskinesia, tremor, drug-induced parkinsonism, akathisia, dystonia and myoclonus with a single instrument. Methods: Based on a literature review, consultation and pilot work, a 12-item instrument was developed, with each item rated on a 0-4 scale. The clinimetric properties of UDIMS were examined in 53 psychiatric patients on psychotropic medications, using established ratings scales for validation. The factor structure of the scale was examined, and the movement disorder correlates of distress and disability were determined. Results: The instrument has good inter-rater reliability. Its correspondence with three other scales - Abnormal Involuntary Movements Scale, Simpson-Angus Scale and Prince Henry Hospital Akathisia Scale - for the relevant items was high. A principal components analysis yielded four factors, considered to represent tremor, parkinsonism, akathisia and dyskinesia. Overall movement-disorder related disability was related to parkinsonism and dyskinesia, while distress to all four components. Conclusions: UDIMS is a reliable and valid scale to quantify a range of drug-induced movement disorders (DIMDs), that obviates the need for the use of multiple rating scales. Its widespread use by both clinicians and researchers, and further refinement based on this, will help promote the detection and treatment of drug-induced movement disorders, thereby reducing both distress and disability.
Homocysteine and the Brain in Midadult Life
Publisher: American Medical Association (AMA)
Date: 09-2004
Can cognitive training prevent the onset of dementia? A systematic review of randomized clinical trials with longitudinal follow up
Publisher: Wiley
Date: 07-2009
Extent and Distribution of White Matter Hyperintensities in Stroke Patients
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2004
DOI: 10.1161/01.STR.0000147034.25760.3D
Abstract: Background and Purpose— White matter hyperintensities (WMHs) on T2-weighted MRI are common in stroke patients and healthy elderly in iduals. The detailed anatomical distribution of these lesions in stroke patients has not been examined. Methods— A total of 112 stroke or transient ischemic attack patients and 87 matched control subjects from the Sydney Stroke Study underwent MRI scans that included a T2-weighted fluid-attenuated inversion recovery (FLAIR) sequence. WMHs were delineated from each FLAIR MRI by an automated method. Region of interest and voxel-wise statistical parametric mapping approaches were applied to examine the volume, distribution, and severity of WMHs of the patient and control groups, and subgroups with large or lacunar infarcts. Results— Stroke subjects had significantly more WMHs than controls in all brain regions except the occipital lobe and in all arterial territories except the anterior callosal and anterior medial lenticulostriate. In the frontotemporal regions, average WMH volumes in patients were .5× those in controls. The total number of discrete WMHs was not different in the 2 groups, but stroke patients had more large ( mm) and high-intensity lesions. Subjects with lacunar infarcts had more WMHs than those with large infarcts, who, in turn, had more WMHs than control subjects. Lacunar infarction subjects had more WMHs than subjects with large thromboembolic or cardioembolic strokes. Those with anterior arterial territory infarction had more WMHs in the frontal regions. Subjects with single or multiple lacunes did not differ in volumes of WMHs. Conclusions— Stroke patients have significantly more WMHs in nearly every brain region than healthy controls. Those with lacunar infarcts are particularly affected. WMHs represent a significant proportion of the ischemic lesion burden in stroke and transient ischemic attack patients.
The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer's disease.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.ARR.2013.06.003
Abstract: Alzheimer's disease (AD) is characterised by extracellular amyloid deposits, neurofibrillary tangles, synaptic loss, inflammation and extensive oxidative stress. Polyphenols, which include resveratrol, epigallocatechin gallate and curcumin, have gained considerable interest for their ability to reduce these hallmarks of disease and their potential to slow down cognitive decline. Although their antioxidant and free radical scavenging properties are well established, more recently polyphenols have been shown to produce other important effects including anti-amyloidogenic activity, cell signalling modulation, effects on telomere length and modulation of the sirtuin proteins. Brain accessible polyphenols with multiple effects on pathways involved in neurodegeneration and ageing may therefore prove efficacious in the treatment of age-related diseases such as AD, although the evidence for this so far is limited. This review aims to explore the known effects of polyphenols from various natural and synthetic sources on brain ageing and neurodegeneration, and to examine their multiple mechanisms of action, with an emphasis on the role that the sirtuin pathway may play and the implications this may have for the treatment of AD.
Increase in PAS-induced neuroplasticity after a treatment courseof transcranial direct current stimulation for depression.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.JAD.2014.05.063
Abstract: Several lines of evidence suggest that neuroplasticity is impaired in depression and improves with effective treatment. However until now, this evidence has largely involved measures such as learning and memory which can be influenced by subject effort and motivation. This pilot study aimed to objectively measure neuroplasticity in the motor cortex using paired associative stimulation (PAS), which induces short term neuroplastic changes. It is hypothesized that neuroplasticity would improve after effective treatment for depression. Neuroplasticity was measured in 18 depressed subjects before and after a course of anodal transcranial direct current stimulation (tDCS), given as treatment for depression. The relationships between PAS results, mood state and brain-derived neurotrophic factor (BDNF) serum levels were examined. Neuroplasticity (PAS-induced change) was increased after a course of tDCS (t(17)=-2.651, p=0.017). Treatment with tDCS also led to significant mood improvement, but this did not correlate with improved neuroplasticity. Serum BDNF levels did not change after tDCS, or correlate with change in neuroplasticity after tDCS treatment. While this study showed evidence of improved neuroplasticity in the motor cortex after effective treatment, we are unable to present evidence that this change is generalized in the depressed brain. Also, the presence of antidepressant medications and the small s le of patients (n=18) meant the study could not definitively resolve the relationship between neuroplasticity, mood and BDNF. This novel preliminary study provides evidence that a treatment course of tDCS can improve neuroplasticity in depressed patients.
Schizophrenia-like psychosis and epilepsy
Publisher: Cambridge University Press
Date: 08-03-2007
Increased reporting of subjective cognitive complaints over time predicts cognitive decline and incident dementia
Publisher: Wiley
Date: 06-07-2021
DOI: 10.1002/GPS.5594
Abstract: Subjective cognitive complaints (SCCs) are a risk factor for dementia however, little is known about their trajectories. Participants were 873 older adults (mage = 78.65 years 55% females) from the Sydney Memory and Ageing Study that were followed‐up biennially. SCCs were measured using the six‐item Memory Complaint Questionnaire. Associations between initial level of SCC reporting, linear change in SCC reporting, and change in global cognition over 6 years was examined using latent growth curve analysis. Risk of dementia was examined over 10 years using Cox regression. After controlling for demographics, mood and personality, results revealed a negative longitudinal association between the slope of SCCs and the slope of global cognition scores ( b = −0.01, p = 0.005, β = −0.44), such that participants who reported increasing SCCs showed a steeper rate of decline in global cognition over 6 years. Cox regression also revealed participants who reported increasing SCCs had a nearly fourfold increased risk of developing dementia over 10 years (hazard ratio 3.70, 1.24–11.01). This study explored whether initial levels of, and change in, SCCs over time are associated with both cognitive decline and risk of dementia. These findings are clinically relevant as GPs should note patients reporting increasing SCCs as they may be at greater risk of cognitive decline and incident dementia.
Impact of White Matter Lesions on Physical Functioning and Fall Risk in Older People
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2011
DOI: 10.1161/STROKEAHA.110.610360
Abstract: White matter lesions (WMLs) are common findings on neuroimaging in older people. This review systematically evaluates the published literature on the associations between WMLs and balance, gait, mobility, and falls in older people. Studies were identified with searches of the MEDLINE databases. Articles reporting associations between WMLs and balance, gait, mobility, and falls in older people in cross-sectional and longitudinal studies were included. Thirty-one articles reporting data from 19 studies met the inclusion criteria. There were consistent findings from both cross-sectional and longitudinal studies indicating greater WML volumes are associated with impaired balance, slower gait, and reduced mobility. Most studies addressing regional WML distributions have reported that WMHs in the frontal lobe and periventricular regions show the strongest relationships with balance, gait, and mobility impairments. In relation to falls, a threshold effect was apparent in that only those with severe WML volumes were found to be at increased risk of falling. The findings of this systematic review indicate that WMLs are common and are significantly associated with impaired balance, gait, mobility, and falls in older people. In many studies, however, impaired mobility and increased fall risk are only evident in people who have the most severe degree of WMLs.
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
Publisher: American Medical Association (AMA)
Date: 04-2020
Dietary mineral intake and risk of mild cognitive impairment: The PATH through life project
Publisher: Frontiers Media SA
Date: 2014
The brain reserve hypothesis, brain atrophy and aging
Publisher: S. Karger AG
Date: 20-10-2007
DOI: 10.1159/000096482
Abstract: i Background: /i Researchers have used the concept of brain reserve to explain the dissociation between pathological brain damage and cognitive and functional performance. A variety of brain reserve hypotheses exist, and different empirical strategies have been employed to investigate these variants. i Objective: /i The study investigates (i) the relationship between measures of brain burden (atrophy, white matter hyperintensities (WMH)) and measures of reserve (education, creativity, and intelligence) (ii) the relationship between cognitive decline and reserve (iii) whether measures of reserve mediate the effect of atrophy on estimated cognitive change, and (iv) the association between brain risk factors, education and atrophy. i Methods: /i A cross-sectional study of a s le of 446 in iduals 60–64 years of age who underwent MRI scans as part of a large epidemiological study. Measures were taken of education, intelligence, creativity, cognitive speed, brain volume, WMH, estimated cognitive decline from earlier in life and brain atrophy. i Results: /i No association was found between estimated cognitive decline and brain burden (atrophy, WMH). Risk factors for brain insult were not associated with greater brain atrophy in the less well educated. Neither education, nor any other measure including intelligence or creativity, provided a buffer for cognitive decline in in iduals with high levels of brain atrophy. i Conclusion: /i Little support was found for the brain reserve hypothesis.
Effects of Statins on Memory, Cognition, and Brain Volume in the Elderly
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.JACC.2019.09.041
Abstract: There is widespread consumer concern that statin use may be associated with impaired memory and cognitive decline. This study sought to examine the association between statin use and changes in memory and global cognition in the elderly population over 6 years and brain volumes over 2 years. Interactions between statin use and known dementia risk factors were examined. Prospective observational study of community-dwelling elderly Australians age 70 to 90 years (the MAS [Sydney Memory and Ageing Study], n = 1,037). Outcome measures were memory and global cognition (by neuropsychological testing every 2 years) and total brain, hippoc al and parahippoc al volumes (by magnetic resonance) in a subgroup (n = 526). Analyses applied linear mixed modeling, including the covariates of age, sex, education, body mass index, heart disease, diabetes, hypertension, stroke, smoking, and apolipoprotein Eε4 carriage. Interactions were sought between statin use and dementia risk factors. Over 6 years there was no difference in the rate of decline in memory or global cognition between statin users and never users. Statin initiation during the observation period was associated with blunting the rate of memory decline. Exploratory analyses found statin use was associated with attenuated decline in specific memory test performance in participants with heart disease and apolipoprotein Eε4 carriage. There was no difference in brain volume changes between statin users and never users. In community-dwelling elderly Australians, statin therapy was not associated with any greater decline in memory or cognition over 6 years. These data are reassuring for consumers concerned about statin use and risk of memory decline.
Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium
Publisher: Cold Spring Harbor Laboratory
Date: 31-08-2023
Reader response: Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-08-2018
White Matter Hyperintensities Are an Independent Predictor of Physical Decline in Community-Dwelling Older People
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000337815
Abstract: b i Background: /i /b Ageing is associated with physical disability, but little is known about the influence of white matter hyperintensities (WMHs) on physical function decline in older people. b i Objective: /i /b To investigate the role of WMHs as a predictor of decline in physical function in cognitively intact older people. b i Methods: /i /b 287 community-dwelling people aged 70–90 years underwent the Physiological Profile Assessment (PPA) and assessments of total and regional WMH volumes, cognitive function and comorbidities. Participants underwent reassessment of the PPA 12 months later, and those in the top quartile for increases in PPA scores over the year were regarded as having declined physically. b i Results: /i /b Multivariate logistic regression analyses revealed that people with WMH volumes in the 4th quartile showed greater physical decline (odds ratio 3.02, 95% confidence interval 1.02–8.95) while controlling for age, baseline physical function, general health, physical activity and cognitive function. Subsequent univariate analyses indicated that WMHs in the deep fronto-parietal and periventricular parieto-occipital regions had the strongest associations with physical decline. b i Conclusions: /i /b These findings indicate that WMHs are an independent predictor of decline in physical function and suggest that interventions that focus on preventing the development or progression of white matter lesions may help preserve physical function in older people.
Dietary minerals and risk of MCI
Publisher: Wiley
Date: 07-2013
Antipsychotic Deprescription for Older Adults in Long-term Care: The HALT Study
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.JAMDA.2018.05.002
Abstract: Despite limited efficacy and significant safety concerns, antipsychotic medications are frequently used to treat behavioral and psychological symptoms of dementia (BPSD) in long-term residential care. This study evaluates the sustained reduction of antipsychotic use for BPSD through a deprescribing intervention and education of health care professionals. Repeated-measures, longitudinal, single-arm study. Long-term residential care of older adults. Nursing staff from 23 nursing homes recruited 139 residents taking regular antipsychotic medication for ≥3 months, without primary psychotic illness, such as schizophrenia or bipolar disorder, or severe BPSD. An antipsychotic deprescribing protocol was established. Education of general practitioners, pharmacists, and residential care nurses focused on nonpharmacological prevention and management of BPSD. The primary outcome was antipsychotic use over 12-month follow-up secondary outcomes were BPSD (Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory, and social withdrawal) and adverse outcomes (falls, hospitalizations, and cognitive decline). The number of older adults on regular antipsychotics over 12 months reduced by 81.7% (95% confidence interval: 72.4-89.0). Withdrawal was not accompanied by drug substitution or a significant increase in pro-re-nata antipsychotic or benzodiazepine administration. There was no change in BPSD or in adverse outcomes. In a selected s le of older adults living in long-term residential care, sustained reduction in regular antipsychotic use is feasible without an increase of BPSD.
Animal models of acute drug-induced akathisia - A review
Publisher: Elsevier BV
Date: 05-2000
DOI: 10.1016/S0149-7634(99)00069-X
Abstract: Akathisia is a complex neurobehavioural side effect of neuroleptics and some other drugs which is characterised by subjective report and objective manifestations of restlessness. Its pathophysiology is poorly understood and there are many limitations to its investigation in humans. This paper reviews the various attempts that have been made in modelling acute akathisia in animals. Homologous as well as isomorphic models have been attempted, but most models are partial as they reproduce either the subjective or the objective features of the syndrome. None of the available models has been fully validated. Neuroleptic-induced defecation in the rat, even though constrained by a lack of symptom similarity and thereby face validity, has been most studied as a model of subjective akathisia. Rat models of restlessness, in particular those involving the use of serotonergic drugs or lesions of the ventral tegmentum or medial prefrontal cortex, are interesting partial models that should be further investigated. Neuroleptic-induced akathisia is observed in primates and has been modelled in dogs, and these should be studied further for their validation. It is also necessary to consider the subtypes of akathisia in the attempts to develop these models.
Changes in Cathepsin D and Beclin-1 mRNA and protein expression by the excitotoxin quinolinic acid in human astrocytes and neurons
Publisher: Springer Science and Business Media LLC
Date: 16-05-2014
DOI: 10.1007/S11011-014-9557-9
Abstract: Quinolinic acid (QUIN) is an excitotoxin that has been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD). While QUIN has been shown to induce neuronal and astrocytic apoptosis as well as excitotoxic cell death, other mechanisms such as autophagy remain unexplored. We investigated the role of Cathepsin D (CatD) and Beclin-1 (Bc1) in QUIN-treated primary human astrocytes and neurons. We demonstrated that the expression patterns of CatD, a lysosomal aspartic protease associated with autophagy, are increased at 24 h after QUIN treatment. However, unlike CatD, the expression patterns of Bc1, a tumour suppressor protein, are significantly reduced at 24 h after QUIN treatment in both brain cell types. Furthermore, we showed that the NMDA ion channel blockers, MK801, can attenuate QUIN-induced changes CatD and Bc1 expression in both astrocytes and neurons. Taken together, these results suggest that induction of deficits in CatD and Bc1 is a significant mechanism for QUIN toxicity in glial and neuronal cells. Maintenance of autophagy may play a crucial role in neuroprotection in the setting of AD.
Enhancing precision of the Telephone Interview for Cognitive Status–Modified (TICS-M) using the Rasch model.
Publisher: American Psychological Association (APA)
Date: 07-2023
DOI: 10.1037/PAS0001233
Age-specific effects of voluntary exercise on memory and the older brain
Publisher: Elsevier BV
Date: 03-2013
Higher normal Fasting plasma glucose is associated with hippocampal atrophy the path study
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-09-2012
Higher fasting plasma glucose is associated with smaller striatal volume and poorer fine motor skills in a longitudinal cohort
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.PSCYCHRESNS.2018.06.002
Abstract: Previous studies have demonstrated associations between higher blood glucose and brain atrophy and functional deficits, however, little is known about the association between blood glucose, striatal volume and striatal function despite sensori-motor deficits being reported in diabetes. This study investigated the relationship between blood glucose levels, striatal volume and fine motor skills in a longitudinal cohort of cognitively healthy in iduals living in the community with normal or impaired fasting glucose or type 2 diabetes. Participants were 271 cognitively healthy in iduals (mean age 63 years at inclusion) with normal fasting glucose levels (<5.6 mmol/L) (n=173), impaired fasting glucose (5.6-6.9 mmol/L) (n=57), or with type 2 diabetes (≥7.0 mmol/L) (n=41). Fasting glucose, Purdue Pegboard scores as measurement of fine motor skills, and brain scans were collected at wave 1, 2 and 4, over a total follow-up of twelve years. Striatal volumes were measured using FreeSurfer after controlling for age, sex and intracranial volume. Results showed that type 2 diabetes was associated with smaller right putamen volume and lower Purdue Pegboard scores after controlling for age, sex and intracranial volume. These findings add to the evidence suggesting that higher blood glucose levels, especially type 2 diabetes, may impair brain structure and function.
Plasma amyloid beta peptides: an Alzheimer’s conundrum or a more accessible Alzheimer’s biomarker?
Publisher: Informa UK Limited
Date: 31-07-2026
Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample
Publisher: Cambridge University Press (CUP)
Date: 28-10-2004
DOI: 10.1017/S0033291704003721
Abstract: Background. Case control studies have supported a relationship between low folic acid and vitamin B 12 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations. Method. A random subs le of 412 persons aged 60–64 years from a larger community s le underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B 12 , homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging. Results. Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B 12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B 12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. Conclusions. Low folic acid and high homocysteine, but not low vitamin B 12 levels, are correlates of depressive symptoms in community-dwelling middle-aged in iduals. The effects of folic acid and homocysteine are overlapping but distinct.
Promoting independence in Lewy body dementia through exercise (PRIDE) study: Protocol for a pilot study
Publisher: Elsevier BV
Date: 12-2019
Genome-wide Meta-analysis Finds the ACSL5-ZDHHC6 Locus Is Associated with ALS and Links Weight Loss to the Disease Genetics
Publisher: Elsevier BV
Date: 10-2020
Texture Features of Magnetic Resonance Images Predict Poststroke Cognitive Impairment: Validation in a Multicenter Study
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2022
DOI: 10.1161/STROKEAHA.122.039732
Abstract: Imaging features derived from T1-weighted (T1w) images texture analysis were shown to be potential markers of poststroke cognitive impairment, with better sensitivity than atrophy measurement. However, in magnetic resonance images, the signal distribution is subject to variations and can limit transferability of the method between centers. This study examined the reliability of texture features against imaging settings using data from different centers. Data were collected from 327 patients within the Stroke and Cognition Consortium from centers in France, Germany, Australia, and the United Kingdom. T1w images were preprocessed to normalize the signal intensities and then texture features, including first- and second-order statistics, were measured in the hippoc us and the entorhinal cortex. Differences between the data led to the use of 2 methods of analysis. First, a machine learning modeling, using random forest, was used to build a poststroke cognitive impairment prediction model using one dataset and this was validated on another dataset as external unseen data. Second, the predictive ability of the texture features was examined in the 2 remaining datasets by ANCOVA with false discovery rate correction for multiple comparisons. The prediction model had a mean accuracy of 90% for in idual classification of patients in the learning base while for the validation base it was ≈ 77%. ANCOVA showed significant differences, in all datasets, for the kurtosis and inverse difference moment texture features when measured in patients with cognitive impairment and those without. These results suggest that texture features obtained from routine clinical MR images are robust early predictors of poststroke cognitive impairment and can be combined with other demographic and clinical predictors to build an accurate prediction model.
Neuroticism scores increase with late‐life cognitive decline
Publisher: Wiley
Date: 12-01-2015
DOI: 10.1002/GPS.4251
Abstract: Neuroticism has been reported as both a risk factor for cognitive decline and a characteristic that increases in parallel with the development of mild cognitive impairment (MCI) and dementia. However, the evidence for these associations is inconclusive, and whether effects are stronger for particular cognitive domains is unknown. We investigated these issues and determined if associations differ among different components of neuroticism. A neuroticism scale (NEO-FFI) and neuropsychological test battery were administered to 603 older adults without dementia, with 493 of these reassessed two years later. Diagnoses of MCI and dementia (at follow-up) were made, and global cognition and performance in six cognitive domains quantified. The neuroticism components were negative affect, self-reproach, and proneness to psychological distress. For the whole s le, neuroticism scores remained stable between baseline (15.3 ± 7.0) and follow-up (15.5 ± 7.0), as did all neuroticism component scores. However, there were declines in global cognition (p < 0.05) and particular cognitive domains (p < 0.001). Higher neuroticism was associated with poorer cognition cross-sectionally (p < 0.01), but did not predict cognitive decline. For 43 participants who developed incident MCI or dementia, there were increases in neuroticism (15.3 ± 6.4 to 17.1 ± 8.3, p < 0.05) and negative affect (p < 0.05). Declines in all cognitive measures except executive function were associated with increases in neuroticism and component scores (p < 0.05). Late-life cognitive decline is associated with an increase in neuroticism scores. However, associations vary between different cognitive domains and components of neuroticism. An increase in neuroticism or negative affect scores may be a sign of MCI or dementia.
Meta-analysis of plasma amyloid beta levels using cross-sectional and longitudinal studies of Alzheimer's disease and dementia
Publisher: Wiley
Date: 07-2010
Factors Predicting Reversion from Mild Cognitive Impairment to Normal Cognitive Functioning: A Population-Based Study
Publisher: Public Library of Science (PLoS)
Date: 27-03-2013
EPIDEMIC KORO SYNDROME IN INDIA
Publisher: Elsevier BV
Date: 11-1982
DOI: 10.1016/S0140-6736(82)92815-X
Abstract: Chromatin structure, a key contributor to the regulation of gene expression, is modulated by a broad array of histone post-translational modifications (PTMs). Taken together, these "histone marks" comprise what is often referred to as the "histone code". The quantitative analysis of histone PTMs by mass spectrometry (MS) offers the ability to examine the response of the histone code to physiological signals. However, few studies have examined the stability of histone PTMs through the process of isolating and culturing primary cells. To address this, we used bottom-up, MS-based analysis of histone PTMs in liver, freshly isolated hepatocytes, and cultured hepatocytes from adult male Fisher F344 rats. Correlations between liver, freshly isolated cells, and primary cultures were generally high, with R2 values exceeding 0.9. However, a number of acetylation marks, including those on H2A K9, H2A1 K13, H3 K4, H3 K14, H4 K8, H4 K12 and H4 K16 differed significantly among the three sources. Inducing proliferation of primary adult hepatocytes in culture affected several marks on histones H3.1/3.2 and H4. We conclude that hepatocyte isolation, culturing and cell cycle status all contribute to steady-state changes in the levels of a number of histone PTMs, indicating changes in histone marks that are rapidly induced in response to alterations in the cellular milieu. This has implications for studies aimed at assigning biological significance to histone modifications in tumors versus cancer cells, the developmental behavior of stem cells, and the attribution of changes in histone PTMs to altered cell metabolism.
Relationships between cognitive function and frontal grey matter volumes and thickness in middle aged and early old-aged adults: The PATH Through Life Study
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.NEUROIMAGE.2011.01.015
Abstract: The study examined the relationship of lateral frontal cortical volume and thickness with cognitive function in two s les of healthy middle aged (MA, 44-48 years old) and early old-age (OA, 64-68 years old) adults. T1-weighted magnetic resonance imaging scans were acquired in 400 MA and 397 OA adults from respective random community s les. Cortical volumes and thickness were measured with a surface-based segmentation procedure (surfer.nmr.mgh.harvard.edu). Volumes of lateral frontal grey matter were found to be significantly lower for OA than MA. Structure-function relationships were investigated using path analyses. In OA, smaller lateral frontal volumes were associated with better episodic memory (EM) (p<0.012, B=-0.117), and Symbol-Digit Modalities Test (SDM) (p<0.031, B=-0.118) performance. Smaller frontal cortical thickness was also associated with better EM (p<0.01) and SDM (p<0.01) performance in OA. However, in MA greater cortical thickness was associated with better EM and (p<0.01) and reaction time (RT) (p<0.01). OA cohort showed significant positive correlations between Total Brain Volume and SDM, Digit-Backwards span and RT. Possible explanations and implications of the relationships in the context of cognitive aging in healthy adults, and limitations of cross-sectional research are discussed.
The Plasma NAD+ Metabolome Is Dysregulated in Normal Aging.
Publisher: Mary Ann Liebert Inc
Date: 04-2018
GSK3B and MAPT polymorphisms are associated with grey matter and intracranial volume in healthy individuals.
Publisher: Public Library of Science (PLoS)
Date: 12-08-2013
The default mode network, depression and Alzheimer’s disease
Publisher: Cambridge University Press (CUP)
Date: 08-2022
Avanafil mediated dual inhibition of IKKβ and TNFR1 in an experimental paradigm of Alzheimer’s disease: in silico and in vivo approach
Publisher: Informa UK Limited
Date: 19-12-2022
Correlates of psychological distress in study partners of older people with and without mild cognitive impairment (MCI) - The Sydney Memory and Ageing Study
Publisher: Informa UK Limited
Date: 03-03-2014
DOI: 10.1080/13607863.2013.875123
Abstract: Psychological effects of supporting someone with mild cognitive impairment (MCI) are often overlooked. We aimed to establish correlates of psychological distress in study partners of in iduals with and without nonclinical MCI. Demographic, psychosocial and health measures were obtained cross-sectionally from 714 participants (39% MCI) and study partners of a longitudinal community-based study on cognitive aging. Study partners (i.e. family members/friends) were categorized as providing support with instrumental everyday activities or not. Psychological distress was measured by the Kessler psychological distress scale. Multiple hierarchical regressions examined determinants of psychological distress within Pearlin's stress process model. Psychological distress was generally low and not associated with MCI or whether study partners provided support or not. Instead, distress was greater if participants were male irrespective of study partners' sex and if study partners reported negative reactions to participants' behavioral symptoms, felt burdened by providing support and showed worse coping abilities overall explaining 37% variance. Self-rated disability and aspects of health-related quality of life explained additional 7%. Objective impairment measures were not associated with distress in partners or supporters. However, study partners' appraisals of functional and behavioral symptoms were linked to increased distress even in this very mildly affected community cohort.
The contributions of twin studies to the understanding of brain ageing and neurocognitive disorders
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2014
Cross-ethnic meta-analysis identifies association of the GPX3-TNIP1 locus with amyotrophic lateral sclerosis
Publisher: Springer Science and Business Media LLC
Date: 20-09-2017
DOI: 10.1038/S41467-017-00471-1
Abstract: Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS ( p = 1.3 × 10 −8 ), with replication support from two independent Australian s les (combined 576 cases and 683 controls, p = 1.7 × 10 −3 ). Both GPX3 and TNIP1 interact with other known ALS genes ( SOD1 and OPTN , respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.
Mild neuritic changes are increased in the brains of fatally injured older motor vehicle drivers
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.AAP.2007.02.008
Abstract: Given the expected increase in the older population and driving in this age group, concerns have been raised about the safety of older drivers. People over 65 years are over-represented in motor vehicle fatalities when calculated by distance driven. They are also at risk of neurodegenerative diseases, such as Alzheimer's disease, that affect cognitive function. We have examined the brains of older drivers (15M:12F) who died as a result of a motor vehicle accident (MVA) to determine the extent of Alzheimer's disease-related neurofibrillary changes (neuritic plaques and neurofibrillary tangles), Lewy body pathology and cerebrovascular disease and compared them to a control group of older licenced drivers (23M:5F) who died of other causes. The prevalence of moderate or severe neuritic plaque pathology was less than expected for the general population of this age and there was no difference between the groups. However, mild neuritic plaque pathology was increased for MVA deaths compared to controls. There was no evidence of vascular dementia or dementia with Lewy bodies. The current mandatory age-related re-licencing procedures in NSW may contribute to the low percentage of drivers with severe pathology. Further research into the role of mild pathology in cognitive impairment and older drivers is warranted.
Recommendations for the Nomenclature of Cognitive Change Associated with Anaesthesia and Surgery—2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2018
DOI: 10.1097/ALN.0000000000002334
Abstract: Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines (Diagnostic and Statistical Manual for Mental Disorders, fifth edition [DSM-5] and National Institute for Aging and the Alzheimer Association [NIA-AA]) are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that ‘perioperative neurocognitive disorders’ be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder) any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).
Genome-wide Studies of Verbal Declarative Memory in Nondemented Older People: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
Publisher: Elsevier BV
Date: 04-2015
The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis
Publisher: SAGE Publications
Date: 25-11-2022
DOI: 10.1177/17474930221137019
Abstract: Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. This study aims to systematically review the prevalence of cSVD in LMICs. Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study s le size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old range: 36.3–80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes, while the type of study was a significant predictor of the prevalence of CMB. The heterogeneity of studies was high ( %). Male participants were overrepresented. This systematic review and meta-analysis provide data on cSVD prevalence in LMICs and demonstrated the high prevalence of the condition. cSVD research in LMICs is being published at an increasing rate, especially between 2010 and 2022. More data are particularly needed from Sub-Saharan Africa and Central Europe, Eastern Europe, and Central Asia.
The Sydney Memory and Ageing Study (MAS): methodology and baseline medical and neuropsychiatric characteristics of an elderly epidemiological non-demented cohort of Australians aged 70–90 years
Publisher: Cambridge University Press (CUP)
Date: 19-07-2010
DOI: 10.1017/S1041610210001067
Abstract: Background: The Sydney Memory and Ageing Study (Sydney MAS) was initiated in 2005 to examine the clinical characteristics and prevalence of mild cognitive impairment (MCI) and related syndromes, and to determine the rate of change in cognitive function over time. Methods: Non-demented community-dwelling in iduals (N = 1037) aged 70–90 were recruited from two areas of Sydney, following a random approach to 8914 in iduals on the electoral roll. They underwent detailed neuropsychiatric and medical assessments and donated a blood s le for clinical chemistry, proteomics and genomics. A knowledgeable informant was also interviewed. Structural MRI scans were performed on 554 in iduals, and subgroups participated in studies of falls and balance, metabolic and inflammatory markers, functional MRI and prospective memory. The cohort is to be followed up with brief telephone reviews annually, and detailed assessments biannually. Results: This is a generally well-functioning cohort mostly living in private homes and rating their health as being better than average, although vascular risk factors are common. Most (95.5%) participants or their informants identified a cognitive difficulty, and 43.5% had impairment on at least one neuropsychological test. MCI criteria were met by 34.8% with19.3% qualifying for amnestic MCI, whereas 15.5% had non-amnestic MCI 1.6% had impairment on neuropsychological test performance but no subjective complaints and 5.8% could not be classified. The rate of MCI was 30.9% in the youngest (70–75) and 39.1% in the oldest (85–90) age bands. Rates of depression and anxiety were 7.1% and 6.9% respectively. Conclusions: Cognitive complaints are common in the elderly, and nearly one in three meet criteria for MCI. Longitudinal follow-up of this cohort will delineate the progression of complaints and objective cognitive impairment, and the determinants of such change.
Dementia in the oldest old
Publisher: Springer Science and Business Media LLC
Date: 04-06-2013
DOI: 10.1038/NRNEUROL.2013.105
Abstract: People over the age of 90 years--the oldest old--are the fastest growing sector of the population. A substantial proportion of these in iduals are affected by dementia, with major implications for the in idual as well as society. Research on dementia in the oldest old is important for service planning, and the absence of dementia at this exceptional old age may serve as a model of successful ageing. This Review summarizes population-based epidemiological studies of dementia and its underlying neuropathology in nonagenarians and centenarians. The available data, although somewhat limited, show an age-specific and sex-specific profile of dementia status in very late life, resulting from a variety of neuropathologies that often co-occur. Extensive overlap in neuropathology between cognitively normal and cognitively impaired in iduals is evident despite challenges to gathering data particular to this population. A complex picture is emerging of multiple pathogenetic mechanisms underlying dementia, and of the potential risk and protective factors for dementia that interact with genetics and lifestyle in normal and exceptional cognitive ageing.
Surviving acute cyanide poisoning: a longitudinal neuropsychological investigation with interval MRI
Publisher: BMJ
Date: 19-03-2014
Cognitive and physical declines and falls in older people with and without mild cognitive impairment: a 7-year longitudinal study
Publisher: Cambridge University Press (CUP)
Date: 20-04-2023
DOI: 10.1017/S1041610223000315
Abstract: We examined longitudinal changes in cognitive and physical function and associations between change in function and falls in people with and without mild cognitive impairment (MCI). Prospective cohort study with assessments every 2 years (for up to 6 years). Community, Sydney, Australia. Four hundred and eighty one people were classified into three groups: those with MCI at baseline and MCI or dementia at follow-up assessments ( n = 92) those who fluctuated between cognitively normal and MCI throughout follow-up (cognitively fluctuating) ( n = 157), and those who were cognitively normal at baseline and all reassessments ( n = 232). Cognitive and physical function measured over 2–6 years follow-up. Falls in the year following participants’ final assessment. In summary, 27.4%, 38.5%, and 34.1% of participants completed 2, 4, and 6 years follow-up of cognitive and physical performance, respectively. The MCI and cognitive fluctuating groups demonstrated cognitive decline, whereas the cognitively normal group did not. The MCI group had worse physical function than the cognitively normal group at baseline but decline over time in physical performance was similar across all groups. Decline in global cognitive function and sensorimotor performance were associated with multiple falls in the cognitively normal group and decline in mobility (timed-up-and-go test) was associated with multiple falls across the whole s le. Cognitive declines were not associated with falls in people with MCI and fluctuating cognition. Declines in physical function were similar between groups and decline in mobility was associated with falls in the whole s le. As exercise has multiple health benefits including maintaining physical function, it should be recommended for all older people. Programs aimed at mitigating cognitive decline should be encouraged in people with MCI.
Hippocampus and amygdala volumes in a random community-based sample of 60-64 year olds and their relationship to cognition
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.PSCYCHRESNS.2007.06.005
Abstract: Reduced volumes of the hippoc us (HC) and amygdala (AG) are potential biomarkers for Alzheimer's disease (AD) and other neuropsychiatric disorders. Published studies on HC and AG volumes suffer from methodological limitations, and a valid and reliable normative database does not exist. This study aimed to establish a database of HC and AG volumes from a large community s le of participants 60-64 years old and relate them to cognition. A total of 452 randomly selected participants (from 622 approached) were retained in the study (238 males, 214 females), and all received brain MRI scans, as well as cognitive and physical assessments. HC and AG volumes were estimated from manual tracings on T1-weighted images, and intracranial volume (ICV) was obtained from an automated program. In both sexes, right hippoc i were larger than left, while left amygdala were larger than right. The only correlation to remain significant after normalization was left HC volume and percent retention of a word list in females. This study provides a HC and AG volumetrics database and describes its relationship with cognitive performance in a representative s le using a standard methodology that will be a reference for future studies. It will therefore have clinical applicability in early AD and other disorders.
Diagnosing mild cognitive impairment – a data-driven approach
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Grey Matter Correlates of Three Language Tests in Non-demented Older Adults
Publisher: Public Library of Science (PLoS)
Date: 05-11-2013
Aging, exceptional longevity and comparisons of the Hannum and Horvath epigenetic clocks
Publisher: Future Medicine Ltd
Date: 05-2017
Abstract: Aim: To examine the relationships between two epigenetic clocks, aging and exceptional longevity. Materials & methods: Participants were from three adult cohorts with blood DNA methylation data (Illumina 450 K, n = 275, 34–103 years). Epigenetic age (DNAmage) and age acceleration measures were calculated using the Hannum and Horvath epigenetic clocks. Results: Across all cohorts, DNAmage was correlated with chronological age. In the long-lived cohort (Sydney Centenarian Study 95+, n = 23), DNAmage was lower than chronological age for both clocks. Mean Sydney Centenarian Study Hannum age acceleration was negative, while the converse was observed for the Horvath model. Conclusion: Long-lived in iduals have a young epigenetic age compared with their chronological age.
Effect of age on proliferation‐regulating factors in human adult neurogenic regions
Publisher: Wiley
Date: 28-09-2010
DOI: 10.1111/J.1471-4159.2010.06992.X
Abstract: Neurogenesis, the birth of new neurons, continues throughout adulthood in the human subventricular zone (SVZ) and hippoc us. It is not known how levels of putative proliferation-regulating factors change with age in human adult neurogenic areas. The current project employed ELISAs to investigate changes in levels of putative proliferation-regulating factors in the healthy human SVZ and dentate gyrus throughout the adult lifespan (18-104 years). Levels of brain-derived neurotrophic factor, basic fibroblast growth factor and interleukin (IL)-1β were significantly higher in the hippoc us than in the SVZ and levels of glial-derived neurotrophic factor and transforming growth factor-α were significantly higher in the SVZ (p < 0.005), suggesting that factors with predominant influences on neurogenesis differ between the two human adult neurogenic areas. Hippoc al levels of transforming growth factor-β1 strongly increased with age (n = 9, p < 0.01), whereas hippoc al and SVZ levels of brain-derived neurotrophic factor, epidermal growth factor, basic fibroblast growth factor, glial-derived neurotrophic factor, heparin-binding epidermal growth factor, insulin-like growth factor-1, IL-1β, IL-6 and transforming growth factor-α did not change significantly with age in the SVZ or hippoc us. These findings suggest regulation of the adult neurogenic environment in the human brain may differ over time from that in other species.
The independent influences of age and education on functional brain networks and cognition in healthy older adults
Publisher: Wiley
Date: 07-07-2017
DOI: 10.1002/HBM.23717
The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study
Publisher: Springer Science and Business Media LLC
Date: 19-08-2012
Sex differences in cortical thickness in middle aged and early old-aged adults: Personality and Total Health Through Life study
Publisher: Springer Science and Business Media LLC
Date: 07-03-2013
DOI: 10.1007/S00234-013-1144-Y
Abstract: The study investigated sex differences in cortical thickness in middle-aged (MA, 44-48 years old, n = 397) and early old-aged (OA, 64-68 years old, n = 398) adults in a community-based s le. T1-weighted three-dimensional structural magnetic resonance imaging scans were acquired in a Fast Field Echo sequence, and cortical thickness was measured with a surface-based segmentation procedure ( surfer.nmr.mgh.harvard.edu ). Results showed that after correcting for age, MA males had predominantly thicker superior temporal cortices, while MA females had thicker occipital, posterior cingulate, precentral, and postcentral cortices. Sex differences in OA adults were less prominent than those in MA adults with females showing thicker temporal and posterior cingulate cortices and males showing thicker rostral middle frontal regions. Between-cohort comparisons revealed that when compared with MA males, OA males showed many regions with significantly thinner cortices, but this pattern was less pronounced for OA females. Our results suggest that sex differences in cortical thickness are age specific, as larger differences in cortical thickness were found in MA compared to OA adults. The results of the present study indicate that the inconsistencies in sexual dimorphism that have been reported in the literature are partly due to the variable and transitory nature of cortical thickness differences with age.
Improving screening for vascular cognitive impairment at three to six months after mild ischemic stroke and transient ischemic attack
Publisher: Cambridge University Press (CUP)
Date: 15-01-2014
DOI: 10.1017/S1041610213002457
Abstract: The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were compared with and without the addition of a brief processing speed test, the symbol digit modalities test (SDMT), for vascular cognitive impairment (VCI) screening at three to six months after stroke. Patients with ischemic stroke and transient ischemic attack were assessed with MoCA and MMSE, as well as a formal neuropsychological battery three to six months after stroke. VCI was defined by impairment in any cognitive domain on neuropsychological testing. The area under the receiver operating characteristic curve (AUC) was used to compare test discriminatory ability. One hundred and eighty-nine patients out of 327 (58%) had VCI, of whom 180 (95%) had vascular mild cognitive impairment (VaMCI), and nine (5%) had dementia. The overall AUCs of the MoCA and MMSE scores and performance at their respective cut-off points were equivalent in detecting VCI (AUCs: 0.87 (95% CI 0.83–0.91) vs. 0.84 (95% CI 0.80–0.88), p = 0.13 cut-offs: MoCA (≤23) vs. MMSE (≤26), sensitivity: 0.78 vs. 0.71 specificity: 0.80 vs. 0.82 positive predictive value: 0.84 vs. 0.84 negative predictive value: 0.72 vs. 0.67 and correctly classified 78.6% vs. 75.5% p = 0.42). The AUCs of MMSE and MoCA were improved significantly by the SDMT (AUCs: MMSE+SDMT 0.90 (95% CI 0.87–0.93), p .001 MoCA+SDMT 0.91 (95% CI 0.88–0.94), p 0.02). The MoCA and MMSE are equivalent and moderately sensitive, and can be supplemented with the SDMT to improve their accuracy in VCI screening.
Psychiatry looks towards the future in neurodegenerative and neurodevelopmental disorders
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2013
Time to diagnosis in young-onset dementia and its determinants: the INSPIRED study
Publisher: Wiley
Date: 25-01-2016
DOI: 10.1002/GPS.4430
Abstract: The objective of this study is to identify factors determining the time to diagnosis for young-onset dementia (YOD), defined as dementia with symptom onset before age 65 years, by mapping the diagnostic pathways. Participants were recruited via healthcare professionals, community support organisations or were self-referred. Information was obtained by interviews with the person with YOD and their carer, and medical record reviews. Clinical dementia diagnoses were independently ratified by consensus review. Participants included 88 people with YOD (mean age of onset = 55.4 years), due to Alzheimer's disease (AD) (53.4%, n = 47), frontotemporal dementia (FTD) (15.9%, n = 14) and other causes (30.7%, n = 27). Median time from symptom onset to first consultation was 2.3 years, to dementia diagnosis 3.2 years, to family awareness of dementia diagnosis 3.5 years and to final diagnosis of the type of dementia 4.7 years. Non-dementia diagnoses occurred in 48.9%, including depression (30.7%) and mild cognitive impairment (MCI) (17.0%). Participants with younger age of onset had significantly longer time to first consultation and family awareness of the dementia diagnosis. The time to dementia diagnosis was significantly longer when the participant presented with MCI or depression and when the dementia was other than AD or FTD. MCI was associated with significantly longer time to family awareness of dementia diagnosis. Factors impacting on time to diagnosis vary with the stage of diagnosis in YOD. Longer time to dementia diagnosis occurred in people who were younger at symptom onset, when MCI or depression was present, and in dementias other than AD and FTD. Copyright © 2016 John Wiley & Sons, Ltd.
Human Induced Pluripotent Stem Cells Derived Under Feeder-Free Conditions Display Unique Cell Cycle and DNA Replication Gene Profiles
Publisher: Mary Ann Liebert Inc
Date: 20-01-2012
IDENTIFICATION OF CEREBRAL METAL ION IMBALANCE IN THE BRAIN OF AGEING OCTODON DEGUS: A NATURAL MODEL FOR ALZHEIMER'S DISEASE
Publisher: Wiley
Date: 07-2017
Body mass index is associated with cortical thinning with different patterns in mid- and late-life
Publisher: Springer Science and Business Media LLC
Date: 10-10-2018
DOI: 10.1038/IJO.2017.254
Abstract: High BMI at midlife is associated with increased risk of dementia as well as faster decline in cognitive function. In late-life, however, high BMI has been found to be associated with both increased and decreased dementia risk. The objective of this study was to investigate the neural substrates of this age-related change in body mass index (BMI) risk. We measured longitudinal cortical thinning over the whole brain, based on magnetic resonance imaging scans for 910 in iduals aged 44-66 years at baseline. Subjects were s led from a large population study (PATH, Personality and Total Health through Life). After attrition and exclusions, the final analysis was based on 792 in iduals, including 387 in iduals aged 60-66 years and 405 in iduals aged 44-49 years. A mixed-effects model was used to test the association between cortical thinning and baseline BMI, as well as percentage change in BMI. Increasing BMI was associated with increased cortical thinning in posterior cingulate at midlife (0.014 mm kg The pattern of cortical thinning-in association with increasing BMI at both midlife and late-life-is consistent with known obesity-related dementia risk. Increased cortical thinning in association with decreasing BMI at late-life may help explain the 'obesity paradox', where high BMI in midlife appears to be a risk factor for dementia, but high BMI in late-life appears, at times, to be protective.
Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia
Publisher: Wiley
Date: 02-2007
DOI: 10.1111/J.1399-5618.2007.00324.X
Abstract: Objective: To examine whether patients with bipolar disorder (BD) have subtle neuropsychological deficits that manifest clinically as cognitive and functional compromise, and this study attempted to determine the pattern of such cognitive deficits and their functional impact across all three phases of BD. We hypothesised that euthymia does not equate with normal neuropsychological function and that each phase has a characteristic pattern of deficits, with disturbance in attention and memory being common across all phases of the illness: (i) bipolar depression – psychomotor slowing and impairment of memory (ii) hypomania by frontal‐executive deficits and (iii) euthymia – a mild disturbance of attention, memory and executive function. Methods: Twenty‐five patients with a diagnosis of bipolar I disorder underwent neuropsychological testing over a period of 30 months in the natural course of their illness while hypomanic and/or depressed and/or euthymic. The results from these assessments were compared with findings from neuropsychological tests conducted on 25 healthy controls matched for age, sex, education and handedness. Results: Initial analyses revealed modest impairment in executive functioning, memory and attention in both hypomanic and depressed bipolar patients, with additional fine motor skills impairment in the latter. Memory deficits, also noted in euthymic patients, were non‐significant after controlling for confounding variables, although bipolar depressed patients remained significantly impaired on tests of verbal recall. Bipolar depressed and hypomanic patients differed with respect to the nature of their memory impairment. Depressed patients were more impaired as compared with euthymic patients on tests of verbal recall and fine motor skills. Psychosocial functioning was impaired across all three patient groups, but only in depressed and hypomanic patients did this correlate significantly with neuropsychological performance. Conclusions: The mood‐state‐related cognitive deficits in both bipolar depression and hypomania compromise psychosocial function when patients are unwell. In euthymic patients, subtle impairments in attention and memory suggest that an absence of symptoms does not necessarily equate to ‘recovery’. The possibility of persistent cognitive deficits in BD is an issue of profound clinical and research interest that warrants further investigation however, future research needs to adopt more sophisticated neuropsychological probes that are able to better define state and trait deficits and determine their functional impact.
Limited relationships between two-year changes in sulcal morphology and other common neuroimaging indices in the elderly
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.NEUROIMAGE.2013.06.058
Abstract: Measuring the geometry or morphology of sulcal folds has recently become an important approach to investigating neuroanatomy. However, relationships between cortical sulci and other brain structures are poorly understood. The present study investigates how age-related changes in sulcal width are associated with age-related changes in traditional indices of brain structure such as cortical thickness, and cortical gray matter (GM), white matter (WM), subcortical, and white matter hyperintensity (WMH) volumes. These indices and sulcal width were measured at baseline and at two-year follow up in 185 community-dwelling in iduals (91 men) aged 70-89 years. There were significant increases in sulcal width and WMH volume, and significant decreases in all other indices between baseline and follow-up. Sulcal widening was associated with decreases in cortical GM, subcortical and WM volumes. A further association between sulcal width and cortical thickness became non-significant when cortical GM volume was controlled for. Our findings give insights into the mechanisms responsible for cortical sulcal morphology. The relationships between sulcal morphology and other common measures suggest that it could be a more comprehensive measure for clinical classifications than traditional neuroimaging metrics, such as cortical thickness.
Getting physical: the management of neuropsychiatric disorders using novel physical treatments
Publisher: Informa UK Limited
Date: 2006
Injury-related hospitalisation in community-dwelling older people across the cognitive spectrum: A population based study
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.ARCHGER.2019.03.028
Abstract: To describe the injury profile, hospitalisation rates and health outcomes for older people with cognitive impairment and to determine whether these differ from those with normal cognition. Participants were 867 community-dwelling 70-90 year olds enrolled in the population-based longitudinal Sydney Memory and Ageing Study (MAS). Participant's cognitive status was classified as normal, mild cognitive impairment (MCI) and dementia at baseline, then 2, 4 and 6 years' follow-up. MAS records were linked to hospital and death records to identify injury-related hospitalisations for the 2-year period following each assessment. There were 335 injury-related hospitalisations for participants 222 (25.6%) participants had at least one injury-related hospitalisation. The injury-related hospitalisation rate for participants with MCI (63.0 [95%CI 51.6-74.4] per 1000 person-years) was higher than for people with normal cognition (39.3 [95%CI 32.4-46.1] per 1000 person-years) but lower than people with dementia (137.1 [95%CI 87.2-186.9] per 1000 person-years). Upper limb fractures (22.1%) were the most common injuries for participants with normal cognition, and non-fracture head injuries for participants with MCI and dementia (25.9% and 23.3% respectively). Participants with dementia had a higher proportion of hip fractures (20.0%, p = 0.0483) than participants with normal cognition. There was no difference in 30-day mortality between participants with normal cognition, MCI and dementia (3.9%, 1.7%, 3.3% respectively). Older people with objectively defined MCI are at higher risk of injury-related hospitalisation than their cognitively intact peers, but lower risk than people with dementia. Falls-risk screening and fall prevention initiatives may be indicated for older people with MCI.
Adiposity estimated using dual energy x-ray absorptiometry and body mass index and its association with cognition in elderly adults
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/JGS.13157
Abstract: To determine whether obesity, estimated according to body mass index (BMI), waist circumference, and body fat and abdominal fat assessed using dual-energy X-ray absorptiometry (DEXA), was associated with cognitive performance. Cross-sectional. Community based. In iduals aged 74-94 (N = 406). BMI, waist circumference, body fat, and abdominal fat were assessed using DEXA. Cognitive performance was assessed using a comprehensive neuropsychological battery. When categorized using BMI, overweight in iduals had higher global cognitive function and executive function scores than normal-weight in iduals. This relationship did not differ according to sex. When categorized according to DEXA, there were no relationships between body fat and cognitive function in the whole group, but women in the middle and highest tertiles of DEXA body fat had better executive function than those in the lowest tertile. Men in the middle tertile of DEXA body fat had significantly better executive function and memory than those in the lowest tertile. BMI had greater power to predict executive function than DEXA body fat. No significant associations were found between cognition and estimates of abdominal adiposity. This study found an association between being overweight and better executive function in elderly adults this association was stronger for the simpler BMI than the more-elaborate DEXA measures.
Within-Occasion Intraindividual Variability and Preclinical Diagnostic Status: Is Intraindividual Variability an Indicator of Mild Cognitive Impairment?
Publisher: American Psychological Association (APA)
Date: 05-2005
DOI: 10.1037/0894-4105.19.3.309
Abstract: Intrain idual variability in cognitive test performance has the potential to be a good marker of preclinical Alzheimer's disease status (S. C. Li & U. Lindenberger, 1999). Using cross-sectional community data from 2,317 in iduals aged 60-64 years, the authors of this study found that variability was greater in in iduals who met criteria for mild cognitive impairment or aging-associated cognitive decline but not for age-associated memory impairment. Higher variability was associated with lower education and a non-English-speaking background. In contrast to previous findings, variability in this study did not contribute uniquely to meeting criteria for mild cognitive impairment. The reasons for the differences may reside in the authors' method of estimating mean independent variability, the use of an occasion-specific measure, or the relatively younger age of the participants. Follow-up of the cohort in 4 years will yield data on the prospective validity of variability as a risk factor for impairment.
Psychosurgical Treatment of Obsessivecompulsive Disorder
Publisher: American Medical Association (AMA)
Date: 07-1992
DOI: 10.1001/ARCHPSYC.1992.01820070076014
Abstract: During a screening programme of 10000 pregnant women by the Guthrie test, a previously unrecognised phenylketonuric woman was detected. A low phenylalanine diet introduced from the 16th week of gestation failed to prevent fetal abnormality and mental retardation. Maternal phenylketonuria requires earlier diagnosis than can be achieved at the initial antenatal clinic visit if its teratogenic effects are to be prevented.
Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
Publisher: Springer Science and Business Media LLC
Date: 02-2015
DOI: 10.1038/MP.2014.188
Abstract: General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts ( N =53 949) in which the participants had undertaken multiple, erse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P =3.93 × 10 −9 , MIR2113 rs17522122, P =2.55 × 10 −8 , AKAP6 rs10119, P =5.67 × 10 −9 , APOE/TOMM40 ). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 ( P =1 × 10 −6 ). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study ( N =6617) and the Health and Retirement Study ( N =5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort ( N =5487 P =1.5 × 10 −17 ). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer’s disease: TOMM40 , APOE , ABCG1 and MEF2C .
Homocysteine and brain atrophy
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.PNPBP.2005.06.026
Abstract: Homocysteine (Hcy) has been implicated as a risk factor for vascular disease as well as brain atrophy. There is evidence to implicate Hcy in increased oxidative stress, DNA damage, the triggering of apoptosis and excitotoxicity, all important mechanisms in neurodegeneration. Hcy is also prothrombotic and proatherogenic, and causes damage to the vessel wall. It is related to brain atrophy in older in iduals, and possibly to white matter hyperintensities (WMH) in the brain. Epidemiological evidence and longitudinal data support Hcy as a risk factor for cognitive impairment and Alzheimer's Disease (AD). This may be due to cerebrovascular as well as direct neurotoxic mechanisms. Its role in Parkinson Disease (PD) is less well supported. High Hcy has been suggested as a mediating factor in alcohol-related brain atrophy. The high prevalence of hyperhomocysteinemia in the population and its easy treatability make Hcy an interesting amino acid for future intervention studies in the prevention of degenerative brain disorders. Intervention studies are necessary to confirm its aetiological role.
Genetically Predicted Blood Pressure and Cognition in Midlife: A UK Biobank Study
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2023
DOI: 10.1161/HYPERTENSIONAHA.123.21612
Abstract: This UK Biobank study uses a mendelian randomization approach to mitigate the variability and confounding that has affected previous analyses of the relationship between measured blood pressure (BP) and cognition and thus delineate the true association between the two. Systolic BP (SBP) and diastolic BP polygenic risk scores (PRSs) were calculated using summary statistics from the International Consortium of Blood Pressure-Genome Wide Association Study (n=299 024). Adjusted nonlinear mixed-effects regression models were used, including a natural splines term for BP-PRS with outcomes of fluid intelligence, reaction time (RT), and composite attention score. Moderating effects of age, sex, and antihypertensive use were assessed in separate models. There were 448 575 participants (mean age, 56.3 years age range, 37–72 years) included in the analysis after genetic and neurological disease exclusions. Genetic propensity for high SBP had an approximately linear association with worsened fluid intelligence ( P =0.0018). This relationship was significantly moderated by age ( P .0001). By contrast, genetic propensity for high and low SBP and diastolic BP predicted worse attention function ( P =0.0099 and P =0.0019), with high PRSs predicting worse function than low PRSs. Genetic propensity for low SBP and diastolic BP was associated with considerably worse RTs, while for high SBP-PRSs, the RT plateaued ( P .0001). The relationships between RT and the PRSs were significantly moderated by sex ( P .0001) and antihypertensive use ( P .0001). Genetic propensity for high and low BP impacts on midlife cognition in subtle ways and differentially affects cognitive domains. While a genetic propensity to low BP may preserve nontimed tests in midlife, it may come at a trade-off with worsened attention scores and RT.
Risk Factors for Mild Cognitive Impairment, Dementia and Mortality: The Sydney Memory and Ageing Study
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.JAMDA.2016.10.014
Abstract: The nature and commonality of late-life risk factors for mild cognitive impairment (MCI), dementia, and mortality remain unclear. Our aim was to investigate potential risk factors, simultaneously in a single cohort including many in iduals initially with normal cognition and followed for 6 years. We classified 873 community-dwelling in iduals (70-90 years old and without dementia at baseline) from the Sydney Memory and Ageing Study as cognitively normal (CN), having MCI or dementia, or deceased 6 years after baseline. Associations with baseline demographic, lifestyle, health, and medical factors were investigated, including apolipoprotein (APOE) genotype, MCI at baseline, and reversion from MCI to CN within 2 years of baseline. Eighty-three (9.5%) participants developed dementia and 114 (13%) died within 6 years nearly 33% had MCI at baseline, of whom 28% reverted to CN within 2 years. A core set of baseline factors was associated with MCI and dementia at 6 years, including older age (per year: odds ratios and 95% confidence intervals = 1.08, 1.01-1.14 for MCI 1.19, 1.09-1.31 for dementia), MCI at baseline (5.75, 3.49-9.49 8.23, 3.93-17.22), poorer smelling ability (per extra test point: 0.89, 0.79-1.02 0.80, 0.68-0.94), slower walking speed (per second: 1.12, 1.00-1.25 1.21, 1.05-1.39), and being an APOE ε4 carrier (1.84, 1.07-3.14 3.63, 1.68-7.82). All except APOE genotype were also associated with mortality (age: 1.11, 1.03-1.20 MCI: 3.87, 1.97-7.59 smelling ability: 0.83, 0.70-0.97 walking speed: 1.18, 1.03-1.34). Compared with stable CN participants, in iduals reverting from MCI to CN after 2 years were at greater risk of future MCI (3.06, 1.63-5.72). Those who reverted exhibited some different associations between baseline risk factors and 6-year outcomes than in iduals with stable MCI. A core group of late-life risk factors indicative of physical and mental frailty are associated with each of dementia, MCI, and mortality after 6 years. Tests for slower walking speed and poorer smelling ability may help screen for cognitive decline. In iduals with normal cognition are at greater risk of future cognitive impairment if they have a history of MCI.
Deep white matter hyperintensities, microstructural integrity and dual task walking in older people
Publisher: Springer Science and Business Media LLC
Date: 03-01-2018
DOI: 10.1007/S11682-017-9787-7
Abstract: To examine neural, physiological and cognitive influences on gait speed under single and dual-task conditions. Sixty-two community-dwelling older people (aged 80.0 ± 4.2 years) participated in our study. Gait speed was assessed with a timed 20-meter walk under single and dual-task (reciting alternate letters of the alphabet) conditions. Participants also underwent tests to estimate physiological fall risk based on five measures of sensorimotor function, cognitive function across five domains, brain white matter (WM) hyperintensities and WM microstructural integrity by measuring fractional anisotropy (FA). Univariate linear regression analyses showed that global physiological and cognitive measures were associated with single (β = 0.594 and β=-0.297, respectively) and dual-task gait speed (β = 0.306 and β=-0.362, respectively). Deep WMHs were associated with dual-task gait speed only (β = 0.257). Multivariate mediational analyses showed that global and executive cognition reduced the strength of the association between deep WMHs and dual-task gait speed by 27% (β = 0.188) and 44% (β = 0.145) respectively. There was a significant linear association between single-task gait speed and mean FA values of the genu (β=-0.295) and splenium (β=-0.326) of the corpus callosum, and between dual-task gait speed and mean FA values of Superior Cerebellar Peduncle (β=-0.284), splenium of the Corpus Callosum (β=-0.286) and Cingulum (β=-0.351). Greater deep WMH volumes are associated with slower walking speed under dual-task conditions, and this relationship is mediated in part by global cognition and executive abilities specifically. Furthermore, both cerebellum and cingulum are related to dual-task walking due to their role in motor skill performance and attention, respectively.
The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium
Publisher: Cambridge University Press (CUP)
Date: 12-2015
DOI: 10.1017/THG.2015.83
Abstract: Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9–11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9–13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47–0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61–78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
Animal models of drug-induced akathisia
Publisher: Elsevier
Date: 2005
Functional alterations in brain activation and deactivation in mild cognitive impairment in response to a graded working memory challenge
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000322112
Abstract: i Aim: /i To investigate dynamic changes in functional brain activity in mild cognitive impairment (MCI) in response to a graded working memory (WM) challenge with increasing memory load. i Methods: /i In an event-related functional magnetic resonance imaging (fMRI) study, 35 MCI and 22 cognitively normal subjects performed a visuospatial associative WM task with 3 load levels. Potential performance differences were controlled for by in idually calibrating the number of items presented at each load. i Results: /i An interaction between group and WM load was observed during stimulus encoding. At lower loads, greater activity in the right anterior cingulate and right precuneus was observed in MCI subjects. As the load increased to higher levels, reduced activation in these regions and greater deactivation in the posterior cingulate-medial precuneus were observed in MCI compared to control subjects. Stronger expression of load-related patterns of activation and deactivation in MCI subjects was associated with greater clinical severity and a more abnormal pattern of performance variability. i Conclusion: /i Patterns of overactivation, underactivation and deactivation during successful encoding in MCI subjects were dependent on WM load. This type of graded cognitive challenge may operate like a ‘memory stress test’ in MCI and may be a useful biomarker of disease at the predementia stage.
Neuropsychological predictors of transition from healthy cognitive aging to mild cognitive impairment: The PATH through life study
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1097/JGP.0B013E3181CDECF1
Abstract: To identify neuropsychological predictors of transition from healthy cognitive aging to mild cognitive impairment (MCI) or any mild cognitive disorder (any-MCD) in a community-based longitudinal study of aging. Longitudinal Two thousand eighty-two in iduals, aged 60–64 years and participating in a prospective epidemiologic study of mental health, and aging were assessed at two time points 4 years apart for MCI using the International Consensus Criteria, the clinical dementia rating scale (CDR, 0.5), or any of a suite of criteria sets for MCDs (any-MCD). Logistic regression was used to assess the neuropsychological predictors of conversion to diagnosis including the Mini-Mental State Examination, immediate and delayed recall (IR and DR), Digit Backward, Spot-the-Word (STW), Symbol Digits Modalities Test (SDMT), simple and choice reaction time, and reaction time variability. Of the 2,082 participants with no cognitive impairment in the first wave of data collection, 18 participants were diagnosed with MCI, 32 with CDR 0.5, and 64 participants presented with any-MCD 4 years later. The main neuropsychological predictors of conversion identified in multivariate analyses were measures of IR/DR, STW, Symbol Digit Modalities Task, and reaction time variability. Although most measures were significant predictors of conversion to MCI or any-MCD when assessed independently, four tests (IR/DR, STW, SDMT, and simple reaction time variability) accounted for the explained variance in diagnosis when all tests were assessed together. When predictive value, stability across clinical categories, and psychometric characteristics were considered together, the reaction time variability measure was the best predictor of future cognitive disorder.
Author response: Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins
Publisher: eLife Sciences Publications, Ltd
Date: 20-07-2020
Macrophage inhibitory cytokine-1/growth differentiation factor 15 as a marker of cognitive ageing and dementia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2016
Genetic influences on four measures of executive functions and their covariation with general cognitive ability: The Older Australian Twins Study
Publisher: Springer Science and Business Media LLC
Date: 03-02-2012
DOI: 10.1007/S10519-012-9526-1
Abstract: "Executive functions" (EF) is a multidimensional construct which encompasses many higher-order cognitive control operations, and is considered a potential mediator of age-associated changes in other cognitive domains. Here we examine the heritability of four measures of EF, and the genetic influences on their covariation with general cognitive abilities (GCA) from the Older Australian Twins Study. Participants included 117 pairs of monozygotic twins, 98 pairs of dizygotic twins, and 42 single twins, with a mean age of 71. Genetic modeling showed that additive genetic factors contributed to 59, 63,29, and 31% of the variance in the four measures: working memory, verbal fluency, response inhibition and cognitive flexibility, respectively. The phenotypic associations among the four EF measures were modest, which is in line with other evidence that EF is a multi-dimensional construct.All of the covariation between the EF measures was attributable to a common genetic factor. Similarly, all of the covariation between EF and General Cognitive Ability was explained by a common genetic factor, with no significant covariance due to environmental (E) factors. The genetic correlations between the measures were moderately high, suggesting that they may have common biological underpinnings. The genetic influence in the covariation of the EF measures and GCA also suggests that some aspects of EF and GCA share the same genes or same set of genes.
DNA methylation of the MAPT gene in Parkinson's disease cohorts and modulation by vitamin E In Vitro
Publisher: Wiley
Date: 27-12-2014
DOI: 10.1002/MDS.25784
Lifespan mental activity predicts diminished rate of hippocampal atrophy
Publisher: Public Library of Science (PLoS)
Date: 09-07-2008
Deep proteome analysis of plasma reveals novel biomarkers of mild cognitive impairment and Alzheimer’s disease: A longitudinal study
Publisher: Cold Spring Harbor Laboratory
Date: 02-2022
DOI: 10.1101/2022.01.30.478370
Abstract: Ageing is the primary risk factor for AD however, there is a poor understanding of the biological mechanisms by which the ageing process contributes to the development of AD in some in iduals, while others progress to advanced age with relatively little AD neuropathology. To halt the progression of AD, the preclinical stage of neurodegeneration (before the onset of clinical symptoms) is anticipated to be the more effective time point for applying potentially disease-modifying interventions in AD. The main objective of this study was to understand the age and disease related proteomic changes are detectable in plasma, based on retrospective analysis of longitudinal data and cross-sectional analyses of clinically diagnosed cases. We conducted an in-depth plasma proteomics analysis using intensive depletion of high-abundant plasma proteins using the Agilent multiple affinity removal liquid chromatography (LC) column-Human 14 (Hu14) followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) technique. In this study, we have begun to address the following questions (1) differences in plasma proteomic profiles between normal ageing, vs ageing with progress to cognitive decline (MCI) or disease (dementia, probable AD), (2) cross-sectional analysis of baseline data, when all subjects are clinically identified as cognitively normal, provides insight into the preclinical changes which precede subsequent progression to AD and potentially provide early biomarkers, and (3) comparison of plasma at the point of progression to clinically diagnosed onset of cognitive decline or AD, can provide potential plasma biomarkers to facilitate clinical diagnosis. Furthermore, our findings also identified some proteins previously discovered in AD CSF and brain proteomics signatures that could provide clinically meaningful information. We identified differentially expressed proteins which were associated with several biological and molecular processes that may serve as therapeutic targets and fluid biomarkers for the disease.
Psychosurgery for Bipolar Affective Disorder
Publisher: Royal College of Psychiatrists
Date: 10-1988
Abstract: Hepatotoxicity from antituberculous therapy is well described, but fortunately severe complications are rare. The optimal methods of monitoring for significant hepatotoxicity while on treatment are uncertain. Some authorities recommend measuring liver enzymes only if symptoms develop, whereas others recommend regular liver enzyme monitoring throughout the course of therapy. In British Columbia, from 1990 to 1997, 2624 active and approximately 8000 chemoprophylaxis cases have been treated, but only two severe complications directly related to antituberculous therapy have occurred. A 33-year-old male developed fulminant hepatic failure seven months after starting isoniazid chemoprophylaxis and required a liver transplant. The other patient died from hepatic failure that developed in the first month of triple-drug therapy for proven active pulmonary tuberculosis. The early and late onset of hepatic failure associated with antituberculous therapy in these cases underline the difficulties in identifying a monitoring protocol that will totally negate the risk of severe complications.
Alginate microcapsule as a 3D platform for propagation and differentiation of human embryonic stem cells (hESC) to different lineages.
Publisher: MyJove Corporation
Date: 09-03-2012
DOI: 10.3791/3608
The Falls Efficacy Scale International (FES-I). A comprehensive longitudinal validation study
Publisher: Oxford University Press (OUP)
Date: 08-01-2010
Abstract: this study aimed to perform a comprehensive validation of the 16-item and 7-item Falls Efficacy Scale International (FES-I) by investigating the overall structure and measurement properties, convergent and predictive validity and responsiveness to change. five hundred community-dwelling older people (70-90 years) were assessed on the FES-I in conjunction with demographic, physiological and neuropsychological measures at baseline and at 12 months. Falls were monitored monthly and fear of falling every 3 months. the overall structure and measurement properties of both FES-I scales, as evaluated with item response theory, were good. Discriminative ability on physiological and neuropsychological measures indicated excellent validity, both at baseline (n = 500, convergent validity) and at 1-year follow-up (n = 463, predictive validity). The longitudinal follow-up suggested that FES-I scores increased over time regardless of any fall event, with a trend for a stronger increase in FES-I scores when a person suffered multiple falls in a 3-month period. Additionally, using receiver-operating characteristic (ROC) curves, cut-points were defined to differentiate between lower and higher levels of concern. the current study builds on the previously established psychometric properties of the FES-I. Both scales have acceptable structures, good validity and reliability and can be recommended for research and clinical purposes. Future studies should explore the FES-I's responsiveness to change during intervention studies and confirm suggested cut-points in other settings, larger s les and across different cultures.
The relationship of current depressive symptoms and past depression with cognitive impairment and instrumental activities of daily living in an elderly population: The Sydney Memory and Ageing Study
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.JPSYCHIRES.2011.08.001
Abstract: Depressive symptoms are common in the elderly and they have been associated with cognitive and functional impairment. However, relatively less is known about the relationship of a lifetime history of depression to cognitive impairment and functional status. The aim of this cross-sectional study was to assess whether current depressive symptoms and past depression are associated with cognitive or functional impairment in a community-based s le representative of east Sydney, Australia. We also examined whether there was an interaction between current and past depression in their effects on cognitive performance. Eight hundred non-demented aged participants received a neuropsychological assessment, a past psychiatric history interview and the 15-item Geriatric Depression Scale. The Bayer-Activities of Daily Living scale was completed by an informant to determine functional ability. Clinically relevant depressive symptoms were present in 6.1% of the s le and 16.6% reported a history of depression. Participants with current depression had significantly higher levels of psychological distress and anxiety, and lower life satisfaction and performed worse on memory and executive function compared to participants without current depression. After controlling for anxiety the effect on executive function was no longer significant while the effect on memory remained significant. A history of depression was associated with worse executive function, higher levels of psychological distress and anxiety, and lower life satisfaction. After controlling for psychological distress the effect of past depression on executive function was no longer significant. There were no significant interactions between current and past depression in their effects on cognitive performance. There were no differences between participants with or without current depression and with or without past depression on functional abilities. These results support the view that current and past depressive episodes are associated with poorer cognitive performance but not with functional abilities.
Idemescence
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2016
The neuropsychiatry of brain iron.
Publisher: American Psychiatric Association Publishing
Date: 02-1993
DOI: 10.1176/JNP.5.1.18
Abstract: In the last two decades, many biological functions of iron have been identified, in particular its role in many enzymatic processes, its effect on dopamine D2 receptor function, its interaction with other neurotransmitters (gamma-aminobutyric acid, serotonin, opiate-peptides), and its catalytic role in the nonenzymatic mechanisms for oxidation, hydroxylation, and peroxidation reactions. The role of iron in Parkinson's disease, Alzheimer's disease, brain injury due to exogenous causes, neuroleptic-induced movement disorders, schizophrenia, and other neuropsychiatric disorders is currently being explored. This study summarizes current understanding of the anatomy and physiology of brain iron with special reference to these disorders.
The many ages of man
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2019
Gene expression in the aging human brain
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2016
Hippocampal size and dementia in stroke patients: The Sydney stroke study
Publisher: Elsevier BV
Date: 09-2007
DOI: 10.1016/J.JNS.2007.04.006
Abstract: Hippoc al atrophy is an early feature of Alzheimer's disease (AD) but it has also been reported in vascular dementia (VaD). It is uncertain whether hippoc al size can help differentiate the two disorders. We assessed 90 stroke/TIA patients 3-6 months after the event, and 75 control subjects, with neuropsychological tests, medical and psychiatric examination and brain MRI scans. A diagnosis of VaD, vascular mild cognitive impairment (VaMCI) or no cognitive impairment (NCI) was reached by consensus on agreed criteria. T1-weighted MRI was used to obtain total intracranial volume (TICV), gray and white matter volume, CSF volume, hippoc us and amygdala volumes, and T2-weighted scans for white matter hyperintensity (WMH) ratings. Stroke/TIA patients had more white matter hyperintensities (WMHs), larger ventricle-to-brain ratios and smaller amygdalae than controls, but hippoc us size and gray and white matter volumes were not different. WMHs and amygdala but not hippoc al volume distinguished stroke/TIA patients with VaD and VaMCI and without NCI and amygdala volumes. Right hippoc us volume significantly correlated with new visual learning. Stroke/TIA patients and patients with post-stroke VaMCI or mild VaD do not have hippoc al atrophy. The amygdala is smaller in stroke/TIA patients, especially in those with cognitive impairment, and this may be accounted for by white matter lesions. The hippoc us volume relates to episodic memory, especially right hippoc us and new visual learning. A longitudinal study of these subjects will determine whether hippoc al atrophy is a late development in VaD.
Hearing loss, cognition, and risk of neurocognitive disorder: evidence from a longitudinal cohort study of older adult Australians
Publisher: Informa UK Limited
Date: 28-12-2022
DOI: 10.1080/13825585.2020.1857328
Abstract: Addressing midlife hearing loss could prevent up to 9% of new cases of dementia, the highest of any potentially modifiable risk factor identified in the 2017 commissioned report in The Lancet. In Australia, hearing loss is the second-most common chronic health condition in older people, affecting 74% of people aged over 70. Estimates indicate that people with severe hearing loss are up to 5-times more likely to develop dementia, but these estimates vary between studies due to methodological limitations. Using data from the Sydney Memory and Aging Study, in which 1,037 Australian men and women aged between 70 and 90 years were enrolled and completed biennial assessments from 2005-2017, investigations between hearing loss and baseline cognitive performance as well as longitudinal risk of neurocognitive disorder were undertaken. In iduals who reported moderate-to-severe hearing difficulties had poorer cognitive performances in the domains of Attention/Processing Speed and Visuospatial Ability, and on an overall index of Global Cognition, and had a 1.5-times greater risk for the neurocognitive disorder during 6-years' follow-up. Hearing loss independently predicted risk for MCI but not dementia. The presence of hearing loss is an important consideration for neuropsychological case formulation in older adults with cognitive impairment. Hearing loss may increase cognitive load, resulting in observable cognitive impairment on neuropsychological testing. In iduals with hearing loss who demonstrate impairment in non-amnestic domains may experience benefits from the provision of hearing devices This study provides support for a randomized control trial of hearing devices for improvement of cognitive function in this group.
Sex and symmetry differences in hippocampal volumetrics: Before and beyond the opening of the crus of the fornix
Publisher: Wiley
Date: 31-10-2006
DOI: 10.1002/HIPO.20133
Abstract: Published normative volumetrics of the hippoc us (HC) vary substantially. While the protocol suggested by Watson et al. (Neurology 42 (1992) 1743-1750 Arch Neurology 54 (1997) 1521-1531) is the most frequently adhered to, this leaves the posterior section of the HC tail unmeasured, which has been estimated to be in the order of 2-4 mm, representing 5-10% of total HC volume. The objective of the current study was to compare HC volumes according to the method of Watson et al. (Neurology 42 (1992) 1743-1750 Arch Neurology 54 (1997) 1521-1531) against those measured to include the posterior tail section. From a random community s le of 60-64 yr old in iduals, 478 subjects underwent magnetic resonance imaging brain scans. Of these, 452 scans (238 males and 214 females) were adequate for hippoc al measurement. The scans comprised whole brain T1- weighted and T2-weighted FLAIR images. One hundred and fifty scans were randomly selected for the measurement of HC volumes beyond the opening of the crus of the fornix by manual tracings on T1-weighted images by a trained operator. Intracranial volume (ICV) and total brain volume (TBV) were measured using an automated program. We found that the posterior HC tail extended for a mean of just over 5 mm and comprised 11% of total HC volume. Males had significantly larger raw HC volumes, and while normalization with ICV or TBV reversed this pattern, it was significant only when the posterior HC tail was included in the measurement. In conclusion, this study showed that including the posterior part of the tail can influence the results of HC measurement. An argument is presented that accurate HC volumes should include the entire HC and not exclude the tail.
Prevalence of Mental Disorders in the Elderly: The Australian National Mental Health and Well-Being Survey
Publisher: Elsevier BV
Date: 06-2007
O4‐06‐05: MCI Diagnosis: Less is More
Publisher: Wiley
Date: 07-2016
Changes in mild cognitive impairment and its subtypes as seen on diffusion tensor imaging
Publisher: Cambridge University Press (CUP)
Date: 27-03-2012
DOI: 10.1017/S1041610212000270
Abstract: Background: Previous studies using diffusion tensor imaging (DTI) have observed microstructural abnormalities in white matter regions in both Alzheimer's disease and mild cognitive impairment (MCI). The aim of this work was to examine the abnormalities in white matter and subcortical regions of MCI and its subtypes in a large, community-dwelling older aged cohort Methods: A community-based s le of 396 in iduals without dementia underwent medical assessment, neuropsychiatric testing, and neuroimaging. Of these, 158 subjects were classified as MCI and 238 as cognitively normal (controls) based on international MCI consensus criteria. Regional fractional anisotropy (FA) and mean diffusivity (MD) measures were calculated from the DTI and compared between groups. The false discovery rate correction was applied for multiple testing. Results: Subjects with MCI did not have significant differences in FA compared with controls after correction for multiple testing, but had increased MD in the right putamen, right anterior limb of the internal capsule, genu and splenium of the corpus callosum, right posterior cingulate gyrus, left superior frontal gyrus, and right and left corona radiata. When compared with controls, changes in left anterior cingulate, left superior frontal gyrus, and right corona radiata were associated with amnestic MCI (aMCI), whereas changes in the right putamen, right anterior limb of the internal capsule, and the right corona radiata were associated with non-amnestic MCI (naMCI). On logistic regression, the FA values in the left superior gyrus and MD values in the anterior cingulate distinguished aMCI from naMCI. Conclusions: MCI is associated with changes in white matter and subcortical regions as seen on DTI. Changes in some anterior brain regions distinguish aMCI from naMCI.
Dysregulation of lipids in Alzheimer's disease and their role as potential biomarkers
Publisher: Wiley
Date: 24-02-2017
DOI: 10.1016/J.JALZ.2017.01.008
Abstract: The brain is highly enriched in lipids, and an intensive study of these lipids may be informative, not only of normal brain function but also of changes with age and in disease. In recent years, the development of highly sensitive mass spectrometry platforms and other high-throughput technologies has enabled the discovery of complex changes in the entire lipidome. This lipidomics approach promises to be a particularly useful tool for identifying diagnostic biomarkers for early detection of age-related neurodegenerative disease, such as Alzheimer's disease (AD), which has till recently been limited to protein- and gene-centric approaches. This review highlights known lipid changes affecting the AD brain and presents an update on the progress of lipid biomarker research in AD. Important considerations for designing large-scale lipidomics experiments are discussed to help standardize findings across different laboratories, as well as challenges associated with moving toward clinical application.
Dual voxel proton magnetic resonance spectroscopy in the healthy elderly: Subcortical-frontal axonal N-acetylaspartate levels are correlated with fluid cognitive abilities independent of structural brain changes
Publisher: Elsevier BV
Date: 12-2000
Global, regional, and national burden of suicide mortality 1990 to 2016: systematic analysis for the Global Burden of Disease Study 2016
Publisher: BMJ
Date: 06-02-2019
DOI: 10.1136/BMJ.L94
Abstract: To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Systematic analysis. Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Parental lifespan and polygenic risk score of longevity are associated with white matter hyperintensities
Publisher: Cold Spring Harbor Laboratory
Date: 05-02-2021
DOI: 10.1101/2021.02.02.21251026
Abstract: Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain ageing. In this study, we investigated the associations of parental lifespan (parental age at death) and polygenic risk score for longevity (longevity-PRS) with structural magnetic resource imaging (MRI) brain metrics considered to reflect the brain ageing process. We used a discovery s le (N = 19136) from the UK Biobank and a replication s le (N =809) from the Sydney Memory and Ageing Study and the Older Australian Twins Study. We found lower cerebral white matter hyperintensity (WMH) volumes to be significantly associated with longer parental lifespan in the discovery and replication s les and higher longevity-PRS in the discovery s le and a similar trend in the replication s le. The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus. Additionally, the effects of longevity-PRS on the association were more prominent in males, especially in the older-male group. Our findings suggest that human longevity-related genes may have an influence on WMH burden, suggesting WMH volume may be a biomarker for longevity and an ageing endophenotype.
Subjective Health and Memory Predictors of Mild Cognitive Disorders and Cognitive Decline in Ageing: The Personality and Total Health (PATH) through Life Study
Publisher: S. Karger AG
Date: 09-12-2011
DOI: 10.1159/000322373
Abstract: i Aims: /i To investigate self-reports of memory and health as predictors of transition to mild cognitive impairment (MCI) or any mild cognitive disorder (any MCD) in a community-based study. i Method: /i 2,082 in iduals, aged 60–64 years, were assessed at 2 time points 4 years apart for MCI using either the International Consensus Criteria, the Clinical Dementia Rating scale (CDR, 0.5), or a suite of criteria sets for mild cognitive disorders (any MCD) and global cognitive change. Logistic and multiple regression was used to assess conversion to diagnosis and cognitive change from the SF-12 self-rated health (SRH) and physical health subscale measures, as well as reports of memory problems. i Results: /i Of the 2,082 participants with no cognitive impairment at wave 1, 18 participants had a diagnosis of MCI, 32 a CDR score of 0.5, and 64 participants presented with any MCD 4 years later. After controlling for age, sex and education, SRH and physical health were significant predictors of MCD, memory interference was the only significant predictor of MCI, and cognitive change was associated with SRH, physical health and memory interference. i Conclusion: /i Brief, short, easily collected self-reports of health, disability and memory can provide useful information on the risk of MCD and cognitive decline in young-old adults.
Abnormal connectivity of the hippocampus in amnestic mild cognitive impairment: A diffusion tensor tractography study [Abstract P4-124]
Publisher: Wiley
Date: 07-2011
Comparison of Single Phase and Biphasic Extraction Protocols for Lipidomic Studies Using Human Plasma
Publisher: Frontiers Media SA
Date: 21-08-2019
PLASMA LIPIDOMICS OF VASCULAR DEMENTIA
Publisher: Wiley
Date: 07-2018
Associations between reaction time measures and white matter hyperintensities in very old age
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2017.01.021
Abstract: In old age, a relationship has been reported between intrain idual variability (IIV) in reaction time and white matter integrity as evidenced by white matter hyperintensities (WMH). However, it is unclear how far such associations are due to incipient neurodegenerative pathology in the s les investigated. The present study examined the relationship between IIV and WMH in older in iduals (N=526) drawn from the Sydney Memory and Ageing Study. Using a complex reaction time (RT) task, greater IIV and mean-RT were related to a higher WMH burden in the frontal lobe. Critically, significant associations remained having taken future dementia into account suggesting that they were not explained by incipient dementia. Additionally, independent measures of executive function accounted for the association between RT metrics and WHM. The results are consistent with the view that frontally-supported cognitive processes are involved in IIV-WMH relations, and that RT measures are sensitive to compromise in white matter structures in non-demented older in iduals.
Mild Cognitive Impairment in a community sample: The Sydney Memory and Ageing Study
Publisher: Wiley
Date: 29-10-2013
DOI: 10.1016/J.JALZ.2011.11.010
Abstract: Mild cognitive impairment (MCI) is associated with an increased dementia risk. This study reports incidence of MCI subtypes, rates of progression to dementia, and stability of MCI classification. We examined 873 community-dwelling adults aged 70 to 90 years over 2 years as part of an ongoing population-based longitudinal study, the Sydney Memory and Ageing Study. Neuropsychological testing assessed five cognitive domains, and a diagnosis of no cognitive impairment, MCI, or dementia (follow-up only) was made according to published criteria. The incidence of MCI was 104.6 (95% confidence interval: 81.6-127.7) per 1000 person-years, with higher incidence in men (men, 156.8 women, 70.3). Incidence rates for single-domain amnestic, multiple-domain amnestic, single-domain nonamnestic, and multiple-domain nonamnestic MCI were 47.7, 7.9, 45.0, and 3.9 per 1000 person-years, respectively. The 2-year rate of progression from MCI at baseline to dementia was 4.8%, being highest for multidomain amnestic MCI (9.1%). Of those with MCI at baseline, 28.2% reverted to no cognitive impairment at follow-up. Sensitivity analyses by redefining criteria for cognitive impairment did not affect stability of diagnosis, although changing the threshold of domain impairment reduced baseline MCI prevalence from 36.7% to 5.7% and incidence to 23.5, and increased 2-year progression rate from MCI to dementia to 14.3%. Incidence rates for MCI are higher than previously reported, particularly in men and for single-domain MCI rates for amnestic and nonamnestic MCI were comparable. Multidomain amnestic MCI was the most likely subtype to progress to dementia, but overall, the diagnosis of MCI, particularly single-domain MCI, shows considerable instability.
Common genetic variants influence human subcortical brain structures
Publisher: Springer Science and Business Media LLC
Date: 21-01-2015
DOI: 10.1038/NATURE14101
THE HERITABILITY OF AMYLOID DEPOSITION IN THE BRAINS OF OLDER PEOPLE: THE OLDER AUSTRALIAN TWINS STUDY
Publisher: Wiley
Date: 07-2017
Conversion to mild cognitive impairment: Predictors in a large longitudinal study of ageing
Publisher: Wiley
Date: 09-2009
Internet-delivered cognitive behavioural therapy for depression
Publisher: SAGE Publications
Date: 14-11-2013
Abstract: Depression is an important health issue amongst older adults. Internet-delivered cognitive behaviour therapy (iCBT) may help to reduce barriers and improve access to treatment, but few studies have examined its use with older adults. The present study evaluated the efficacy, acceptability and feasibility of a brief iCBT program, the Managing Your Mood Program, to treat depression amongst adults aged 60 years and older. Using an open trial design, 20 participants with elevated symptoms of depression (Patient Health Questionnaire 9-item (PHQ-9) total scores ≥ 10) received access to five educational lessons and homework summaries, additional resources, a moderated discussion forum and weekly telephone or email contact from a clinical psychologist. Eighty percent of the s le met diagnostic criteria for a major depressive episode at pre-treatment. Completion rates and response rates were high, with 16/20 participants completing the five lessons within the 8 weeks, and post-treatment and 3-month follow-up data being collected from 17/20 participants. Participants improved significantly on the PHQ-9 and Geriatric Depression Scale (GDS), with large within-group effect sizes (Cohen’s d) at follow-up of 1.41 and 2.04, respectively. The clinician spent a mean time of 73.75 minutes (SD = 36.10 minutes) contacting participants within the trial and the program was rated as highly acceptable by participants. The results are encouraging and support the potential value of iCBT in the treatment of depressive symptoms amongst older adults.
A WHO blueprint for action to reshape dementia research
Publisher: Springer Science and Business Media LLC
Date: 18-05-2023
Progression of cognitive impairment in stroke/TIA patients over 3 years
Publisher: BMJ
Date: 21-03-2014
Abstract: To examine how cognitive deficits progress in the years following a stroke or transient ischaemic attack (TIA). A follow-up study, with neuropsychological and MRI assessments undertaken 3 years after baseline assessments made 3-6 months poststroke in 183 stroke/TIA patients and 97 healthy controls participating in the Sydney Stroke Study. Additional measures included cardiovascular risk factors and apolipoprotein E (APOE) genotype. Stroke/TIA patients had poorer cognitive function and more vascular risk factors than controls at baseline, but did not show greater decline in cognitive function over 3 years except for verbal memory. Patients with a subsequent stroke/TIA showed greater decline in global cognitive function and a number of domains. Rates of incident dementia were 5.9% per year in patients and 0.4% in controls. Both groups showed increased atrophy of the hippoc us, amygdala and whole brain, and an increase in white matter hyperintensities over 3 years whole brain atrophy was greater in patients. Cognitive decline was greater in women and in those with smaller hippoc i at baseline. For patients without a subsequent stroke/TIA, those with smaller hippoc i or the APOE ε4 allele had greater global cognitive and verbal memory decline. In poststroke patients, cognitive decline was not greater than in comparison subjects, except for verbal memory, unless they had another stroke/TIA. However, dementia incidence was higher in patients, as might be expected from their poorer baseline cognitive functioning. Smaller hippoc i were associated with an increased risk of decline in memory, and APOE ε4 was a risk factor in those without a subsequent stroke/TIA.
Effects of left temporal lobectomy and amygdalohippocampectomy on memory.
Publisher: Elsevier BV
Date: 07-1997
DOI: 10.1016/S0967-5868(97)90098-9
Abstract: This study examined the effects of left (dominant) temporal lobe surgery on verbal and visual memory in 38 patients with temporal lobe epilepsy. Twenty-five patients had anterior temporal lobectomy (ATL) and 13 had selective amygdalohippoc ectomy (AH). All were administered the Rey Auditory Verbal Learning Test and a Complex Figure Test preoperatively and 1 year after surgery. ATL resulted in better seizure control overall. The ATL group as a whole showed a greater postoperative decline of their verbal memory than the AH group. A closer examination of the ATL patients showed there was a subgroup (n = 11) with better preoperative memory functioning that had the most significant decline. In contrast, only three patients in the AH group had better preoperative memory, and the majority (n = 10) matched the 'memory impaired' ATL patients. The changes in memory performance of the 'memory impaired' ATL and AH patients did not reach statistical significance. Postoperatively all patient groups improved in their verbal fluency.
Basic treatment principles for psychotic disorders in patients with epilepsy
Publisher: Wiley
Date: 03-2013
DOI: 10.1111/EPI.12102
Abstract: In patients with epilepsy, coexisting psychoses, either interictal (IIP) or postictal (PIP), are associated with serious disturbance in psychosocial function and well-being, and often require the care of a specialist. Unfortunately, evidence-based treatment systems for psychosis in patients with epilepsy have not yet been established. This article aims to propose concise and practical treatment procedures for IIP and PIP based on currently available data and international consensus statements, and primarily targeting nonpsychiatrist epileptologists who are often the first to be involved in the management of these complex patients. Accurate and early diagnosis of IIP and PIP and their staging in terms of acuity and severity form the essential first step in management. It is important to suspect the presence of psychosis whenever patients manifest unusual behavior. Knowledge of psychopathology and both in idual and epilepsy-related vulnerabilities relevant to IIP and PIP facilitate early diagnosis. Treatment for IIP involves (1) obtaining consent to psychiatric treatment from the patient, whenever possible, (2) optimization of antiepileptic drugs, and (3) initiation of antipsychotic pharmacotherapy in line with symptom severity and severity of behavioral and functional disturbance. Basic psychosocial interventions will help reinforce adherence to treatment and should be made available. Due consideration must be given to patients' ability to provide informed consent to treatment in the short term, with the issue being revisited regularly over time. Given the often prolonged and recurrent nature of IIP, treatment frequently needs to be long-term. Treatment of PIP consists of two aspects, that is, acute protective measures and preventive procedures in repetitive episodes. Protective measures prioritize the management of risk in the early stages, and may involve sedation with or without the use of antipsychotic drugs, and the judicious application of local mental health legislation if appropriate. As for preventative procedures, optimizing seizure control by adjusting antiepileptic drugs or by surgical treatment is necessary.
An Atypical Variant of a Common Neurodegenerative Disorder
Publisher: Springer International Publishing
Date: 2016
Associations between corpus callosum size and ADHD symptoms in older adults: The PATH through life study
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.PSCYCHRESNS.2016.08.009
Abstract: Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed deviations of the corpus callosum in children and adolescents. However, little is known about the link between callosal morphology and symptoms of inattention or hyperactivity in adulthood, especially later in life. Here, we investigated in a large population-based s le of 280 adults (150 males, 130 females) in their late sixties and early seventies whether ADHD symptoms correlate with callosal thickness. In addition, we tested for significant sex interactions, which were followed by correlation analyses stratified by sex. Within males, there were significant negative correlations with respect to inattention and hyperactivity in various callosal regions, including the anterior third, anterior and posterior midbody, isthmus, and splenium. A thinner corpus callosum may be associated with fewer fibers or less myelination of fibers. Thus, the observed negative correlations suggest impaired inter-hemispheric communication channels necessary to sustain motor control and attention, which may contribute to symptoms of hyperactivity, impulsivity and/or inattention. Interestingly, within females, callosal thickness was positively related to hyperactivity in a small area within the rostral body, suggesting a sexually dimorphic neurobiology of ADHD symptoms. Altogether, the present results may reflect a lasting relationship between callosal morphology and ADHD symptoms throughout life.
Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery—2018
Publisher: Elsevier BV
Date: 11-2018
Plasma lipidome variation during the second half of the human lifespan is associated with age and sex but minimally with BMI.
Publisher: Public Library of Science (PLoS)
Date: 20-03-2019
The Validity of Vascular Depression as a Diagnostic Construct
Publisher: Springer International Publishing
Date: 2016
Risk Factors of Transition from Normal Cognition to Mild Cognitive Disorder: The PATH through Life Study
Publisher: S. Karger AG
Date: 2009
DOI: 10.1159/000229025
Abstract: i Aims: /i The aim of this study was to identify physical and mental health and lifestyle predictors of transition from normal cognition to mild cognitive disorder (MCD). i Methods: /i A total of 2,082 in iduals, aged 60–64 years, were assessed at 2 time-points 4 years apart for mild cognitive impairment (MCI) and other MCDs. i Results: /i The main predictors of conversion to MCI and to other mild cognitive disorders were past alcohol intake, current anxiety and depression medication, increased systolic blood pressure, and past smoking. i Conclusion: /i Participants with a history of smoking or harmful alcohol consumption, hypertension, or who took medication for anxiety or depression were at increased risk of transitioning to MCI or any MCD. Strategies targeted at managing the above risk factors may have benefits in preventing mild cognitive decline in relatively healthy middle-aged in iduals living in the community.
Differentiation of vascular dementia from AD on neuropsychological tests.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1999
DOI: 10.1212/WNL.53.4.670
Abstract: Background: The concept of vascular dementia (VaD) is currently in a state of evolution. Memory impairment is emphasized as a primary criterion, reflecting the influence of AD on the concept of dementia. We have systematically reviewed whether the nature of neuropsychological dysfunction is distinct in AD and VaD, and whether similar defining criteria for the concept of dementia in both disorders can be supported. Methods: We searched five bibliographic databases (Medline, Biological Abstracts, EMBASE, PsychINFO, PsychLIT) for research articles in which VaD and AD had been compared using neuropsychological tests and that met criteria for scientific merit. Results: Of the 45 studies, 18 were excluded because of inadequacies, and the remaining 27 were analyzed. There were a number of similarities of dysfunction between VaD and AD. However, when matched for age, education, and severity of dementia, VaD patients had relatively superior function in verbal long-term memory and more impairment in frontal executive functioning compared with AD patients. Interpretation of the results is limited by uncertainty in diagnostic criteria for VaD, possible inclusion bias due to use of clinical diagnosis alone, possible overlap of AD and VaD, and the methodologic shortcomings of some studies. Conclusions: The neuropsychological differentiation of VaD from AD was consistent with the different neuroimaging findings in the two disorders, and argues for differential criteria for the definition of the syndromes. The simple application of Alzheimer’s dementia criteria to VaD, with the inclusion of cerebrovascular disease etiology, may not be sufficient to capture the uniqueness of VaD.
Deep brain stimulation of anteromedial globus pallidus interna for severe tourette's syndrome
Publisher: American Psychiatric Association Publishing
Date: 08-2012
DOI: 10.1176/APPI.AJP.2012.11101583
Abstract: Multiple anatomical targets for deep brain stimulation (DBS) have been proposed for the treatment of severe Tourette's syndrome. In this open study, the authors evaluated the effectiveness of DBS of the anteromedial globus pallidus interna on tic severity and common comorbidities. Eleven patients (eight of them men, mean age=39 years) with severe and medically intractable Tourette's syndrome underwent implantation of Medtronic quadripolar electrodes in the globus pallidus interna bilaterally. The primary outcome measure was the Yale Global Tic Severity Scale. Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, the Gilles de la Tourette Syndrome-Quality of Life Scale, and the Global Assessment of Functioning Scale. Follow-up occurred at 1 month and then at a mean of 14 months after surgery (range=4-30 months). Ten patients (91%) reported improvement in tic severity soon after DBS. Overall, there was a 48% reduction in motor tics and a 56.5% reduction in phonic tics at final follow-up. Six patients (54.5%) had a more than 50% reduction, sustained for at least 3 months, in Yale Global Tic Severity Scale score. Only two patients required ongoing pharmacotherapy for tics after surgery, and patients improved significantly on all secondary measures. One patient did not tolerate DBS and discontinued treatment after 3 months. Greater anxiety in two patients and hardware malfunction in three patients were noteworthy adverse outcomes. The results suggest anteromedial globus pallidus interna DBS for Tourette's syndrome is an effective and well-tolerated treatment for a subgroup of patients with severe Tourette's syndrome.
Using sulcal and gyral measures of brain structure to investigate benefits of an active lifestyle
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.NEUROIMAGE.2014.01.008
Abstract: Physical activity is associated with brain and cognitive health in ageing. Higher levels of physical activity are linked to larger cerebral volumes, lower rates of atrophy, better cognitive function and a lower risk of cognitive decline and dementia. Neuroimaging studies have traditionally focused on volumetric brain tissue measures to test associations between factors of interest (e.g. physical activity) and brain structure. However, cortical sulci may provide additional information to these more standard measures. Associations between physical activity, brain structure, and cognition were investigated in a large, community-based s le of cognitively healthy in iduals (N=317) using both sulcal and volumetric measures. Physical activity was associated with narrower width of the Left Superior Frontal Sulcus and the Right Central Sulcus, while volumetric measures showed no association with physical activity. In addition, Left Superior Frontal sulcal width was associated with processing speed and executive function. These findings suggest sulcal measures may be a sensitive index of physical activity related to cerebral health and cognitive function in healthy older in iduals. Further research is required to confirm these findings and to examine how sulcal measures may be most effectively used in neuroimaging.
Subjective memory difficulties are associated with hippocampal atrophy over four years: The Path Through Life Study
Publisher: Wiley
Date: 07-2012
The Relationship of White Matter Hyperintensities to depression and apathy in Mild Cognitive Impairment [Abstract P1-415]
Publisher: Wiley
Date: 07-2010
Periodic limb movements and other movement disorders in sleep: Neuropsychiatric dimensions
Publisher: Informa UK Limited
Date: 08-2005
DOI: 10.1080/09540260500104557
Abstract: Movement disorders such as Parkinson's disease and Tourette's syndrome, primarily manifest during wakefulness, intrude into sleep. There are some disorders, however, such as periodic limb movements in sleep, restless legs syndrome, paroxysmal nocturnal dystonia, bruxism, and somnambulism, which occur primarily during sleep. The diagnosis and management of these disorders pose a challenge to neuropsychiatric practice, not only because they may be difficult to distinguish from other neuropsychiatric disorders, but also because psychiatric disorders are often co-morbid with them. Study of these disorders is necessary for an understanding of the interaction of sleep and movement, and how disturbance in one may affect the other.
Genetic architecture of subcortical brain structures in 38,851 individuals
Publisher: Springer Science and Business Media LLC
Date: 21-10-2019
Treatment of Major Depressive Disorder by Transcranial Random Noise Stimulation: Case Report of a Novel Treatment
Publisher: Elsevier BV
Date: 08-2012
Olfaction identification in older adults: A genome-wide association study
Publisher: Wiley
Date: 07-2012
Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics
Publisher: Royal College of Psychiatrists
Date: 07-2012
DOI: 10.1192/BJP.BP.111.105189
Abstract: Reports of neuroleptic malignant syndrome (NMS) induced by second-generation antipsychotic drugs highlight a propensity for atypical clinical presentations. To systematically compare the clinical profile of NMS induced by first- (1G-NMS) and second-generation antipsychotic drugs (2G-NMS). The Australian Adverse Drug Reaction Advisory Committee (ADRAC) database was searched to identify in iduals with NMS reported between April 1994 and September 2010. The clinical characteristics of 208 people with NMS induced by monotherapy with first- or second-generation antipsychotic drugs, as well as presenting features of NMS, were compared. The in iduals with 2G-NMS were younger and more likely to have a psychotic disorder diagnosis. The features of NMS in the two groups were very similar, except that people with 2G-NMS were less likely to present with rigidity or extrapyramidal signs compared with those with 1G-NMS. This difference was due to the lower rates of rigidity in those with clozapine-induced NMS. Mortality was considerably lower for those with 2G-NMS (3.0%) compared with 1G-NMS (16.3%), and the former were more likely to have received supportive treatment. The clinical profile of 2G-NMS is largely similar to 1G-NMS, with clozapine-induced NMS being differentiated by the relative lack of rigidity as a feature. Mortality is lower for 2G-NMS.
The prevalence of 'cognitive impairment no dementia' in community-dwelling elderly: A pilot study
Publisher: SAGE Publications
Date: 09-2004
COGNITIVE DECLINE AND EFFECTS OF SEX, EDUCATION AND APOLIPOPROTEIN E GENOTYPE ON COGNITIVE PERFORMANCE IN DIVERSE ETHNO-CULTURAL AND GEOGRAPHICAL REGIONS INTERNATIONALLY: THE COSMIC COLLABORATION
Publisher: Wiley
Date: 07-2016
Deep brain stimulation for treatment-refractory obsessive-compulsive disorder should be an accepted therapy in Australia
Publisher: SAGE Publications
Date: 15-07-2021
DOI: 10.1177/00048674211031482
Abstract: Deep brain stimulation has shown promise for the treatment of severe, treatment-refractory obsessive-compulsive disorder. With the recent publication of the first Australian, randomised, sham-controlled trial of deep brain stimulation for obsessive-compulsive disorder, there are now four placebo-controlled trials demonstrating the efficacy of this therapy. Together with recent data identifying a biological substrate of effective stimulation that can predict response and that has been successfully reproduced, studies comparing and finding equivalent efficacy among different targets, as well as recent, large, open trials supporting the long-term effectiveness of deep brain stimulation, we argue that this should now be considered an accepted therapy for a select group of patients in the Australasian setting. We call on the Royal Australian and New Zealand College of Psychiatrists to revise their memorandum describing deep brain stimulation for obsessive-compulsive disorder as an ‘ experimental’ treatment and recognise that it has proven efficacy. We stress that this should remain a therapy offered only to those with high treatment-refractory illnesses and only at specialised centres where there is an experienced multidisciplinary team involved in work-up, implantation and follow-up and also where frameworks are in place to provide careful clinical governance and ensure appropriate fully informed consent.
Validity of the mediterranean diet and culinary index (Medicul) for online assessment of adherence to the ‘traditional’ diet and aspects of cuisine in older adults
Publisher: MDPI AG
Date: 04-12-2018
DOI: 10.3390/NU10121913
Abstract: The Mediterranean diet is associated with multiple health benefits. Yet, no tool has been specifically developed to assess adherence to the ‘traditional’ Mediterranean diet and cuisine within a Western cohort, and validated for online use. We tested the reliability and validity of online administration of the Mediterranean Diet and Culinary Index (MediCul) among middle-aged and older adults. Participants were recruited in January–March 2017 from the 45 and Up Study, completing MediCul twice. Test-retest reliability was assessed using the paired t-test, intra-class correlation coefficient (ICC) and Bland-Altman plot. Validity was tested against a three-day food record (FR)-derived MediCul score using Bland-Altman and nutrient trends across the MediCul score tertiles. Participants (n = 84 60% female 65.4 years (SD = 5.9)), were overweight (BMI 26.1 SD = 4.0) with 1.7 (SD = 1.5) chronic illnesses/conditions. Sequential MediCul tool scores were 56.1/100.0 and 56.8/100.0, respectively (t = −1.019 p = 0.311). Reliability via ICC (ICC = 0.86, 95% CI: 0.789, 0.910, p 0.0001) and Bland-Altman was good. In Bland-Altman validity analyses, the tool over-reported FR MediCul score by 5.6 points with no systematic bias ((y = 8.7 − 0.06*x) (95% CI: −0.278, 0.158, p = 0.584)). Nutrient trends were identified for MediCul consistent with expected Mediterranean patterns. Online MediCul administration demonstrated good reliability and moderate validity for assessing adherence to a ‘traditional’ Mediterranean pattern among older Australians.
The relationship between cortical sulcal variability and cognitive performance in the elderly
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.NEUROIMAGE.2011.03.015
Abstract: The relationship between cognitive functions and brain structure has been of long-standing research interest. Most previous research has attempted to relate cognition to volumes of specific brain structures or thickness of cortical regions, with relatively few studies examining other features such as cortical surface anatomy. In this study, we examine the relationship between cortical sulcal features and cognitive function in a s le (N=316) of community-dwelling subjects aged between 70 and 90 years (mean=78.06±4.75 male/female=130/186) who had detailed neuropsychological assessments and brain MRI scans. Using automated methods on 3D T1-weighted brain scans, we computed global sulcal indices (g-SIs) of the whole brain and average sulcal spans of five prominent sulci. The g-SI, which reflects the complexity of sulcal folds across the cerebral hemispheres, showed a significant positive correlation with performance in most cognitive domains including attention rocessing speed, memory, language and executive function. Regionally, a negative correlation was found between some cognitive functions and sulcal spans, i.e. poorer cognitive performance was associated with a wider sulcal span. Of the five cognitive domains examined, the performance of processing speed was found to be correlated with the spans of most sulci, with the strongest correlation being with the superior temporal sulcus. Memory did not show a significant correlation with any in idual sulcal index, after correcting for age and sex. Of the five sulci measured, the left superior temporal sulcus showed the highest sensitivity, with significant correlations with performances in all cognitive domains except memory, after controlling for age, sex, years of education and brain size. The results suggest that regionally specific sulcal morphology is associated with cognitive function in elderly in iduals.
Homocysteine, cerebrovascular disease and brain atrophy
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.JNS.2004.09.006
Abstract: Homocysteine (Hcy) is known to increase the risk of cerebrovascular disease (CVD). Recent evidence suggests its direct contribution to brain atrophy, cognitive impairment and possibly Alzheimer disease (AD). This paper reports the results of two studies of the impact of Hcy on the brain. In the Sydney Stroke Study (N=131 stroke patients, 81 healthy controls), higher Hcy levels were related to increased number of strokes and greater cognitive impairment, in particular, frontal-executive function and attention. In the control group, Hcy was related to increased subcortical atrophy. In the PATH Through Life Study, involving 60-64 years old community-dwelling in iduals (N=385), Hcy was related to an increase in white matter hyperintensities, as well as impairment in verbal memory and fine motor speed. Hcy increases the risk of micro- and macrovascular disease as well as brain atrophy, and thereby impaired cognition. Remediation of high Hcy levels should begin early in life.
The influence of memory on cortical correlations in the elderly
Publisher: Elsevier BV
Date: 07-2009
A sham-controlled trial of left and right temporal rTMS for the treatment of auditory hallucinations
Publisher: Cambridge University Press (CUP)
Date: 06-08-2010
DOI: 10.1017/S0033291709990900
Abstract: Several studies have reported reduction of auditory hallucinations (AH) after repetitive transcranial magnetic stimulation (rTMS) to the left temporal cortex. This study explored the effects of rTMS to the left and right temporal cortex. Eighteen subjects with schizophrenia and frequent AH were enrolled in a double-blind, cross-over trial of 3 days of active rTMS to the left or right temporal cortex, or sham rTMS to the vertex (control condition), followed by an open treatment phase. The effects on AH were assessed by a blinded rater, using the Auditory Hallucination Rating Scale (AHRS). During the double-blind phase, active temporal rTMS did not result in significantly greater improvement in hallucination scores than sham rTMS to the vertex, apart from a reduction in distress scores. Hallucination scores improved during the open continued treatment phase. This study did not demonstrate an advantage for left temporal rTMS compared to right temporal and sham stimulation, over a 3-day stimulation period, but found modest improvement in hallucinations during continued open label treatment.
Inappropriate Sexual Behaviors in Dementia
Publisher: Elsevier BV
Date: 04-2017
P4‐124: Recent findings from the Older Australian Twins Study (OATS)
Publisher: Wiley
Date: 07-2012
Cognitive generation of affect in hypomania: an fMRI study
Publisher: Wiley
Date: 28-06-2004
Drug Treatments for Alzheimer’s Disease: Hopes and Challenges
Publisher: Springer New York
Date: 2014
Risk Profiles for Mild Cognitive Impairment Vary by Age and Sex: The Sydney Memory and Ageing Study
Publisher: Elsevier BV
Date: 10-2012
Do people become more apathetic as they grow older? A longitudinal study in healthy individuals
Publisher: Cambridge University Press (CUP)
Date: 15-12-2009
DOI: 10.1017/S1041610209991335
Abstract: Background: The aim of this study was to determine levels, rates and progression of apathy in healthy older persons and to investigate factors associated with its progression. Methods: Seventy-six healthy elderly subjects, aged 58–85 years (mean 69.9), who were recruited by general advertisement and through local community groups, participated as a control group for a longitudinal study of stroke patients. Data were collected on demographic, psychological, neuropsychological and neuroimaging (MRI) variables and apathy was rated by informants on the Apathy Evaluation Scale (AES). Results: Apathy scores and rates increased over 5 years, especially in men. Change of apathy was associated with informant ratings of cognitive decline in the years prior to baseline assessment but not to subsequent neuropsychological, neuroimaging or functional changes. Conclusions: Apathy increases with age in otherwise healthy community-dwelling in iduals, particularly in men.
A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder
Publisher: Springer Science and Business Media LLC
Date: 29-03-2021
DOI: 10.1038/S41398-021-01307-9
Abstract: Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham ( p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points ( χ 2 (11) = 39.8, p = 3.8 × 10 −5 ), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points ( p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s in idualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippoc us and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippoc al, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for in iduals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.
The Meta VCI Map consortium for meta‐analyses on strategic lesion locations for vascular cognitive impairment using lesion‐symptom mapping: Design and multicenter pilot study
Publisher: Wiley
Date: 12-04-2019
The canine sand maze: an appetitive spatial memory paradigm sensitive to age-related change in dogs.
Publisher: Wiley
Date: 2011
Prevalence, incidence, and risk factors of lacunar infarcts in a community sample.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-07-2009
Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2016
Effects of Clear-Fell Harvest on Bat Home Range
Publisher: Public Library of Science (PLoS)
Date: 22-01-2014
The Relationship Between Plasma Aβ Levels, Cognitive Function and Brain Volumetrics: Sydney Memory and Ageing Study
Publisher: Bentham Science Publishers Ltd.
Date: 12-02-2016
DOI: 10.2174/1567205013666151218150202
Abstract: Determine whether (1) a relationship exists between plasma amyloid-β (Aβ)1- 40 and 1-42 peptide levels, brain volumetrics and cognitive performance in elderly in iduals with and without amnestic mild cognitive impairment (aMCI), (2) plasma Aβ peptide levels differ between apolipoprotein E (APOE) ε4 carriers and non-carriers and (3) longitudinal changes in cognition and brain volume relate to Aβ levels. Subjects with aMCI (n = 89) and normal cognition (n = 126) were drawn from the Sydney Memory and Aging Study (Sydney MAS), a population based study of non-demented 70-90 year old in iduals 39 Alzheimer's disease (AD) patients were recruited from a specialty clinic. Sydney MAS participants underwent brain MRI scans and were assessed on 19 cognitive measures and were APOE ε4 genotyped. Plasma levels of Aβ1-40 and 1-42 were quantified using ELISA. Wave1 plasma levels of Aβ peptides and Aβ1-42/1-40 ratio were lower in aMCI and AD, and Aβ1-42 was positively associated with global cognition and hippoc al volume and negatively with white matter hyperintensities. The relationships of Aβ1-40 and Aβ1-42 were predominantly observed in ε4 allele carriers and non-carriers respectively. Longitudinal analysis revealed greater decline in global cognition and memory for the highest quintiles of Aβ1-42 and the ratio measure. Plasma Aβ levels and the Aβ1-42/1-40 ratio are related to cognition and hippoc al volumes, with differential associations of Aβ1-40 and Aβ1-42 in ε4 carriers and non-carriers. These data support the Aβ sink model of AD pathology, and suggest that plasma Aβ measures may serve as biomarkers of AD.
Diabetes and the elderly brain: Sweet memories?
Publisher: SAGE Publications
Date: 12-2012
Abstract: Type 2 diabetes is common in older people and is associated with higher risk of both vascular dementia and Alzheimer’s disease. This review examines the evidence for increased risk of dementia and mild cognitive impairment in patients with diabetes and the role of potential confounders. The relationship of diabetes and impaired fasting glucose with brain structure is also reviewed, focusing on longitudinal studies in older people. The pathophysiology underlying cognitive change in type 2 diabetes is examined with reference to vascular disease, hypoglycaemia, inflammation and insulin levels. Implications for clinical care in older people with diabetes are discussed, with a recommendation for cognitive evaluation as a routine part of end-organ, diabetes complication review.
Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer’s Disease
Publisher: MDPI AG
Date: 14-09-2023
Orientational changes of white matter fibers in Alzheimer's disease and amnestic mild cognitive impairment
Publisher: Wiley
Date: 19-08-2021
DOI: 10.1002/HBM.25628
Abstract: White matter abnormalities represent early neuropathological events in neurodegenerative diseases such as Alzheimer's disease (AD), investigating these white matter alterations would likely provide valuable insights into pathological changes over the course of AD. Using a novel mathematical framework called “Director Field Analysis” (DFA), we investigated the geometric microstructural properties (i.e., splay, bend, twist, and total distortion) in the orientation of white matter fibers in AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) in iduals from the Alzheimer's Disease Neuroimaging Initiative 2 database. Results revealed that AD patients had extensive orientational changes in the bilateral anterior thalamic radiation, corticospinal tract, inferior and superior longitudinal fasciculus, inferior fronto‐occipital fasciculus, and uncinate fasciculus in comparison with CN. We postulate that these orientational changes of white matter fibers may be partially caused by the expansion of lateral ventricle, white matter atrophy, and gray matter atrophy in AD. In contrast, aMCI in iduals showed subtle orientational changes in the left inferior longitudinal fasciculus and right uncinate fasciculus, which showed a significant association with the cognitive performance, suggesting that these regions may be preferential vulnerable to breakdown by neurodegenerative brain disorders, thereby resulting in the patients' cognitive impairment. To our knowledge, this article is the first to examine geometric microstructural changes in the orientation of white matter fibers in AD and aMCI. Our findings demonstrate that the orientational information of white matter fibers could provide novel insight into the underlying biological and pathological changes in AD and aMCI.
The effect of breed on age-related changes in behavior and disease prevalence in cognitively normal older community dogs, Canis lupus familiaris
Publisher: Elsevier BV
Date: 07-2015
Association of Dilated Perivascular Spaces With Cognitive Decline and Incident Dementia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-03-2021
DOI: 10.1212/WNL.0000000000011537
Abstract: To determine whether severe perivascular space (PVS) dilation is associated with longitudinal cognitive decline and incident dementia over 4 and 8 years, respectively, we analyzed data from a prospective cohort study. A total of 414 community-dwelling older adults aged 72–92 years were assessed at baseline and biennially for up to 8 years, with cognitive assessments, consensus dementia diagnoses, and 3T MRI. The numbers of PVS in 2 representative slices in the basal ganglia (BG) and centrum semiovale (CSO) were counted and severe PVS pathology defined as the top quartile. The effects of severe PVS pathology in either region or both regions and those with severe BG PVS and severe CSO PVS were examined. White matter hyperintensity volume, cerebral microbleed number, and lacune number were calculated. Participants with severe PVS pathology in both regions or in the CSO alone had greater decline in global cognition over 4 years, even after adjustment for the presence of other small vessel disease neuroimaging markers. The presence of severe PVS pathology in both regions was an independent predictor of dementia across 8 years (odds ratio 2.91, 95% confidence interval 1.43–5.95, p = 0.003). The presence of severe PVS pathology in all groups examined was associated with greater dementia risk at either year 4 or 6. Severe PVS pathology is a marker for increased risk of cognitive decline and dementia, independent of other small vessel disease markers. The differential cognitive associations for BG and CSO PVS may represent differences in their underlying pathology.
Parental Life Span and Polygenic Risk Score of Longevity Are Associated With White Matter Hyperintensities
Publisher: Oxford University Press (OUP)
Date: 23-10-2021
Abstract: Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain aging. Here, we used a discovery s le (N = 19 136, aged 45–81 years) from the UK Biobank and a replication s le (N = 809, aged 66–93 years) from the Sydney Memory and Ageing Study and the Older Australian Twins Study to investigate the associations between both parental life span (parental age at death) and polygenic risk score (PRS) for longevity (longevity-PRS) and structural magnetic resonance imaging brain metrics, which are considered to reflect the brain aging process, namely white matter hyperintensities (WMHs), total gray matter, and cortical volumes. We found lower volumes of WMHs to be significantly associated with longer parental life span in the discovery (whole WMH, β = −0.0323, padj = .0002) and replication s les (whole WMH, β = −0.0871, padj = .0208) and higher longevity-PRS in the discovery s le (whole WMH, β = −0.0331, padj = .0015) and a similar trend in the replication s le (significant before multiple comparison adjustment). The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus (whole WMH, β = −0.0297, padj = .0048). While total gray matter and cortical volumes were related to parental life span in the discovery s le, they were not significantly associated with longevity-PRS. Additionally, the effects of longevity-PRS on the association were more prominent in males. Our findings suggest that enrichment of longevity-related alleles may provide some protection against WMH burden and highlight the important aspect of genetic relationship between longevity and WMH.
Transcranial magnetic stimulation (TMS) in controlled treatment studies: Are some 'sham' forms active?
Publisher: Elsevier BV
Date: 02-2000
DOI: 10.1016/S0006-3223(99)00285-1
Abstract: Carefully designed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation (TMS) in psychiatric disorders. A major methodological concern is the design of the "sham" control for TMS. An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment. Strategies employed so far include alterations in the position of the stimulating coil, but there has been little systematic study of their validity. In this study, we investigated the effects of different coil positions on cortical activation and scalp sensation. In nine normal subjects, single TMS pulses were administered at a range of intensities with a "figure eight" coil held in various positions over the left primary motor cortex. Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle. Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed. None of the coil positions studied met the criteria for an ideal sham. Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex. The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive "stimulation." Further research is needed to develop the best sham condition for a range of applications.
Does Antihypertensive Use Moderate the Effect of Blood Pressure on Cognitive Decline in Older People?
Publisher: Oxford University Press (OUP)
Date: 12-10-2021
Abstract: While midlife hypertension is deleterious, late-life hypertension has been associated with better cognitive outcomes in several studies. Many questions remain, including the relative benefit or harm of a blood pressure (BP) target and antihypertensive therapy of & in very old in iduals. The Sydney Memory and Aging Study (n = 1015) comprises a cohort of 70- to 90-year-olds, who were followed biennially for 8 years. Global cognition was assessed with a battery of 10 neuropsychological tests. Blood pressure was measured at Waves 1 and 2 and classified into 3 systolic groupings: group 1 (≤120 mmHg), group 2 (121–140 mmHg), and group 3 (& mmHg). Multiple regression, linear mixed modeling, and Cox regression examined the effect of BP and antihypertensives. There were no overall significant differences in global cognition or dementia between the disparate BP groups. However, in those not taking antihypertensives, the systolic BP (SBP) & 140 mmHg group had a significantly worse global cognitive trajectory compared to SBP ≤ 120 mmHg (b = −0.067, 95% CI [−0.129, −0.006], p = .030). Within the SBP ≤ 120 mmHg group those taking antihypertensives had significantly worse global cognition trajectories compared to those not taking antihypertensives even when controlling for past history of hypertension (b = −0.077, 95% CI [−0.147, −0.007], p = .030). Untreated hypertension in old age is related to worse global cognitive decline. However, ongoing treatment at new recommendations of lower SBP targets may be related to poorer cognitive decline and should be considered carefully in older populations.
Modifiable risk factors for dementia interact with APOE and sex to predict hippocampal atrophy
Publisher: Wiley
Date: 07-2010
An inverse relationship between serum macrophage inhibitory cytokine-1 levels and brain white matter integrity in community-dwelling older individuals
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.PSYNEUEN.2015.07.610
Abstract: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a marker of inflammation that has been associated with atherosclerosis. We have previously demonstrated its relationships with cognitive decline and cerebral gray matter volumes, suggesting its role as a biomarker of cognitive impairment. Considering that it is widely distributed in the brain, and both inflammation and vascular pathology impact on white matter (WM) integrity, we examined the relationship between MIC-1/GDF15 and measures of WM integrity, including WM volumes, mean fractional anisotropy (FA) values and WM hyperintensity (WMH) volumes in a community-dwelling non-demented s le of older in iduals (n=327, 70-90 years old). We found that the mean FA values were negatively associated with MIC-1/GDF15 serum levels, after Bonferroni correction. The voxel-wise analysis showed negative relationships between MIC-1/GDF15 serum levels and FA values in corticospinal tract, corpus callosum (including genu, body and splenium parts), superior longitudinal fasciculus, cingulum, as well as anterior and posterior thalamic radiation. Whole brain WMH volumes, especially deep WMH volumes, showed a non-significant trend for a positive association with MIC-1/GDF15 serum levels. The associations between MIC-1/GDF15 serum levels and WM integrity showed a non-significant trend of being stronger for the in iduals classified as mild cognitive impairment, compared to the normal ageing participants. The findings suggest that high serum MIC-1/GDF15 levels indicate reduced WM integrity and possibly greater WM pathology.
P2‐321: Influence of Linguistic and Acculturation Characteristics on Traditional and Computerised Neuropsychological Test Performances in Non‐Native Proficient English Speakers from the Sydney Memory
Publisher: Wiley
Date: 07-2016
Reaction Time Measures Predict Incident Dementia in Community-Living Older Adults: The Sydney Memory and Ageing Study
Publisher: Elsevier BV
Date: 03-2016
VALIDATED DEMENTIA RISK MEASURE IS ASSOCIATED WITH REGIONAL BRAIN VOLUMES: THE ANU ALZHEIMER’S DISEASE RISK INDEX (ANU-ADRI)
Publisher: Wiley
Date: 07-2016
Double-Blind Controlled Investigation of Transcranial Magnetic Stimulation for the Treatment of Resistant Major Depression
Publisher: American Psychiatric Association Publishing
Date: 06-1999
Abstract: The efficacy and safety of left prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, controlled study. Eighteen medication-resistant depressed subjects were randomly assigned to 2 weeks of real or sham rTMS, then permitted up to 4 weeks of real rTMS. Effects on mood, neuropsychological function, EEG, and hearing were assessed. The groups receiving real and sham rTMS improved in mood significantly over the 2-week double-blind period, but there was no significant difference between groups. Repetitive transcranial magnetic stimulation did not provide significantly greater improvement than did sham treatment. A 4-week course of rTMS, as administered in this study, was safe.
Genetic Influences on Individual Differences in Longitudinal Changes in Global and Subcortical Brain Volumes: Results of the ENIGMA Plasticity Working Group
Publisher: Wiley
Date: 05-06-2017
DOI: 10.1002/HBM.23672
Ionotropic receptors in the central nervous system and neurodegenerative disease
Publisher: Springer New York
Date: 2014
Pain and anxiety mediate the relationship between dizziness and falls in older people
Publisher: Wiley
Date: 25-01-2013
DOI: 10.1111/JGS.12131
Abstract: To identify medical, psychological, and physiological mediators of the relationship between dizziness and falls in older adults. Secondary analysis of a prospective cohort study. Community. Five hundred sixteen community-dwelling adults aged 73 to 92. Participants completed questionnaires related to health and psychological well-being and underwent a tilt table blood pressure test, the Physiological Profile Assessment (PPA vision, reaction time, proprioception, postural sway, and quadriceps strength), and leaning balance tests. Prospective falls data were collected using monthly calendars for 12 months. Participants were categorized into dizzy and nondizzy groups based on self-report of dizziness, vertigo, and light-headedness. Two hundred seventeen (42%) participants reported vertigo or dizziness (10%), light-headedness (16%), or both (16%). The dizzy participants were significantly more likely to report neck and back pain, past transient ischemic attacks, and feeling dizzy upon upright tilting. They also had poorer balance and less strength and scored higher on measures of depression and anxiety (P < .05). There were no blood pressure measurement-related differences between the groups. Dizziness increased the risk of multiple falls in an unadjusted analysis (relative risk (RR) = 1.55, 95% confidence interval = 1.08-2.23). After controlling for PPA scores, neck and back pain and anxiety were mediators that reduced the RR of the relationship between dizziness and faller status the most (14%) in a modified Poisson regression model. Suffering from neck and back pain and anxiety were mediators of the relationship between dizziness and falls after controlling for poor sensorimotor function and balance. Older people with dizziness might benefit from interventions targeting these mediators such as pain management and cognitive behavioral therapy.
A longitudinal study examining the independence of apathy and depression after stroke: The Sydney Stroke Study
Publisher: Cambridge University Press (CUP)
Date: 18-08-2011
DOI: 10.1017/S1041610209991116
Abstract: Background: There is growing recognition that apathy is not only a symptom of depression but may be an independent syndrome. This is the first study to investigate the relationship of apathy and depression longitudinally following stroke and to examine the association with dementia. Method: 106 consecutive eligible participants following stroke received extensive medical, psychiatric and neuropsychological assessments at three to six months (index assessment) and 15 months (follow-up assessment) after their stroke. A subset of participants received magnetic resonance imaging (MRI) scans at index assessment. Ratings were made for DSM-IV major or minor depression and for apathy using the Apathy Evaluation Scale (AES). Results: While there was no significant overlap between apathy and depression at index assessment (OR = 1.79, 95% CI 0.48, 6.66), the overlap was significant a year later (OR = 7.75, 95% CI 2.60, 23.13). Dementia at index assessment was a common risk factor for both apathy and depression at follow-up (OR = 12.45, 95% CI 2.98, 52.02 and OR = 10.35, 95% CI 2.84, 37.72, respectively). Conclusions: Apathy and depression after stroke have a common predictor and overlap longitudinally. The overlap might be due to cumulative vascular pathology and because of the relationship of each of these syndromes to dementia, which was an important, possibly causal, predictor for both.
SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study
Publisher: Oxford University Press (OUP)
Date: 24-03-2021
DOI: 10.1093/BJS/ZNAB101
Abstract: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351 best case 196, worst case 816) or non-cancer surgery (733 best case 407, worst case 1664). Both exceeded the NNV in the general population (1840 best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
Influence of population versus convenience sampling on sample characteristics in studies of cognitive aging
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.ANNEPIDEM.2013.10.005
Abstract: We examined whether differences in findings of studies examining mild cognitive impairment (MCI) were associated with recruitment methods by comparing s le characteristics in two contemporaneous Australian studies, using population-based and convenience s ling. The Sydney Memory and Aging Study invited participants randomly from the electoral roll in defined geographic areas in Sydney. The Australian Imaging, Biomarkers and Lifestyle Study of Ageing recruited cognitively normal (CN) in iduals via media appeals and MCI participants via referrals from clinicians in Melbourne and Perth. Demographic and cognitive variables were harmonized, and similar diagnostic criteria were applied to both s les retrospectively. CN participants recruited via convenience s ling were younger, better educated, more likely to be married and have a family history of dementia, and performed better cognitively than those recruited via population-based s ling. MCI participants recruited via population-based s ling had better memory performance and were less likely to carry the apolipoprotein E ε4 allele than clinically referred participants but did not differ on other demographic variables. A convenience s le of normal controls is likely to be younger and better functioning and that of an MCI group likely to perform worse than a purportedly random s le. S ling bias should be considered when interpreting findings.
Mild cognitive disorders are associated with different patterns of brain asymmetry than normal aging: The PATH through life study
Publisher: Frontiers Media SA
Date: 2010
Relationship between changes in body weight and cognitive function in middle-aged and older women
Publisher: Wiley
Date: 11-10-2012
DOI: 10.1002/GPS.2797
Abstract: Although several longitudinal studies indicate that weight loss precedes dementia in men and women, the relationship between weight changes and cognitive performance is unclear. This study investigated the relationship between changes in adiposity and cognitive function in community-dwelling women. Data were derived from the Longitudinal Assessment of Women Study, a population-based study of 511 urban women initially aged 40-79 years. We analyzed data from 334 women who had complete information on demographics, cardiovascular risk factors, medical status, weight, height, and waist-to-hip ratio and cognitive scores at baseline and after a mean of 7.45 years of follow-up. Cognition was assessed at baseline and follow-up using the Mini Mental State Examination the Auditory Delayed Index, Visual Delayed Index, and Working Memory Index from the Wechsler Memory Scale, Third Edition and the Processing Speed Index from the Wechsler Adult Intelligence Scale, Third Edition. Associations were adjusted for age, education, baseline cognitive performance, cardiovascular risk factors, menopausal status, and apolipoprotein E-4 status. In multivariate analysis, both weight gain and loss were associated with poor Visual Delayed Index performance at follow-up compared with stable weight (β = -4.02 ± 1.57, p = 0.011 β = -6.50 ± 2.39, p = 0.007, respectively). No significant associations were found between body mass index, waist circumference, or waist-to-hip ratio and any cognitive domains at follow-up. Changes in cognitive performance were not associated with changes in adiposity measures. Weight loss and weight gain were associated with poor cognitive performance in middle-aged and older women compared with women with stable weight.
Low-dose apomorphine challenge in tardive akathisia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1993
DOI: 10.1212/WNL.43.3_PART_1.544
Abstract: We challenged seven tar e akathisia patients with low-dose apomorphine (0.01 mg/kg) SC and placebo in a double-blind, random design. Apomorphine caused a significantly greater reduction in the objective (movement) but not the subjective (distress) component of akathisia.
Chronic repetitive transcranial magnetic stimulation is antidepressant but not anxiolytic in rat models of anxiety and depression
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.PSYCHRES.2005.07.008
Abstract: Transcranial magnetic stimulation (TMS) has been proposed as a treatment for depression and anxiety disorders. While the antidepressant effect has been modelled in animals, there have been few attempts to examine a possible anxiolytic effect of repetitive TMS (rTMS) in animal models. We administered 18 days of rTMS to male Sprague-Dawley rats. On days 10 through 18, rats were tested in several anxiety models (social interaction, emergence, elevated plus-maze, and predator odor avoidance) and in the forced swim test. No group differences were apparent on any of the anxiety models, while TMS produced an antidepressant effect in the forced swim test. Interestingly, on day 1 of the forced swim test, the home cage control group displayed increased swimming behaviour compared with sham-treated animals, suggesting an observable level of stress may have accompanied sham treatment. The results from the forced swim test suggested that TMS had modest antidepressant properties, but it did not show anxiolytic properties in the models examined. The study also suggested that stress associated with handling should be taken into account in the interpretation of TMS studies in animals.
Continuation transcranial direct current stimulation for the prevention of relapse in major depression
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.JAD.2012.10.012
Abstract: Transcranial direct current stimulation (tDCS) is gaining attention as an effective new treatment for major depression. Little is known, however, of the duration of antidepressant effects following acute treatment. In this study, we describe the use of continuation tDCS treatment for up to 6 months following clinical response to an acute treatment course. Twenty-six participants pooled from two different studies involving different tDCS protocols received continuation tDCS treatment on a weekly basis for 3 months and then once per fortnight for the final 3 months. Mood ratings were completed at 3 and 6 months. Analyses examined clinical predictors of relapse during continuation tDCS treatment. The cumulative probability of surviving without relapse was 83.7% at 3 months and 51.1% at 6 months. Medication resistance was found to be a predictor of relapse during continuation tDCS. This was an open label prospective study with no control group. Two different forms of tDCS were used. Similar to other antidepressant treatments, continuation tDCS appears to be a useful strategy to prevent relapse following clinical response. These preliminary data suggest that the majority of patients maintained antidepressant benefit with a continuation schedule of at least weekly treatment. Future controlled studies are required to confirm these findings.
The psychological health of 207 near-centenarians (95–99) and centenarians from the Sydney Centenarian Study
Publisher: SAGE Publications
Date: 17-05-2019
Abstract: While near-centenarians (95–99) and centenarians are the fastest growing sectors of the population in many countries, few studies have investigated their psychological health. We aimed to compare levels of psychological distress and life satisfaction in in iduals aged 95 or above (95+) with younger age groups and identify the factors associated with psychological distress and life satisfaction in near-centenarians and centenarians. We assessed the physical, cognitive, social and psychological health of 207 participants aged 95+ in the Sydney Centenarian Study. Psychological distress and life satisfaction were rated on the Kessler Psychological Distress Scale (K10) and Satisfaction with Life Scale, respectively. Cross-sectional univariate comparisons were performed with participants aged 70–90 years from the Sydney Memory and Ageing Study. Factors associated with psychological distress and life satisfaction among Sydney Centenarian Study participants were examined using multiple regression analyses. In Sydney Centenarian Study and Memory and Ageing Study, mean K10 scores were 15.3 (±5.9) and 13.4 (±3.6), and clinical levels of psychological distress (K10 ⩾ 20) were 19% and 7%, respectively. Sydney Centenarian Study participants demonstrated significantly higher levels and rates of psychological distress ( t = 3.869, p 0.001 χ 2 = 27.331, p 0.001). In Sydney Centenarian Study, more psychotropic medications and having fewer relatives and friends were associated with higher psychological distress. Sydney Centenarian Study participants reported significantly higher levels of life satisfaction than Memory and Ageing Study participants, mean scores 6.0 (±1.5) and 5.6 (±1.3) t = 5.835, p 0.001. Lower Mini-Mental State Examination scores and having fewer relatives and friends were associated with lower life satisfaction in Sydney Centenarian Study. Despite showing higher levels of psychological distress in the prior 4 weeks than younger age groups, near-centenarians and centenarians remained highly satisfied with their overall lives. The identification of risk and protective factors for psychological distress and life satisfaction provides opportunities for interventions to maintain good psychological health in this vulnerable population.
Epileptic psychoses are underrecognized by French neurologists and psychiatrists
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.YEBEH.2019.106528
Abstract: This study evaluates the knowledge about psychotic disorders associated with epilepsy among medical practitioners in France. A self-report questionnaire was sent, and responses of 486 participants were collected. Results showed the rate of correct responses being higher among neurologists compared to psychiatrists, respectively 70.6% and 58.3% (p < 10
Referring a Patient for Psychosurgery?
Publisher: SAGE Publications
Date: 10-1994
Dementia in older dogs: A data-driven approach to ecologically valid diagnosis and assessment
Publisher: Wiley
Date: 09-2009
Lifespan mental activity predicts diminished rate of hippocampal atrophy
Publisher: Wiley
Date: 09-2009
07-02 TMS treatment for depression: overview of efficacy and report on a sham-controlled trial of twice daily left prefrontal rTMS
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Bilateral orbitomedial leucotomy for obsessive-compulsive disorder: a single-case study using positron emission tomography.
Publisher: SAGE Publications
Date: 10-2001
Abstract: Objective: The objective of this report is to correlate the clinical outcome of neurosurgery for obsessive–compulsive disorder (OCD) with regional cerebral glucose metabolic changes. Clinical picture: The patient was a 37-year-old female patient with severe and intractable OCD. Treatment: The patient was treated with bilateral stereotactic lesions in the frontal white matter superior to the orbito-medial cortex. Outcome: She had a remarkable improvement in her obsessive–compulsive symptoms, which was sustained up to 3 years of follow up. A positron emission tomography (PET) scan performed 18 days after surgery demonstrated an obvious reduction of metabolism in the caudate head, anterior cingulate and orbital, medial and lateral prefrontal cortices and the thalamus. At 1 year postsurgery, metabolic rate was still reduced in the anterior cingulate gyrus, caudate and thalamus compared with preoperative baseline. The patient demonstrated no long-term cognitive effects of the surgery. Conclusions: This case supports some of the cortical-subcortical circuit dysfunction models of OCD and argues for the further evaluation of neurosurgery for the treatment of a severe and intractable disorder.
Mediation of Cognitive Function Improvements by Strength Gains After Resistance Training in Older Adults with Mild Cognitive Impairment: Outcomes of the Study of Mental and Resistance Training
Publisher: Wiley
Date: 24-10-2017
DOI: 10.1111/JGS.14542
Abstract: To determine whether improvements in aerobic capacity (VO Randomized, double-blind, double-sham, controlled trial. University research facility. Community-dwelling older adults (aged ≥55) with mild cognitive impairment (MCI) (N = 100). PRT and cognitive training (CT), 2 to 3 days per week for 6 months. Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) global, executive, and memory domains peak strength (1 repetition maximum) and VO PRT increased upper (standardized mean difference (SMD) = 0.69, 95% confidence interval = 0.47, 0.91), lower (SMD = 0.94, 95% CI = 0.69-1.20) and whole-body (SMD = 0.84, 95% CI = 0.62-1.05) strength and percentage change in VO High-intensity PRT results in significant improvements in cognitive function, muscle strength, and aerobic capacity in older adults with MCI. Strength gains, but not aerobic capacity changes, mediate the cognitive benefits of PRT. Future investigations are warranted to determine the physiological mechanisms linking strength gains and cognitive benefits.
Geriatric psychiatry: is the jury still out on the cognitive effects of homocysteine and one-carbon metabolism?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2003
Mixed handedness is associated with greater age-related decline in volumes of the hippocampus and amygdala: The PATH through life study
Publisher: Wiley
Date: 11-2011
DOI: 10.1002/BRB3.24
A longitudinal study of brain atrophy over two years in community-dwelling older individuals
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.NEUROIMAGE.2013.08.022
Abstract: Most previous neuroimaging studies of age-related brain structural changes in older in iduals have been cross-sectional and/or restricted to clinical s les. The present study of 345 community-dwelling non-demented in iduals aged 70-90years aimed to examine age-related brain volumetric changes over two years. T1-weighted magnetic resonance imaging scans were obtained at baseline and at 2-year follow-up and analyzed using the FMRIB Software Library and FreeSurfer to investigate cortical thickness and shape and volumetric changes of subcortical structures. The results showed significant atrophy across much of the cerebral cortex with bilateral transverse temporal regions shrinking the fastest. Atrophy was also found in a number of subcortical structures, including the CA1 and subiculum subfields of the hippoc us. In some regions, such as left and right entorhinal cortices, right hippoc us and right precentral area, the rate of atrophy increased with age. Our analysis also showed that rostral middle frontal regions were thicker bilaterally in older participants, which may indicate its ability to compensate for medial temporal lobe atrophy. Compared to men, women had thicker cortical regions but greater rates of cortical atrophy. Women also had smaller subcortical structures. A longer period of education was associated with greater thickness in a number of cortical regions. Our results suggest a pattern of brain atrophy with non-demented people that resembles a less extreme form of the changes associated with Alzheimer's disease (AD).
The preventative role of antioxidants (selegiline and vitamin E) in a rat model of tardive dyskinesia
Publisher: Elsevier BV
Date: 12-1999
DOI: 10.1016/S0006-3223(99)00091-8
Abstract: We examined the potential protective effects of two potent antioxidants, selegiline and vitamin E, in a rodent model of tar e dyskinesia (TD), viz. neuroleptic-induced spontaneous orofacial movements. Rats were treated with fortnightly injections of fluphenazine decanoate for 12 weeks, and examined at baseline and at fortnightly intervals for vacuous chewing movements, mouth tremors and tongue protrusions. The administration of fluphenazine led to a progressive increase of all three types of orofacial movements. In the first study, the impact of the concomitant administration of selegiline on orofacial movements was examined. Selegiline led to a reduction in orofacial movements in neuroleptic-treated rats to the level of control rats not being administered a neuroleptic drug. In the second study, rats were fed diets either high or low in their vitamin E content. High and low vitamin E diets did not significantly affect neuroleptic-induced orofacial movements. Our studies provide some support for the hypothesis that oxidative injury may play a role in the genesis of neuroleptic-induced movement disorder, and prompt further examination of this hypothesis in both animals and humans.
Timing of surgery following SARS‐CoV‐2 infection: an international prospective cohort study
Publisher: Wiley
Date: 09-03-2021
DOI: 10.1111/ANAE.15458
Abstract: Peri‐operative SARS‐CoV‐2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS‐CoV‐2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre‐operative SARS‐CoV‐2 infection were compared with those without previous SARS‐CoV‐2 infection. The primary outcome measure was 30‐day postoperative mortality. Logistic regression models were used to calculate adjusted 30‐day mortality rates stratified by time from diagnosis of SARS‐CoV‐2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre‐operative SARS‐CoV‐2 diagnosis. Adjusted 30‐day mortality in patients without SARS‐CoV‐2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre‐operative SARS‐CoV‐2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3–4.8), 3.9 (2.6–5.1) and 3.6 (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARS‐CoV‐2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9–2.1)). After a ≥ 7 week delay in undertaking surgery following SARS‐CoV‐2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS‐CoV‐2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
P2‐212: COMT AND BDNF GENE INTERACTIONS PREDICT BRAIN STRUCTURE IN AGEING
Publisher: Wiley
Date: 07-2014
Regional cerebral blood flow deficits in mild Alzheimer's disease using high resolution single photon emission computerized tomography
Publisher: Wiley
Date: 06-2005
DOI: 10.1111/J.1440-1819.2005.01372.X
Abstract: In spite of its wide availability, single photon emission computerized tomography (SPECT) scanning is uncommonly used in the assessment of Alzheimer's disease (AD) and related dementias. In light of recent advances in scanning protocols and image analysis, SPECT needs to be re-examined as a tool in the diagnosis of dementia. A total of 18 subjects with early AD and 10 healthy elderly control subjects were examined with high resolution SPECT during the performance of a simple word discrimination task. SPECT images were coregistered with in idual magnetic resonance imaging scans, allowing delineation of predetermined neuroanatomical Regions of Interest (ROI). There was a gradation of regional cerebral blood flow (rCBF) values in both groups, with the lowest values being in the hippoc us and the highest in the striatum, thalamus and cerebellum. Compared to healthy controls, AD subjects demonstrated lower relative rCBF in parietal and prefrontal cortices. Analysis of in idual ROI demonstrated bilateral reduction of rCBF in prefrontal poles, posterior temporal and anterior parietal cortex, and unilateral reduction of rCBF in left dorsolateral prefrontal cortex, right posterior parietal cortex and the left cingulate body. There were no significant differences for hippoc al, occipital or basal ganglia rCBF. Discriminant function analysis indicated that rCBF in the prefrontal polar regions achieved the best classification of cases. SPECT has utility in the diagnostic assessment of AD if standardized and semiquantitative techniques are used.
Discrete Neuroanatomical Networks Are Associated with Specific Cognitive Abilities in Old Age
Publisher: Society for Neuroscience
Date: 26-01-2011
DOI: 10.1523/JNEUROSCI.4085-10.2011
Abstract: There have been many attempts at explaining age-related cognitive decline on the basis of regional brain changes, with the usual but inconsistent findings being that smaller gray matter volumes in certain brain regions predict worse cognitive performance in specific domains. Additionally, compromised white matter integrity, as suggested by white matter hyperintensities or decreased regional white matter fractional anisotropy, has an adverse impact on cognitive functions. The human brain is, however, a network and it may be more appropriate to relate cognitive functions to properties of the network rather than specific brain regions. We report on graph theory-based analyses of diffusion tensor imaging tract-derived connectivity in a s le of 342 healthy in iduals aged 72–92 years. The cognitive domains included processing speed, memory, language, visuospatial, and executive functions. We examined the association of these cognitive assessments with both the connectivity of the whole brain network and in idual cortical regions. We found that the efficiency of the whole brain network of cortical fiber connections had an influence on processing speed and visuospatial and executive functions. Correlations between connectivity of specific regions and cognitive assessments were also observed, e.g., stronger connectivity in regions such as superior frontal gyrus and posterior cingulate cortex were associated with better executive function. Similar to the relationship between regional connectivity efficiency and age, greater processing speed was significantly correlated with better connectivity of nearly all the cortical regions. For the first time, regional anatomical connectivity maps related to processing speed and visuospatial and executive functions in the elderly are identified.
Who does well after a stroke? the Sydney Stroke Study
Publisher: Informa UK Limited
Date: 09-2009
DOI: 10.1080/13607860902845525
Abstract: Research addressing positive outcomes one year after stroke has been limited. The s le comprised 125 participants with complete Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Mini-Mental State Examination (MMSE) scale scores at baseline ( approximately 4 months after ischaemic stroke) and at follow-up (1 year later), 31 persons were defined as having a favourable outcome (an MMSE score of >or=28/30 and combined ADL/IADL score equal to 14/14 at follow-up) and 94 as having a poorer outcome. Predictors of a favourable outcome following stroke included being younger, having higher premorbid IQ, no atrial fibrillation, no dementia, less apathy and fewer intercurrent cerebrovascular events. We conclude that people can have good outcomes in the year after stroke except if they experience further cerebrovascular events and/or have risk factors for cerebrovascular disease. Brain reserve appears to be protective.
The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample.
Publisher: Springer Science and Business Media LLC
Date: 14-07-2008
Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System
Publisher: Springer Science and Business Media LLC
Date: 20-10-2016
DOI: 10.1038/SREP35391
Abstract: Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of s les including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.
Glutamate in the Pathogenesis of Gliomas
Publisher: Springer New York
Date: 2014
Mid-sagittal anatomy in late-onset schizophrenia
Publisher: Cambridge University Press (CUP)
Date: 07-1999
DOI: 10.1017/S0033291799008685
Abstract: Background. Of the midline brain structures, abnormalities have been demonstrated in the corpus callosum and cerebellum in young schizophrenic patients. Whether similar abnormalities are also present in late-onset schizophrenia (LOS) is not known. Methods. The mid-sagittal cross-sectional areas of brain regions, in particular the corpus callosum and cerebellum, on magnetic resonance imaging were examined in a group of patients with late-onset schizophrenia ( N =25) and contrasted with two comparison groups – early-onset schizophrenia (EOS) ( N =2524) and healthy volunteers (NC) ( N =2530) matched for age and gender. Results. While the mean corpus callosum area in the LOS group was smaller than in the EOS (by 10·2%) and NC (by 6·2%) groups, the three groups did not differ statistically in the corpus callosum area or the corpus callosum to cerebrum ratios. The cross-sectional cerebellar areas or the cerebellum: cerebrum ratios also did not differ across the groups. The brainstem was smaller in the schizophrenic groups because of smaller cross-sectional areas of the pons, a statistically significant difference which could not be accounted for by any gross lesions on visual inspection. Conclusion. We found no abnormality in the mid-sagittal area of the corpus callosum and cerebellum in our early- or late-onset schizophrenia subjects. The significance of the finding of a smaller pontine cross-sectional area is unclear and speculation on it awaits independent replication using a volumetric measure.
The contribution of twins to the study of cognitive ageing and dementia: The Older Australian Twins Study
Publisher: Informa UK Limited
Date: 12-2013
DOI: 10.3109/09540261.2013.870137
Abstract: The Older Australian Twins Study (OATS) is a major longitudinal study of twins, aged ≥ 65 years, to investigate genetic and environmental factors and their interactions in healthy brain ageing and neurocognitive disorders. The study collects psychiatric, neuropsychological, cardiovascular, metabolic, biochemical, neuroimaging, genomic and proteomic data, with two-yearly assessments, and is currently in its third wave. The initial cohort comprises 623 in iduals (161 monozygotic and 124 dizygotic twin pairs 1 MZ triplets 27 single twins and 23 non-twin siblings), of whom 426 have had wave 2 assessment. A number of salient findings have emerged thus far which assist in the understanding of genetic contributions to cognitive functions such as processing speed, executive ability and episodic memory, and which support the brain reserve hypothesis. The heritability of brain structures, both cortical and subcortical, brain spectroscopic metabolites and markers of small vessel disease, such as lacunar infarction and white matter hyperintensities, have been examined and can inform future genetic investigations. Work on amyloid imaging and functional magnetic resonance imaging is proceeding and epigenetic studies are progressing. This internationally important study has the potential to inform research into cognitive ageing in the future, and offers an excellent resource for collaborative work.
Neuroleptic and anticholinergic drug use in Chinese patients with schizophrenia resident in a state psychiatric hospital in Singapore.
Publisher: SAGE Publications
Date: 12-2000
DOI: 10.1080/000486700274
Abstract: Objective: The objective of this study was to survey the prescribing pattern in Chinese patients with chronic schizophrenia in a state mental hospital in Singapore, and to compare our findings with those of surveys of Chinese patients in other countries. Method: We surveyed the use of neuroleptic and anticholinergic agents among Chinese patients with chronic schizophrenia (n = 534) in a state mental hospital in Singapore. Results: Fifty-nine per cent of the patients received two or more neuroleptics (median daily dose of 400 mg chlorpromazine equivalents, range 50–2875 mg). There were no differences in gender distribution between those prescribed multiple neuroleptics as against an older group of those receiving none or only one neuroleptic medication. Sixty-six per cent of the patients were receiving depot neuroleptics, with more than half of these subjects also receiving additional oral neuroleptics. Patients who were prescribed multiple neuroleptics received significantly higher total doses than those receiving just one neuroleptic. Only 1% of patients were prescribed an atypical neuroleptic. Sixty-five per cent of patients were prescribed an anticholinergic agent. Those prescribed anticholinergic agents were younger, in receipt of higher doses of neuroleptic medications and had lower Simpson-Angus scores for extrapyramidal side-effects. Conclusions: The pervasive use of multiple typical neuroleptics, marked under-utilisation of atypical neuroleptics, and the lack of anticholinergic medication in patients who might benefit from such treatment are issues of substantial concern, warranting action in both psychiatry practice and mental health policy.
Self-paced and reprogrammed saccades: Differences between melancholic and non-melancholic depression
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.NEURES.2006.07.003
Abstract: Motor disturbances in major depressive disorder (MDD) are increasingly recognized and may differentiate melancholic, from non-melancholic depression. Motor impairments in melancholic depression have been likened to Parkinson's disease and proposed to have a frontostriatal basis. This study investigated self-pacing and reprogramming skills, thought to rely on frontostriatal functioning, in groups of healthy in iduals (n=15), non-melancholic depression patients (n=10) and melancholic depression patients (n=9) using ocular motor tasks. Self-paced saccades were requested to be performed at a rhythm of 1 Hz between two continuously illuminated targets, before and after external cueing. Saccade reprogramming, for direction and litude, was explored using a saccadic "oddball" task. Results indicated no group differences for accuracy, intersaccadic intervals (during the self-paced task), latency or peak velocity. However, the melancholic group showed greater intrasubject variability of latencies than the control group, lower peak saccade velocities compared to the non-melancholic group, and reduced accuracy of the primary saccade when compared to the control and the non-melancholic groups. These findings provide further support for distinct motor impairments associated with melancholia that may reflect frontostriatal abnormalities.
Intensive Neurodiagnostic Monitoring in Psychiatry
Publisher: SAGE Publications
Date: 06-1990
DOI: 10.3109/00048679009077688
Abstract: A series of technological advances have made it possible to closely monitor electrophysiological and behavioural manifestations of episodic clinical events over prolonged periods of time, with the ability to review the records at leisure or to submit them to computer analysis. The more promising techniques are time-locked video/EEG monitoring, cable telemetry, radiotelemetry, ambulatory cassette recording, intensive plasma anti-epileptic drug monitoring and continuous neuropsychological monitoring. The greatest promise of these techniques is for the diagnosis, research and management of epilepsy. For psychiatry, they offer additional help in the differential diagnosis of non-epileptic events from epilepsy, the most important of which are psychogenic seizures and episodes of aggression. This paper discusses the potential role of these techniques in the assessment of non-epileptic events and transient cognitive impairment in clinical psychiatry.
Cortical Similarities in Psychiatric and Mood Disorders Identified in Federated VBM Analysis via COINSTAC
Publisher: Cold Spring Harbor Laboratory
Date: 28-09-2023
Genetic and Environmental Influences on Language Ability in Older Adults: Findings from the Older Australian Twins Study
Publisher: Springer Science and Business Media LLC
Date: 04-04-2018
DOI: 10.1007/S10519-018-9897-Z
Abstract: We used a sub-s le from the Older Australian Twins Study to estimate the heritability of performance on three tests of language ability: Boston Naming Test (BNT), Letter/Phonemic Fluency (FAS) and Category/Semantic Fluency (CFT) Tests. After adjusting for age, sex, education, mood, and global cognition (GC), heritability estimates obtained for the three tests were 0.35, 0.59, and 0.20, respectively. Multivariate analyses showed that the genetic correlation were high for BNT and CFT (0.61), but low for BNT and FAS (0.17), and for FAS and CFT (0.28). Genetic modelling with Cholesky decomposition indicated that the covariation between the three measures could be explained by a common genetic factor. Environmental correlations between the language ability measures were low, and there were considerable specific environmental influences for each measure. Future longitudinal studies with language performance and neuroimaging data can further our understanding of genetic and environmental factors involved in the process of cognitive aging.
Recent rodent models for Alzheimer's disease: Clinical implications and basic research
Publisher: Springer Science and Business Media LLC
Date: 16-11-2012
DOI: 10.1007/S00702-011-0731-5
Abstract: Alzheimer's disease (AD) is the most common origin of dementia in the elderly. Although the cause of AD remains unknown, several factors have been identified that appear to play a critical role in the development of this debilitating disorder. In particular, amyloid precursor protein (APP), tau hyperphosphorylation, and the secretase enzymes, have become the focal point of recent research. Over the last two decades, several transgenic and non-transgenic animal models have been developed to elucidate the mechanistic aspects of AD and to validate potential therapeutic targets. Transgenic rodent models over-expressing human β-amyloid precursor protein (β-APP) and mutant forms of tau have become precious tools to study and understand the pathogenesis of AD at the molecular, cellular and behavioural levels, and to test new therapeutic agents. Nevertheless, none of the transgenic models of AD recapitulate fully all of the pathological features of the disease. Octodon degu, a South American rodent has been recently found to spontaneously develop neuropathological signs of AD in old age. This review aims to address the limitations and clinical relevance of transgenic rodent models in AD, and to highlight the potential for O. degu as a natural model for the study of AD neuropathology.
Automated detection of amnestic mild cognitive impairment in community-dwelling elderly adults: A combined spatial atrophy and white matter alteration approach
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.NEUROIMAGE.2011.08.013
Abstract: Amnestic mild cognitive impairment (aMCI) is a syndrome widely considered to be prodromal Alzheimer's disease. Accurate diagnosis of aMCI would enable earlier treatment, and could thus help minimize the prevalence of Alzheimer's disease. The aim of the present study was to evaluate a magnetic resonance imaging-based automated classification schema for identifying aMCI. This was carried out in a s le of community-dwelling adults aged 70-90 years old: 79 with a clinical diagnosis of aMCI and 204 who were cognitively normal. Our schema was novel in using measures of both spatial atrophy, derived from T1-weighted images, and white matter alterations, assessed with diffusion tensor imaging (DTI) tract-based spatial statistics (TBSS). Subcortical volumetric features were extracted using a FreeSurfer-initialized Large Deformation Diffeomorphic Metric Mapping (FS+LDDMM) segmentation approach, and fractional anisotropy (FA) values obtained for white matter regions of interest. Features were ranked by their ability to discriminate between aMCI and normal cognition, and a support vector machine (SVM) selected an optimal feature subset that was used to train SVM classifiers. As evaluated via 10-fold cross-validation, the classification performance characteristics achieved by our schema were: accuracy, 71.09% sensitivity, 51.96% specificity, 78.40% and area under the curve, 0.7003. Additionally, we identified numerous socio-demographic, lifestyle, health and other factors potentially implicated in the misclassification of in iduals by our schema and those previously used by others. Given its high level of performance, our classification schema could facilitate the early detection of aMCI in community-dwelling elderly adults.
Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis
Publisher: Springer Science and Business Media LLC
Date: 27-02-2020
DOI: 10.1038/S41525-020-0118-3
Abstract: We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands s le (area under the curve, AUC = 0.65, CI 95% = [0.62–0.68], p = 8.3 × 10 −22 ). The maximum AUC achieved was 0.69 (CI 95% = [0.66–0.71], p = 4.3 × 10 −34 ) when cell-type proportion was included in the predictor.
More Highly Myelinated White Matter Tracts are Associated with Faster Processing Speed in Healthy Adults
Publisher: Cold Spring Harbor Laboratory
Date: 27-06-2017
DOI: 10.1101/152546
Abstract: The objective of this study was to investigate whether the myelin content of white matter tracts is predictive of cogni–tive processing speed and whether such associations are modulated by age. Associations between myelin content and processing speed was assessed in 570 community-living in iduals (277 middle-age, 293 older-age). Myelin content was measured using the mean T1w/T2w magnetic resonance ratio, in six white matter tracts (anterior corona radiata, superior corona radiata, pontine crossing tract, anterior limb of the internal capsule, genu of the corpus callosum, and splenium of the corpus callosum). Processing speed was estimated by extracting a principal component from 5 sep–arate tests of processing speed. It was found that myelin content of the bilateral anterior limb of the internal capsule and left splenium of the corpus callosum were significant predictors of processing speed, even after controlling for socio-demographic, health and genetic variables and correcting for multiple comparisons. A 1 SD increase in the myelin content of the anterior limb of the internal capsule was associated with 2.53% increase in processing speed and within the left splenium of the corpus callosum with a 2.20% increase in processing speed. In addition, significant differences in myelin content between middle-age and older participants were found in all six white matter tracts. The present results indicate that myelin content, estimated in vivo using a neuroimaging approach in healthy older adults is sufficiently precise to predict variability in processing speed in behavioural measures.
RISK FACTORS FOR MCI AND DEMENTIA OVER 6 YEARS: THE SYDNEY MEMORY AND AGEING STUDY
Publisher: Wiley
Date: 07-2016
Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)
Publisher: Cold Spring Harbor Laboratory
Date: 17-08-2017
DOI: 10.1101/176511
Abstract: General cognitive function is a prominent human trait associated with many important life outcomes 1,2 , including longevity 3 . The substantial heritability of general cognitive function is known to be polygenic, but it has had little explication in terms of the contributing genetic variants 4,5,6 . Here, we combined cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N=280,360 age range = 16 to 102). We found 9,714 genome-wide significant SNPs ( P x 10 −8 ) in 99 independent loci. Most showed clear evidence of functional importance. Among many novel genes associated with general cognitive function were SGCZ , ATXN1 , MAPT , AUTS2 , and P2RY6 . Within the novel genetic loci were variants associated with neurodegenerative disorders, neurodevelopmental disorders, physical and psychiatric illnesses, brain structure, and BMI. Gene-based analyses found 536 genes significantly associated with general cognitive function many were highly expressed in the brain, and associated with neurogenesis and dendrite gene sets. Genetic association results predicted up to 4% of general cognitive function variance in independent s les. There was significant genetic overlap between general cognitive function and information processing speed, as well as many health variables including longevity.
Plasma lipidome is dysregulated in Alzheimer’s disease and is associated with disease risk genes
Publisher: Springer Science and Business Media LLC
Date: 07-06-2021
DOI: 10.1038/S41398-021-01362-2
Abstract: Lipidomics research could provide insights of pathobiological mechanisms in Alzheimer’s disease. This study explores a battery of plasma lipids that can differentiate Alzheimer’s disease (AD) patients from healthy controls and determines whether lipid profiles correlate with genetic risk for AD. AD plasma s les were collected from the Sydney Memory and Ageing Study (MAS) Sydney, Australia (aged range 75–97 years 51.2% male). Untargeted lipidomics analysis was performed by liquid chromatography coupled–mass spectrometry (LC–MS/MS). We found that several lipid species from nine lipid classes, particularly sphingomyelins (SMs), cholesterol esters (ChEs), phosphatidylcholines (PCs), phosphatidylethanolamines (PIs), phosphatidylinositols (PIs), and triglycerides (TGs) are dysregulated in AD patients and may help discriminate them from healthy controls. However, when the lipid species were grouped together into lipid subgroups, only the DG group was significantly higher in AD. ChEs, SMs, and TGs resulted in good classification accuracy using the Glmnet algorithm (elastic net penalization for the generalized linear model [glm]) with more than 80% AUC. In general, group lipids and the lipid subclasses LPC and PE had less classification accuracy compared to the other subclasses. We also found significant increases in SMs, PIs, and the LPE/PE ratio in human U251 astroglioma cell lines exposed to pathophysiological concentrations of oligomeric Aβ 42 . This suggests that oligomeric Aβ 42 plays a contributory, if not causal role, in mediating changes in lipid profiles in AD that can be detected in the periphery. In addition, we evaluated the association of plasma lipid profiles with AD-related single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) of AD. We found that FERMT2 and MS4A6A showed a significantly differential association with lipids in all lipid classes across disease and control groups. ABCA7 had a differential association with more than half of the DG lipids (52.63%) and PI lipids (57.14%), respectively. Additionally, 43.4% of lipids in the SM class were differentially associated with CLU . More than 30% of lipids in ChE, PE, and TG classes had differential associations with separate genes (ChE- PICALM , SLC24A4 , and SORL1 PE- CLU and CR1 TG- BINI ) between AD and control group. These data may provide renewed insights into the pathobiology of AD and the feasibility of identifying in iduals with greater AD risk.
Tardive and chronically recurrent oculogyric crises
Publisher: Wiley
Date: 1993
Abstract: Six patients with chronically recurrent oculogyric crises (OGC) are reported. Four of these were derived from a study of 100 schizophrenic patients on maintenance neuroleptic medication, thereby giving a prevalence of 4% in such patients. Three of the six had the OGC develop as a tar e side-effect, and in one patient the episodes persisted for some months after the cessation of the offending neuroleptic drug. The episodes of ocular dystonia were associated with other dystonic movements and a number of psychiatric symptoms, with obsessional thoughts and hallucinations being the outstanding features in one patient each. This paper argues for an increased recognition of chronically recurrent and tar e OGC. It also draws attention to the fact that drug-induced OGC may be a multifaceted disorder with disturbances of movement, thought, behavior, and emotion, reminiscent of the OGC described in association with epidemic encephalitis lethargica.
Neuropsychiatry: Towards a Philosophy of Praxis
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.RCP.2017.07.001
Abstract: Neuropsychiatry is a specialized clinical, academic and scientific discipline with its field located in the borderland territory between neurology and psychiatry. In this article, we approach the theoretical definition of neuropsychiatry, and in order to address the practical aspects of the discipline, we describe the profile of a neuropsychiatric liaison service in the setting of a large hospital for neurological diseases in a middle-income country. An audit of consecutive in-patients requiring neuropsychiatric assessment at the National Institute of Neurology and Neurosurgery of Mexico is reported, comprising a total of 1212 patients. The main neurological diagnoses were brain infections (21%), brain neoplasms (17%), cerebrovascular disease (14%), epilepsy (8%), white matter diseases (5%), peripheral neuropathies (5%), extrapyramidal diseases (4%), ataxia (2%), and traumatic brain injury and related phenomena (1.8%). The most frequent neuropsychiatric diagnoses were delirium (36%), depressive disorders (16.4%), dementia (14%), anxiety disorders (8%), frontal syndromes (5%), adjustment disorders (4%), psychosis (3%), somatoform disorders (3%), and catatonia (3%). The borderland between neurology and psychiatry is a large territory that requires the knowledge and clinical skills of both disciplines, but also the unique expertise acquired in a clinical and academic neuropsychiatry program.
Akathisia and second-generation antipsychotic drugs
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
DOI: 10.1097/YCO.0B013E32832A16DA
Abstract: Akathisa is one of the most common and distressing neuroleptic-induced extrapyramidal side effects. Although it is well recognized in the context of conventional antipsychotic medications, there have been recent concerns raised by clinicians and researchers that this syndrome is overlooked in relation to second-generation or atypical antipsychotics. This review examines the recent literature relevant to second-generation antipsychotic (SGA)-induced akathisia. Recent studies using large databases clearly indicate that extrapyramidal side effects, in particular akathisia, do occur with the SGAs, although the frequency is not as high as with the conventional antipsychotics. Risk factors include use of high doses, high potency SGAs, or combinations of SGAs with other psychotropic drugs, bipolar depression, palliative care settings, and comorbid substance abuse in psychosis. The dopamine hypothesis remains plausible for understanding the pathophysiology of akathisia. There is emerging evidence that mirtazapine may be useful in the treatment of acute akathisia. Even though akathisia is less prevalent with SGAs than with the first-generation drugs, it remains clinically important and all clinicians should be conversant with its recognition and management.
Identification of Cerebral Metal Ion Imbalance in the Brain of Aging Octodon degus
Publisher: Frontiers Media SA
Date: 29-03-2017
P2‐432: What is the Contribution Of Potentially Modifiable Environmental and Lifestyle Risk Factors to Young Onset Dementia? Preliminary Results from the Inspired Study
Publisher: Wiley
Date: 07-2016
P4‐157: INTRA‐INDIVIDUAL VARIABILITY OF REACTION TIME PERFORMANCE IS A SENSITIVE MARKER OF MORTALITY RISK IN OLD AGE: FINDINGS FROM THE SYDNEY MEMORY AND AGEING STUDY
Publisher: Wiley
Date: 07-2014
Resveratrol as a Potential Therapeutic Candidate for the Treatment and Management of Alzheimer';s Disease
Publisher: Bentham Science Publishers Ltd.
Date: 29-04-2016
DOI: 10.2174/1568026616666160204121431
Abstract: Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phytochemical present in red wine, grapes, berries, chocolate and peanuts. Clinically, resveratrol has exhibited significant antioxidant, anti-inflammatory, anti-viral, and anti-cancer properties. Although resveratrol was first isolated in 1940, it was not until the last decade that it was recognised for its potential therapeutic role in reducing the risk of neurodegeneration, and Alzheimer's disease (AD) in particular. AD is the primary cause of progressive dementia. Resveratrol has demonstrated neuroprotective effects in several in vitro and in vivo models of AD. Apart from its potent antioxidant and anti-inflammatory roles, evidence suggests that resveratrol also facilitates non-amyloidogenic breakdown of the amyloid precursor protein (APP), and promotes removal of neurotoxic amyloid beta (Aβ) peptides, a critical step in preventing and slowing down AD pathology. Resveratrol also reduces damage to neuronal cells via a variety of additional mechanisms, most notably is the activation of NAD(+)-dependent histone deacetylases enzymes, termed sirtuins. However in spite of the considerable advances in clarifying the mechanism of action of resveratrol, it is unlikely to be effective as monotherapy in AD due to its poor bioavailability, biotransformation, and requisite synergism with other dietary factors. This review summarizes the relevance of resveratrol in the pathophysiology of AD. It also highlights why resveratrol alone may not be an effective single therapy, and how resveratrol coupled to other compounds might yet prove an effective therapy with multiple targets.
The prolongation of QTc-interval by thioridazine.
Publisher: SAGE Publications
Date: 30-12-2001
Cognitive lifestyle and long-term risk of dementia and survival after diagnosis in a multicenter population-based cohort.
Publisher: Oxford University Press (OUP)
Date: 04-03-2011
DOI: 10.1093/AJE/KWQ476
Abstract: An active cognitive lifestyle has been linked to dementia incidence and survival, but the separate and combined effects of its subcomponents are not clear. Data were derived from the Medical Research Council Cognitive Function and Ageing Study, a population-based study of 13,004 in iduals in England and Wales first interviewed in 1991-1992 and followed over a 10-year period for dementia incidence and 12 years for mortality. A Cognitive Lifestyle Score (CLS), defined as a composite of cognitive activity including education, occupational complexity, and social engagement, was available for 12,600 in iduals in 3 stages of life. A higher CLS was protective of dementia (odds ratio = 0.6, 95% confidence interval: 0.4, 0.9). Sensitivity analyses found this main effect to be reliable and replicable even when considering just 2 components of the score, either education and occupation or education and late-life social engagement. No single CLS factor was associated with dementia incidence on its own. Survival differences did not reach statistical significance. Our data suggest that more years of education, as well as further stimulatory experiences in either midlife or late life. are necessary for a protective link with dementia incidence. There was little evidence of an effect of cognitive lifestyle on survival after dementia diagnosis.
Cross-Lagged Modeling of Cognition and Social Network Size in the Sydney Memory and Ageing Study
Publisher: Oxford University Press (OUP)
Date: 07-11-2021
Abstract: This study assessed whether reciprocal relationships exist between cognitive function and the social network size of older adults, controlling for age, sex, education, medical conditions, and depressive symptoms. Data were collected at biennial follow-ups over 6 years in the Sydney Memory and Ageing Study, a longitudinal cohort study including 1,037 community-based Sydney residents aged 70–90 years without dementia at baseline. We used random intercept cross-lagged panel models to investigate reciprocal associations between social network size and scores in each of 7 cognitive domains including a global score. Standardized models indicated that within-person deviation in expected language score predicted deviation in expected network size. Within-person deviation in prior expected social network size predicted deviation in expected executive function at year 6. Cross-lagged effects in models of both global cognition and memory, respectively, could not be attributed solely to within-person change. Findings support a co-constitutive view of cognitive function and social relationships in older age. Although both cognition and network size declined over time, slower than expected decline in language ability predicted less than expected contraction in social networks. A similar influence of network size on executive functioning indicated that relationships with friends and family outside of the home contributed significantly to the maintenance of higher order cognitive abilities in older late life. Diverse patterns of influence between cognitive domains and social network size over 6 years underscore the importance of assessing the complex and nuanced interplay between brain health and social relationships in older age.
The quality and clinical applicability of recommendations in pressure injury guidelines: A systematic review of clinical practice guidelines
Publisher: Elsevier BV
Date: 03-2021
How Can We Best Categorize Cognitive Impairment in Nondemented Older Adults?
Publisher: Elsevier BV
Date: 08-2010
Brain and cognitive reserve
Publisher: Elsevier BV
Date: 03-2009
Strength measures are better than muscle mass measures in predicting health-related outcomes in older people: time to abandon the term sarcopenia?
Publisher: Springer Science and Business Media LLC
Date: 09-07-2017
DOI: 10.1007/S00198-016-3691-7
Abstract: There is no clear consensus on definition, cut-points or standardised assessments of sarcopenia. We found a lower limb strength assessment was at least as effective in predicting balance, mobility and falls in 419 older people as muscle mass-based measures of sarcopenia. There is currently no consensus on the definition, cut-points or standardised assessments of sarcopenia. This study aimed to investigate whether several published definitions of sarcopenia differentiate between older people with respect to important functional and health outcomes. Four hundred nineteen community-living older adults (mean age 81.2 ± 4.5, 49 % female) completed assessments of body composition (dual-energy X-ray absorptiometry), strength, balance, mobility and disability. Falls were recorded prospectively for a year using monthly calendars. Sarcopenia was defined according to four skeletal mass-based definitions, two strength-based definitions (handgrip or knee extensor force) and a consensus algorithm (low mass and low strength or slow gait speed). Obesity was defined according to percentage fat mass or waist circumference. The four skeletal mass-based definitions varied considerably with respect to the percentage of participants classified as sarcopenic and their predictive accuracy for functional and health outcomes. The knee extension strength-based definition was equivalent to or better than the mass-based and consensus algorithm definitions i.e. weaker participants performed poorly in tests of leaning balance, stepping reaction time, gait speed and mobility. They also had higher physiological fall risk scores and were 43 % more likely to fall at home than their stronger counterparts. Adding obesity to sarcopenia definitions identified participants with greater self-reported disability. A simple lower limb strength assessment was at least as effective in predicting balance, functional mobility and falls in older people as more expensive and time-consuming muscle mass-based measures. These findings imply that functional terms such as muscle weakness or motor impairment are preferable to sarcopenia.
Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease
Publisher: Springer Science and Business Media LLC
Date: 12-08-2016
DOI: 10.1038/SREP31450
Abstract: Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, yet current therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of cell and animal models however a comprehensive assessment has not been performed in a human model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin. The iPSC-derived AD neurons demonstrated a hyper-excitable calcium signalling phenotype, elevated levels of nitrite, increased cytotoxicity and apoptosis, reduced neurite length and increased susceptibility to inflammatory stress challenge from activated murine microglia, in comparison to control neurons. We identified that apigenin has potent anti-inflammatory properties with the ability to protect neurites and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in inflammatory cells. In addition, we show that apigenin is able to protect iPSC-derived AD neurons via multiple means by reducing the frequency of spontaneous Ca 2+ signals and significantly reducing caspase-3/7 mediated apoptosis. These data demonstrate the broad neuroprotective action of apigenin against AD pathogenesis in a human disease model.
Relating education, brain structure, and cognition: The role of cardiovascular disease risk factors
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/271487
Abstract: The protective effect of education on cognitive and brain health is well established. While the direct effects of in idual cardiovascular disease (CVD) risk factors (i.e., hypertension, smoking, diabetes, and obesity) on cerebral structure have been investigated, little is understood about the possible interaction between the protective effect of education and the deleterious effects of CVD risk factors in predicting brain ageing and cognition. Using data from the PATH Through Life study ( N = 266 ) , we investigated the protective effect of education on cerebral structure and function and tested a possible mediating role of CVD risk factors. Higher education was associated with larger regional grey/white matter volumes in the prefrontal cortex in men only. The association between education and cognition was mediated by brain volumes but only for grey matter and only in relation to information processing speed. CVD risk factors did not mediate the association between regional volumes and cognition. This study provides additional evidence in support for a protective effect of education on cerebral structures and cognition. However, it does not provide support for a mediating role of CVD risk factors in these associations.
Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise
Publisher: Springer Science and Business Media LLC
Date: 22-03-2016
DOI: 10.1038/MP.2016.19
Treatment of obsessive‐compulsive disorder by psychosurgery
Publisher: Wiley
Date: 03-1993
DOI: 10.1111/J.1600-0447.1993.TB03356.X
Abstract: We report a longitudinal study of 26 patients with medically intractable obsessive-compulsive disorder (OCD) who were treated with psychosurgery and had a comprehensive follow-up for a mean 10 years. Seventeen patients had combined orbitomedial and cingulate lesions, 6 cingulate lesions only and 3 orbitomedial lesions only. Eighteen patients were interviewed personally and lesions verified on magnetic resonance imaging scans in fourteen. On a 6-point global rating scale, 10 (38%) patients had obvious improvement, another 6 (23%) showed mild improvement of doubtful clinical value, and the remaining 10 showed either no change (n = 6 23%) or were judged to be worse (n = 4 15%). Both obsessive and compulsive symptoms improved, and this change was independent of the changes in anxiety and depression scores. No significant predictors of improvement were identified. Patients with cingulate lesions only fared worse. Eight patients who had a second operation did not show much improvement. A comparison of a subgroup of patients with 10 matched nonsurgical OCD controls supported the contention that the improvement in OCD was attributable to the psychosurgery. Important adverse effects in the stereotactic surgery group (n = 20) were epilepsy (1 patient) and personality change (2 patients). The psychosurgery group performed relatively poorly on the Wisconsin Card Sort Test but did not show any deterioration in Wechsler Intelligence and Memory scores.
07-04 Direct current and deep brain stimulation with lessons from neurosurgery.
Publisher: Cambridge University Press (CUP)
Date: 12-2006
The narrative in neurology and psychiatry
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
Associations between plasma antioxidants and hypertension in a community-based sample of 415 Australians aged 60–64
Publisher: Springer Science and Business Media LLC
Date: 02-12-2004
Abstract: It has been suggested that increased oxidative stress may be both a cause as well as a consequence of hypertension. In vivo oxidation of low-density lipoproteins by oxygen-free radicals may increase hypertension-related atherogenesis, and antioxidants may be beneficial in this regard. Previous findings concerning associations between serum measures of antioxidants and hypertension have however been inconsistent. Plasma levels of beta-carotene, Vitamin A, E, uric acid, homocysteine and total antioxidant capacity, as well as two markers of oxidative stress, malondialdehyde (MDA) and protein carbonyls, were measured in morning fasting blood s les provided by 415 Australians aged 60-64 years, selected randomly from the community. Participants also provided information on sociodemographic attributes, mental and physical health, and provided two measures of resting blood pressure, allowing a diagnosis of definite or borderline hypertension. Those with hypertension had lower levels of beta-carotene and higher levels of uric acid and MDA compared to normotensive participants. The last two of these associations persisted when the analyses controlled for lifestyle and health factors. The findings from this study offer limited support for the proposition that lower antioxidant status and higher oxidative stress are associated with hypertension, and suggest the need for longitudinal studies to examine causality and intervention studies to determine the benefit of antioxidants in this group.
Mana, Tapu, Noa: Maori cultural constructs with medical and psycho-social relevance
Publisher: Cambridge University Press (CUP)
Date: 11-1989
DOI: 10.1017/S0033291700005687
Abstract: This paper discusses three concepts, mana, tapu and noa , that lie at the heart of Maori culture. These concepts are inter-related and concern power and influence, with political (or secular) authority implicit in mana and ritual (or religious) authority determined by tapu and noa . The paper explores their importance for the understanding of the ethnic views on aetiology and management of illness, the mechanisms of social organization and control, and the behaviour of in iduals. Although the belief in these concepts exists in only an attenuated form in modern Maori society, their importance becomes obvious to any psychiatrist or physician working with Maori patients.
The association between financial hardship and amygdala and hippocampal volumes: Results from the PATH through life project
Publisher: Oxford University Press (OUP)
Date: 06-05-2012
DOI: 10.1093/SCAN/NSR027
Prevalence and predictors of 'subjective cognitive complaints' in The Sydney Memory and Ageing Study
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1097/JGP.0B013E3181DF49FB
Abstract: To document the prevalence of self- and informant report of cognitive problems, usually referred to as "subjective cognitive complaints" (SCCs), in a community-dwelling s le of older adults and to examine the relationship between SCCs and objective impairment, mood, and personality measures. Eight hundred twenty-seven nondemented community-dwelling adults aged 70-90 years. Participants were asked 24 SCC questions, including the Memory Complaint Questionnaire (MAC-Q), and completed neuropsychological testing in the domains of memory, language, executive function, visuospatial skills, and psychomotor speed. The Geriatric Depression Scale, Goldberg Anxiety Scale, and Neuroticism, Openness, and Conscientiousness from the NEO-Five Factor Inventory were used as measures of participants' psychological status. Informants completed 19 SCC questions, including a modified short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Overall, 95.5% of participants or their informants endorsed at least one SCC. Although participants were more likely to endorse a memory complaint, informants seemed more accurate in endorsing a complaint when cognitive impairment was objectively present. SCC correlated with participants' scores on measures of depression, anxiety, neuroticism, and inversely with measures of openness and conscientiousness. Age, education, and sex had little impact on these effects. Regression analysis showed that psychological factors explained the number of complaints more than cognitive performance. The usefulness of SCCs as a criterion for mild cognitive impairment is questioned because of their high prevalence and their relationship to psychological factors. This may be helpful for clinicians to bear in mind when presented with patients with cognitive complaints.
Gray matter reduction is correlated with white matter hyperintensity volume: A voxel-based morphometric study in a large epidemiological sample
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.NEUROIMAGE.2005.08.057
Abstract: Both brain atrophy and T2-weighted white matter hyperintensities (WMH) are common findings in the brains of asymptomatic elderly in iduals as well as in disease-specific brains. The study of the relationship between these two salient features is therefore important. To investigate such a relationship, we performed a brain magnetic resonance imaging (MRI) study on 397 asymptomatic in iduals aged between 60 and 64 years, who were recruited randomly from a large community s le. WMH were delineated on T2-weighted fluid attenuation inversion recovery (FLAIR) whole brain scans using an automated procedure. The results showed that gray matter reduction, subarachnoid CSF (SA-CSF) increase and lateral ventricular dilation were significantly correlated with WMH load. Deep white matter hyperintensity (DWMH) had significant correlation with all three global atrophy indices, but periventricular white matter hyperintensity (PVWMH) was correlated only with gray matter volume. Voxel-based morphometric (VBM) analysis showed that regional gray matter reduction correlated more closely with WMH load of the proximate region than with WMH elsewhere. The results suggest that WMH have a relationship with brain atrophy in middle age, although the study cannot determine which process, i.e. the development of WMH or atrophy, is primary. The study also demonstrates that DWMH has a more significant relationship with structural brain changes, and may therefore be more functionally relevant than PVWMH. Further delineation of this relationship needs a longitudinal study of the changes in both WMH and indices of brain atrophy.
Sub-Cortical Infarcts and the Risk of Falls in Older People: Combined Results of TASCOG and Sydney MAS Studies
Publisher: SAGE Publications
Date: 10-2014
DOI: 10.1111/IJS.12279
Abstract: White matter hyperintensities increase the risk of multiple falls in older people, but the effect of sub-cortical infarcts is unknown. By pooling data from two Australian population-based studies, we aimed to investigate the association between subcortical infarcts and multiple falls and whether this relationship, and that of white matter hyperintensities, is mediated or modified by cognitive or sensorimotor factors. Participants underwent structural magnetic resonance imaging and cognitive and sensorimotor assessments. Falls were prospectively measured over 12 months. Subcortical infarcts were detected visually. Total white matter hyperintensity volume was quantified using automated segmentation methods. Generalized linear models were used to examine if sub-cortical infarcts and white matter hyperintensities predicted falls. The mean age of the s le ( n = 655) was 74·5 (standard deviation 6·7) years, 336 (51·3%) males. Overall, 114 (17·4%) had multiple falls. The majority had no sub-cortical infarcts ( n = 491, 75·0%), while 90 had one (13·7%), 41 had two (6·3%), and 33 had more than or equal to three sub-cortical infarcts (5·0%). The risk of multiple falls was elevated in people with more than or equal to three sub-cortical infarcts (adjusted relative risk 1·89, 95% confidence interval 1·03, 3·46) and in the highest quarter of white matter hyperintensity volume (adjusted relative risk 1·46, 95% confidence interval 1·00, 2·13). The effect of sub-cortical infarcts on falls was lified by poorer vision ( P = 0·03). The effect of white matter hyperintensities was lified by poorer vision ( P = 0·008), proprioception ( P = 0·03), and muscle strength ( P = 0·008). There was no modifying effect of cognitive function. Increasing burdens of sub-cortical infarcts and white matter hyperintensities are associated with a risk of falling. Interventions targeting sensorimotor factors along with strategies to prevent sub-cortical infarcts and white matter hyperintensities may reduce the risk of falls.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
Publisher: Proceedings of the National Academy of Sciences
Date: 15-05-2018
Abstract: Left–right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population and how biological factors such as age, sex, and genetic variation affect these asymmetries. Here, we describe by far the largest-ever study of cerebral cortical asymmetry, based on data from 17,141 participants. We found a global anterior–posterior “torque” pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an online resource that will serve future studies of human brain anatomy in health and disease.
P2‐134: APOE E4 carriers are associated with amnestic but not nonamnestic mild cognitive impairment in an elderly community sample
Publisher: Wiley
Date: 07-2010
Dementia registries around the globe and their applications: A systematic review
Publisher: Wiley
Date: 30-05-2017
Sixty Years of Psychosurgery: Its Present Status and its Future
Publisher: SAGE Publications
Date: 08-1997
DOI: 10.3109/00048679709065065
Abstract: After its introduction 60 years ago, psychosurgery witnessed a remarkable rise followed by a decline. In the 1990s, it is a marginal treatment practised by a few psychiatrists in some specialised centres around the world. The psychiatric profession, however, continues to support it, and there is some evidence for a recent renewal of interest in the procedure. In this paper, the reasons for this reluctant acceptance of psychosurgery are examined, and the factors that are likely to determine its future are identified. The profession is urged to keep the interest in psychosurgery alive until further theoretical and empirical developments can either announce its death or lead to a resurgence of psychiatric neurosurgery in its present or modified form.
Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients
Publisher: Elsevier BV
Date: 04-2001
DOI: 10.1016/S0006-3223(00)00996-3
Abstract: The safety of repetitive transcranial magnetic stimulation (rTMS) has only previously been formally studied in volunteers receiving a single session of stimulation or in a small number of depressed subjects receiving a 2-week treatment course. This study examined safety issues in depressed subjects receiving up to 4 weeks of rTMS. Efficacy results from this study have been previously reported. Eighteen subjects with DSM-IV major depression participated in a 2-week, parallel, double-blind, sham-controlled study of rTMS treatment. Twelve subjects then went on to receive 4 weeks active rTMS in an open follow-up. We examined the effects of rTMS on neuropsychologic function (up to 4 weeks), auditory threshold (up to 6 weeks exposure to rTMS noise), and an electroencephalogram (after 2 weeks). Data were analyzed by repeated measures analysis. There were trends for improvement in neuropsychologic performance, probably due to practice effects. No mean changes in auditory threshold occurred, but two patients showed mild high-frequency hearing loss after several weeks of rTMS. Electroencephalograms in two patients, one of whom had sham stimulation, showed minor abnormality. No significant mean deficits were demonstrated in this cohort. Overall, rTMS for up to 4 weeks is safe, but in idual results suggest caution and the need for further investigation of the safety of several weeks of rTMS.
Risk factors for tardive dystonia: a case‐control comparison with tardive dyskinesia
Publisher: Wiley
Date: 08-1993
DOI: 10.1111/J.1600-0447.1993.TB03421.X
Abstract: The objective of this study was to determine the putative risk factors for the development of tar e dystonia (TDt) in contrast with tar e dyskinesia (TD). Fifteen TDt patients seen in the Movement Disorders Clinic were compared with 2 groups of 15 TD controls each. The first control group was drawn from the Clinic and matched with the TDt cases for severity, using degree of dysfunction as the matching variable. The second control group comprised mild TD cases drawn from a separate study of drug-induced movement disorders in chronic schizophrenia and were matched for age and sex with the TDt cases. A number of demographic, treatment-related, diagnosis-related and historical variables suggested in the literature were examined. Most risk factors for TDt that have been suggested by previous studies were not supported. The first control group was significantly older than the TDt cases. The TDt patients had a more frequent past history of acute drug-induced dystonia and of postural tremor prior to the onset of the mental illness, although only the former reached statistical significance. The results suggested that TDt and TD do not differ in most putative risk factors, although the small s le size increases the likelihood of a type II error. It is inconclusive on the role of young age and male sex as risk factors. TDt cases may, however, be in iduals vulnerable to the development of dystonia, with neuroleptics probably bringing out such a vulnerability. This finding needs to be examined in larger studies.
Lifetime and current prevalence of common DSM-IV mental disorders, their demographic correlates, and association with service utilisation and disability in older Australian adults
Publisher: SAGE Publications
Date: 13-06-2014
Abstract: To describe lifetime and 12 month prevalence of common DSM-IV mental disorders, their demographic correlates, and association with service utilisation and disability in Australians aged 65–85 years of age. The s le included Australian residents aged 65–85 years who participated in the 2007 Australian National Survey of Mental Health and Well-being ( n=1905). The prevalence of DSM-IV mental disorders was estimated using the lay-interviewer administered World Mental Health version of the Composite International Diagnostic Interview. Eight percent had experienced an affective disorder, 10% an anxiety disorder, and 12% a substance use disorder at some point in their life. Sex, age, and marital status were significant correlates of any lifetime mental disorder. Approximately, 2%, 4%, and 1% of old age respondents met criteria for mood, anxiety, and substance use disorders in the past 12 months, respectively. The presence of physical disorder, disability, and greater treatment service use were associated with any mental disorder in the past 12 months. Prevalence of lifetime and 12 month disorders by age band revealed a decrease as age increased. A substantial number of community dwelling old age Australians have experienced a mental disorder in their lifetime. Demographic correlates of mental disorder were relatively consistent between lifetime and 12 month prevalence of disorders, although sex made less of an impact and the presence of physical disorders more of an impact in recent disorders. Twelve month prevalence data suggest that a high proportion of old age Australians still experience mental disorders, predominantly anxiety and major depression.
Aging Is Associated With Multidirectional Changes in Social Cognition: Findings From an Adult Life-Span Sample Ranging From 18 to 101 Years
Publisher: Oxford University Press (OUP)
Date: 19-08-2023
Abstract: Normal adult aging is associated with changes in social cognition. Although 4 social cognitive domains have been identified (social perception, theory of mind [ToM], affective empathy, and social behavior), no study has tested all 4 domains concurrently in a life-span s le, limiting understanding of the relative magnitude of age-related changes across domains. This study addresses this gap by providing the first assessment of all 4 social cognitive domains in an adult life-span s le. Three hundred and seventy-two participants ranging from 18 to 101 years of age took part in this study. Participants completed a testing battery that assessed social perception, ToM, affective empathy, and social behavior, as well as broader cognitive function and well-being. The results showed that adult aging is associated with multidirectional changes in social cognitive abilities, with ToM and social perception showing nonlinear decline across much of the life-span, and affective empathy and social behavior showing improvement. Age remained a significant predictor of all 4 social cognitive domains, even after accounting for broader cognitive function. Weak associations emerged between some of the social cognitive abilities and and indices of broader well-being. These findings provide novel and important evidence that normative aging is associated with both gains and losses in social cognition that occur at distinct points of the adult life-span, and that are at least partially independent of general age-related cognitive decline.
Differential expression of sirtuins in the aging rat brain
Publisher: Frontiers Media SA
Date: 08-05-2015
Distinct Genetic Influences on Cortical and Subcortical Brain Structures
Publisher: Springer Science and Business Media LLC
Date: 06-09-2016
DOI: 10.1038/SREP32760
Abstract: This study examined the heritability of brain grey matter structures in a subs le of older adult twins (93 MZ and 68 DZ twin pairs mean age 70 years) from the Older Australian Twins Study. The heritability estimates of subcortical regions ranged from 0.41 (amygdala) to 0.73 (hippoc us), and of cortical regions, from 0.55 (parietal lobe) to 0.78 (frontal lobe). Corresponding structures in the two hemispheres were influenced by the same genetic factors and high genetic correlations were observed between the two hemispheric regions. There were three genetically correlated clusters, comprising (i) the cortical lobes (frontal, temporal, parietal and occipital lobes) (ii) the basal ganglia (caudate, putamen and pallidum) with weak genetic correlations with cortical lobes, and (iii) the amygdala, hippoc us, thalamus and nucleus accumbens grouped together, which genetically correlated with both basal ganglia and cortical lobes, albeit relatively weakly. Our study demonstrates a complex but patterned and clustered genetic architecture of the human brain, with ergent genetic determinants of cortical and subcortical structures, in particular the basal ganglia.
A taste of facility a sartrean look at psychiatry
Publisher: SAGE Publications
Date: 09-1983
DOI: 10.1177/002076408302900304
Abstract: Jean-Paul Sartre (1905-1979) was a French intellectual, philosopher and literateur who stood on a common platform of philosophy and psychology. His importance to us lies not only in his great impact on twentieth century thought, but also because he outlined a fairly elaborate system of descriptive psychology as a prelude to his ontological description of the world. His treatises on 'Imagination' and 'Emotions' are classics in the existential tradition. His novels and plays are based on the same themes as concern a psychiatrist in his daily clinic. His principal text of philosophy, 'Being and Nothingness', contains a whole chapter on 'Existential Psychoanalysis'. Not surprisingly, therefore, he has had a significant impact on our approach to mental patients. With the increasing emphasis on the scientific method, the philosophical moorings of medical science became more and more blurred. The result was an impersonal view of the diseased. Thus during this period it had become common practice to view human beings as objects worthy of study from the disease view point. As a result the disease and its causation became more important than the diseased person himself. It must be granted that progress in medicine often results from this passion with causation. However, a causal view of phenomena presupposes that clarity about the phenomena exists among us. Prior to the problem of establishing the etiological basis of a disease entity, there is the problem of uncovering the phenomenal character of the disease in question. This task may not be formidable in most branches of medicine, but in the case of psychiatry the disease entities are human realities themselves expressed in the life activities of fellow-men. This is where empirical psychology breaks down and why some psychiatrists tend to resort to the existential-ontological departure. The point is to liberate man from the speculative subject-object relationship and to stress his uniqueness and in iduality. This movement started with Binswanger (1881-1966) who was the first psychoanalyst to use Heidegger's principles to criticize Freud (4,5). He was in the quest of a genuine psychology (7). There have been other psychiatrists of repute who emulated his ex le. Some prominent psychologists who have been influenced to varying degrees by existentialism are Allport, Angyal, Fromm, Goldstein, Maslow and Rogers (10). At the same time, existential philosophers have themselves been keenly interested in psychology and psychiatry. Karl Jaspers began life as a psychiatrist and his first major work was his General Psychopathology' (12). Jean-Paul Sartre has been keenly interested in psychology and has written a lot on the subject (17). Admittedly, Sartre's impact on psychiatry and psychotherapy has not been as significant as on literature and politics (7). But he has, along with Heidegger, provided a unification which has helped in the understanding of the normal human mind as well as the abnormal one. The series of steps Sartre took towards his totalization of human experience are of great interest to a psychologist because of his investigation of psychic phenomena in the process. This detailed evaluation of in idual phenomena is, he says, the only way we can make psychology progress. His insistence on the unambiguous description of such phenomena is in the great Husserlian tradition (28). Here, we shall take a look at the series of steps Sartre took towards his composite view of human psychology.
Clinical Characteristics and Predisposing Factors in Acute Drug-Induced Akathisia
Publisher: American Medical Association (AMA)
Date: 12-1994
DOI: 10.1001/ARCHPSYC.1994.03950120035007
Abstract: As subtypes of drug-induced akathisia have become accepted and attempts have been made at establishing diagnostic criteria, a prospective study of the clinical features and predisposing factors of acute akathisia is a significant deficiency in the literature. One hundred consecutive inpatients with non-organic psychotic disorders, not receiving neuroleptics or other drugs and free of akathisia and related disorders at admission, were assessed for psychiatric status and movement disorders at baseline and daily for 2 weeks, with detailed examinations on days 7 and 14. Multiple operational criteria for akathisia were used. The following risk factors were examined: age, sex, current neuroleptic dose, rate of increment of dose, drug type, duration of illness, past use of neuroleptics, extrapyramidal side effects score, Zung Depression Scale score, Spielberger State Anxiety Inventory score, psychosis score, and smoking. Using a global rating, mild akathisia developed in 41% and moderate-to-severe akathisia in 21%. The symptoms that best discriminated akathisia from non-akathisia were shifting weight from foot to foot or walking on the spot, inability to keep legs still, feelings of inner restlessness, and shifting of body position in the chair. The subjective and objective symptoms loaded on separate factors. Akathisia ratings had low correlations with the anxiety and Zung scores. Receiver operating characteristic analysis suggested a cutoff score of 4 on our 10-item Akathisia Scale as optimal for the diagnosis of akathisia, with a stricter criterion of scores of 2 or more on both the subjective and objective items being more suitable for research diagnosis. The most significant predisposing factors were the extrapyramidal side effects score and current neuroleptic dose and its rate of increment, with lesser contributions from serum iron status and medication type. Predictability was, however, modest. Acute akathisia is a common syndrome with well-defined clinical features. Its occurrence can be predicted with only modest accuracy.
Sirtuins in cognitive ageing and Alzheimer's disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2012
A study using transcranial magnetic stimulation to investigate motor mechanisms in psychomotor retardation in depression
Publisher: Oxford University Press (OUP)
Date: 30-04-2008
Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2016
DOI: 10.1038/MP.2016.57
Post-Stroke Cognitive Impairment, Depression and Apathy: Untangling the Relationship
Publisher: Elsevier BV
Date: 03-2018
Leisure Activity, Health, and Medical Correlates of Neurocognitive Performance Among Monozygotic Twins: The Older Australian Twins Study
Publisher: Oxford University Press (OUP)
Date: 13-05-2013
Abstract: We aimed to examine associations between each of three leisure activities (Cognitive, Physical, and Social) and performance in selected cognitive domains (Speed, Memory, Verbal ability, and Executive functions) and global cognition. We also aimed to explore associations between medical and health factors and late-life cognition. Our s le comprised 119 pairs of monozygotic twins from the Older Australian Twins Study. Their mean age was 71 years and 66% were women. We used a discordant co-twin design, with cognitive performance measures as dependent variables and leisure activities as independent variables. Multiple regression analyses were performed, adjusting for potentially relevant medical and health factors. Discordance in Cognitive Activity and Social Activity participation was positively associated with discordance in performance on some cognitive domains. There were no associations between Physical Activity participation and cognition. Discordance in several cardiovascular, frailty, and sensory variables was associated with discordance in cognitive performance measures. This study identified lifestyle and health-related influences on late-life cognition. Our findings not only help in understanding the neurobiological mechanisms, they also have practical implications for interventions to prevent or slow age-related cognitive decline.
P4–327: MAPT methylation and implications for late‐onset Alzheimer's disease
Publisher: Wiley
Date: 07-2013
The role of cognitive function and physical activity in physical decline in older adults across the cognitive spectrum
Publisher: Informa UK Limited
Date: 25-05-2019
DOI: 10.1080/13607863.2018.1474446
Abstract: The aim of this study was to investigate physical decline over 1-year in a cohort of older people across the cognitive spectrum. Physical function was assessed using the Physiological Profile Assessment (PPA) in 593 participants (cognitively normal [CN]: n = 342, mild cognitive impairment [MCI]: n = 77, dementia: n = 174) at baseline and in 490 participants available for reassessment 1-year later. Neuropsychological performance and physical activity (PA) were assessed at baseline. Median baseline PPA scores for CN, MCI and dementia groups were 0.41 (IQR = -0.09-1.02), 0.66 (IQR = -0.06-1.15) and 2.37 (IQR = 0.93-3.78) respectively. All baseline neuropsychological domains and PA were significantly associated with baseline PPA. There were significant interaction terms (Time × Cognitive Group, Global Cognition, Processing Speed, Executive Function and PA) in the models investigating PPA decline. In multivariate analysis the Time × Executive Function and PA interaction terms were significant, indicating that participants with poorer baseline executive function and reduced PA demonstrated greater physical decline when compared to in iduals with better executive function and PA respectively. Having MCI or dementia is associated with greater physical decline compared to CN older people. Physical inactivity and executive dysfunction were associated with physical decline in this s le, which included participants with MCI and dementia. Both factors influencing physical decline are potentially amenable to interventions e.g. exercise.
The Antidepressant Effect of Laser Acupuncture: A Comparison of the Resting Brain's Default Mode Network in Healthy and Depressed Subjects During Functional Magnetic Resonance Imaging
Publisher: Mary Ann Liebert Inc
Date: 04-2013
Neuroleptic malignant syndrome associated with atypical antipsychotic drugs
Publisher: Springer Science and Business Media LLC
Date: 05-2009
DOI: 10.2165/00023210-200923060-00003
Abstract: Neuroleptic malignant syndrome (NMS) is a rare but potentially severe idiosyncratic adverse reaction usually seen in the context of treatment with antipsychotic drugs. Although NMS is historically associated with the classic or 'typical' antipsychotic drugs, it is also a potential adverse effect of atypical antipsychotic drugs. The widespread use of atypical antipsychotic drugs highlights the need to examine the data relating to the symptomatology, diagnosis, classification and management of NMS with these newer agents. We used MEDLINE and EMBASE to identify NMS case reports and systematic reviews published to June 2008 related to the atypical antipsychotic drugs clozapine, olanzapine, risperidone, paliperidone, aripiprazole, ziprasidone, amisulpride and quetiapine. Case reports and reviews were systematically examined. Our review suggests that, in general, NMS associated with atypical antipsychotic drugs manifests in a typical manner. One notable exception is clozapine-induced NMS, which appears less likely to manifest with extrapyramidal features, including rigidity and tremor. The available literature highlights the ergence of opinion relating to the core diagnostic features of NMS and its conceptualization as a categorical versus dimensional disorder. Both these issues have relevance for the identification of atypical or milder forms of NMS, which are sometimes seen with atypical antipsychotic drugs.
Blood pressure, brain structure, and cognition: Opposite associations in men and women
Publisher: Oxford University Press (OUP)
Date: 26-08-2015
DOI: 10.1093/AJH/HPU120
Abstract: Research on associations between blood pressure, brain structure, and cognitive function has produced somewhat inconsistent results. In part, this may be due to differences in age ranges studied and because of sex differences in physiology and/or exposure to risk factors, which may lead to different time course or patterns in cardiovascular disease progression. The aim of this study was to investigate the impact of sex on associations between blood pressure, regional cerebral volumes, and cognitive function in older in iduals. In this cohort study, brachial blood pressure was measured twice at rest in 266 community-based in iduals free of dementia aged 68-73 years who had also undergone a brain scan and a neuropsychological assessment. Associations between mean blood pressure (MAP), regional brain volumes, and cognition were investigated with voxel-wise regression analyses. Positive associations between MAP and regional volumes were detected in men, whereas negative associations were found in women. Similarly, there were sex differences in the brain-volume cognition relationship, with a positive relationship between regional brain volumes associated with MAP in men and a negative relationship in women. In this cohort of older in iduals, higher MAP was associated with larger regional volume and better cognition in men, whereas opposite findings were demonstrated in women. These effects may be due to different lifetime risk exposure or because of physiological differences between men and women. Future studies investigating the relationship between blood pressure and brain structure or cognitive function should evaluate the potential for differential sex effects.
Impact of APOE ε3 and ε4 genotypes on plasma proteome signatures in Alzheimer's disease
Publisher: Research Square Platform LLC
Date: 20-04-2022
DOI: 10.21203/RS.3.RS-1535069/V1
Abstract: Background: The ε 4 allele of the apolipoprotein E ( APOE ) gene is a high-risk factor for Alzheimer's disease (AD). However, approximately 25%–40% of patients with AD do not carry the APOEe4 allele, and the pathophysiological mechanisms underlying AD are less evident in these in iduals. The main objective of this study was to understand the changes in plasma that may contribute to disease pathogenesis in AD and how APOEe3 and APOEe4 contribute to plasma biomarker profiles in AD. Methods: We conducted an in-depth plasma proteomics analysis using intensive depletion of high-abundant plasma proteins with Agilent multiple affinity removal liquid chromatography (LC) column- Human 14 (Hu14) followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) technique coupled with Q-Exactive Plus mass spectrometer (Thermo Electron, Bremen, Germany). Two search engines were used to analyze the raw files, including ProteomeDiscoverer v2.4 (Thermo Fisher Scientific, Waltham, MA) and Scaffold Q+ software v 4.11.0 (Proteome Software, Portland). Results: In our study, we have expanded the depth of plasma proteome coverage to reveal new differentially expressed proteins (DEPs) that correlated with AD pathogensis. The identification of 134 proteins in AD APOE ε 3 relative to ε 3 controls and 71 in AD APOE ε 4 relative to ε 4 controls are reported in this study. Mainly signature proteins identified were associated with molecular functions including complement cascade, glycolysis, metabolism, plasma lipoprotein assembly, remodeling, and clearance. Here, we have shown a list of proteins such as MB, GPI and PKM reflecting the biochemical changes that are associated with pathogenesis of AD despite the APOE genotypes. The increase plasma proteome depth allowed us to identify a large number of proteins which are previously reported in brain tissue or cerebrospinal fluid in AD cohorts are likely much stronger candidates for future validation work. Conclusion: This study performed an in-depth proteome analysis to identify plasma proteome signatures associated with APOE ε 3 and APOE ε 4 genotypes. Further analysis of proteome correlation with APOE genotpyes will yield clinically meaningful information into the biological basis of AD.
The Relationship between Cerebral White Matter Integrity and Cognitive Function in Mild Stroke with Basal Ganglia Region Infarcts
Publisher: Springer Science and Business Media LLC
Date: 30-05-2018
DOI: 10.1038/S41598-018-26316-5
Abstract: Mild stroke is a known risk factor for dementia. The relationship between cerebral white matter (WM) integrity and cognitive impairment (CI) in mild stroke patients with basal ganglia region infarcts is unknown. Total of 33 stroke patients and 19 age-matched controls underwent diffusion tensor imaging scans and a formal neuropsychological test battery. CI was defined as having a performance score 1.5 SD below the established norm. We compared the differences in Z-scores and Fraction Anisotropy (FA) values among controls, stroke with no CI (NCI) and stroke with CI groups. Multiple linear regressions were performed between FA values in affected regions and neuropsychological tests in stroke patients. The majority of stroke patients were in their 50s (56.90 ± 9.23 years). CI patients exhibited a significantly decreased Z score in visual delayed memory and remarkably decreased FA values in the right external capsule and right fornix (FWE-corrected) compared with NCI patients and controls. In stroke patients, the FA value in the right fornix was positively correlated with delayed visual memory. Mild stroke with basal ganglia region infarcts may be related to widespread abnormality of WM integrity. The lower WM integrity in the right fornix may be a marker of impaired delayed visual memory.
Relationships between serum vitamin D levels, neuromuscular and neuropsychological function and falls in older men and women.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2011
DOI: 10.1007/S00198-011-1637-7
Abstract: Among 463 community dwellers aged 70-90 years, those with vitamin D insufficiency showed reduced neuromuscular function, balance control and stepping ability and performed worse in tests of cognitive function. In men, vitamin D insufficiency was associated with an increased risk of falling. The purpose of this study was to investigate the relationship between serum 25-hydroxy vitamin D (serum 25OHD) levels, physiological and neuropsychological function in older people, and to examine the relationship between serum 25OHD and prospective falls. Four hundred sixty-three community-dwelling people aged 70-90 years underwent an assessment of physiological and neuropsychological performance and structured interviews relating to comorbidity and disability. Fall frequency during the 12 months follow-up was monitored with monthly falls diaries. Twenty-one percent of the men and 44% of the women were vitamin D insufficient (serum 25OHD ≤ 50 nmol/L). Participants with vitamin D insufficiency had weaker upper and lower limb strength, slower simple finger press and choice stepping reaction time, poorer leaning balance and slower gait speed, after controlling for age and body mass index, and, poorer executive function and visuospatial ability, after controlling for age and education. Vitamin D insufficiency significantly increased the rate of falls in men (IRR = 1.94, 95% CI = 1.19-3.15, p = 0.008) but not in women. These findings highlight the associations between vitamin D insufficiency and impairments in physiological and neuropsychological function that predispose older people to fall. The significant relationship between vitamin D insufficiency and falls found in the men may relate to the stronger association found between serum 25OHD levels and dynamic balance measures evident in this male population.
The Relationship of Serum Macrophage Inhibitory Cytokine – 1 Levels with Gray Matter Volumes in Community-Dwelling Older Individuals
Publisher: Public Library of Science (PLoS)
Date: 13-04-2015
Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment
Publisher: Elsevier BV
Date: 11-2020
Amyloid precursor proteins, neural differentiation of pluripotent stem cells and its relevance to Alzheimer's disease
Publisher: Mary Ann Liebert Inc
Date: 05-2012
Abstract: Alzheimer's disease (AD) is a leading cause of age-related dementia that is characterized by an extensive loss of neurons and synaptic transmission. The pathological hallmarks of AD are neurofibrillary tangles and deposition of β-amyloid (Aβ) plaques. Previous research has investigated how Aβ fragments disrupt synaptic mechanisms in the vulnerable regions of the brain. There is a tremendous potential for stem cell technology to extend upon this research, not only in terms of developing therapeutic applications, but also in modeling AD. Indeed, the advent of induced pluripotent stem cell technology has opened up exciting new avenues for generating patient and disease-specific cell lines from somatic cells that may be used to model AD. Amyloid precursor protein (APP) is a key protein in neuronal development and this article reviews the role of APP in AD. Stem cell technology offers the opportunity to make use of APP in the directed differentiation of induced pluripotent stem cells into functional neurons, a process that may help generate a model of AD and thereby facilitate an understanding of the mechanisms underlying this disease.
Homocysteine in neuropsychiatric disorders of the elderly
Publisher: Wiley
Date: 2002
DOI: 10.1002/GPS.723
Abstract: There is increasing interest in homocysteine as a risk factor for neuropsychiatric disorders such as stroke, dementia, depression and Parkinson's disease. This article reviews the current literature on the relationship between homocysteine and these disorders to ascertain if any clinical recommendations can be made. A MEDLINE and EMBASE search was made for English language publications between 1966 and 2002 using the search terms 'Homocysteine' and 'Stroke', 'Dementia', 'Vascular Dementia', 'Alzheimer's dementia', 'Cognition disorders or cognitive decline or memory disorders', 'Depression or depressive disorders' or 'Parkinson's disease'. In addition, in idual articles were hand searched for relevant references. Cross-sectional studies consistently suggest that elevated homocysteine increases the risk of stroke, and may also increase the risk of leukoariosis, vascular dementia (VaD), cognitive impairment and Alzheimer's disease (AD). Longitudinal studies of homocysteine as a risk factor are few and inconsistently supportive of these associations. No intervention trials to determine the effect of lowering homocysteine levels have yet been published. The pathological mechanisms for homocysteine-mediated disease await complete elucidation. Mild hyperhomocysteinemia is common in the elderly population, and folate supplementation can decrease homocysteine levels. The epidemiological evidence for homocysteine as a risk factor for neuropsychiatric disease is an emerging area of great interest. Screening the population for hyperhomocysteinemia cannot be recommended at this stage, but in iduals at increased risk of cerebrovascular disease or cognitive impairment should be investigated and treated for elevated homocysteine levels.
Core Curriculum in Neuropsychiatry of the International Neuropsychiatric Association*
Publisher: Springer Japan
Date: 2010
Schizophrenia-like psychosis and traumatic brain injury
Publisher: Cambridge University Press
Date: 04-02-2010
Structural MRI correlates of verbal fluency performance in late life – a DARTEL-based VBM Study
Publisher: Elsevier BV
Date: 07-2009
COGNITIVE DECLINE AND ITS DETERMINANTS IN DIVERSE ETHNO-REGIONAL GROUPS: THE COSMIC COLLABORATION
Publisher: Oxford University Press (OUP)
Date: 30-06-2017
Higher Fasting Plasma Glucose is Associated with Increased Cortical Thinning Over 12 Years: The PATH Through Life Study
Publisher: Springer Science and Business Media LLC
Date: 27-01-2017
DOI: 10.1007/S10548-017-0544-4
Abstract: Recent evidence suggests that type 2 diabetes (T2D) is associated with accelerated brain ageing, consistent with the observation of increased risk of cognitive impairment and dementia in affected in iduals. Even non-diabetic in iduals with impaired fasting plasma glucose (IFG) levels have shown increased cerebral atrophy, compared to in iduals with normal glucose levels. We tested whether longitudinal rates of age-related cortical thinning were associated with fasting plasma glucose levels in a large s le (n = 322) of early-old age in iduals (60-66 years) who were scanned with magnetic resonance imaging (1.5 T) on up to four occasions over 12 years. Higher plasma glucose levels (measured on up to three occasions) were associated with increased cortical thinning in in iduals with T2D as well as those with IFG, with a similar trend for in iduals with normal fasting glucose (NFG) levels. Across groups, a 1 mmol/l increase in plasma glucose (above 5 mmol/l in NFG and IFG and above 6.1 mmol/l in T2D) resulted in a 10-13% increase in annual cortical thinning. Increased cortical thinning was detected in insular cortex, as well as posterior cingulate, parahippoc us and medial orbitofrontal cortex. Our results provide support for the idea that raised plasma glucose levels, even in the normal range, are associated with accelerated age-related cortical atrophy.
Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery—2018
Publisher: Wiley
Date: 16-10-2018
DOI: 10.1111/AAS.13250
Abstract: Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder) any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).
P4–332: γ‐glutamylcysteine (GGC)‐mediated upregulation of glutathione levels can ameliorate toxicity of natural beta‐amyloid oligomers in primary adult human neurons
Publisher: Wiley
Date: 07-2013
The differentiation of mild frontotemporal dementia from Alzheimer's disease and healthy aging by neuropsychological tests
Publisher: Cambridge University Press (CUP)
Date: 03-2005
DOI: 10.1017/S1041610204000778
Abstract: Frontotemporal dementia (FTD) is difficult to diagnose in the early stages and may be misdiagnosed as Alzheimer's disease (AD) or as a psychiatric disorder. This study aimed to investigate neuropsychological function in FTD of mild severity and compare it to that of mild AD and healthy control participants. The study comprised 11 in iduals with FTD, 29 with AD and 27 healthy controls. Participants completed a comprehensive neuropsychological assessment in which each area of cognitive function was examined with several widely used clinical tests. Test scores were converted to age-corrected scaled scores and combined to form indices for six areas of cognitive function. These indices were attention, psychomotor speed, memory acquisition, memory recall, executive function and constructional ability. The FTD group performed below the level of the controls in all areas except constructional ability. FTD and AD groups showed distinct patterns of neuropsychological performance. The FTD group showed predominantly executive dysfunction with less impaired memory function, while the AD group showed the opposite pattern. The capacity of the tests to discriminate between groups was good overall, with 90% of the total s le correctly classified. Predictive success for the FTD group was 64%, given a base rate of 16%. Administration of a comprehensive neuropsychological protocol including several tests of executive function allows increased certainty about accurate clinical diagnosis of mild FTD.
Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: An open-label pilot study
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.JAD.2011.05.018
Abstract: Several recent trials have reported transcranial direct current stimulation (tDCS) to be effective in treating depression, though the relative benefits of different electrode montages remain unexplored. Whereas all recent studies have used a bifrontal (BF) electrode montage, studies published in the 1960s and 1970s placed one electrode in an extracephalic position, with some positive reports of efficacy. This study investigated the efficacy and safety of tDCS given with a fronto-extracephalic (F-EX) montage. 2 mA tDCS was administered for 20 min every weekday over four weeks in 11 participants with a Major Depressive Episode who had previously shown inadequate response to, or relapsed following, a course of BF tDCS. For F-EX tDCS the anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right upper arm. Depression severity and neuropsychological function were assessed before and after the treatment course. Antidepressant response was compared across an equivalent treatment period for both montages. F-EX tDCS was shown to be safe and well tolerated. Depression ratings improved after acute treatment on the Montgomery Åsberg Depression Rating Scale (p < 0.001). Participants showed greater initial treatment response with F-EX tDCS than with BF tDCS (p < 0.001). This was an open label pilot study. The two comparison treatments were applied consecutively. F-EX tDCS appears to be safe and to have antidepressant effects, and may lead to more rapid improvement than tDCS given with a BF montage.
Preface
Publisher: Cambridge University Press
Date: 2010
Prospective Memory Function Predicts Future Cognitive Decline and Incident Dementia
Publisher: Oxford University Press (OUP)
Date: 17-02-2023
Abstract: This study aimed to test whether prospective memory (PM) was an early cognitive marker of future cognitive decline and incident dementia using longitudinal data spanning 8 years from the Sydney Memory and Ageing Study. At baseline, 121 participants aged 72–91 years were tested in PM using a validated PM task, Virtual Week, which included time- and event-based tasks presented with varying regularity. Responses were scored “Correct” if completed accurately and “Missed” if the target was not remembered at any time. Measures of cognition were taken at baseline and 2-year intervals over 8 years. Dementia diagnoses were made by expert consensus panels using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Linear mixed models and Cox proportional hazards regression models were used to analyze the data, controlling for potential confounds. Both decreased PM accuracy and missed PM responses were associated with rate of cognitive decline measured by Mini-Mental State Examination over 8 years and global cognitive decline over 4 years. Risk of incident dementia increased with poorer baseline PM ability and missed responses. These effects remained significant after controlling for baseline cognition and were strongest for event-based and regular PM tasks. PM is a sensitive early marker of future cognitive decline and risk of incident dementia. PM tasks supported by spontaneous retrieval (event-based) and those with lower retrospective memory demands (regular tasks) function as particularly sensitive predictors. In other words, deficits in performing less effortful PM tasks best predicted cognitive decline. These findings may encourage clinicians to incorporate PM tasks in clinical assessments.
A rating scale for acute drug-induced akathisia: development, reliability, and validity
Publisher: Elsevier BV
Date: 02-1994
DOI: 10.1016/0006-3223(94)91257-2
Abstract: This paper describes the process of developing a new rating scale for acute neuroleptic-induced akathisia. Previously reported clinical characteristics of akathisia were used to construct the initial version of the scale. This was administered to 100 consecutively admitted psychiatric patients treated with neuroleptic medication. The scale was then subjected to a reliability analysis, and the number of items reduced. A factor analysis of the ratings supported the decision to rate subjective and objective items separately. The new version of the scale (The Prince Henry Hospital Akathisia Rating Scale) was further standardized in its administration. A preliminary examination of its construct validity was performed by calculating the correlations with the ratings on the analogue and global scales, as well as those of depression, anxiety, and hyperactivity. The new scale was administered to 50 new subjects to examine its interrater reliability and concurrent validity with respect to the Barnes Akathisia Rating Scale.
Incidental brain MRI abnormalities in 60-to 64-year-old community-dwelling individuals: data from the Personality and Total Health Through Life study
Publisher: Cambridge University Press (CUP)
Date: 04-2008
DOI: 10.1111/J.1601-5215.2008.00273.X
Abstract: There have been limited data available on the prevalence of structural brain abnormalities in asymptomatic in iduals and a growing interest in the various ethical issues related to reporting of such findings. This study evaluated the prevalence of incidental abnormalities on brain magnetic resonance imaging (MRI) in a random s le of 60- to 64-year-old community-dwelling in iduals as well as successfully followed a referral pathway taking into account of the various ethical issues related to the referral process. The Personality and Total Health ( PATH) Project was designed to study the risk and protection factors of normal ageing, dementia and other neuropsychiatric disorders. MRI scans were performed in randomly selected 478 healthy, community-dwelling 60- to 64-year-old in iduals. All scans were reported for abnormalities by a radiologist. Abnormalities were detected in 22 (4.8%) subjects, comprising 10 tumours (pituitary adenoma 4, meningioma 3, suprasellar tumour 1, cavernous haemangioma 1, subarachnoid lipoma 1), 6 infarct-like lesions, 2 arachnoid cysts, 1 possible normal pressure hydrocephalus, and 1 each of unconfirmed aneurysm and mesial temporal sclerosis. Further evaluation led to novel intervention in one case of pituitary adenoma, and adjustment of drug treatment to modify risk factors in two cases with subclinical infarction. While no case required immediate referral or urgent surgical intervention, the change in the outcome of treatment of some cases suggests that appropriate referral process should be in place when researchers study large number of subjects in the community using MRI of the brain.
Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney Memory and Aging Study
Publisher: Wiley
Date: 19-07-2013
DOI: 10.1111/ACEL.12116
Abstract: Higher levels of macrophage inhibitory cytokine-1, also known as growth differentiation factor 15 (MIC-1/GDF15), are associated with adverse health outcomes and all-cause mortality. The aim of this study was to examine the relationships between MIC-1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70-90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C-reactive protein, tumor necrosis factor-α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC-1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross-sectional associations were found between MIC-1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, in iduals with high MIC-1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC-1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC-1/GDF15 cutoff values associated with cognitive decline and showed that a MIC-1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC-1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship.
The brain effects of laser acupuncture in depressed individuals: an fMRI investigation
Publisher: Springer Science and Business Media LLC
Date: 2013
Whither neuropsychiatry?
Publisher: American Psychiatric Association Publishing
Date: 05-2005
DOI: 10.1176/JNP.17.2.140
The concept of organicity and its application to schizophrenia
Publisher: Cambridge University Press
Date: 04-02-2010
White matter hyperintensities segmentation using an ensemble of neural networks
Publisher: Wiley
Date: 27-10-2021
DOI: 10.1002/HBM.25695
Abstract: White matter hyperintensities (WMHs) represent the most common neuroimaging marker of cerebral small vessel disease (CSVD). The volume and location of WMHs are important clinical measures. We present a pipeline using deep fully convolutional network and ensemble models, combining U‐Net, SE‐Net, and multi‐scale features, to automatically segment WMHs and estimate their volumes and locations. We evaluated our method in two datasets: a clinical routine dataset comprising 60 patients (selected from Chinese National Stroke Registry, CNSR) and a research dataset composed of 60 patients (selected from MICCAI WMH Challenge, MWC). The performance of our pipeline was compared with four freely available methods: LGA, LPA, UBO detector, and U‐Net, in terms of a variety of metrics. Additionally, to access the model generalization ability, another research dataset comprising 40 patients (from Older Australian Twins Study and Sydney Memory and Aging Study, OSM), was selected and tested. The pipeline achieved the best performance in both research dataset and the clinical routine dataset with DSC being significantly higher than other methods ( p .001), reaching .833 and .783, respectively. The results of model generalization ability showed that the model trained on the research dataset (DSC = 0.736) performed higher than that trained on the clinical dataset (DSC = 0.622). Our method outperformed widely used pipelines in WMHs segmentation. This system could generate both image and text outputs for whole brain, lobar and anatomical automatic labeling WMHs. Additionally, software and models of our method are made publicly available at rojects/what_v1 .
Schizophrenia-like psychosis and epilepsy
Publisher: Cambridge University Press
Date: 04-02-2010
Computer-delivered cognitive behavioural therapy: Effective and getting ready for dissemination
Publisher: Faculty Opinions Ltd
Date: 14-07-2010
DOI: 10.3410/M2-49
The role of concern about falling on stepping performance during complex activities
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1186/S12877-019-1356-Z
Abstract: There is limited understanding of the underlying mechanisms explaining the role of concern about falling on fall risk in older people. Anxiety is known to interact with cognitive resources and, as people get older, they require more cognitive resources to maintain balance. This might affect an in idual’s ability to perform cognitive-motor tasks concurrently. The aim of this study was to investigate the effect of a visuospatial dual-task on stepping performance in older people with and without concern about falling and the impact of repeating this task in those with high concern about falling. Three-hundred-eight community-dwelling older people, aged 70 to 90 years old, participated in the study. Participants were asked to perform a Choice Stepping Reaction Time (CSRT) task in two conditions once without any other tasks (single task condition), and once while simultaneously performing a visuospatial task (dual-task condition). Participants were asked to rate their levels of concern and confidence specifically related to each of the 25 stepping trials (before/after). We also measured general concern about falling, affect, and sensorimotor and cognitive functioning. Total stepping reaction times increased when participants also performed the visuospatial task. The relation between general concern about falling and stepping reaction time, was affected by sensorimotor and executive functioning. Generalised linear mixed models showed that the group with moderate to high levels of general concern about falling had slower total stepping reaction times than those with lower levels of concern about falling, especially during the dual-task condition. In iduals with greater general concern about falling showed reduced confidence levels about whether they could do the stepping tasks under both conditions. Repeatedly performing the stepping task reduced the immediate task-specific concern about falling levels and increased confidence in all participants. These findings reveal that people with higher general concern about falling experienced more difficulties during a dual-task condition than people with lower levels of concern. Of further interest, better sensorimotor and cognitive functioning reduced this effect. Graded exposure has potential to reduce concern about falling during fear-evoking activities, especially in conjunction with therapies that improve balance, mood and cognitive function.
Multiple biological pathways link cognitive lifestyle to protection from dementia.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.BIOPSYCH.2011.07.036
Abstract: An active cognitive lifestyle is linked to diminished dementia risk, but the underlying mechanisms are poorly understood. Potential mechanisms include disease modification, neuroprotection, and compensation. Prospective, population-based brain series provide the rare opportunity to test the plausibility of these mechanisms in humans. Participants came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study, comprising 13,004 in iduals aged over 65 years and followed for 14 years. In study 1, a Cognitive Lifestyle Score (CLS) was computed on all Cognitive Function and Ageing Study subjects to define low, middle, and high groups. By August 2004, 329 in iduals with CLS data had come to autopsy and underwent Consortium to Establish a Registry of Alzheimer's Disease assessment. Study 2 involved more detailed quantitative histology in the hippoc us and Brodmann area 9 in 72 clinically matched in iduals with high and low CLS. CLS groups did not differ on several Alzheimer disease neuropathologic measures however, high CLS men had less cerebrovascular disease after accounting for vascular risk factors, and women had greater brain weight. No group differences were evident in hippoc al neuronal density. In Brodmann area 9, cognitively active in iduals had significantly greater neuronal density, as well as correlated increases in cortical thickness. An active cognitive lifestyle was associated with protection from cerebrovascular disease in men, but there was no evidence for Alzheimer disease modification or hippoc al neuroprotection. Men and women both exhibited neurotrophic changes in the prefrontal lobe linked to cognitive lifestyle, consistent with a compensatory process. Lifespan complex cognitive activity may therefore protect against dementia through multiple biological pathways.
Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease
Publisher: Cold Spring Harbor Laboratory
Date: 10-05-2022
DOI: 10.1101/2022.05.10.22274858
Abstract: Polygenic risk scores (PRSs) can boost risk-prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E ( APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in 1) unaffected in iduals having high PRSs for LOAD, and 2) unaffected APOE - ε 4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected in iduals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic-risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected in iduals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.
Predicting the development of mild cognitive impairment: A new use of pattern recognition
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.NEUROIMAGE.2012.01.084
Abstract: While the conversion from mild cognitive impairment to Alzheimer's disease has received much recent attention, the transition from normal cognition to mild cognitive impairment is largely unexplored. The present pattern recognition study addressed this by using neuropsychological test scores and neuroimaging morphological measures to predict the later development of mild cognitive impairment in cognitively normal community-dwelling in iduals aged 70-90years. A feature selection algorithm chose a subset of neuropsychological and FreeSurfer-derived morphometric features that optimally differentiated between in iduals who developed mild cognitive impairment and in iduals who remained cognitively normal. Support vector machines were used to train classifiers and test prediction performance, which was evaluated via 10-fold cross-validation to reduce variability. Prediction performance was greater when using a combination of neuropsychological scores and morphological measures than when using either of these alone. Results for the combined method were: accuracy 78.51%, sensitivity 73.33%, specificity 79.75%, and an area under the receiver operating characteristic curve of 0.841. Of all the features investigated, memory performance and measures of the prefrontal cortex and parietal lobe were the most discriminative. Our prediction method offers the potential to detect elderly in iduals with apparently normal cognition at risk of imminent cognitive decline. Identification at this stage will facilitate the early start of interventions designed to prevent or slow the development of Alzheimer's disease and other dementias.
Effects of different frequencies of transcranial magnetic stimulation (TMS) on the forced swim test model of depression in rats
Publisher: Elsevier BV
Date: 03-2002
Measurement of grey matter atrophy in mild cognitive impairment using MRI
Publisher: Elsevier BV
Date: 07-2009
Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis
Publisher: Springer Science and Business Media LLC
Date: 24-05-2016
DOI: 10.1038/MP.2016.72
Changing topological patterns in normal aging using large-scale structural networks
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1016/J.NEUROBIOLAGING.2010.06.022
Abstract: We examine normal aging from the perspective of topological patterns of structural brain networks constructed from two healthy age cohorts 20 years apart. Based on graph theory, we constructed structural brain networks using 90 cortical and subcortical regions as a set of nodes and the interregional correlations of grey matter volumes across in idual brains as edges between nodes, and further analyzed the topological properties of the age-specific networks. We found that the brain structural networks of both cohorts had small-world architecture, and the older cohort (N = 374 mean age = 66.6 years, range 64-68) had lower global efficiency but higher local clustering in the brain structural networks compared with the younger cohort (N = 428 mean age = 46.7, range 44-48). The older cohort had reduced hemispheric asymmetry and lower centrality of certain brain regions, such as the bilateral hippoc us, bilateral insula, left posterior cingulated, and right Heschl gyrus, but that of the prefrontal cortex (PFC) was not different. These structural network differences may provide the basis for changes in functional connectivity and indeed cognitive function as we grow older.
Network Modeling of microRNA–mRNA Interactions in Neuroblastoma Tumorigenesis Identifies miR-204 as a Direct Inhibitor of MYCN
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2018
DOI: 10.1158/0008-5472.CAN-17-3034
Abstract: Neuroblastoma is a pediatric cancer of the sympathetic nervous system where MYCN lification is a key indicator of poor prognosis. However, mechanisms by which MYCN promotes neuroblastoma tumorigenesis are not fully understood. In this study, we analyzed global miRNA and mRNA expression profiles of tissues at different stages of tumorigenesis from TH-MYCN transgenic mice, a model of MYCN-driven neuroblastoma. On the basis of a Bayesian learning network model in which we compared pretumor ganglia from TH-MYCN+/+ mice to age-matched wild-type controls, we devised a predicted miRNA–mRNA interaction network. Among the miRNA–mRNA interactions operating during human neuroblastoma tumorigenesis, we identified miR-204 as a tumor suppressor miRNA that inhibited a subnetwork of oncogenes strongly associated with MYCN- lified neuroblastoma and poor patient outcome. MYCN bound to the miR-204 promoter and repressed miR-204 transcription. Conversely, miR-204 directly bound MYCN mRNA and repressed MYCN expression. miR-204 overexpression significantly inhibited neuroblastoma cell proliferation in vitro and tumorigenesis in vivo. Together, these findings identify novel tumorigenic miRNA gene networks and miR-204 as a tumor suppressor that regulates MYCN expression in neuroblastoma tumorigenesis. Significance: Network modeling of miRNA–mRNA regulatory interactions in a mouse model of neuroblastoma identifies miR-204 as a tumor suppressor and negative regulator of MYCN. Cancer Res 78(12) 3122–34. ©2018 AACR.
Intraindividual Stepping Reaction Time Variability Predicts Falls in Older Adults With Mild Cognitive Impairment
Publisher: Oxford University Press (OUP)
Date: 03-09-2016
Abstract: Reaction time measures have considerable potential to aid neuropsychological assessment in a variety of health care settings. One such measure, the intrain idual reaction time variability (IIV), is of particular interest as it is thought to reflect neurobiological disturbance. IIV is associated with a variety of age-related neurological disorders, as well as gait impairment and future falls in older adults. However, although persons diagnosed with Mild Cognitive Impairment (MCI) are at high risk of falling, the association between IIV and prospective falls is unknown. We conducted a longitudinal cohort study in cognitively intact (n = 271) and MCI (n = 154) community-dwelling adults aged 70-90 years. IIV was assessed through a variety of measures including simple and choice hand reaction time and choice stepping reaction time tasks (CSRT), the latter administered as a single task and also with a secondary working memory task. Logistic regression did not show an association between IIV on the hand-held tasks and falls. Greater IIV in both CSRT tasks, however, did significantly increase the risk of future falls. This effect was specific to the MCI group, with a stronger effect in persons exhibiting gait, posture, or physiological impairment. The findings suggest that increased stepping IIV may indicate compromised neural circuitry involved in executive function, gait, and posture in persons with MCI increasing their risk of falling. IIV measures have potential to assess neurobiological disturbance underlying physical and cognitive dysfunction in old age, and aid fall risk assessment and routine care in community and health care settings.
Genome-Wide Gene Expression Signature Of Depression
Publisher: Elsevier BV
Date: 2017
White matter integrity and late-life depression in community-dwelling individuals: Diffusion tensor imaging study using tract-based spatial statistics
Publisher: Royal College of Psychiatrists
Date: 10-2014
DOI: 10.1192/BJP.BP.113.142109
Abstract: Late-life depression has been associated with white matter changes in studies using the regions of interest approach. To investigate the cross-sectional and longitudinal relationship between white matter integrity and depression in community-dwelling in iduals using diffusion tensor imaging with tract-based spatial statistics. The s le comprised 381 participants aged between 72 and 92 years who were assessed twice within 2 years. Depressive symptoms were measured with the Geriatric Depression Scale. Tract-based spatial statistics were applied to investigate white matter integrity in currently depressed v. non-depressed elderly people and in those with a history of depression v. no history of depression. The relationship between white matter integrity and development of depressive symptoms after 2 years were analysed with logistic regression. In iduals with current depression had widespread white matter integrity reduction compared with non-depressed elderly people. Significant fractional anisotropy reductions were found in 45 brain areas with the most notable findings in the frontal lobe, association and projection fibres. A history of depression was not associated with reduced fractional anisotropy. White matter changes in the superior frontal gyrus, posterior thalamic radiation, superior longitudinal fasciculus and in the body of corpus callosum predicted depression at follow-up. Reduced white matter integrity is associated with late-life depression and predicts future depressive symptoms whereas a history of depression is not related to white matter changes. Disruption to white matter integrity may be a biomarker to predict late-life depression.
Posttraumatic Psychosis
Publisher: American Psychiatric Publishing
Date: 04-03-2013
Spatial false discovery rate control for magnetic resonance imaging studies
Publisher: IEEE
Date: 11-2013
White Matter Hyperintensities Are under Strong Genetic Influence
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2016
DOI: 10.1161/STROKEAHA.116.012532
Abstract: The genetic basis of white matter hyperintensities (WMH) is still unknown. This study examines the heritability of WMH in both sexes and in different brain regions, and the influence of age. Participants from the Older Australian Twins Study were recruited (n=320 92 monozygotic and 68 dizygotic pairs) who volunteered for magnetic resonance imaging scans and medical assessments. Heritability, that is, the ratio of the additive genetic variance to the total phenotypic variance, was estimated using the twin design. Heritability was high for total WMH volume (0.76), and for periventricular WMH (0.64) and deep WMH (0.77), and varied from 0.18 for the cerebellum to 0.76 for the occipital lobe. The genetic correlation between deep and periventricular WMH regions was 0.85, with one additive genetics factor accounting for most of the shared variance. Heritability was consistently higher in women in the cerebral regions. Heritability in deep but not periventricular WMH declined with age, in particular after the age of 75. WMH have a strong genetic influence but this is not uniform through the brain, being higher for deep than periventricular WMH and in the cerebral regions. The genetic influence is higher in women, and there is an age-related decline, most markedly for deep WMH. The data suggest some heterogeneity in the pathogenesis of WMH for different brain regions and for men and women.
Effect of Different Impairment Criteria on Prevalence of Objective Mild Cognitive Impairment in a Community Sample
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1097/JGP.0B013E3181D6B6A9
Abstract: Objective cognitive impairment determined by neuropsychological test performance is a core criterion for the diagnosis of mild cognitive impairment (MCI), yet no consensus has been reached on how this criterion should be operationalized. The aims of this study were to investigate the effect of varying the criteria used to determine cognitive impairment (CI) on prevalence and case definition and to examine comparability of different criteria. Cross-sectional study. Sydney Memory and Ageing Study, Australia. Nine hundred eighty-seven nondemented community-dwelling adults aged 70-90 years were enrolled in this study. Participants received a comprehensive neuropsychological test battery measuring four cognitive domains. They were classified as normal or cognitively impaired by applying two types of “impairment” rule that varied the statistical threshold for impairment and the criteria used to determine impairment for each cognitive domain. Prevalence of four MCI cognitive subtypes was determined according to nine different criteria and two types of normative data. Rates of CI were compared in persons of English-speaking and non-English-speaking backgrounds (NESB). Prevalence of CI ranged from 4 to 70% depending on the impairment criteria used. Agreement between different criteria was poor to moderate. This lack of consistency had greatest impact on MCI subtype classifications with many being reclassified as “normal” or into a different subtype when stringency of the criteria was increased or decreased. Higher rates of impairment were found in persons of NESB across all cognitive domains. The prevalence of CI was strongly affected by the choice of neuropsychological assessment parameters. Guidelines for operationalizing CI are required.
The impact of white matter hyperintensity volumes on the topological patterns structural cortical network
Publisher: Elsevier BV
Date: 07-2009
Associations between Alzheimer’s disease polygenic risk scores and hippocampal subfield volumes in 17,161 UK Biobank participants
Publisher: Cold Spring Harbor Laboratory
Date: 27-10-2020
DOI: 10.1101/2020.10.24.20218925
Abstract: Hippoc al volume is an important biomarker of Alzheimer’s disease (AD), and genetic risk of AD is associated with hippoc al atrophy. However, the hippoc us is not a uniform structure and has a number of subfields, the associations of which with age, sex, and polygenic risk score for AD (PRS AD ) have been inadequately investigated. We examined these associations in 17,161 cognitively normal UK Biobank participants (44-80 years). Age was negatively associated with all the hippoc al subfield volumes and females had smaller volumes than men. Higher PRS AD was associated with lower volumes in the bilateral whole hippoc us, hippoc al-amygdala-transition-area (HATA), and hippoc al tail right subiculum left cornu ammonis (CA)1, CA4, molecular layer, and granule cell layer of dentate gyrus (CG-DG), with associations being greater on the left side. Older in iduals (median age 63 years, n=8984) showed greater subfield vulnerability to high PRS AD compared to the younger group (n=8177), but the effect did not differ by sex. The pattern of subfield involvement in relation to the PRS AD in community dwelling healthy in iduals sheds additional light on the pathogenesis of AD.
The 10-Item Kessler Psychological Distress Measure (K10) as a Screening Instrument in Older Individuals
Publisher: Elsevier BV
Date: 04-2012
Vascular cognitive disorder [6]
Publisher: Wiley
Date: 05-1999
DOI: 10.1002/(SICI)1099-1166(199905)14:5<402::AID-GPS958>3.0.CO;2-H
Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2022
DOI: 10.1161/STROKEAHA.121.035796
Abstract: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using in idual participant data from the Stroke and Cognition Consortium. Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step in idual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. A total of 1488 patients (mean age, 66.3 years SD, 11.1 98% ischemic stroke) were followed for a median of 2.68 years (25th–75th percentile: 1.21–4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (−0.053 SD/year [95% CI, −0.073 to −0.033] P .001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=−0.078 SD/year [95% CI, −0.11 to −0.045] P .001 for global cognition in a subgroup analysis). Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.
Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins
Publisher: eLife Sciences Publications, Ltd
Date: 22-07-2020
DOI: 10.7554/ELIFE.58954
Abstract: The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h 2 = 0.28–0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.
Friedreich's Ataxia and schizophrenia-like psychosis
Publisher: Cambridge University Press
Date: 04-02-2010
The Vascular Impairment of Cognition Classification Consensus Study
Publisher: Wiley
Date: 10-12-2016
DOI: 10.1016/J.JALZ.2016.10.007
Abstract: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research.
Pharmacotherapy in patients with epilepsy and psychosis
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.YEBEH.2018.09.001
Abstract: The recognition and treatment of psychosis in persons with epilepsy (PWE) is recommended with the apparent dilemma between treating psychosis and opening the possibility of exacerbating seizures. The pooled prevalence estimate of psychosis in PWE is 5.6%. It has been proposed that a 'two hit' model, requiring both aberrant limbic activity and impaired frontal control, may account for the wide range of clinical phenotypes. The role of antiepileptic drugs in psychosis in PWE remains unclear. Alternating psychosis, the clinical phenomenon of a reciprocal relationship between psychosis and seizures, is unlikely to be an exclusively antiepileptic drug-specific phenomenon but rather, linked to the neurobiological mechanisms underlying seizure control. Reevaluation of antiepileptic treatment, including the agent/s being used and degree of epileptic seizure control is recommended. The authors found very few controlled studies to inform evidence-based treatment of psychosis in PWE. However, antipsychotics and benzodiazepines are recommended as the symptomatic clinical treatments of choice for postictal and brief interictal psychoses. The general principle of early symptomatic treatment of psychotic symptoms applies in epilepsy-related psychoses, as for primary psychotic disorders. In the authors' experience, low doses of antipsychotic medications do not significantly increase clinical risk of seizures in PWE being concurrently treated with an efficacious antiepileptic regimen.
Huntington's Disease and related disorders and their association with schizophrenia-like psychosis
Publisher: Cambridge University Press
Date: 04-02-2010
The need for a reliable oxytocin assay
Publisher: Springer Science and Business Media LLC
Date: 30-04-2021
Genetic influences on cognitive functions in the elderly: A selective review of twin studies
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.BRAINRESREV.2010.02.001
Abstract: In this review, we examined the published reports on the heritability of cognitive functioning in old age. Twenty-four papers from five study centers, comprising of participants with a mean age of 65 years and above were examined. The comparability of findings from different studies was compromised by the use of different measures for the same cognitive domain, and with large scale twin studies in cognitive aging limited to a few Scandinavian countries. While the results from cross-sectional s les appear to lend support for the notion that heritability of cognitive functions decreases in the elderly, the findings are best considered inconclusive. Longitudinal reports show little evidence for genetic effects, but an increase in unique environmental influences on the rate of cognitive change as age increases. In relation to the two prominent theories of cognitive aging, the genetic influence on processing speed as a major contributor to cognitive aging has been indicated in three reports, whereas the genetic relationship between executive functions and other cognitive functions has not been explored. Only two studies have focused on sex difference and did not find sex-specific genetic influence in cognitive abilities. This review indicates that there are complex relationships between heritability, environmental influence, and cognitive functions in the elderly. It highlights the need for more research, with consistent and appropriate cognitive measures, with data obtained from larger and more geographically and culturally erse twin s les.
Prospective memory function and cue salience in mild cognitive impairment: Findings from the Sydney Memory and Ageing Study
Publisher: Informa UK Limited
Date: 02-2017
DOI: 10.1080/13803395.2017.1281382
Abstract: Prospective memory (PM) is crucial to the maintenance of functional independence in late adulthood and is consistently impaired in mild cognitive impairment (MCI). There remains a need for brief but valid measures of this construct that can be used as part of a comprehensive clinical assessment of cognition. Since the distinctiveness of PM cues is argued to determine the degree of strategic, controlled demands of PM paradigms, two variants of a brief measure were developed, one of which presented low-salience and the other high-salience PM cues. A large cohort of older adults with normal cognition or MCI was assessed with one of the two variants of our brief, novel measure of PM. Participants were asked to remember to execute PM tasks where the target cue was either high or low in salience, while concurrently engaged in an ongoing task of olfactory assessment. The task was able to discriminate between groups of participants with MCI or no cognitive impairment, albeit with a small effect size. The high-salience cue improved performance on the PM task however, there was no interaction of cue salience with group. These results suggest that the temporal reliability and construct validity of very brief measures of the type used in this study need further exploration to determine their potential to provide meaningful insights into PM function. This measure may have utility as a brief screening tool, with identified deficits being followed up with a more comprehensive PM assessment.
The Sydney Centenarian Study: methodology and profile of centenarians and near-centenarians
Publisher: Cambridge University Press (CUP)
Date: 19-03-2013
DOI: 10.1017/S1041610213000197
Abstract: Background: The study of exceptionally long-living in iduals can inform us about the determinants of successful aging. There are few population-based studies of centenarians and near-centenarians internationally, but none in Australia. Methods: In iduals 95 years and older were recruited from seven electoral districts in Sydney using the electoral roll, Medicare lists, and multiple other strategies to obtain a representative s le. Physical and mental health and cognitive status were assessed using standard instruments in multiple sessions, with assessments in idually adapted. An informant was interviewed, and participants were invited to donate a blood s le, undergo an MRI scan, and enrol into the brain donation program. Results: Preliminary data on the first 200 participants are reported. Mean age was 97.4 years (range 95–106), with 29.5% being men, and 58.5% living in a private dwelling. Rates of heart disease and diabetes were lower than in octogenarians, but hearing and visual deficits were common. The mean mini-mental state examination (MMSE) score was 21.1, with men performing better. Rates of psychological distress were low and satisfaction with life high (mean 5.91 out of a maximum of 7) 54% scored on MMSE 39.5% were impaired on both MMSE and a functional measure and 20% had previous diagnosis of dementia. Conclusions: This is a preliminary report describing the methodology of the study. It provides further evidence that dementia is not inevitable at this age and independent living is common. The study provides an excellent resource to determine the genetic and environmental contributions to long and successful cognitive aging.
Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global B
Publisher: Elsevier BV
Date: 11-2018
The Epidemiology of Drug-induced Akathisia: Part I. Acute Akathisia
Publisher: Oxford University Press (OUP)
Date: 1995
Abstract: This article reviews the epidemiological data on drug-induced acute akathisia, examining studies in which akathisia was the primary focus as well as those in which it was one of a number of drug side effects studied. The studies are erse in methodology and suffer from many limitations. Incidence rates for acute akathisia with conventional neuroleptics vary from 8 to 76 percent, with 20 to 30 percent being a conservative estimate preliminary evidence suggests that the newer atypical antipsychotic drugs are less likely to produce acute akathisia. A number of nonneuroleptic drugs--in particular the serotonin-specific reuptake inhibitors--have been implicated in the development of akathisia, but the epidemiological data are limited. Risk factors for neuroleptic-induced akathisia are not completely understood. Drug dose, rate of increment of dose, and drug potency seem to be important, but the role of sociodemographic factors and other treatment-related variables is modest. Drug-induced parkinsonism is significantly correlated with akathisia. Evidence for iron deficiency as a risk factor is conflicting, and its contribution is likely to be minor.
The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
Publisher: Springer Science and Business Media LLC
Date: 08-01-2014
Behavioural problems following stroke - is there a relationship with cognitive impairment?
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Early extrapyramidal side-effects as risk factors for later tardive dyskinesia: a prospective study.
Publisher: SAGE Publications
Date: 06-2004
Brain structural covariances in the ageing brain in the UK Biobank
Publisher: Cold Spring Harbor Laboratory
Date: 28-07-2022
DOI: 10.1101/2022.07.26.501635
Abstract: Brain structural covariances or pairwise correlations describe how morphologic properties of brain regions are related to one another across in iduals. Although it is reported that brain structural covariance changes during brain development, it is not clear how structural covariance relates to the ageing process. Here we investigated the human brain structural covariances of cortical thickness and subcortical volumes in the ageing brain and their associations with age, cognition, and longevity polygenic risk score (longevity-PRS) by using cross-sectional data from the UK Biobank (N = 42075, aged 45-83 years, M/F=19752 /22323). The s le of participants was ided into 84 non-overlapping groups based on their age. The older the age group, the greater the variability in the whole brain structural covariance. However, there was a differential rate of age-related increase of variance between males and females. The variance of females started lower than those of males and then increased with age with a greater gradient than that of males. There was a consistent and significant enrichment of pairwise correlations within the occipital lobe in ageing process. The cortical thickness and subcortical covariances in older groups were significantly different from those in the youngest group. Sixty-two of the total 528 pairs of cortical thickness correlations and 10 of the total 21 pairs of subcortical volume correlations were significantly associated with age after Bonferroni correction. Specifically, with an increasing age, most decreased cortical thickness correlations were found between the regions within the frontal lobe as well as between the frontal lobe regions and regions in other lobes, while pairwise correlations within occipital lobe regions were all strengthening. Most of these correlations were also associated with global cognition and weakly associated with longevity-PRS. These findings revealed that the structural covariance was not stable during ageing. Given the thinning of the cortex and the volumetric reduction of subcortical structures seen in the ageing process, an increased pairwise correlation between the brain regions in the older brain suggested a strengthened coordinated decline between the brain regions involved. However, some of the brain regions demonstrated a differentiated rate of decline which was shown as the inversed or reduced pairwise correlations between these regions.
Amygdala in stroke/transient ischemic attack patients and its relationship to cognitive impairment and psychopathology: The Sydney stroke study
Publisher: Elsevier BV
Date: 06-2007
A Combined Epigenetic and Non-Genetic Approach for Reprogramming Human Somatic Cells
Publisher: Public Library of Science (PLoS)
Date: 19-08-2010
Brief screening tests during acute admission in patients with mild stroke are predictive of vascular cognitive impairment 3-6 months after stroke
Publisher: BMJ
Date: 11-04-2012
Abstract: To determine the prognostic value of brief cognitive screening tests administered in the subacute stroke phase (initial 2 weeks) for the detection of significant cognitive impairment 3-6 months after stroke, the authors compared the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Patients with ischaemic stroke and transient ischaemic attack were assessed with both MoCA and MMSE within 14 days after index stroke, followed by a formal neuropsychological evaluation of seven cognitive domains 3-6 months later. Cognitive outcomes were dichotomised as either no-mild (impairment in ≤2 cognitive domains) or moderate-severe (impairment in ≥ 3 cognitive domains) vascular cognitive impairment. Area under the receiver operating characteristic (ROC) curve analysis was used to compare discriminatory ability. 300 patients were recruited, of whom 239 received formal neuropsychological assessment 3-6 months after the stroke. 60 (25%) patients had moderate-severe VCI. The overall discriminant validity for detection of moderate-severe cognitive impairment was similar for MoCA (ROC 0.85 (95% CI 0.79 to 0.90) and MMSE (ROC 0.83 (95% CI 0.77 to 0.89)), p=0.96). Both MoCA (21/22) and MMSE (25/26) had similar discriminant indices at their optimal cutoff points sensitivity 0.88 versus 0.88 specificity 0.64 versus 0.67 70% versus 72% correctly classified. Moreover, both tests had similar discriminant indices in detecting impaired cognitive domains. Brief screening tests during acute admission in patients with mild stroke are predictive of significant vascular cognitive impairment 3-6 months after stroke.
[IC‐03–01]: WHAT HAPPENS TO THE HIPPOCAMPUS 12 MONTHS AFTER TRAINING? LONGITUDINAL LINEAR MIXED‐EFFECTS MODEL ANALYSIS OF MILD COGNITIVE IMPAIRMENT IN THE SMART TRIAL
Publisher: Wiley
Date: 07-2017
Site and size of lesion and psychosurgical outcome in obsessive-compulsive disorder: A magnetic resonance imaging study
Publisher: Elsevier BV
Date: 04-1996
Vascular dementia
Publisher: Informa UK Limited
Date: 1993
PROTEOMICS OF THE ALZHEIMER'S DISEASE BRAIN: NEUROPATHOLOGY AND NEURORESILIENCE
Publisher: Wiley
Date: 07-2017
The Sub-Classification of Amnestic Mild Cognitive Impairment Using MRI-Based Cortical Thickness Measures
Publisher: Frontiers Media SA
Date: 21-05-2014
“My Body Is My Template”: Why Do People Suffering from Anorexia Nervosa See Their Bodies Differently?
Publisher: Springer New York
Date: 2011
O1‐01‐05: Brain changes on structural MRI from the eighth to eleventh decades of life
Publisher: Wiley
Date: 07-2015
O3‐01‐04: Why Aren't People with Young Onset Dementia and their Carers using Formal Services?
Publisher: Wiley
Date: 07-2016
Dementia in people with intellectual disability: Insights and challenges in epidemiological research with an at-risk population
Publisher: Informa UK Limited
Date: 12-2013
DOI: 10.3109/09540261.2013.866938
Abstract: The population with intellectual disability (ID) is ageing, but age-related health concerns such as dementia have received little research attention thus far. We review evidence regarding the prevalence and incidence of dementia in people with ID, and discuss some possible explanations for an increased risk, such as shared genetic risk factors, co-morbid physical and mental disorders, lifestyle factors, trauma, and lowered brain reserve. We discuss practical and theoretical challenges facing researchers in this field, before highlighting the implications of findings to date for future research and clinical care. Research on dementia in this at-risk population has the potential to help us understand dementia in general and to improve services for this group of vulnerable in iduals.
DSM-V neurocognitive disorders cluster: General principles
Publisher: Wiley
Date: 07-2010
Causes and diagnosis of Alzheimer's disease: A proteomics approach
Publisher: Bentham Science Publishers Ltd.
Date: 07-2006
The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-03-2004
DOI: 10.1212/01.WNL.0000115108.65264.4B
Abstract: Objective: To characterize the neuropsychological profile of vascular cognitive impairment (VCI) and vascular dementia (VaD). Methods: The authors examined 170 patients with stroke or TIA at 3 to 6 months after the vascular event, and 96 age-matched healthy controls, with detailed neuropsychological and medical-psychiatric assessments, with a majority (66.7%) undergoing MRI brain scans. The subjects were diagnosed as having VaD, VCI, or no cognitive impairment by consensus. The neuropsychological tests were classified into cognitive domains, and composite z-scores adjusted for age and education. Results: VaD subjects had disturbance in all cognitive domains, with verbal memory, especially retention, being less affected. VCI subjects had similar but less severe disturbance. The domains that best discriminated cognitively impaired from unimpaired patients were abstraction, mental flexibility, information processing speed, and working memory. Cognitive impairment had a significant correlation with deep white matter hyperintensities, but not with volume and number of infarctions, even though the VaD subjects had larger infarct volumes than VCI subjects. The MRI variables did not provide additional discrimination between subgroups. Conclusions: The cognitive deficits in VaD and VCI are characterized by disturbance of frontal functions, with less verbal memory impairment. VaD and VCI differ in severity but not pattern of disturbance. The brain lesions that best account for these deficits are noninfarct subcortical white matter and gray matter changes due to ischemia. The picture of VaD/VCI presented shows subcortical deficits embellished by cognitive deficits from cortical infarctions.
Effects of Sociodemographic and Health Variables on Mini-Mental State Exam Scores in Older Australians
Publisher: Elsevier BV
Date: 06-2007
Novel ThickNet features for the discrimination of amnestic MCI subtypes
Publisher: Elsevier BV
Date: 2014
Association of type 2 diabetes with depression, brain atrophy, and reduced fine motor speed in a 60- to 64-year-old community sample
Publisher: Elsevier BV
Date: 12-2008
The association of regional white matter lesions with cognition in a community-based cohort of older individuals
Publisher: Elsevier BV
Date: 2018
Neuropsychiatry - A discipline for the future
Publisher: Elsevier BV
Date: 08-2002
Good memory as a predictor of falls: fact or artefact
Publisher: Oxford University Press (OUP)
Date: 08-02-2012
Abstract: accurate classification of older people into fallers and non-fallers is crucial for falls research, but largely dependent on the accuracy of fall reporting by the participants. to investigate the influence of memory in relation to fall reporting. five hundred community-dwelling adults aged 70-90 years. memory and executive functioning were assessed using the Rey Auditory Verbal Learning and Trail Making test, respectively. Fall risk was estimated using the physiological profile assessment (PPA). Falls were recorded prospectively for 12 months using monthly falls diaries and follow-up phone calls as required. Spearman correlations showed that falls were significantly correlated to worse executive functioning, worse PPA scores and better memory. People with better memory had an increased risk of being classified as single fallers and multiple fallers, but not when reported injuries were included as part of the definition. good memory appears to influence the recording of falls in community-dwelling older people and likely reflects a reporting bias. In research studies, there may be value in using a combination of injurious falls and multiple falls when classifying people into faller and non-faller groups.
The subclassifcation of amnestic MCI using MRI-based cortical thickness measures
Publisher: Wiley
Date: 07-2013
A Multifactorial Approach to Understanding Fall Risk in Older People
Publisher: Wiley
Date: 09-2010
DOI: 10.1111/J.1532-5415.2010.03017.X
Abstract: To identify the interrelationships and discriminatory value of a broad range of objectively measured explanatory risk factors for falls. Prospective cohort study with 12-month follow-up period. Community s le. Five hundred community-dwelling people aged 70 to 90. All participants underwent assessments on medical, disability, physical, cognitive, and psychological measures. Fallers were defined as people who had at least one injurious fall or at least two noninjurious falls during a 12-month follow-up period. Univariate regression analyses identified the following fall risk factors: disability, poor performance on physical tests, depressive symptoms, poor executive function, concern about falling, and previous falls. Classification and regression tree analysis revealed that balance-related impairments were critical predictors of falls. In those with good balance, disability and exercise levels influenced future fall risk-people in the lowest and the highest exercise tertiles were at greater risk. In those with impaired balance, different risk factors predicted greater fall risk-poor executive function, poor dynamic balance, and low exercise levels. Absolute risks for falls ranged from 11% in those with no risk factors to 54% in the highest-risk group. A classification and regression tree approach highlighted interrelationships and discriminatory value of important explanatory fall risk factors. The information may prove useful in clinical settings to assist in tailoring interventions to maximize the potential benefit of falls prevention strategies.
New avenue for the geriatric depression scale: Rasch transformation enhances reliability of assessment
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.JAD.2019.11.100
Abstract: Depression is a common problem in older adults. The 15-item Geriatric Depression Scale (GDS-15) is a widely used psychometric tool for measuring depression in the elderly, but its psychometric properties have not been yet rigorously investigated. The aim was to evaluate psychometric properties of the GDS-15 and improve precision of the instrument by applying Rasch analysis and deriving conversion tables for transformation of raw scores into interval level data. The data was extracted from the prospective cohort Sydney Memory and Ageing Study of initially not demented in iduals aged 70 years and older. The GDS-15 items scores of 212 participants (47.2% males) were analysed using the dichotomous Rasch model. Initially poor reliability of the GDS-15, Person Separation Index (PSI) = 0.68, was improved by combining locally dependent items into seven super-items. These modifications improved reliability of the GDS-15 (PSI = 0.78) and resulted in the best Rasch model fit (χ Presence of participants with cognitive impairment may be a potential limitation. Reliability and psychometric characteristics of the GDS-15 were improved by minor modifications and now satisfy expectations of the unidimensional Rasch model. By using Rasch transformation tables published here psychiatrists, psychologists and researchers can transform GDS raw scores into interval-level data, which improves reliability of the GDS-15 without the need to modify its original response format. These findings increase accuracy of clinical psychometric assessments, leading to more precise diagnosis of depression in the elderly.
COMT AND BDNF GENE INTERACTIONS PREDICT BRAIN STRUCTURE IN AGEING
Publisher: Wiley
Date: 07-2014
The Epidemiology of Drug-induced Akathisia: Part II. Chronic, Tardive, and Withdrawal Akathisias
Publisher: Oxford University Press (OUP)
Date: 1995
Abstract: This article examines the epidemiological data on chronic akathisia, tar e akathisia, and withdrawal akathisia. The limitations of the data are discussed--in particular, the lack of consistent definitions of the syndromes. The studies suggest that a significant proportion of patients chronically treated with neuroleptics suffer from akathisia. The prevalence may be as high as 40 percent, although a conservative estimate would be closer to 30 percent. Risk factors for the development of chronic akathisia and tar e akathisia are poorly understood, but old age, female sex, iron deficiency, negative symptoms, cognitive dysfunction, and affective disorder diagnosis need to be studied further for their potential role. While there is convincing evidence that akathisia may develop after neuroleptic cessation or reduction in dose, the prevalence and risk factors for withdrawal akathisia are not known. Reports of akathisia in children and the elderly have been few, and more systematic research is necessary. Akathisia appears to be common in in iduals with mental retardation treated chronically with neuroleptics.
COSMIC (Cohort Studies of Memory in an International Consortium): an international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups.
Publisher: Springer Science and Business Media LLC
Date: 06-11-2013
Clinical assessment of social cognitive function in neurological disorders
Publisher: Springer Science and Business Media LLC
Date: 16-12-2015
DOI: 10.1038/NRNEUROL.2015.229
Abstract: Social cognition broadly refers to the processing of social information in the brain that underlies abilities such as the detection of others' emotions and responding appropriately to these emotions. Social cognitive skills are critical for successful communication and, consequently, mental health and wellbeing. Disturbances of social cognition are early and salient features of many neuropsychiatric, neurodevelopmental and neurodegenerative disorders, and often occur after acute brain injury. Its assessment in the clinic is, therefore, of paramount importance. Indeed, the most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) introduced social cognition as one of six core components of neurocognitive function, alongside memory and executive control. Failures of social cognition most often present as poor theory of mind, reduced affective empathy, impaired social perception or abnormal social behaviour. Standard neuropsychological assessments lack the precision and sensitivity needed to adequately inform treatment of these failures. In this Review, we present appropriate methods of assessment for each of the four domains, using an ex le disorder to illustrate the value of these approaches. We discuss the clinical applications of testing for social cognitive function, and finally suggest a five-step algorithm for the evaluation and treatment of impairments, providing quantitative evidence to guide the selection of social cognitive measures in clinical practice.
Pharmacology of NAD+boosters
Publisher: Elsevier
Date: 2023
An emotional Stroop functional MRI study of euthymic bipolar disorder
Publisher: Wiley
Date: 14-10-2005
DOI: 10.1111/J.1399-5618.2005.00255.X
Abstract: To identify the brain regions associated with emotional processing in euthymic bipolar patients. The study examined 12 euthymic bipolar patients using functional magnetic resonance imaging (fMRI) while performing an emotional Stroop (eStroop) task. The task comprised emotionally valent and neutral words presented in alternating blocks that was designed to implicitly induce affect. In conjunction with fMRI, galvanic skin responses (GSR) were measured to monitor arousal. Euthymic bipolar patients had diminished activation in response to the affective stimuli in both cortical and subcortical brain regions when compared with healthy subjects. In particular, patients had less activation in the left ventral prefrontal cortex suggesting a potential trait deficit. Patients were slower to react than healthy controls, but did not differ with respect to accuracy. Euthymic bipolar patients are perhaps constrained in their ability to engage affective processing. Diminished ventral prefrontal cortex activation corroborates previous reports of a potential trait deficit, suggesting that 'all is not well in euthymia', although the effects of medication cannot be overlooked.
Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease.
Publisher: SAGE Publications
Date: 11-05-2016
Abstract: Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan–rescan procedure either in single or multicenter settings (2) the acquisition-related sources of variability and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease.
Variation in longitudinal trajectories of cortical sulci in normal elderly
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.NEUROIMAGE.2017.10.010
Abstract: Sulcal morphology has been reported to change with age-related neurological diseases, but the trajectories of sulcal change in normal ageing in the elderly is still unclear. We conducted a study of sulcal morphological changes over seven years in 132 normal elderly participants aged 70-90 years at baseline, and who remained cognitively normal for the next seven years. We examined the fold opening and sulcal depth of sixteen (eight on each hemisphere) prominent sulci based on T1-weighted MRI using automated methods with visual quality control. The trajectory of each in idual sulcus with respect to age was examined separately by linear mixed models. Fold opening was best modelled by cubic fits in five sulci, by quadratic models in six sulci and by linear models in five sulci, indicating an accelerated widening of a number of sulci in older age. Sulcal depth showed significant linear decline in three sulci and quadratic trend in one sulcus. Turning points of non-linear trajectories towards accelerated widening of the fold were found to be around the age between 75 and 80, indicating an accelerated atrophy of brain cortex starting in the age of late 70s. Our findings of cortical sulcal changes in normal ageing could provide a reference for studies of neurocognitive disorders, including neurodegenerative diseases, in the elderly.
Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Publisher: Springer Science and Business Media LLC
Date: 05-2019
DOI: 10.1038/S41467-019-10160-W
Abstract: Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.
MRI Hyperintensities and Depressive Symptoms in a Community Sample of Individuals 60–64 Years Old
Publisher: American Psychiatric Association Publishing
Date: 04-2005
DOI: 10.1176/APPI.AJP.162.4.699
Abstract: Previous studies have found associations of magnetic resonance imaging (MRI) signal hyperintensities with depression in the elderly. The present study investigates the association in a younger community s le (age 60-64 years) of depressed subjects and comparison groups for potential mediating and confounding variables. A subs le of 475 persons 60-64 years of age from a larger community survey underwent brain MRI scans. White matter hyperintensities were quantified by using an automated procedure, and basal ganglia hyperintensities were quantified by using semiquantitative visual ratings. The study also assessed depressive symptoms and use of antidepressant medication. Potential mediating or confounding variables assessed included physical disability, hypertension, stroke, diabetes, head injury, cortisol, thyroid-stimulating hormone, cognitive functioning, smoking, and alcohol use. Depressive symptoms were found to be related to total brain white matter hyperintensities but not to basal ganglia hyperintensities. However, associations disappeared when statistical adjustment was made for physical disability and smoking. Depressive symptoms are related to white matter hyperintensities in mid-adult life in a community s le. Physical disability appears to play an important role in this association.
Is CHCHD10 Pro34Ser pathogenic for frontotemporal dementia and amyotrophic lateral sclerosis?
Publisher: Oxford University Press (OUP)
Date: 07-05-2015
DOI: 10.1093/BRAIN/AWV115
Usability and feasibility of PreventS-MD web app for stroke prevention
Publisher: SAGE Publications
Date: 19-08-2023
DOI: 10.1177/17474930231190745
Abstract: Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0–50 unacceptable 51–68 poor 68–80.3 good .3 excellent) were used to determine usability of PreventS-MD. Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2 95% CI [77.0–84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7 95% CI [79.1–84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations. The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and in iduals at risk of stroke/CVD. In iduals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD.
Effects of specific dopamine D1 and D2 receptor antagonists and agonists and neuroleptic drugs on emotional defecation in a rat model of akathisia
Publisher: Elsevier BV
Date: 12-1998
DOI: 10.1016/S0165-1781(98)00118-8
Abstract: An increase in emotional defecation in rats in a well-habituated environment induced by neuroleptic drugs (NDef) has been proposed as a model for neuroleptic-induced akathisia. We examined the effects of dopamine receptor antagonists and agonists on this model. A selective dopamine D1 antagonist (SCH 23390) and a selective D2 antagonist (raclopride) induced increased defecation at higher doses, and demonstrated a synergistic effect at lower doses. Selective D1 (SKF 82958) and D2 (quinpirole) agonists did not have a significant effect on defecation, nor did they reverse the effect of haloperidol. In a further pilot study, we explored the effects of typical and atypical neuroleptics on this model. The haloperidol and risperidone treated rats produced more faecal boli than those treated with clozapine, thioridazine and chlorpromazine, with the former being non-significantly greater than the vehicle-treated group. The results of our studies suggest that NDef is most probably an effect of central dopamine antagonism that is not specific to D1 or D2 receptors, but that the two receptor subtypes have a synergistic effect. It is unlikely to be due to actions of neuroleptics on 5HT2 or alpha1 receptors as has sometimes been suggested. The results have implications for our understanding of the pathogenesis of akathisia.
Operationalizing the Diagnostic Criteria for Mild Cognitive Impairment: The Salience of Objective Measures in Predicting Incident Dementia
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.JAGP.2016.12.012
Abstract: Mild cognitive impairment (MCI) is considered an intermediate stage between normal aging and dementia. It is diagnosed in the presence of subjective cognitive decline and objective cognitive impairment without significant functional impairment, although there are no standard operationalizations for each of these criteria. The objective of this study is to determine which operationalization of the MCI criteria is most accurate at predicting dementia. Six-year longitudinal study, part of the Sydney Memory and Ageing Study. Community-based. 873 community-dwelling dementia-free adults between 70 and 90 years of age. Persons from a non-English speaking background were excluded. Seven different operationalizations for subjective cognitive decline and eight measures of objective cognitive impairment (resulting in 56 different MCI operational algorithms) were applied. The accuracy of each algorithm to predict progression to dementia over 6 years was examined for 618 in iduals. Baseline MCI prevalence varied between 0.4% and 30.2% and dementia conversion between 15.9% and 61.9% across different algorithms. The predictive accuracy for progression to dementia was poor. The highest accuracy was achieved based on objective cognitive impairment alone. Inclusion of subjective cognitive decline or mild functional impairment did not improve dementia prediction accuracy. Not MCI, but objective cognitive impairment alone, is the best predictor for progression to dementia in a community s le. Nevertheless, clinical assessment procedures need to be refined to improve the identification of pre-dementia in iduals.
Progression of cognitive impairment in stroke patients
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-11-2004
DOI: 10.1212/01.WNL.0000142964.83484.DE
Abstract: To examine the progression of neuropsychological deficits in stroke patients with and without cognitive impairment. The authors assessed the Sydney Stroke Study cohort 1 year after index assessment with detailed neuropsychological and medical-psychiatric assessments. The neuropsychological tests were classified into cognitive domains, and composite z-scores adjusted for age and education. Changes in cognitive test scores were compared between groups and predictors of cognitive change examined. Patients (n = 128) had a mean decline of 0.83 (SD 2.2) points on the Mini-Mental State Examination (MMSE) compared to an increase of 0.76 (1.3) in controls (n = 78) (p < 0.0001), and a small but significant decline in informant ratings of function and cognition. The decline on a composite index of cognitive function was not significantly different in the groups after correction for age, education, and index assessment cognitive function. Stroke/transient ischemic attack patients, however, had greater decline in verbal memory and visuoconstructive function. The occurrence of an interval stroke (n = 14) significantly increased the cognitive decline to a mean 2.0 points on the MMSE. The rate of change had a significant correlation (r = 0.24) with white matter hyperintensity volume at index assessment. On regression analysis the only predictor of cognitive change was years of education, which had a protective function. Subjects with cerebrovascular disease have a slow decline in cognitive functioning in the absence of further cerebrovascular events, although the occurrence of such an event accentuates the dysfunction. Education plays a protective role.
Attention deficit hyperactivity disorder in adults
Publisher: Cambridge University Press (CUP)
Date: 05-1999
DOI: 10.1017/S003329179800720X
Abstract: Adults with putative attention deficit hyperactivity disorder (ADHD) are increasingly being referred to psychiatric clinics, often following a self-diagnosis, and demanding a prescription for stimulant medication. This has disconcerted many clinicians and started a debate on the appropriateness of this diagnosis in adults (Shaffer, 1994 Lomas, 1995 Diller, 1996) that is reminiscent of the controversies of the childhood diagnosis in previous years ( Lancet , 1986). At issue is not only concern about the widespread use of stimulant medication, but also a neurobiological understanding of impulsivity, hyperactivity and antisocial behaviour and the genesis of some psychiatric disorders in adults. How is the validity of this disorder in adults then to be established?
Is Kleine-Levin syndrome a variant of bipolar disorder? An hypothesis
Publisher: Cambridge University Press (CUP)
Date: 08-2008
Mild cogitive impairment in the 60s
Publisher: Wiley
Date: 07-2011
More highly myelinated white matter tracts are associated with faster processing speed in healthy adults
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.NEUROIMAGE.2017.12.069
Abstract: The objective of this study was to investigate whether the estimated myelin content of white matter tracts is predictive of cognitive processing speed and whether such associations are modulated by age. Associations between estimated myelin content and processing speed were assessed in 570 community-living in iduals (277 middle-age, 293 older-age). Myelin content was estimated in-vivo using the mean T1w/T2w magnetic resonance ratio, in six white matter tracts (anterior corona radiata, superior corona radiata, pontine crossing tract, anterior limb of the internal capsule, genu of the corpus callosum, and splenium of the corpus callosum). Processing speed was estimated by extracting a principal component from 5 separate tests of processing speed. It was found that estimated myelin content of the bilateral anterior limb of the internal capsule and left splenium of the corpus callosum were significant predictors of processing speed, even after controlling for socio-demographic, health and genetic variables and correcting for multiple comparisons. One SD higher in the estimated myelin content of the anterior limb of the internal capsule was associated with 2.53% faster processing speed and within the left splenium of the corpus callosum with 2.20% faster processing speed. In addition, significant differences in estimated myelin content between middle-age and older participants were found in all six white matter tracts. The present results indicate that myelin content, estimated in vivo using a neuroimaging approach in healthy older adults, is sufficiently precise to predict variability in processing speed in behavioural measures.
A comprehensive neuropsychiatric study of elderly twins: The Older Australian Twins Study
Publisher: Cambridge University Press (CUP)
Date: 12-2009
Abstract: The Older Australian Twins Study (OATS) was recently initiated to investigate genetic and environmental factors and their associations and interactions in healthy brain ageing and ageing-related neurocognitive disorders. The study extends the classic MZ-DZ design to include one or two equivalently aged siblings for each twin pair and utilizes the rich resources of the Australian Twin Registry. The study has a number of distinguishing features including comprehensive psychiatric, neuropsychological, cardiovascular, metabolic, and neuroimaging assessments, a longitudinal design and links with a brain donor program. The study measures many behavioral and environmental factors, but in particular lifetime physical and mental activity, physical and psychological trauma, loss of parent early in life, later losses and life events, early-life socioeconomic environment, alcohol and drug use, occupational exposure, and nutrition. It also includes comprehensive cardiovascular assessment, blood biochemistry, genetics and proteomics. The socio-demographic and health data on the first 172 pairs of twins participating in this study are presented. Prevalence of mild cognitive impairment is 12.8% and of dementia 1.5% in the s le. The target s le size is 1000, with at least 400 pairs of twins aged 65–90 years. The cohort will be assessed every two years, with in-depth assessments being repeated. OATS offers an excellent opportunity for collaboration with other similar studies as well as researchers who share the same interests.
Slowness of movement in melancholic depression
Publisher: Elsevier BV
Date: 02-1994
DOI: 10.1016/0006-3223(94)91256-4
Abstract: We studied 10 subjects each with melancholic depression evidencing significant motor retardation (RM), Parkinson's disease (PD) with bradykinesia, and normal healthy controls (NC), matched closely for age and gender, on measurements of motor function and depression, and their performance of simple and complex ballistic movements. The simple movements involved the execution of 10 degrees, 20 degrees, and 40 degrees angular movements using a methodology adapted from Hallett and Khoshbin (1980). The complex movements involved the performance by the right arm and hand of a squeeze and a flexion movement, both sequentially and simultaneously, using a methodology adopted from Benecke et al (1986, 1987). The RM and PD groups demonstrated a smaller increase in the angular velocity as the angle of the movement increased from 10 degrees to 40 degrees than did the NC group. Many PD and RM subjects showed multiple electromyographic (EMG) bursts during the ballistic movements. The RM and PD subjects tended take longer to perform the simultaneous and sequential movements, but nonsignificantly so. The RM group performed the squeeze movement slower when executed as part of the simultaneous movement than when performed as a simple movement. The pause time between the movements when performed sequentially was longer (nonsignificantly) for the RM subjects. Our study demonstrated a disturbance in the execution of simple and complex movements by RM subjects that resembled the disturbance seen in PD. This argues for a common pathophysiological basis for at least some aspects of motor retardation in the two disorders. Reduced dopamine function is one common abnormality that may partially account for these findings.
Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study
Publisher: Wiley
Date: 19-10-2017
DOI: 10.1016/J.JALZ.2017.09.007
Abstract: Progress in understanding and management of vascular cognitive impairment (VCI) has been h ered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration.
Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals
Publisher: Public Library of Science (PLoS)
Date: 11-06-2012
Changes in the plasma proteome at asymptomatic and symptomatic stages of autosomal dominant Alzheimer’s disease
Publisher: Springer Science and Business Media LLC
Date: 06-07-2016
DOI: 10.1038/SREP29078
Abstract: The autosomal dominant form of Alzheimer’s disease (ADAD) is far less prevalent than late onset Alzheimer’s disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose metabolism. Fewer changes were observed at the asymptomatic than symptomatic stage with seven and 16 proteins altered significantly in aMC and sMC, respectively. This included complement components C3, C5, C6, apolipoproteins A-I, A-IV, C-I and M, histidine-rich glycoprotein, heparin cofactor II and attractin, which are involved in inflammation, lipid metabolism and vascular health. Proteins involved in lipid metabolism differed only at the symptomatic stage, whereas changes in inflammation and vascular health were evident at asymptomatic and symptomatic stages. Due to increasing evidence supporting the usefulness of ADAD as a model for LOAD, these proteins warrant further investigation into their potential association with early stages of LOAD.
Enhancing precision of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) using Rasch methodology
Publisher: Cambridge University Press (CUP)
Date: 19-11-2021
DOI: 10.1017/S1041610221002568
Abstract: This study aimed to investigate psychometric properties and enhance precision of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) up to interval-level scale using Rasch methodology. Partial Credit Rasch model was applied to the IQCODE-16 scores using longitudinal data spanning 10 years of biennial follow-up. Community-dwelling older adults aged 70–90 years and their informants, living in Sydney, Australia, participated in the longitudinal Sydney Memory and Ageing Study (MAS). The s le included 400 participants of the MAS aged 70 years and older, 109 out of those were diagnosed with dementia 10 years after the baseline assessment. The IQCODE-16. Initial analysis indicated excellent reliability of the IQCODE-16, Person Separation Index (PSI) = 0.92, but there were four misfitting items and local dependency issues. Combining locally dependent items into four super-items resulted in the best Rasch model fit with no misfitting or locally dependent items, strict unidimensionality, strong reliability, and invariance across person factors such as participants’ diagnosis and relationship to their informants, as well as informants’ age and sex. This permitted the generation of conversion algorithms to transform ordinal scores into interval data to enhance precision of measurement. The IQCODE-16 demonstrated strong reliability and satisfied expectations of the unidimensional Rasch model after minor modifications. Ordinal-to-interval transformation tables published here can be used to increase accuracy of the IQCODE-16 without altering its current format. These findings could contribute to enhancement of precision in assessing clinical conditions such as cognitive decline in older people.
Regional Gray Matter Changes in Bipolar Disorder: A Voxel-Based Morphometric Study
Publisher: SAGE Publications
Date: 04-2007
DOI: 10.1080/00048670701213229
Abstract: Objective: To investigate structural abnormalities in bipolar disorder (BD) using optimized voxel-based morphometry (VBM) in closely matched patients and controls, and to examine the relationship of clinical features with regional gray matter (GM) volumes. Methods: Twenty-four patients (six male) aged 19–59 years (mean=38.21 years, SD=11.04 years) with DSM-IV bipolar I disorder were compared with 25 control subjects, matched on age, sex, and years of education. VBM analyses were conducted on high-resolution T1-weighted brain magnetic resonance imaging to detect regional GM volume differences between groups, ensuring statistical correlation for age, sex and total intracranial volumes. Within the patient groups, regional GM changes were also investigated. Results: Compared to controls, BD patients had increased GM volume in left parahippoc al gyrus and decreased GM volume in left middle temporal gyrus. Family history, psychotic symptoms and lithium status were associated with regional GM abnormalities in BD patients. Conclusions: This study presents evidence of gray matter volume abnormalities in adults with bipolar I disorder. Regional variation in relation to clinical factors suggests a neurobiological basis for clinical heterogeneity and posits the possibility of trait deficits.
The relationship of cerebral microbleeds to cognition and incident dementia in non-demented older individuals
Publisher: Springer Science and Business Media LLC
Date: 25-05-2018
DOI: 10.1007/S11682-018-9883-3
Abstract: Cerebral microbleeds (CMB), suspected markers of hemorrhage-prone microangiopathy, are common in patients with cerebrovascular disease and in those with cognitive impairment. Their longitudinal relationship with cognitive decline and incident dementia in non-demented community-dwelling older in iduals has been insufficiently examined. 302 adults aged 70-90 participating in the population-based Sydney Memory and Ageing Study underwent a susceptibility-weighted imaging (SWI) MRI sequence. The relationship of CMB with performance on neuropsychological tests was examined both cross-sectionally and longitudinally, over a mean of 4 years. The association with cases of incident dementia during this period was also examined. The prevalence of CMB was 20%. In cross-sectional analysis, after adjusting for demographics and vascular risk factors, there was a significant association between the presence of CMB and poorer executive function. CMB were not associated with global cognition or other cognitive domains. On longitudinal analysis, after adjusting for demographics and vascular risk factors, there was a greater decline in visuospatial ability in those with CMB compared to those without. The presence of CMB was not associated with increased progression to dementia. CMB are associated with impairments in specific cognitive domains: executive function and decline in visuospatial ability, independent of other markers of CVD including white matter hyperintensities. This suggests a direct contribution of CMB to cognitive impairment although no significant difference in incident dementia rates was observed.
Research diagnostic criteria for drug-induced akathisia: conceptualization, rationale and proposal
Publisher: Springer Science and Business Media LLC
Date: 02-1994
DOI: 10.1007/BF02245462
Depression in mild cognitive impairment in a community sample of individuals 60–64 years old
Publisher: Cambridge University Press (CUP)
Date: 08-02-2006
Clinical Significance of Delirium With Catatonic Signs in Patients With Neurological Disorders
Publisher: American Psychiatric Association Publishing
Date: 04-2022
DOI: 10.1176/APPI.NEUROPSYCH.18120364
Abstract: According to DSM-5, catatonia and delirium are mutually exclusive clinical syndromes. The investigators explored the co-occurrence of delirium and catatonia (i.e., catatonic delirium) and the clinical significance of this syndrome with a s le of neurological patients. This prospective study with consecutive s ling included patients diagnosed with delirium at the National Institute of Neurology and Neurosurgery of Mexico. DSM-5 criteria for delirium, the Confusion Assessment Method, and the Delirium Rating Scale-Revised-98 were used to select and characterize patients. Catatonia was assessed using the Bush-Francis Catatonia Rating Scale and DSM-5 diagnostic criteria. Logistic regression analysis was performed to identify etiological factors associated with catatonic delirium. A total of 264 patients with delirium were included, 61 (23%) of whom fulfilled the criteria for catatonia and delirium simultaneously. Brain tumors, subarachnoid hemorrhage, acute hydrocephalus, and ischemic stroke were associated with delirium without catatonic signs. Catatonic delirium was observed among patients with encephalitis, epilepsy, brain neoplasms, and brain tuberculosis. After multivariate analysis, the association between catatonic delirium and encephalitis (both viral and anti- Delirium is a common complication of neurological diseases, and it can coexist with catatonia. The recognition of catatonic delirium has clinical significance in terms of etiology, as it was significantly associated with viral and anti-NMDAR encephalitis.
Mild cognitive impairment: a risk factor for injury in older people [Abstract PA 15-3-1767]
Publisher: BMJ Publishing Group Ltd
Date: 20-09-2018
Clinical and Neuroimaging Correlates of Mild Cognitive Impairment in a Middle-Aged Community Sample: The Personality and Total Health through Life 60+ Study
Publisher: S. Karger AG
Date: 15-12-2005
DOI: 10.1159/000089251
Abstract: This cross-sectional study aimed at determining the clinical and structural brain magnetic resonance imaging correlates of mild cognitive impairment (MCI). The data presented here are from the first wave of the longitudinal Personality and Total Health through Life 60+ project. 2,551 community-dwelling in iduals in the age range of 60–64 years were recruited randomly through the electoral roll. They were screened using Mini-Mental State Examination and a short cognitive battery. Those who screened positive underwent detailed medical and neuropsychological assessments. Of the 224 subjects who screened positive, 117 underwent a detailed assessment. Twenty-nine subjects fulfilled the Mayo Clinic criteria for MCI. Magnetic resonance imaging scans were analyzed for 26 subjects with MCI as well as normal controls. Subjects were clinically evaluated for depressive symptoms and major and minor depression syndromes. Logistic regression analysis was performed predicting MCI from anterior and mid-ventricular brain ratios, cortical atrophy measures, hippoc al volumes, volumes of amygdala and white matter hyperintensities after adjusting for age, gender, years of education, depression and physical disability. None of the neuroanatomical substrates appeared as predictors of MCI. The only predictors were higher depression scores and fewer years of education. Structural neuroimaging may not have an added advantage in the detection of MCI in middle-aged community-dwelling subjects. It may be that this age group is too young for such brain changes to be identified.
Magnetoencephalography in neuropsychiatry: ready for application?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2010
Plasma biomarkers for mild cognitive impairment and Alzheimer's disease
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.BRAINRESREV.2009.05.003
Abstract: With the move toward development of disease modifying treatments, there is a need for more specific diagnosis of early Alzheimer's disease (AD) and mild cognitive impairment (MCI), plasma biomarkers are likely to play an important role in this. We review the current state of knowledge on plasma biomarkers for MCI and AD, including unbiased proteomics and very recent longitudinal studies. With the use of proteomics methodologies, some proteins have been identified as potential biomarkers in plasma and serum of AD patients, including alpha-1-antitrypsin, complement factor H, alpha-2-macroglobulin, apolipoprotein J, apolipoprotein A-I. The findings of cross-sectional studies of plasma amyloid beta (A beta) levels are conflicting, but some recent longitudinal studies have shown that low plasma A beta 1-42 or A beta 1-40 levels, or A beta 1-42/A beta 1-40 ratio may be markers of cognitive decline. Other potential biomarkers for MCI and AD reflecting a variety of pathophysiological processes have been assessed, including isoprostanes and homocysteine (oxidative stress), total cholesterol and ApoE4 allele (lipoprotein metabolism), and cytokines and acute phase proteins (inflammation). A panel of 18 signal proteins was reported as markers of MCI and AD. A variety of potential plasma biomarkers for AD and MCI have been identified, however the findings need replication in longitudinal studies. This area of research promises to yield interesting results in the near future.
Homocysteine and Alzheimer disease: An intervention study
Publisher: Springer Science and Business Media LLC
Date: 2011
Self-Reported History of Chemotherapy and Cognitive Decline in Adults Aged 60 and Older: The PATH Through Life Project
Publisher: Oxford University Press (OUP)
Date: 24-12-2015
Abstract: There is a lack of data from cohort studies assessing cognitive function prior to and after chemotherapy. We evaluated the effect of self-reported cancer chemotherapy on cognitive function in a cohort assessed at baseline, 4 and 8 years. Participants were from the population-based PATH Through Life Study. Of the 2,551 participants aged 60-64 at baseline without cognitive impairment, 1,949 completed wave 3 and had data on cancer and chemotherapy and cognitive function. Linear mixed models were used to analyze the data. At wave 3, participants reporting history of chemotherapy (n = 76) had lower scores on memory, processing speed, and executive function compared with those reporting cancer without chemotherapy (n = 289) and no cancer history (n = 1508). After adjustment for depression and disability, effects remained for processing speed and memory. Chemotherapy prior to the study commencement (n = 24), but not between waves 1 and 3 (n = 81), was associated with greater decline in delayed recall (β = -.21 [95% CI -0.38, -.03], p = .02) and digits backwards β = -.05 [95% CI -0.09, -.01], p = .02) over 8 years compared with those with no cancer history (n = 1562). Women reporting chemotherapy for breast cancer after wave 1 (n = 26) had slower choice reaction time (-0.81 (95% CI -1.28, -0.34), p = .001) but did not decline faster on this measure compared with those reporting no breast cancer history (n = 818). Results suggest chemotherapy prior to old age is associated with faster decline in memory in late life but that it does not affect decline in other domains of cognitive function.
Recent findings from the Sydney Memory and Ageing Study (Sydney MAS)
Publisher: Wiley
Date: 07-2012
Genetics of microstructure of the corpus callosum in older adults
Publisher: Public Library of Science (PLoS)
Date: 16-12-2014
Correction: Grey Matter Correlates of Three Language Tests in Non-demented Older Adults
Publisher: Public Library of Science (PLoS)
Date: 17-01-2014
DOI: 10.1371/ANNOTATION/2E4D150F-C396-4867-B170-E43CCFF9FCD7
Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning
Publisher: Springer Science and Business Media LLC
Date: 16-08-2200
DOI: 10.1038/S41380-022-01710-8
Abstract: Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke ( N = 53,637). We identified novel loci in the intronic region of CDH18 , and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent s le. Functional and bioinformatic analyses supported many of these loci and further implicated POC1 . We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
A Critique of ‘Organic’ and its Proposed Alternatives
Publisher: SAGE Publications
Date: 04-1996
DOI: 10.3109/00048679609076090
Abstract: Objective: A critical examination of the term ‘organic’ in psychiatry and its proposed alternatives. Method: An examination of the published literature on the concepts of ‘organicity’ in mental syndromes, and of the mind-brain problem. Results: The term ‘organic’ presents a number of problems, some of which can be described as those of historical schism, duality, method, practice, scholasticism and semantics. The currently available alternatives are not without their difficulties, and ex les are provided. Conclusion: Whether the term ‘organic’ is retained or replaced, we are condemned to an unsatisfactory position while we await a radically new paradigm to understand the role of neurobiological and psychosocial factors in psychiatric disorders.
Sex differences in the causes and consequences of white matter hyperintensities
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.NEUROBIOLAGING.2007.08.023
Abstract: To examine sex differences in white matter hyperintensities (WMHs) on T2-weighted magnetic resonance imaging (MRI), reported to be more severe in older women. A random community s le of 228 men and 204 women, aged 60-64, underwent brain MRI scans. WMHs on T2-weighted FLAIR MRI scans were measured using an automated procedure. Subjects were assessed for physical health, cognitive function, vascular risk factors and Apolipoprotein E (APOE) genotyping. Women had more WMHs in both deep and periventricular regions. Hypertension, heart disease and high homocysteine were significant determinants in men and current smoking in women. Hormone replacement therapy and APOE*E4 allele did not have an association with WMHs. WMHs were related to reduced processing speed in men, and had an association with poor physical health and lowered grip strength in both sexes. WMHs are more common in women, with somewhat different putative causes and consequences than men, but >80% of the variance in their causation remains unexplained. The focus in the investigation of WMHs should move beyond the examination for cerebrovascular disease.
Savant-like skills exposed in normal people by suppressing the left fronto-temporal lobe.
Publisher: World Scientific Pub Co Pte Lt
Date: 12-2003
DOI: 10.1142/S0219635203000287
Abstract: The astonishing skills of savants have been suggested to be latent in everyone, but are not normally accessible without a rare form of brain impairment. We attempted to simulate such brain impairment in healthy people by directing low-frequency magnetic pulses into the left fronto-temporal lobe. Significant stylistic changes in drawing were facilitated by the magnetic pulses in four of our 11 participants. Some of these "facilitated" participants also displayed enhanced proofreading ability. Our conclusions are derived from 11 right-handed male university students, eight of whom underwent placebo stimulation. We examined performance before, during and after exposure to the stimulation.
Regional cerebral blood flow in late-onset schizophrenia: A SPECT study using 99mTc-HMPAO
Publisher: Elsevier BV
Date: 10-1997
DOI: 10.1016/S0920-9964(97)00088-1
Abstract: Functional neuroimaging studies have been performed in many young patients with schizophrenia, but late-onset schizophrenia (LOS) remains largely unexamined by these techniques. We predicted that LOS would demonstrate regional cerebral blood flow (rCBF) abnormalities similar to those seen in early-onset schizophrenia (EOS), but with a basis in demonstrable coarse brain disease. The subjects were 15 LOS and 7 EOS patients and 27 healthy controls. Each was given a detailed clinical and neuropsychological assessment and underwent MRI and Tc99m-HMPAO single photon emission computed tomography (SPECT) scans. The LOS subjects had a significantly lower cerebral hemispheric perfusion than controls, with a lower perfusion in the frontal and temporal lobes bilaterally. The LOS group also had significantly lower left-to-right hemisphere blood flow ratios. EOS subjects had a lower frontal perfusion than the controls, which was significant in the left frontal region. The temporal perfusion in the EOS subjects was greater than in the LOS group, and not different from the control subjects. Left temporal perfusion was the most discriminating variable between LOS and control subjects on logistic regression. Correlations of perfusion with MRI were generally low with the exception that the asymmetry indices were significantly correlated, and basal ganglia perfusion correlated with basal ganglia hyperintensities on MRI. The total cerebral perfusion index correlated significantly with the mini-mental state examination (MMSE) score, and the temporal lobe perfusion correlated with MMSE scores and some verbal memory measures. In the schizophrenic groups, perfusion correlated nonsignificantly with symptom profiles. We conclude that our findings of temporal and frontal rCBF abnormalities, especially on the left side, in LOS are similar to those reported in schizophrenia in general. The results do not provide evidence for coarse brain disease underlying the rCBF abnormalities in LOS, or support the specificity of these abnormalities for particular subsyndromes of schizophrenia.
The topography of white matter hyperintensities on brain MRI in healthy 60- to 64-year-old individuals
Publisher: Elsevier BV
Date: 05-2004
Exercise for Individuals with Lewy Body Dementia: A Systematic Review
Publisher: Public Library of Science (PLoS)
Date: 03-06-2016
Cortical responses to a graded working memory challenge predict functional decline in mild cognitive impairment
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.BIOPSYCH.2011.03.006
Abstract: Early detection of progressive cognitive decline offers an opportunity for preventative interventions with enormous public health implications. Functional neuroimaging during cognitive activity in in iduals at risk of dementia has the potential to advance this objective. In a prior study, we evaluated the utility of a novel functional magnetic resonance imaging paradigm that incorporated a graded working memory (WM) task to detect changes associated with mild cognitive impairment (MCI). We observed greater deactivation of posteromedial cortex (PMC) under conditions of increased WM load in MCI compared with control subjects. Our objective here is to test whether this paradigm can predict ensuing functional decline. Thirty in iduals with MCI who underwent baseline functional magnetic resonance image scanning were followed clinically for 2 years. Multiple linear regression analyses were used to determine whether deactivation in PMC under increased load at baseline independently predicted decline in instrumental activities of daily living (IADL). Greater deactivation in PMC to increased load predicted greater decline in IADL after controlling for baseline clinical severity, MCI subtype, apolipoprotein ε4 carrier status, gray matter, PMC and hippoc al volumes, and task performance. Increased deactivation observed at baseline was a harbinger of subsequent functional decline as measured by IADL in a cohort with MCI. This graded WM challenge may operate like a memory stress test by producing a threshold effect beyond which abnormal deactivation is elicited in MCI subjects who are at greatest risk of functional decline.
Long-term outcome of late-onset schizophrenia: 5-year follow-up study
Publisher: Royal College of Psychiatrists
Date: 09-2003
Abstract: There is controversy about whether late-onset schizophrenia is a precursor of cognitive decline. To examine the long-term outcome of a group of patients with late-onset schizophrenia. Patients with onset of DSM–III–R schizophrenia at age 50 years or over, but without dementia, and a healthy control group were assessed at baseline ( n =27 and n =34, respectively), after 1 year and after 5 years ( n =19 and n =24, respectively) on measures of psychopathology, cognition and general functioning, and compared on rates of decline and incidence of dementia. Nine patients with late-onset schizophrenia and none of the control group were found to have dementia (5 Alzheimer type, 1 vascular, 3 dementia of unknown type) at 5-year follow-up. There appeared to be a subgroup of late-onset schizophrenia patients without signs of dementia at baseline or at 1 year follow-up who subsequently declined. Late-onset schizophrenia may be a prodrome of Alzheimer-type dementia. More longitudinal studies are required to determine its nosological status.
Classification of Neurocognitive Disorders in DSM-5: A Work in Progress
Publisher: Elsevier BV
Date: 03-2011
NAD+ metabolism, and oxidative stress in the brain of aging Wistar rats: Is there a link?
Publisher: Wiley
Date: 07-2012
Geriatric psychiatry research in Australia
Publisher: Elsevier BV
Date: 06-2007
P2‐335: To what extent does cognitive and functional decline in older persons affect the psychological well‐being of cohabiting family members?
Publisher: Wiley
Date: 07-2012
P1‐247: Associations between APOE ε4 and Instrumental Daily Activities of Living in A Community Sample of Older Adults
Publisher: Wiley
Date: 07-2011
Neural stem cell therapy for neuropsychiatric disorders
Publisher: Cambridge University Press (CUP)
Date: 02-2007
DOI: 10.1111/J.1601-5215.2007.00176.X
Abstract: To conduct a comprehensive literature review of the area of neural stem cells and neuropsychiatry. ‘Neural stem cells’ (NSCs) and ‘neurogenesis’ were used as keywords in Medline (1966 – November 2006) to identify relevant papers in the areas of Alzheimer’s disease (AD), depression, schizophrenia and Parkinson’s disease (PD). This list was supplemented with papers from reference lists of seminal reviews. The concept of a ‘stem cell’ continues to evolve and is currently defined by operational criteria related to symmetrical renewal, multipotency and functional viability. In vivo adult mammalian neurogenesis occurs in discrete niches in the subventricular and subgranular zones – however, functional precursor cells can be generated in vitro from a wide variety of biological sources. Both artificial and physiological microenvironment is therefore critical to the characteristics and behaviour of neural precursors, and it is not straightforward how results from the laboratory can be extrapolated to the living organism. Transplant strategies in PD have shown that it is possible for primitive neural tissue to engraft into neuropathic brain areas, become biologically functional and lead to amelioration of clinical signs and symptoms. However, with long-term follow-up, significant problems related to intractable side-effects and potential neoplastic growth have been reported. These are therefore the potentials and pitfalls for NSC technology in neuropsychiatry. In AD, the physiology of amyloid precursor protein may directly interact with NSCs, and a role in memory function has been speculated. The role of endogenous neurogenesis has also been implicated in the etiology of depression. The significance of NSCs and neurogenesis for schizophrenia is still emerging. There are a number of technical and conceptual challenges ahead before the promise of NSCs can be harnessed for the understanding and treatment of neuropsychiatric disorders. Further research into fundamental NSC biology and how this interacts with the neuropsychiatric disease processes is required.
Body mass index and waist circumference predict health-related quality of life, but not satisfaction with life, in the elderly
Publisher: Springer Science and Business Media LLC
Date: 07-06-2018
DOI: 10.1007/S11136-018-1904-6
Abstract: While obesity has been linked with lower quality of life in the general adult population, the prospective effects of present obesity on future quality of life amongst the elderly is unclear. This article investigates the cross-sectional and longitudinal relationships between obesity and aspects of quality of life in community-dwelling older Australians. A 2-year longitudinal s le of community dwellers aged 70-90 years at baseline, derived from the Sydney Memory and Ageing Study (MAS), was chosen for the study. Of the 1037 participants in the original MAS s le, a baseline (Wave 1) s le of 926 and a 2-year follow-up (Wave 2) s le of 751 subjects were retained for these analyses. Adiposity was measured using body mass index (BMI) and waist circumference (WC). Quality of life was measured using the Assessment of Quality of Life (6 dimensions) questionnaire (AQoL-6D) as well as the Satisfaction with Life Scale (SWLS). Linear regression and analysis of covariance (ANCOVA) were used to examine linear and non-linear relationships between BMI and WC and measures of health-related quality of life (HRQoL) and satisfaction with life, adjusting for age, sex, education, asthma, osteoporosis, depression, hearing and visual impairment, mild cognitive impairment, physical activity, and general health. Where a non-linear relationship was found, established BMI or WC categories were used in ANCOVA. Greater adiposity was associated with lower HRQoL but not life satisfaction. Regression modelling in cross-sectional analyses showed that higher BMI and greater WC were associated with lower scores for independent living, relationships, and pain (i.e. worse pain) on the AQoL-6D. In planned contrasts within a series of univariate analyses, obese participants scored lower in independent living and relationships, compared to normal weight and overweight participants. Longitudinal analyses found that higher baseline BMI and WC were associated with lower independent living scores at Wave 2. Obesity is associated with and predicts lower quality of life in elderly adults aged 70-90 years, and the areas most affected are independent living, social relationships, and the experience of pain.
Linking self-perceived cognitive functioning questionnaires using item response theory: The subjective cognitive decline initiative.
Publisher: American Psychological Association (APA)
Date: 05-2023
DOI: 10.1037/NEU0000888
Design and Development of the Brain Training System for the Digital “Maintain Your Brain” Dementia Prevention Trial (Preprint)
Publisher: JMIR Publications Inc.
Date: 2019
Abstract: ementia is the leading cause of disability worldwide, and interventions aimed at reducing the prevalence and burden of the disease are urgently needed. Maintain Your Brain (MYB) is a randomized controlled trial of a multimodal digital health intervention targeting modifiable dementia risk factors to combat cognitive decline and potentially prevent dementia. In addition to behavioral modules targeting mood, nutrition, and physical exercise, a new Brain Training System (BTS) will deliver computerized cognitive training (CCT) throughout the trial to provide systematic, challenging, and personally adaptive cognitive activity. his paper aimed to describe the design and development of BTS. TS has been designed with a central focus on the end user. Raw training content is provided by our partner NeuroNation and delivered in several innovative ways. A baseline cognitive profile directs selection and sequencing of exercises within and between sessions and is updated during the 10-week 30-session module. Online trainers are available to provide supervision at different levels of engagement, including face-to-face share-screen coaching, a key implementation resource that is triaged by a “red flag” system for automatic tracking of user adherence and engagement, or through user-initiated help requests. In idualized and comparative feedback is provided to aid motivation and, for the first time, establish a social support network for the user based on their real-world circle of friends and family. he MYB pilot was performed from November 2017 to March 2018. We are currently analyzing data from this pilot trial (n=100), which will make up a separate research paper. The main trial was launched in June 2018. Process and implementation data from the first training module (September to November 2018) are expected to be reported in 2019 and final trial outcomes are anticipated in 2022. he BTS implemented in MYB is focused on maximizing adherence and engagement with CCT over the short and long term in the setting of a fully digital trial, which, if successful, could be delivered economically at scale. ustralian New Zealand Clinical Trials Registry ACTRN12618000851268 www.anzctr.org.au /Trial/Registration/TrialReview.aspx?id=370631& isReview=true
Genome-wide study of DNA methylation in Amyotrophic Lateral Sclerosis identifies differentially methylated loci and implicates metabolic, inflammatory and cholesterol pathways
Publisher: Cold Spring Harbor Laboratory
Date: 24-03-2021
DOI: 10.1101/2021.03.12.21253115
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability of around 50%. DNA methylation patterns can serve as biomarkers of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study (EWAS) meta-analysis in 10,462 s les (7,344 ALS patients and 3,118 controls), representing the largest case-control study of DNA methylation for any disease to date. We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We show that DNA-methylation-based proxies for HDL-cholesterol, BMI, white blood cell (WBC) proportions and alcohol intake were independently associated with ALS. Integration of these results with our latest GWAS showed that cholesterol biosynthesis was causally related to ALS. Finally, we found that DNA methylation levels at several DMPs and blood cell proportion estimates derived from DNA methylation data, are associated with survival rate in patients, and could represent indicators of underlying disease processes.
The role of epigenetics in cognitive ageing.
Publisher: Wiley
Date: 07-08-2014
DOI: 10.1002/GPS.4183
Abstract: As the population is ageing, a better understanding of the underlying causes of age-related cognitive decline (cognitive ageing) is required. Epigenetic dysregulation is proposed as one of the underlying mechanisms for cognitive ageing. We review the current knowledge on epigenetics and cognitive ageing and appraise the potential of epigenetic preventative and therapeutic interventions. Articles on cognitive ageing and epigenetics in English were identified. Epigenetic dysregulation occurs with cognitive ageing, with changes in histone post-translational modifications, DNA methylation and non-coding RNA reported. However, human studies are lacking, with most being cross-sectional using peripheral blood s les. Pharmacological and lifestyle factors have the potential to change aberrant epigenetic profiles but few studies have examined this in relation to cognitive ageing. The relationship between epigenetic modifications and cognitive ageing is only beginning to be investigated. Epigenetic dysregulation appears to be an important feature in cognitive ageing, but whether it is an epiphenomenon or a causal factor remains to be elucidated. Clarification of the relationship between epigenetic profiles of different cell types is essential and would determine whether epigenetic marks of peripheral tissues can be used as a proxy for changes occurring in the brain. The use of lifestyle and pharmacological interventions to improve cognitive performance and quality of life of older adults needs more investigation.
Schizophrenia-like psychosis following traumatic brain injury.
Publisher: American Psychiatric Association Publishing
Date: 11-2001
DOI: 10.1176/JNP.13.4.533
Is it time to retire the term dementia?
Publisher: American Psychiatric Association Publishing
Date: 05-2000
DOI: 10.1176/JNP.12.2.276
Risk Factors for Late-Life Cognitive Decline and Variation with Age and Sex in the Sydney Memory and Ageing Study
Publisher: Public Library of Science (PLoS)
Date: 14-06-2013
Restlessness: The Anatomy of a Neuropsychiatric Symptom
Publisher: SAGE Publications
Date: 02-1996
DOI: 10.3109/00048679609076071
Abstract: Objective: The aim of the paper is to review the literature on restlessness and related syndromes in order to examine the different causes and clinical descriptions, and to present a pathogenetic model that would incorporate its erse aetiology. Method: A literature search was undertaken with restlessness, agitation, akathisia, hyperactivity, fidgetiness and jitteriness as key words. Results: Causes of restlessness are erse, and its distinction from other descriptions, such as agitation and hyperactivity, is poorly defined in the literature. Detailed descriptions of the syndromes are therefore lacking. The neuroanatomical basis of restlessness may consist of abnormalities in the corticc-subcortical neuronal circuits, the complex regulation of which may explain why different causes often lead to a common end result. Conclusions: The terms used to describe restlessness and related disorders should be standardised, and the clinical manifestations investigated pedanti- cally. Human and animal studies should investigate the pathophysiology so that intervention can be based on the underlying mechanisms.
1H MRS in stroke patients with and without cognitive impairment
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.NEUROBIOLAGING.2004.07.008
Abstract: The pathophysiological basis of cognitive impairment in patients with cerebrovascular disease (CVD) is not well understood, particularly in relation to the role of non-infarction ischemic change and associated Alzheimer-type pathology. We used single voxel 1H MRS to determine the differences in brain neurometabolites in non-infarcted frontal white matter and occipito-parietal gray matter of 48 stroke patients with or without cognitive impairment and 60 elderly controls. The results showed that there were no significant neurometabolite differences between the stroke cohort and healthy elderly controls, but there was a difference in NAA/H2O between the stroke patients that had cognitive impairment (vascular dementia (VaD) and vascular cognitive impairment (VCI)) compared with those patients with no impairment. This was significant in the occipito-parietal gray matter, but not in the frontal white matter, although the results were in the same direction for the latter. This suggests that cognitive impairment in stroke patients may be related to cortical neuronal dysfunction rather than purely subcortical change. Moreover, cortical regions not obviously infarcted may have dysfunctional neurons, the pathophysiological basis for which needs further study.
Muscle Strength Is Impaired In Peripheral Arterial Disease And Predicts Flat Ground Walking Ability.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
To know or not to know: an update of the literature on the psychological and behavioral impact of genetic testing for Alzheimer disease risk.
Publisher: Mary Ann Liebert Inc
Date: 08-2012
Abstract: Alzheimer disease (AD) is a genetically heterogenous disorder in rare cases autosomal dominantly inherited mutations typically cause early-onset familial AD (EOAD), whereas the risk for late-onset AD (LOAD) is generally modulated by genetic variants with relatively low penetrance but high prevalence, with variants in apolipoprotein E (APOE) being a firmly established risk factor. This article presents an overview of the current literature on the psychological and behavioral impact of genetic testing for AD. The few studies available for presymptomatic testing for EOAD showed that only a very small proportion of in iduals had poor psychological outcomes as a result. Initial interest in testing for EOAD decreases significantly after identification of a specific mutation in a kindred, suggesting that interest and potential for knowledge may not translate into actual testing uptake. The majority of in iduals from both the general population and those with a family history of AD had positive attitudes towards, and were interested in, susceptibility testing for APOE. Motivations for genetic testing included to provide information for future planning and to learn about one's own and one's children's risks of developing AD. Although susceptibility testing for APOE genotype is not currently recommended due to the lack of clinical utility, this review demonstrates that there is interest in testing and no obvious adverse psychological effects to those who have been tested.
Novel physical treatments for the management of neuropsychiatric disorders
Publisher: Elsevier BV
Date: 08-2002
Is deep brain stimulation a form of psychosurgery?
Publisher: SAGE Publications
Date: 04-2007
DOI: 10.1080/10398560601148333
Abstract: Objective: To examine the potential for the experimental treatment of deep brain stimulation for neuropsychiatric disorders, and to debate the argument that it should be considered another form of psychosurgery. Conclusions: Psychosurgery is an old term with considerable pejorative connotations. It should be replaced with the more descriptive and accurate ‘neurosurgery for psychiatric disorders’. Moreover, neurosurgery should reflect ablative neurosurgery, and surgery for brain stimulation should be categorised as brain stimulation rather than neurosurgery, or indeed psychosurgery. This will prevent legislative restrictions on the development of brain stimulation techniques and not tar them with the lobotomy brush.
Integrity of the grey/white matter border is associated with cognitive performance in ageing: The PATH Through Life Project.
Publisher: Frontiers Media SA
Date: 2015
High Normal Blood Glucose Is Associated with Decreased Brain Volume and Cognitive Performance in the 60s: The PATH through Life Study
Publisher: Public Library of Science (PLoS)
Date: 04-09-2013
Hormone replacement therapy, brain volumes and white matter in postmenopausal women aged 60-64 years
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-01-2006
DOI: 10.1097/01.WNR.0000194385.10622.8E
Abstract: Research on the structural and functional effects of hormone replacement therapy on the brain has produced inconsistent results. This paper reports on cross-sectional associations between hormone replacement therapy use and volumes of brain structures measured using magnetic resonance imaging in 213 postmenopausal women aged 60-64 years recruited from a large population study. Of these, 64 were current hormone replacement therapy users, 69 previous users and 80 had never used hormone replacement therapy. No differences were observed between groups in total grey matter, white matter, hippoc al or amygdalar volumes, severity or volume of white matter hyperintensities, or in different measures of brain atrophy. While acknowledging the limitations of a cross-sectional study, the results argue against hormone replacement therapy being protective against brain changes associated with ageing in women in their early 60s.
Alginate microcapsule as a 3D platform for the efficient differentiation of human embryonic stem cells to dopamine neurons
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.SCR.2013.06.005
Abstract: Human embryonic stem cells (hESCs) are emerging as an attractive alternative source for cell replacement therapy since the cells can be expanded in culture indefinitely and differentiated into any cell types in the body. In order to optimize cell-to-cell interaction, cell proliferation and differentiation into specific lineages as well as tissue organization, it is important to provide a microenvironment for the hESCs which mimics the stem cell niche. One approach is to provide a three-dimensional (3D) environment such as encapsulation. We present an approach to culture and differentiate hESCs into midbrain dopamine (mdDA) neurons in a 3D microenvironment using alginate microcapsules for the first time. A detailed gene and protein expression analysis during neuronal differentiation showed an increased gene and protein expression of various specific DA neuronal markers, particularly tyrosine hydroxylase (TH) by >100 folds after 2 weeks and at least 50% higher expression after 4 weeks respectively, compared to cells differentiated under conventional two-dimensional (2D) platform. The encapsulated TH(+) cells co-expressed mdDA neuronal markers, forkhead box protein A-2 (FOXA2) and pituitary homeobox-3 (PITX3) after 4 weeks and secreted approximately 60pg/ml/10(6) cells higher DA level when induced. We propose that the 3D platform facilitated an early onset of DA neuronal generation compared to that with conventional 2D system which also secretes more DA under potassium-induction. It is a very useful model to study the proliferation and directed differentiation of hESCs to various lineages, particularly to mdDA neurons. This 3D system also allows the separation of feeder cells from hESCs during the process of differentiation and also has potential for immune-isolation during transplantation studies.
ICC-dementia (International Centenarian Consortium - dementia): an international consortium to determine the prevalence and incidence of dementia in centenarians across diverse ethnoracial and sociocultural groups.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2016
Co-expression network analysis of peripheral blood transcriptome identifies dysregulated protein processing in endoplasmic reticulum and immune response in recurrent MDD in older adults
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JPSYCHIRES.2018.09.017
Abstract: The molecular factors involved in the pathophysiology of major depressive disorder (MDD) remain poorly understood. One approach to examine the molecular basis of MDD is co-expression network analysis, which facilitates the examination of complex interactions between expression levels of in idual genes and how they influence biological pathways affected in MDD. Here, we applied an unsupervised gene-network based approach to a prospective experimental design using microarray genome-wide gene expression from the peripheral whole blood of older adults. We utilised the Sydney Memory and Ageing Study (sMAS, N = 521) and the Older Australian Twins Study (OATS, N = 186) as discovery and replication cohorts, respectively. We constructed networks using Weighted Gene Co-expression Network Analysis (WGCNA), and correlated identified modules with four subtypes of depression: single episode, current, recurrent, and lifetime MDD. Four modules of highly co-expressed genes were associated with recurrent MDD (N = 27) in our discovery cohort (FDR<0.2), with no significant findings for a single episode, current or lifetime MDD. Functional characterisation of these modules revealed a complex interplay between dysregulated protein processing in the endoplasmic reticulum (ER), and innate and adaptive immune response signalling, with possible involvement of pathogen-related pathways. We were underpowered to replicate findings at the network level in an independent cohort (OATS), however we found a significant overlap for 9 in idual genes with similar co-expression and dysregulation patterns associated with recurrent MDD in both cohorts. Overall, our findings support other reports on dysregulated immune response and protein processing in the ER in MDD and provide novel insights into the pathophysiology of depression.
Koro epidemic in north-east India
Publisher: SAGE Publications
Date: 12-1985
DOI: 10.1080/00048678509158852
Abstract: Koro is an unusual psychogenic syndrome reported, until recently, predominantly in men of the Chinese race who live in southern China and south-east Asia. Issues concerning its phenomenology, diagnosis and nosology are still controversial. This paper describes an epidemic of koro in north-east India. A psychiatric analysis of thirty-one cases is presented. Probable reasons for the rapid spread of the illness are discussed. The majority of the in iduals affected were from the lower socio-economic strata, were poorly educated and in the age group of 20–40 years. Many women were affected. There was no evidence of significant premorbid or sexual psychopathology in most cases. Some patients had a number of episodes but with only minor residual symptoms. The author compares these findings with earlier reports and discusses the implications for its nosology and psychodynamics.
Authors' reply
Publisher: Royal College of Psychiatrists
Date: 08-2005
Differentiation of Alzheimer’s disease based on local and global parameters in personalized Virtual Brain models
Publisher: Cold Spring Harbor Laboratory
Date: 08-03-2018
DOI: 10.1101/277624
Abstract: Alzheimer’s disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. In idual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, “The Virtual Brain (TVB)”, based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with in idual differences in cognition. In particular, we modeled in idual resting-state functional activity of 124 in iduals across the behavioral spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.
The value of the metabolic syndrome concept in elderly adults: Is it worth less than the sum of its parts?
Publisher: Wiley
Date: 06-08-2012
DOI: 10.1111/J.1532-5415.2012.04105.X
Abstract: To determine whether the metabolic syndrome (MetS) or its components were more closely associated with disease states and inflammation in elderly adults. Sydney Memory and Ageing Study. Cross-sectional, observational cohort. Population-derived, community-dwelling elderly adults. Nine hundred thirty in iduals aged 70 to 90. Age- and sex-adjusted odds ratios (ORs) for disease states fasting circulating inflammatory markers and oxidative metabolism byproducts. MetS was associated with diabetes mellitus (OR = 4.1, P < .001) and bowel cancer (OR = 9.1, P = .03) but not in analyses that controlled for component conditions. Models containing component conditions had the strongest associations with heart disease. Disease associations were improved after addition of component conditions to the MetS model. The reverse did not hold: disease associations were not improved when MetS was added to the components model. Low high-density lipoprotein cholesterol (HDL-C) was independently associated with myocardial infarction (OR = 2.32) and angina pectoris (OR = 2.59) (both P < .008). Waist circumference was independently associated with cancer (OR = 1.82, P = .008). Although MetS was associated with higher C-reactive protein, vascular cell adhesion molecule, interleukin-6, amyloid A, homocysteine, and malondialdehyde, it explained less than half of the variance of models containing its components. The observation that MetS is associated with disease states and markers of circulating inflammation in the elderly is explained mainly by abdominal obesity and low HDL-C. Longitudinal data will further clarify these cross-sectional findings that MetS appears to be less than the sum of its parts in elderly adults.
Differential Brain Effects of Laser and Needle Acupuncture at Lr8 Using Functional Mri
Publisher: SAGE Publications
Date: 09-2013
DOI: 10.1136/ACUPMED-2012-010297
Abstract: While needle acupuncture is a well-accepted technique, laser acupuncture is being increasingly used in clinical practice. The differential effects of the two techniques are of interest. We examine this in relation to brain effects of activation of LR8, a putative acupuncture point for depression, using functional MRI (fMRI). Sixteen healthy participants were randomised to receive low intensity laser acupuncture to LR8 on one side and needle acupuncture to the contralateral LR8. Stimulation was in an on-off block design and brain patterns were recorded under fMRI. Significant activation occurred in the left precuneus during laser acupuncture compared with needle acupuncture and significant activation occurred in the left precentral gyrus during needle acupuncture compared with laser acupuncture. Laser and needle acupuncture at LR8 in healthy participants produced different brain patterns. Laser acupuncture activated the precuneus relevant to mood in the posterior default mode network while needle acupuncture activated the parietal cortical region associated with the primary motor cortex. Further investigations are warranted to evaluate the clinical relevance of these effects.
Is intraindividual reaction time variability an independent cognitive predictor of mortality in old age? Findings from the Sydney Memory and Ageing Study
Publisher: Public Library of Science (PLoS)
Date: 09-08-2017
Vascular dementia as a frontal subcortical system dysfunction
Publisher: Cambridge University Press (CUP)
Date: 09-2000
DOI: 10.1017/S003329179900269X
Abstract: Vascular dementia (VaD) is the second most common subtype of dementia in Western countries (Desmond, 1996) and, overall, may be the most common subtype of dementia in the world (Henderson, 1994). Furthermore, the recognition of some major risk factors of cerebrovascular disease makes VaD a form of ‘preventable senility’ (Hachinski, 1992). The last decade has seen a major re-evaluation of the concept of VaD (Erkinjuntti & Hachinski, 1993 Hachinski, 1994), with new diagnostic criteria having been proposed (World Health Organization, 1993 American Psychiatric Association, 1994) but without any consensus (Wetterling et al . 1996). Indeed, some investigators have called for the abandonment of the diagnosis of VaD and the adoption of alternative nosology (Hachinski, 1994). It is therefore time to re-examine the concept of VaD and evaluate its distinctive features.
Clinical characteristics of 15 patients with tardive dystonia
Publisher: American Psychiatric Association Publishing
Date: 03-1993
Abstract: Clinical characteristics of 15 consecutively referred patients with tar e dystonia are reported. The onset of tar e dystonia occurred in all age groups and in both sexes, with some preponderance in men. There was considerable overlap with tar e dyskinesia and tar e akathisia. Six subjects reported past acute dystonia, and four had histories of essential tremor, suggesting a vulnerability to the development of dystonia.
Uptake and mitochondrial dysfunction of alpha-synuclein in human astrocytes, cortical neurons and fibroblasts
Publisher: Springer Science and Business Media LLC
Date: 04-10-2013
Abstract: The accumulation and aggregation of alpha-synuclein (α-syn) in several tissue including the brain is a major pathological hallmark in Parkinson’s disease (PD). In this study, we show that α-syn can be taken up by primary human cortical neurons, astrocytes and skin-derived fibroblasts in vitro . Our findings that brain and peripheral cells exposed to α-syn can lead to impaired mitochondrial function, leading to cellular degeneration and cell death, provides additional evidence for the involvement of mitochondrial dysfunction as a mechanism of toxicity of α-syn in human cells.
Depressive symptoms increase fall risk in older people, independent of antidepressant use, and reduced executive and physical functioning
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.ARCHGER.2014.09.003
Abstract: Depressive symptoms and antidepressant use are associated with greater fall risk in older people. This prospective study investigated interactions between depressive symptoms, antidepressant use and physical and cognitive function measures in relation to injurious or multiple falls in a large s le of community-living older people. Four-hundred and eighty-eight community-dwelling older people aged 70 years and over, underwent a comprehensive psychological, cognitive and physiological assessment and were prospectively monitored for falls over a 12-month follow up period. Substantial depressive symptoms were defined by a Geriatric Depression Scale (GDS) (15-item) score ≥5 and fallers were defined as people who had at least one injurious or two non-injurious falls during follow-up. In univariate analyses, the presence of depressive symptoms (RR=1.50 95% CI=1.06-2.11), antidepressant use (RR=1.56 95% CI=1.08-2.27), high physiological fall risk (RR=1.61 95% CI=1.20-2.15) and poorer executive functioning (RR=1.40 95% CI=1.05-1.88) were significant risk factors for falls. Multivariate models revealed that depressive symptomatology and antidepressant use were independent of each other, and independent of the presence of a high physiological fall risk and poorer executive functioning in the prediction of falls. Fall risk increased with the number of risk factors present: i.e. by 55% in participants with any two risk factors (RR=1.55 95% CI=1.17-2.04) and by 144% in participants with three or four risk factors (RR=2.44 95% CI=1.75-3.43). The study findings indicate that higher depressive symptoms and antidepressant use predict falls over 12-months, independent of reduced executive and physical functioning. Treatment of depressive symptoms using non-pharmacological approaches should be considered as part of fall prevention programs, especially in populations at high risk of falls.
Inhibition of indoleamine 2,3 dioxygenase activity by H2O2
Publisher: Elsevier BV
Date: 06-2006
DOI: 10.1016/J.ABB.2006.03.003
Abstract: Indoleamine 2,3-dioxygenase is the first and rate limiting enzyme of the kynurenine pathway of tryptophan metabolism, has potent effects on cell proliferation and mediates antimicrobial, antitumorogenic, and immunosuppressive effects. As a potent cytotoxic effector, the mechanisms of indoleamine 2,3-dioxygenase inhibition deserve greater attention. The work presented here represents the first systematic study exploring the mechanisms by which low levels of hydrogen peroxide (10-100 microM) inhibit indoleamine 2,3-dioxygenase in vitro. Following brief peroxide exposure both enzyme inhibition and structural changes were observed. Loss of catalysis was accompanied by oxidation of several cysteine residues to sulfinic and sulfonic acids, observed by electrospray and MALDI mass spectrometry. Enzyme activity could in part be preserved in the presence of sulfhydryl containing compounds, particularly DTT and methionine. However, these structural alterations did not prevent substrate (l-tryptophan) binding. Some enzyme activity could be recovered in the presence of thioredoxin, indicating that the inhibitory effect of H(2)O(2) is at least partially reversible in vitro. We present evidence that cysteine oxidation represents one mechanism of indoleamine 2,3-dioxygenase inhibition.
Regional Gray Matter Volumes Are Related to Concern About Falling in Older People: A Voxel-Based Morphometric Study
Publisher: Oxford University Press (OUP)
Date: 02-2015
Abstract: Concern about falling is common in older people. Various related psychological constructs as well as poor balance and slow gait have been associated with decreased gray matter (GM) volume in old age. The current study investigates the association between concern about falling and voxel-wise GM volumes. A total of 281 community-dwelling older people aged 70-90 years underwent structural magnetic resonance imaging. Concern about falling was assessed using Falls Efficacy Scale-International (FES-I). For each participant, voxel-wise GM volumes were generated with voxel-based morphometry and regressed on raw FES-I scores (p < .05 family-wise error corrected on cluster level). FES-I scores were negatively correlated with total brain volume (r = -.212 p ≤ .001), GM volume (r = -.210 p ≤ .001), and white matter volume (r = -.155 p ≤ .001). Voxel-based morphometry analysis revealed significant negative associations between FES-I and GM volumes of (i) left cerebellum and bilateral inferior occipital gyrus (voxels-in-cluster = 2,981 p < .001) and (ii) bilateral superior frontal gyrus and left supplementary motor area (voxels-in-cluster = 1,900 p = .004). Additional adjustment for vision and physical fall risk did not alter these associations. After adjustment for anxiety, only left cerebellum and bilateral inferior occipital gyrus remained negatively associated with FES-I scores (voxels-in-cluster = 2,426 p < .001). Adjustment for neuroticism removed all associations between FES-I and GM volumes. Our study findings show that concern about falling is negatively associated with brain volumes in areas important for emotional control and for motor control, executive functions and visual processing in a large s le of older men and women. Regression analyses suggest that these relationships were primarily accounted for by psychological factors (generalized anxiety and neuroticism) and not by physical fall risk or vision.
Differentiation of Alzheimer's disease based on local and global parameters in personalized Virtual Brain models
Publisher: Elsevier BV
Date: 2018
Severe depression masquerading as Creutzfeldt-Jakob disease
Publisher: BMJ
Date: 19-04-2014
Oral Health and Cognitive Function in Older Adults: A Systematic Review
Publisher: S. Karger AG
Date: 2019
DOI: 10.1159/000496730
Abstract: b i Background: /i /b It has often been argued that there is a relationship between oral health and cognitive decline in late adulthood, but a recent systematic review concluded that it was unclear “how or whether” any relationship exists. However, most of the studies that contributed to this review operationalised cognitive function using a brief cognitive screen and/or dementia status. b i Objective: /i /b An updated systematic review was conducted that focused on how oral health relates to specific cognitive abilities in older adults (specifically, the neurocognitive domains specified in the DSM-5: learning and memory, perceptual motor function, language, executive function, complex attention, and social cognition). b i Methods: /i /b A systematic review was undertaken and completed in August 2018. From a total of 1,304 potentially relevant articles, 23 were identified that assessed oral health and at least one of the specific cognitive domains in an older adult cohort. b i Results: /i /b The most consistent relationships were identified with learning and memory, complex attention, and executive function. For each of these cognitive domains, most studies identified significant unadjusted associations with oral health where adjustments for covariates were made, at least one of the associations with oral health remained significant in half or more of the studies. Results were less clear for the domains of language and perceptual motor function. No study assessed the relationship between social cognition and oral health. b i Conclusions: /i /b This systematic review provides evidence of an association between learning and memory, complex attention, and executive function with oral health in old age. Gaining a detailed picture of how specific types of cognitive decline relate to oral health has potential implications for earlier identification of older adults who experience oral health problems, and may also inform the development of more effective interventions focused on enhancing oral health outcomes in this group.
Visual memory tests enhance the identification of amnestic MCI cases at greater risk of Alzheimer’s disease
Publisher: Cambridge University Press (CUP)
Date: 25-10-2018
DOI: 10.1017/S104161021800145X
Abstract: To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer’s disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests. 4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and in idual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates. All aMCI groups ( n = 760) had a greater risk-AD than NC ( n = 4,011 HR range = 3.66 – 9.25). The risk-AD was not different between visual ( n = 208, 17 converters) and verbal aMCI ( n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI ( n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs . NC. Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI.
The association between pulse wave velocity and cognitive function: the Sydney Memory and Ageing Study
Publisher: Public Library of Science (PLoS)
Date: 30-04-2013
Metabolic burden and disease and mortality risk associated with impaired fasting glucose in elderly adults
Publisher: Wiley
Date: 07-2015
DOI: 10.1111/JGS.13482
Abstract: To examine whether impaired fasting glucose (IFG) represents an intermediary condition between normal fasting glucose and diabetes mellitus and, specifically, whether elderly adults with IFG have higher disease burden, cardiovascular risk, and systemic inflammation and higher 2-year mortality and incident disease. Prospective observational study. Population-derived cohort. In iduals with a mean age of 78.6 ± 4.7 (N = 945). Disease was ascertained using a standardized questionnaire at baseline and 2 years. Fasting metabolic, inflammatory, and oxidative metabolism markers were measured. Disease prevalence, cardiovascular risk, and biochemical markers were compared to determine disease burden and metabolic disturbances in IFG. Adjusted odds ratios (ORs) for 2-year all-cause mortality and incident disease were determined. IFG prevalence was 41%. In iduals with IFG had higher baseline rates of heart disease than those with normal fasting glucose (NFG), similar to that in in iduals with diabetes mellitus. IFG was characterized by higher inflammatory markers and oxidative metabolism end products and was an intermediary between NFG and diabetes mellitus for triglycerides and malondialdehyde. Discriminant analysis showed that IFG was independently associated with stroke and higher triglycerides and oxidative stress. Two-year all-cause mortality was 3.9%. The 2-year adjusted ORs for all-cause mortality, incident cardiac disease, stroke, and cancer were similar between IFG and NFG, using both American Diabetes Association and World Health Organization IFG criteria. IFG did not predict secondary cardiac events, stroke, or cancer. IFG was an intermediary condition for heart disease, inflammation, and oxidative stress in elderly adults but not for 2-year incident disease or all-cause mortality. Longer-term prospective studies are needed to clarify whether IFG in elderly adults portends greater morbidity and mortality.
The audiogenic startle reflex in Tourette's syndrome
Publisher: Elsevier BV
Date: 04-1997
DOI: 10.1016/S0006-3223(96)00101-1
Abstract: We report the first ex le of selective Pd
Brain White Matter Hyperintensities, Executive Dysfunction, Instability, and Falls in Older People: A Prospective Cohort Study
Publisher: Oxford University Press (OUP)
Date: 08-03-2012
Abstract: White matter hyperintensities (WMHs) are associated with fall risk factors in older people including reduced cognitive functioning and impaired balance and gait. This prospective study investigated relationships between WMHs, sensorimotor performance, executive functioning, and falls in a large s le of community-living older people. Two hundred and eighty-seven community-dwelling people aged 70-90 years, underwent structural magnetic resonance imaging and assessments of executive function (Trail-Making Tests), sensorimotor performance (Physiological Profile Assessment), and prospective monitoring of falls. Total WMH volume was quantified using an automated method. Fallers were defined as people who had at least one injurious or two noninjurious falls during the 12-month follow-up period. Participants with severe WMH burden (WMH volumes as a percentage of intracranial volume in the fourth quartile) performed poorly in the Trail-Making Test and Physiological Profile Assessment (p < .05) and had an increased risk of falls during the 12-month follow-up (relative risk = 1.63, 95% confidence interval 1.11-2.40). The association between WMHs and falls was little changed after adjusting for Trail-Making Test and Physiological Profile Assessment scores, age, sex, education, and a range of cardiovascular risk factors (relative risk = 1.55, 95% confidence interval 1.06-2.26). Greater WMH burden predicts falls over 12 months, and the association between greater burden of WMHs and falls appears to be independent of reduced executive function and sensorimotor performance. Strategies to reduce the development and progression of WMHs may contribute to future falls prevention in older people.
Age Progression of Neuropathological Markers in the Brain of the Chilean Rodent Octodon degus, a Natural Model of A lzheimer's Disease
Publisher: Wiley
Date: 10-02-2015
DOI: 10.1111/BPA.12226
Clozapine-Induced Increase in Plasma Levels of Soluble Interleukin-2 Receptors-Reply
Publisher: American Medical Association (AMA)
Date: 10-1995
Under diagnosis of canine cognitive dysfunction: A cross-sectional survey of older companion dogs
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.TVJL.2009.11.007
Abstract: Canine cognitive dysfunction (CCD) is a neurobehavioural syndrome affecting aged dogs. Using a large cross-sectional epidemiological study of older dogs, this study aimed to estimate the prevalence of CCD amongst community based dogs (mean age 11.67years range 8-19.75) and to determine the rate of veterinary diagnosis amongst affected dogs. An 84-item questionnaire was used to obtain information across six behavioural domains. Of the eligible survey responses obtained (n=957) a randomly selected one-half (n=497) was used for this study. Using a provisional diagnosis based on 27 significant behavioural items, the prevalence rate of CCD was estimated to be 14.2%. This was in contrast with only 1.9% diagnosed with CCD by a veterinarian. There was an exponential increase in prevalence of CCD with age (R2=0.9435), but prevalence did not differ by breed size or between longevity groups. The prevalence rate of CCD reported here is consistent with previous findings, and further supports the contention that the majority of these dogs do not receive a formal diagnosis.
Is age-related variance in episodic memory mediated by processing speed or executive function?
Publisher: Wiley
Date: 07-2011
Is psychosurgery antimanic?
Publisher: Elsevier BV
Date: 02-1990
Personalised predictive modelling with brain-inspired spiking neural networks of longitudinal MRI neuroimaging data and the case study of dementia
Publisher: Elsevier BV
Date: 12-2021
Does statin use cause memory decline in the elderly?
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.TCM.2016.03.009
Abstract: Statin therapy has strong evidence supporting health benefits and mortality reduction in cardiovascular disease, stroke, diabetes, renal disease, and genetic lipid disorders. Further, reports that statin therapy might be protective against Alzheimer's disease have subsequently been refuted in randomized trials. Low-level evidence based on case reports suggests that statins may adversely affect memory, a significant consumer concern. In this review, the published evidence on statins and memory in the elderly in randomized controlled trials and prospective observational cohort studies was examined in detail. Overall, there was moderate-strength evidence that statin therapy did not increase the risk of dementia in the elderly and low-strength evidence for no increased risk for Alzheimer's disease. Further, there was moderate-strength evidence that statin therapy in the elderly did not increase the risk for mild cognitive impairment or worsen global cognitive performance in the cognitively intact or impaired. There was moderate-strength evidence for no deterioration of memory function in the elderly. On balance, there was a moderate level of evidence of neither harm nor benefit on memory however, the published literature contains a number of deficiencies that are detailed in this review, not limited to selection biases and deficiencies of detailed testing.
Upregulation of glycolytic enzymes, mitochondrial dysfunction and increased cytotoxicity in glial cells treated with Alzheimer's disease plasma.
Publisher: Public Library of Science (PLoS)
Date: 18-03-2015
Being overweight is associated with hippocampal atrophy: The PATH Through Life Study
Publisher: Springer Science and Business Media LLC
Date: 04-06-2015
DOI: 10.1038/IJO.2015.106
Abstract: The prevalence of obesity has increased dramatically in the past two decades, with major implications for in idual well-being, population health and the economy. Of particular concern is the risk obesity presents for brain health and its consequences in an ageing population. These associations and their time course are not well understood, particularly after middle age. The aim of this study was to investigate whether being overweight/obese or having an increasing body weight is associated with hippoc al atrophy in early old age. Participants were 420 unimpaired (Mini-Mental State Examination >26) in iduals aged 60-64 years, living in the community and taking part in a large prospective study of ageing over an 8 year follow-up. Magnetic resonance imaging scans were collected at three assessments and the hippoc us was manually traced by expert neuroscientists. Multi-level analyses assessing the relationship between body mass index (BMI) and hippoc al atrophy over 8 years while controlling for important covariates were conducted. Analyses showed that BMI was negatively associated with left (coefficient: -10.65 mm(3) s.e. 4.81 P=0.027) and right (coefficient: -8.18 mm(3) s.e. 4.91 P=0.097) hippoc al volume at the first assessment. Over the follow-up period, those with a higher BMI experienced greater hippoc al atrophy and more so in the left (P=0.001) than in the right (P=0.058) hippoc us. The findings from this study provide important evidence indicating that being overweight or obese is associated with poorer brain health. These results are consistent with those of previous animal and human studies and further stress the importance of reducing the rate of obesity through education, population health interventions and policy.
A novel approach to investigate depression symptoms in the aging population using generalizability theory.
Publisher: American Psychological Association (APA)
Date: 07-2022
DOI: 10.1037/PAS0001129
Abstract: As depression is common in older people and confers significant risk for dementia, its accurate assessment is essential. The 15-item Geriatric Depression Scale (GDS-15) is a widely used assessment tool for measuring depression in aged populations, and its psychometric properties have been recently improved using Rasch analysis. However, its temporal reliability and ability to distinguish between dynamic and enduring symptoms of depression have not been examined using the appropriate methodology. Generalizability theory (G theory) is a suitable method to distinguish between enduring and dynamic symptoms of depression and to evaluate the reliability of the GDS-15 scores and sources of measurement error. We applied G theory to the longitudinal GDS-15 data of 354 participants from the Sydney Memory and Ageing Study, collected biennially over 10 years, from in iduals aged 70 years and older. The GDS-15 demonstrated strong reliability and generalizability of its test scores in measuring enduring symptoms of depression (
Corpus callosum size, reaction time speed and variability in mild cognitive disorders and in a normative sample
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2006.11.020
Abstract: Intra-in idual variability in reaction time increases with age and with neurological disorders, but the neural correlates of this increased variability remain uncertain. We hypothesized that both faster mean reaction time (RT) and less intra-in idual RT variability would be associated with larger corpus callosum (CC) size in older adults, and that these associations would be stronger in adults with mild cognitive disorders. A normative s le (n=432) and a s le with mild cognitive disorders (n=57) were compared on CC area, RT mean and RT variability adjusting for age, sex, education, APOE genotype, smoking, alcohol consumption, grip strength, visual acuity, handedness and lung function. S les did not differ in CC area or intra-cranial volume. In the normative s le, simple RT (SRT) and choice RT (CRT) were negatively associated with CC area but there were minimal associations between CC area and intra-in idual RT variability. In the mild cognitive disorders s le, SRT, CRT and intra-in idual variability on the SRT task were associated with CC area. Increased RT variability explained up to 12.7 percent of the variance in CC area in the s le with mild cognitive disorders, but less than 1 percent of the variance in CC area in the normative s le. There were no associations with APOE genotype. We conclude that intra-in idual variability is associated with CC area in mild cognitive disorders, but not in normal aging. We propose that biological limits on reserve capacity must occur in mild cognitive disorders that result in stronger brain-behavior relationships being observed.
Using Base Rate of Low Scores to Identify Progression from Amnestic Mild Cognitive Impairment to Alzheimer's Disease
Publisher: Wiley
Date: 10-05-2018
DOI: 10.1111/JGS.15412
Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease
Publisher: Springer Science and Business Media LLC
Date: 25-07-2022
DOI: 10.1038/S41398-022-02055-0
Abstract: Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E ( APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected in iduals having high PRSs for LOAD, and (2) unaffected APOE -ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected in iduals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected in iduals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.
The current status of tardive dyskinesia.
Publisher: SAGE Publications
Date: 06-2000
DOI: 10.1080/J.1440-1614.2000.00737.X
Abstract: Objective: This paper aims to provide an overview of the current knowledge on neuroleptic-induced tar e dyskinesia (TD) in relation to its clinical features, risk factors, pathophysiology and management. Method: The published literature was selectively reviewed and assessed. Results: Tar e diskinesia is a common neurological side-effect of neuroleptic medication, the cumulative incidence of which increases with increasing duration of treatment. Its clinical manifestations are erse and subsyndromes have been described. Many risk factors for TD are now recognised, but increasing age remains pre-eminent as a risk factor. The pathophysiology of TD is not completely understood. Of the neurotransmitter hypotheses, the dopamine receptor supersensitivity hypothesis and the γ-aminobutyric acid insufficiency hypothesis are the main contenders. There is increasing recognition that TD may in fact be caused by neuroleptic-induced neuronal toxicity through free radical and excitotoxic mechanisms. The occurrence of spontaneous dyskinesias in schizophrenic patients and even healthy subjects suggests that neuroleptics act on a substratum of vulnerability to dyskinesia. As no effective treatment for TD is available, the primary emphasis is on prevention. Many drugs can be tried to reduce symptoms in established cases. The increasing use of atypical neuroleptics has raised the possibility of a lower incidence of TD in the future. Conclusions: After four decades of clinical recognition, the pathophysiology of TD is still not understood and no effective treatment is available. Its prevention with the optimal usage of currently available drugs and regular monitoring of patients on long-term neuroleptic treatment remain the best strategies to reduce its impact.
Hippocampal and amygdala volumes in an older bipolar disorder sample
Publisher: Cambridge University Press (CUP)
Date: 29-08-2012
DOI: 10.1017/S1041610212001469
Abstract: Background: Brain volumetric magnetic resonance imaging (MRI) studies of adult bipolar disorder s les, compared with healthy controls, have reported conflicting results in hippoc al and amygdala volumes. Among these, few have studied older bipolar s les, which would allow for examination of the effects of greater duration in mood episodes on brain volumes. The aim of this study was to compare hippoc al and amygdala volumes in older bipolar patients with controls. Methods: High-resolution MRI scans were used to determine hippoc al and amygdala volumes that were manually traced using established protocols in 18 euthymic patients with DSM-IV bipolar I disorder (mean age 57 years) and 21 healthy controls (mean age 61 years). Analysis of covariance (ANCOVA) was used to explore group differences while controlling for intracranial volume (ICV), age, sex, and years of education. Results: While gray matter, white matter, and cerebrospinal fluid volumes did not differ between the groups, bipolar disorder patients had smaller ICV (t = 2.54, p = 0.015). After correcting for ICV, the bipolar group had smaller hippoc al (left hippoc us F = 13.944, p = 0.001 right hippoc us F = 10.976, p = 0.002 total hippoc us F = 13.566 p = 0.001) and right amygdala (F = 13.317, p = 0.001) volumes. Total hippoc al volume was negatively associated with the duration of depressive (r = −0.636 p = 0.035) and manic (r = −0.659 p = 0.027) episodes, but not lithium use. Amygdala volumes were not associated with the duration of mood episodes. Conclusions: Older bipolar disorder patients had smaller hippoc al and amygdala volumes. That smaller hippoc al volume was associated with the duration of mood episodes may suggest a neuroprogressive course related to the severity of the disorder.
The preparation and crystal structure of ammonium bis[citrato(3-)]cuprate(II)
Publisher: CSIRO Publishing
Date: 1991
DOI: 10.1071/CH9911495
Abstract: The copper(II) complex with citric acid (NH4)4 [Cu(C6H5O7)2] has been prepared, and its structure determined by X-ray diffraction, giving a residual R 0.035 for 1208 observed reflections. Crystals are monoclinic, space group P21/c with Z 2 in a cell of dimensions a 8.755(3), b 13.185(4), c 9.364(2)Ǻ, β 113.73(2)°. The complex is a centrosymmetric six-coordinate monomer which is isomorphous with ammonium zinc(II) citrate. However, the Cu-O(hydroxyl) bonds [2.341(3)Ǻ] show Jahn-Teller distortion relative to the Cu-O(carboxyl) bonds [1.969(3) and 1.977(3)Ǻ].
Recent trends in testing social cognition
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
VALIDATED DEMENTIA RISK MEASURE IS ASSOCIATED WITH REGIONAL BRAIN VOLUMES: THE ANU ALZHEIMER’S DISEASE RISK INDEX (ANU-ADRI)
Publisher: Wiley
Date: 07-2016
Accelerating Alzheimer's research through 'natural' animal models.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
Augmenting Transcranial Direct Current Stimulation With D-Cycloserine for Depression
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2013
Harmonizing brain magnetic resonance imaging methods for vascular contributions to neurodegeneration
Publisher: Wiley
Date: 25-02-2019
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
Publisher: Research Square Platform LLC
Date: 21-10-2021
DOI: 10.21203/RS.3.RS-963149/V1
Abstract: Perivascular space burden (PVS) is an emerging and possibly the earliest magnetic resonance imaging (MRI)-marker of cerebral small vessel disease (cSVD), a leading cause of stroke and dementia. Its molecular underpinnings are unknown. Genome-wide and whole-exome association studies in 40,095 participants (21 population-based cohorts, 66.3±8.6 years) revealed 24 genome-wide significant PVS risk loci. These showed association with white matter PVS already at age 20, suggesting an important role of early-life factors. PVS loci were enriched in genes causing early-onset leukodystrophies and genes expressed in fetal brain endothelial cells. Mendelian randomization analyses supported causal associations of high blood pressure with basal ganglia (BG) and hippoc al PVS, and of BG PVS with stroke. Transcriptome-wide association studies suggest causal implication of 11 genes, to prioritize for experimental follow-up as putative biotargets for cSVD. Two-thirds of PVS loci point to novel pathways, involving extracellular matrix, membrane transport, and developmental processes, with enrichment in targets of existing drugs for vascular/cognitive disorders.
The effects of β-adrenoceptor antagonists on a rat model of neuroleptic-induced akathisia
Publisher: Elsevier BV
Date: 09-1997
DOI: 10.1016/S0165-1781(97)00096-6
Abstract: Neuroleptic-induced defecation in rats in a well-habituated environment has been proposed as a model of the subjective component of akathisia. In this study, we examined the effects of two lipophilic beta-adrenoceptor antagonists - the non-selective drug propranolol and the relatively beta1-selective metoprolol - and one non-selective hydrophilic drug nadolol in this model. Young male Wistar rats were randomly assigned to one of eight groups (n = 12 in each group) and treated with haloperidol or vehicle, with or without one of the beta-antagonists. Haloperidol-treated rats had higher bolus counts than vehicle-treated rats, and this increase was significantly reversed by the lipophilic but not the hydrophilic beta-antagonists. This finding is consistent with the reported anti-akathisia effects of these drugs in humans, suggesting that this effect is central in origin and achievable with relatively selective beta1-antagonism. The B-antagonist drugs significantly reduced the cataleptic effect of haloperidol and this effect warrants further examination.
Genetic Influences on Four Measures of Executive Functions and Their Covariation with General Cognitive Ability: The Older Australian Twins Study (vol 42, pg 528, 2012)
Publisher: Springer Science and Business Media LLC
Date: 20-03-2012
Age-associated differences on structural brain MRI in nondemented individuals from 71 to 103 years
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.NEUROBIOLAGING.2016.01.006
Abstract: Successful brain aging in the oldest old (≥90 years) is underexplored. This study examined cross-sectional brain morphological differences from 8th to 11th decades of life in nondemented in iduals by high-resolution magnetic resonance imaging. Two hundred seventy-seven nondemented community-dwelling participants (71-103 years) from Sydney Memory and Ageing Study and Sydney Centenarian Study comprised the s le, including a subs le of 160 cognitively high-functioning elders. Relationships between age and magnetic resonance imaging-derived measurements were studied using general linear models and structural profiles of the ≥90 years were delineated. In full s le and the subs le, significant linear negative relationship of gray matter with age was found, with the greatest age effects in the medial temporal lobe and parietal and occipital cortices. This pattern was further confirmed by comparing directly the ≥90 years to the 71-89 years groups. Significant quadratic age effects on total white matter and white matter hyperintensities were observed. Our study demonstrated heterogeneous differences across brain regions between the oldest old and young old, with an emphasis on hippoc us, temporoposterior cortex, and white matter hyperintensities.
Grey matter atrophy of basal forebrain and hippocampus in mild cognitive impairment
Publisher: BMJ
Date: 03-11-2010
Abstract: The basal forebrain area (BFA) is closely connected to the hippoc us by virtue of cholinergic neuronal projections. Structural neuroimaging studies have shown reduced volumes of both structures in Alzheimer's disease and its prodromal stage mild cognitive impairment (MCI), but generally not in the same investigation. By combining voxel based morphometry and region of interest methods, we measured the grey matter (GM) volumes of the two brain regions with the goal of elucidating their contributions to MCI and its two subtypes (amnestic MCI and non-amnestic MCI) in an elderly epidemiological s le. The results replicated previous findings that the atrophies of both brain regions were associated with an increased likelihood of MCI and its two subtypes. However, in a regression model for the prediction of MCI with GM volumes for both regions used as predictors, only hippoc al atrophy remained significant. Two possible interpretations for this pattern of results were discussed. One is that the observed correlation between BFA atrophy and MCI is spurious and due to the hippoc al atrophy correlated with both. Alternatively, our observation is consistent with the possibility that BFA atrophy has a causal effect on MCI, which is mediated via its influence on hippoc al atrophy. Furthermore, we found that the left hippoc al atrophy had a stronger effect than the right hippoc us and bilateral BFA in the prediction of amnestic MCI occurrence when the four unilateral areas were entered into one regression model. In addition, a slight but statistically significant difference was found in the left hippoc al volume between APOE ε4 allele carriers and non-carriers, consistent with prior studies.
Alleviating the social, health, and economic costs of apathy in dementia
Publisher: Cambridge University Press (CUP)
Date: 27-04-2023
Fasting blood glucose levels are associated with white matter hyperintensities’ burden in older individuals with and without type 2 diabetes
Publisher: Elsevier BV
Date: 10-2015
Psychiatric Illness in the New Zealand Maori
Publisher: SAGE Publications
Date: 12-1989
DOI: 10.3109/00048678909062622
Abstract: This paper compares psychiatric illness in the contemporary Maori with that in the non-Maori New Zealander. The ethnic data available are all from secondary sources. The limitations of this and the problems of achieving a satisfactory definition of “a Maori” are discussed. The data suggest that the Maori have a slightly greater risk of psychiatric hospitalization than the non-Maori. First admission rates for schizophrenia are higher for the Maori, as are the readmission rates. First admission rates for major affective illness are roughly comparable in the two groups, and those for neuroses and neurotic depression are lower in the Maori. Rates of admission for alcohol abuse, alcohol dependence and personality disorders are much higher for the Maori male aged 20–40 years and this group is at greatest risk of psychiatric hospitalization. A larger proportion of Maori are admitted involuntarily, especially under the Criminal Justice Act. The median stay in hospital is not longer for the Maori but their re-admissions are more frequent. The Maori have shown an increase in first psychiatric admission rates since the 1950s, with rapid increases in the early 60s and the 80s. The rates for psychotic disorders have been relatively constant and the most significant changes have been for alcohol abuse, alcohol dependence and personality disorders. The author relates this historical change to socioeconomic and politico-cultural factors, particularly the stress of rapid urbanization.
Factors associated with odour identification in older Indonesian and white Australian adults
Publisher: Springer Science and Business Media LLC
Date: 21-11-2019
Reliability and validity of a Mediterranean diet and culinary index (MediCul) tool in an older population with mild cognitive impairment
Publisher: Cambridge University Press (CUP)
Date: 07-11-2018
DOI: 10.1017/S0007114518002428
Abstract: Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling in iduals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 ( sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test–retest reliability was assessed using intra-class correlation coefficients (ICC), Bland–Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland–Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test–retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P ·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient ( y =−2·30+0·17 x ) (95 % CI −0·027, 0·358 P =0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older in iduals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.
Cognitive Deficits Are Associated with Frontal and Temporal Lobe White Matter Lesions in Middle-Aged Adults Living in the Community
Publisher: Public Library of Science (PLoS)
Date: 21-10-2010
Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-05-2002
Abstract: The authors examined the association of total plasma homocysteine (Hcy) levels with measures of atrophy and white matter disease on MRI scans in 36 healthy elderly in iduals. Hcy had a significant positive relationship with lateral ventricle-brain ratios in the anterior (r = 0.49) and middle (r = 0.43) ventricular regions as measures of central atrophy, but not with cortical atrophy or white matter hyperintensities. In a logistic regression analysis, elevated Hcy was a significant determinant of increased anterior ventricle-brain ratio (> or =0.34) after controlling for age, folate, B12, creatinine, and white matter disease (OR = 2.3 CI, 1.03-5.09).
Comment
Publisher: SAGE Publications
Date: 02-2003
Publishing by Australasian psychiatrists.
Publisher: SAGE Publications
Date: 06-2003
Long-term outcome of neurosurgery for the treatment of resistant depression.
Publisher: American Psychiatric Association Publishing
Date: 11-2005
DOI: 10.1176/JNP.17.4.478
Abstract: Between 1973 and 1995, a total of 76 patients were treated with bilateral stereotactic, orbitomedial lesions for resistant severe depression at the Neuropsychiatric Institute, Sydney, Australia. On follow up after a mean 14.4 years, 24 (31.6%) subjects were confirmed dead, with six having committed suicide. Of the 52 patients still alive (mean age 62.9 years), 23 were interviewed in detail, and lesions verified in 18 with magnetic resonance imaging (MRI). On a 6-point global outcome rating scale, rated by consensus between two independent psychiatrists, five (22.7%) were judged to be completely recovered and another 11 (50%) showed significant improvement. The improvement was noted within days or weeks of the surgery. Adverse effects were epilepsy (2 subjects), marked personality change (1), weight gain (2), and mild personality change (5). Any reported cognitive impairment was mild. No definite predictors of improvement were identified.
Neuropsychiatry
Publisher: American Psychiatric Association Publishing
Date: 05-2003
Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: Commentary
Publisher: Cambridge University Press (CUP)
Date: 02-2007
Magnetic resonance spectroscopy and its applications in psychiatry
Publisher: SAGE Publications
Date: 02-2002
DOI: 10.1046/J.1440-1614.2002.00992.X
Abstract: Objective: This paper briefly describes neuroimaging using magnetic resonance spectroscopy (MRS) and provides a systematic review of its application to psychiatric disorders. Method: A literature review ( Index Medicus/ Medline) was carried out, as well as a review of other relevant papers and data known to the authors. Results: Magnetic resonance spectroscopy is a complex and sophisticated neuroimaging technique that allows reliable and reproducible quantification of brain neurochemistry provided its limitations are respected. In some branches of medicine it is already used clinically, for instance, to diagnose tumours and in psychiatry its applications are gradually extending beyond research. Neurochemical changes have been found in a variety of brain regions in dementia, schizophrenia and affective disorders and promising discoveries have also been made in anxiety disorders. Conclusions: Magnetic resonance spectroscopy is a non-invasive investigative technique that has provided useful insights into the biochemical basis of many neuropsychiatric disorders. It allows direct measurement, in vivo, of medication levels within the brain and has made it possible to track the neurochemical changes that occur as a consequence of disease and ageing or in response to treatment. It is an extremely useful advance in neuroimaging technology and one that will undoubtedly have many clinical uses in the near future.
Are the brain's vascular and Alzheimer pathologies additive or interactive?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2018
Nicotinamide adenine dinucleotide and its related precursors for the treatment of Alzheimer's disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2018
Diagnosing mild cognitive impairment: the problem with subjective complaints.
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Junior clinical academic psychiatrists in Australia: The University of New South Wales initiative
Publisher: SAGE Publications
Date: 20-12-2019
Abstract: We examined current pathways of training for junior clinical academic psychiatrists in Australia. An initiative of the School of Psychiatry, University of New South Wales, is described from the perspective of two junior clinical academics. Australia has limited defined clinical academic pathways for psychiatrists when compared internationally. Numerous challenges for junior psychiatrists entering academia include tensions between clinical and academic roles, reduced remuneration, difficulty building a competitive track record and a scarcity of funding. Potential solutions lie with universities and local health districts partnering to fund clinical academic roles and offering flexible entry points across specialty training. Fostering research engagement in junior psychiatrists will develop the next generation of clinical academics with benefit for clinical and academic domains.
An International Consensus Study of Neuroleptic Malignant Syndrome Diagnostic Criteria Using the Delphi Method
Publisher: Physicians Postgraduate Press, Inc
Date: 28-06-2011
DOI: 10.4088/JCP.10M06438
Pharmacological characterization of tardive akathisia
Publisher: Elsevier BV
Date: 11-1990
DOI: 10.1016/0006-3223(90)90515-4
Abstract: A patient with tar e neuroleptic-induced akathisia was investigated with multiple pharmacological challenges. It was noted that the patient responded positively to benztropine, bromocriptine, and propranolol, and negatively to physostigmine, and showed little or no response to discontinuation of neuroleptics and challenges with metoclopramide, metoprolol, atenolol, and clonidine. The implications of this pharmacological characterization for the understanding of the pathophysiology of tar e akathisia in relation to acute akathisia and tar e dyskinesia are discussed.
Post-Starburst Galaxies: Why Aren’t They Forming Stars?
Publisher: AIP
Date: 2010
DOI: 10.1063/1.3458466
Posterior compensatory network mediates spatial working memory in those with proficient cognition despite hippocampal atrophy
Publisher: Wiley
Date: 07-2011
Viral-free generation and characterization of a human induced pluripotent stem cell line from dermal fibroblasts
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.SCR.2018.09.014
Abstract: Peripheral dermal fibroblasts (DF) from a healthy 56 year old female were obtained from the Centre for Healthy Brain Ageing (CHeBA) Biobank, University of New South Wales, under the material transfer agreement with the University of Wollongong. DFs were reprogrammed via mRNA-delivered transcription factors into induced pluripotent stem cells (iPSCs). The generated iPSCs were confirmed to be pluripotent, capable of three germ layer differentiation and are thus a useful resource for creating iPSC-derived healthy human cells of any lineage. Resource table.
Diffusion tensor imaging of the posterior cingulate is a useful biomarker of mild cognitive impairment.
Publisher: Elsevier BV
Date: 07-2009
A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression
Publisher: Oxford University Press (OUP)
Date: 12-08-2009
Neuropsychological Functioning of Adults with Attention Deficit Hyperactivity Disorder
Publisher: Informa UK Limited
Date: 02-2000
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
Publisher: BMJ
Date: 11-2021
DOI: 10.1136/BMJOPEN-2021-050830
Abstract: Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis. Prospective, international, multicentre, observational cohort study. Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative). 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality. This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p .001), age years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787). Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with in idualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups. NCT04323644
Head injury slightly increases risk of non-affective psychosis but not schizophrenia: Commentary
Publisher: BMJ
Date: 08-2007
DOI: 10.1136/EBMH.10.3.92
Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer's disease
Publisher: Springer Science and Business Media LLC
Date: 13-06-2013
DOI: 10.1007/S00702-012-0839-2
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that leads to a progressive decline in a person's memory and ability to communicate and carry out daily activities. The brain pathology in AD is characterized by extensive neuronal loss, particularly of cholinergic neurons, intracellular neurofibrillary tangles composed of the tau protein (NFTs) and extracellular deposition of plaques composed of β-amyloid (Aβ), a cleavage product of the amyloid precursor protein (APP). These two insoluble protein aggregates are accompanied by a chronic inflammatory response and extensive oxidative damage. Whereas dys-regulation of APP expression or processing appears to be important for the familial, early-onset form of AD, controversy exists between the "Baptists" (in favour of Aβ) and the "Tauists" (in favour of tau) as to which of these two protein dysfunctions occur at the earliest stages or are the most important contributors to the disease process in sporadic AD. However, more and more "non-amyloid" and "non-tau" causes have been proposed, including, glycation, inflammation, oxidative stress and dys-regulation of the cell cycle. However, to get an insight into the ultimate cause of AD, and to prove that any drug target is valuable in AD, disease-relevant models giving insight into the pathogenic processes in AD are urgently needed. In the absence of a good animal model for sporadic AD, we propose in this review that induced pluripotent stem cells, derived from dermal fibroblasts of AD patients, and differentiated into cholinergic neurons, might be a promising novel tool for disease modelling and drug discovery for the sporadic form of AD.
A POLLEN DIAGRAM FROM LAKE EURAMOO, NORTH-EAST QUEENSLAND, AUSTRALIA
Publisher: Wiley
Date: 07-1970
Psychotic Symptoms Preceding Ocular Deviation in a Patient with Tardive Oculogyric Crises
Publisher: SAGE Publications
Date: 12-1992
DOI: 10.3109/00048679209072104
Abstract: This report describes a patient with schizophrenia who developed episodes of ocular dystonia as a delayed side effect of neuroleptic medication. Each episode was preceded and accompanied by marked agitation, stereotypic behaviour and exacerbation of hallucinations. Both the psychotic and dystonic symptoms responded to anticholinergic medication. The theoretical and practical implications of this observation are discussed.
Memory and executive functioning in obsessive–compulsive disorder: A selective review
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.JAD.2007.02.023
Abstract: The neurocognitive deficits that underlie the unique features of obsessive-compulsive disorder (OCD) are not yet completely understood. This paper reviews the main neuropsychological findings in memory and executive functioning in this disorder, and examines a number of challenges facing this area of research. A selective review of the neuropsychological literature on OCD was conducted using MEDLINE and drawing on literature known to the authors. The neuropsychological profile of OCD appears to be one of primary executive dysfunction. Although memory functioning may be affected, these deficits appear secondary to an executive failure of organizational strategies during encoding. On tasks of executive functioning patients with OCD demonstrate increased response latencies, perseveration of responses, and difficulties utilizing feedback to adapt to change. A statistical meta-analysis was not performed and only the cognitive domains of memory and executive functioning were examined. Given the prominence of chronic doubt and indecision in clinical settings, it is surprising that decision making as a cognitive construct as related to OCD has not received greater attention in the neuropsychological literature. On the basis of emerging literature we suggest that it is a potential area of dysfunction and one that warrants further investigation as it may assist in enhancing our understanding of the pathophysiology of OCD.
Amygdalo-Hippocampectomy for Pathological Aggression
Publisher: SAGE Publications
Date: 12-1992
DOI: 10.3109/00048679209072105
Abstract: Two patients are reported, one with severe brain damage and epilepsy, and the other with limbic epilepsy, who were treated with unilateral microsurgical amygdalo-hippoc ectomy for the control of rage and aggression. Both had significant improvement in their aggressiveness, and the second patient also improved in the frequency of his seizures and psychotic episodes. The significance of these observations for our understanding of the morphophysiological basis of rage and aggression is discussed.
Subjective cognitive decline and rates of incident Alzheimer's disease and non–Alzheimer's disease dementia
Publisher: Wiley
Date: 13-12-2019
Editorial introductions
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2007
A slower rate of sulcal widening in the brains of the nondemented oldest old
Publisher: Elsevier BV
Date: 04-2021
Mapping NAD+ metabolism in the brain of ageing Wistar rats: Potential targets for influencing brain senescence
Publisher: Springer Science and Business Media LLC
Date: 17-12-2014
DOI: 10.1007/S10522-013-9489-5
Abstract: Over the last decade, the importance of NAD(+) has expanded beyond its role as an essential cofactor for energy metabolism. NAD(+) has emerged as a major signalling molecule that serves as the sole substrate for several enzymatic reactions including the DNA repair enzyme, poly(ADP-ribose) polymerase (PARP), NAD-dependent protein deacetylases or CD38, and transcriptional factors by a new class of histone deacetylases known as sirtuins. NAD(+) levels are regulated by the metabolic status and cellular stress caused by oxidative stress and DNA damage. Since a detailed study of NAD(+) metabolism in the healthy ageing mammalian brain is nascent, we examined the effect of ageing on intracellular NAD(+) metabolism in different brain regions in female Wistar rats in young (3 months), middle aged (12 months) and older adults (24 months). Our results are the first to show a significant decline in intracellular NAD(+) levels and NAD:NADH ratio with ageing in the CNS, occurring in parallel to an increase in lipid peroxidation and protein oxidation (o- and m-tyrosine) and a decline in total antioxidant capacity. Hyperphosphorylation of H2AX levels was also observed together with increased PARP-1 and PARP-2 expression, and CD38 activity, concomitantly with reduced NAD(+) and ATP levels and SIRT1 function in the cortex, brainstem, hippoc us and cerebellum. Reduced activity of mitochondrial complex I-IV and impaired maximum mitochondrial respiration rate were also observed in the ageing rat brain. Among the multiple physiological pathways associated with NAD(+) catabolism, our discovery of CD38 as the major regulator of cellular NAD(+) levels in rat neurons indicates that CD38 is a promising therapeutic target for the treatment of age-related neurodegenerative diseases.
The relationship between voxel-based metrics of resting state functional connectivity and cognitive performance in cognitively healthy elderly adults
Publisher: Springer Science and Business Media LLC
Date: 20-02-2018
DOI: 10.1007/S11682-018-9843-Y
Abstract: In previous studies, resting-state functional connectivity (FC) metrics of specific brain regions or networks based on prior hypotheses have been correlated with cognitive performance. Without constraining our analyses to specific regions or networks, we employed whole-brain voxel-based weighted degree (WD), a measure of local FC strength, to be correlated with three commonly used neuropsychological assessments of language, executive function and memory retrieval in both positive and negative directions in 67 cognitively healthy elderly adults. We also ided voxel-based WD into short-ranged and long-ranged WDs to evaluate the influence of FC distance on the WD-cognition relationship, and performed three validation tests. Our results showed that for language and executive function tests, positive WD correlates were located in the frontal and temporal cortices, and negative WD correlates in the precuneus and occipital cortices for memory retrieval, positive WD correlates were located in the inferior temporal cortices, and negative WD correlates in the anterior cingulate cortices and supplementary motor areas. An FC-distance-dependent effect was also observed, with the short-ranged WD correlates of language and executive function tests located in the medial brain regions and the long-ranged WD correlates in the lateral regions. Our findings suggest that inter-in idual differences in FC at rest are predictive of cognitive ability in the elderly adults. Moreover, the distinct patterns of positive and negative WD correlates of cognitive performance recapitulate the dichotomy between task-activated and task-deactivated neural systems, implying that a competition between distinct neural systems on functional network topology may have cognitive relevance.
An epigenome-wide association study of educational attainment (n = 10,767)
Publisher: Cold Spring Harbor Laboratory
Date: 07-03-2017
DOI: 10.1101/114637
Abstract: The epigenome has been shown to be influenced by biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption, and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here, we provide evidence on the associations between epigenetic modifications—in our case, CpG methylation—and educational attainment (EA), a biologically distal environmental factor that is arguably among of the most important life-shaping experiences for in iduals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10,767 in iduals. While we find that 9 CpG probes are significantly associated with EA, only two remain associated when we restrict the s le to never-smokers. These two are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, their effect sizes on EA are far smaller than the known associations between CpG probes and biologically proximal environmental factors. Two analyses that combine the effects of many probes—polygenic methylation score and epigenetic-clock analyses—both suggest small associations with EA. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.
Should we distinguish between periventricular and deep white matter hyperintensities? [4] (multiple letters)
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2005
SIRTUIN PROTEIN AND RELATED ENERGY METABOLITE CHANGES IN THE ALZHEIMER BRAIN
Publisher: Wiley
Date: 07-2017
Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-02-2022
DOI: 10.1126/SCITRANSLMED.ABJ0264
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 s les passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
Demographic, Clinical, and Lifestyle Correlates of Subjective Memory Complaints in the Australian Population
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JAGP.2013.04.004
Abstract: To provide estimates of the prevalence and correlates of subjective memory complaints in older in iduals by using population-based Australian data. 2007 National Survey of Mental Health and Well-Being. Australia. 1,905 community-dwelling participants aged 65-85 years. Subjective memory complaints were assessed by using two questions reflecting: (1) poorer memory compared with others of the same age ("worse memory") and (2) a decline in memory performance over the previous 5 years ("declining memory"). Twelve-month and lifetime diagnoses were derived from structured diagnostic interviews. Other correlates investigated included chronic physical conditions, lifestyle factors, and service use. Analyses adjusted for scores on the Mini-Mental State Examination. Subjective memory complaints were reported by one-third (33.5%) of respondents. Those who reported either complaint were more likely to report psychological distress, poor functioning, service use, and negative self-assessed mental and physical health. "Declining memory" over the past 5 years was also related to an increase in the rates of psychiatric disorders. After adjusting for other variables of interest, associations were established between subjective memory complaints and psychological distress, poor functioning, negative self-assessed mental health, and alcohol use disorders. Except for the association between "declining memory" and anxiety and depression, these associations remained significant after excluding those with scores <27 on the Mini-Mental State Examination. Subjective memory complaints were associated with several negative clinical characteristics that should be considered when interpreting these complaints. Subjective memory complaints may be valid indicators of psychopathology and the need for clinical assessment.
The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study
Publisher: Springer Science and Business Media LLC
Date: 09-01-2014
Neuroleptic-induced movement disorders and body iron status
Publisher: Elsevier BV
Date: 09-1992
DOI: 10.1016/0278-5846(92)90021-6
Abstract: 1. The distribution of iron in the human brain, what is known about its biological functions, and the interaction of neuroleptics with iron suggest that this trace metal may play an important role in the pathogenesis of neuroleptic-induced movement disorders (NIMD). 2. The availability of magnetic resonance imaging has made some of the hypotheses testable in human subjects. 3. This article is a brief overview of the current literature on the association between NIMD and brain iron.
Growing old gracefully-Behavioral changes associated with successful aging in the dog, Canis familiaris
Publisher: Elsevier BV
Date: 11-2011
Can mild cognitive impairment be accurately diagnosed in English speakers from linguistic minorities? results from the sydney memory and ageing study
Publisher: Elsevier BV
Date: 10-2012
P1‐082: SORL1 gene variants are associated with brain white matter hyperintensities and dementia
Publisher: Wiley
Date: 07-2010
P2‐097: The Sydney Memory and Ageing Study (MAS): A population‐based longitudinal investigation of cognitive health in the elderly
Publisher: Wiley
Date: 07-2009
Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes
Publisher: Mary Ann Liebert Inc
Date: 10-01-2019
[Homocysteine and neuropsychiatric disorders].
Publisher: EDITORA SCIENTIFIC
Date: 03-2004
DOI: 10.1590/S1516-44462004000100013
Abstract: O autor apresenta uma visão geral da literatura atual sobre homocisteína como um fator de risco para os transtornos neuropsiquiátricos. Foram pesquisados os bancos de dados MEDLINE, Current Contents e EMBASE (entre 1966 e 2002) para publicações em língua inglesa utilizando as palavras-chave ''Homocisteína'' e ''AVC'' ''Doença de Alzheimer'' ''Déficit Cognitivo'', ''Epilepsia'', ''Depressão'' ou ''Doença de Parkinson''. Artigos in iduais foram pesquisados para referências cruzadas relevantes. É biologicamente plausível que altos níveis de homocisteína possam causar lesão cerebral e transtornos neuropsiquiátricos. A homocisteína é pró-aterogênica e pró-trombótica. Dessa forma, aumenta o risco de acidente vascular cerebral, podendo ter um efeito neurotóxico direto. Evidências de que a homocisteína seja um fator de risco para doença microvascular cerebral são conflitantes, mas justificam maiores estudos. Estudos transversais e alguns longitudinais suportam a crescente prevalência de acidente vascular cerebral e demência vascular em in íduos com hiper-homocisteinemia. As evidências de crescente neurodegeneração estão se acumulando. A relação com a depressão ainda é experimental, da mesma forma como com a epilepsia. Atualmente, estudos sobre tratamentos são necessários para colocar as evidências sobre bases mais sólidas. Os pacientes de alto risco também devem ser pesquisados para hiper-homocisteínemia, cujo tratamento deve ser feito com ácido fólico. Mais evidências são necessárias antes que pesquisas populacionais possam ser recomendadas.
Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
Publisher: Cold Spring Harbor Laboratory
Date: 05-11-2018
DOI: 10.1101/460444
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small s le sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3,337 in iduals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippoc us, thalamus and nucleus accumbens (NAcc) –three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of in idual CpGs revealed genome-wide significant associations with hippoc al volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. CpG sites associated with hippoc us volume were significantly enriched within cancer-related genes and within regulatory elements containing the transcriptionally repressive histone H3K27 tri-methylation mark that is vital for stem cell fate specification. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippoc al volume. DNA methylation at these loci affected expression of proximal genes involved in in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Correction: Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
Publisher: Springer Science and Business Media LLC
Date: 31-01-2019
Social behavior in mild cognitive impairment and early dementia
Publisher: Informa UK Limited
Date: 10-2012
DOI: 10.1080/13803395.2012.683855
Abstract: Social behavioral abnormalities are commonly seen in the later stages of dementia. However, there has been only limited empirical study of social functioning in the earlier stages of the disease, or in in iduals diagnosed with mild cognitive impairment (MCI). The aim of the present study was to test whether these clinical groups show more socially inappropriate and prejudicial behavior relative to controls, as rated by informants. No group differences were identified for ratings of either socially appropriate behavior or stereotyping and prejudice. However, the results also indicated that informants rated participants with dementia as showing the most inappropriate behavior, and that these ratings were related to participants' degree of immediate logical memory impairment, but not to delayed memory recall or to more general neurocognitive decline as indexed by the Mini Mental State Examination. Together, these results have implications for an understanding of some of the changes in social function seen in abnormal adult aging.
Deep Learning Approach for Classification of Mild Cognitive Impairment Subtypes
Publisher: SCITEPRESS - Science and Technology Publications
Date: 2017
O3‐09‐02: THE DEVELOPMENT OF PSYCHOLOGICAL DISTRESS IN INFORMANTS OF INITIALLY DEMENTIA‐FREE OLDER PEOPLE: THE SYDNEY MEMORY AND AGEING STUDY
Publisher: Wiley
Date: 07-2014
Age Differences in Neural Activity during Slot Machine Gambling: An fMRI Study
Publisher: Public Library of Science (PLoS)
Date: 28-11-2012
Neuroleptic-induced movement disorders: An overview
Publisher: Elsevier BV
Date: 03-2005
Intravenous benztropine and propranolol challenges in tardive akathisia
Publisher: Springer Science and Business Media LLC
Date: 11-1993
DOI: 10.1007/BF02244343
Impairment in instrumental activities of daily living with high cognitive demand is an early marker of mild cognitive impairment: the Sydney Memory and Ageing Study
Publisher: Cambridge University Press (CUP)
Date: 11-01-2013
DOI: 10.1017/S003329171200308X
Abstract: Criteria for mild cognitive impairment (MCI) consider impairment in instrumental activities of daily living (IADL) as exclusionary, but cross-sectional studies suggest that some high-level functional deficits are present in MCI. This longitudinal study examines informant-rated IADL in MCI, compared with cognitively normal (CN) older in iduals, and explores whether functional abilities, particularly those with high cognitive demand, are predictors of MCI and dementia over a 2-year period in in iduals who were CN at baseline. A s le of 602 non-demented community dwelling in iduals (375 CN and 227 with MCI) aged 70–90 years underwent baseline and 24-month assessments that included cognitive and medical assessments and an interview with a knowledgeable informant on functional abilities with the Bayer Activities of Daily Living Scale. Significantly more deficits in informant-reported IADL with high cognitive demand were present in MCI compared with CN in iduals at baseline and 2-year follow-up. Functional ability in CN in iduals at baseline, particularly in activities with high cognitive demand, predicted MCI and dementia at follow-up. Difficulties with highly cognitively demanding activities specifically predicted amnestic MCI but not non-amnestic MCI whereas those with low cognitive demand did not predict MCI or dementia. Age, depressive symptoms, cardiovascular risk factors and the sex of the informant did not contribute to the prediction. IADL are affected in in iduals with MCI, and IADL with a high cognitive demand show impairment predating the diagnosis of MCI. Subtle cognitive impairment is therefore likely to be a major hidden burden in society.
Hippocampal volume is positively associated with behavioural inhibition (BIS) in a large community-based sample of mid-life adults: The PATH through life study
Publisher: Oxford University Press (OUP)
Date: 29-07-2008
DOI: 10.1093/SCAN/NSN018
The heritability of brain metabolites on proton magnetic resonance spectroscopy in older individuals
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.NEUROIMAGE.2012.04.043
Abstract: Twin studies have shown that many aspects of brain structure are heritable, suggesting a strong genetic contribution to brain structure. Less is known about functional aspects of the brain, in particular biologically relevant metabolites in the brain such as those measured by proton magnetic resonance spectroscopy (((1))H MRS), N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myoinositol (ml), which have been suggested as possible markers of brain aging and early dementia. We examined 296 (56 male/108 female monozygotic and 43 male/89 female dizygotic) older twins (mean age 72.2 ± 5.5 years, range 65-88), for the levels of these metabolites relative to the H(2)O signal in the posterior cingulate cortex using ((1))H MRS. All metabolites showed substantial heritability, which was greatest for the neuronal integrity marker NAA (72%), and less so for the others - Cr (51%), Cho (33%) and ml (55%). The heritability of these markers did not change significantly with age or sex. The genetic determination of NAA, along with the evidence that NAA levels change in aging and neurodegenerative diseases suggest that it is a potential endophenotype of brain aging and dementia.
IMPACT OF COMPLETED AND INCOMPLETE PREGNANCIES ON THE RISK OF ALZHEIMER’S DISEASE
Publisher: Wiley
Date: 07-2018
An agenda for neuropsychiatry as a 21st century discipline
Publisher: Cambridge University Press (CUP)
Date: 02-2007
Reliability and validity of ratings of signal hyperintensities on MRI by visual inspection and computerised measurement
Publisher: Elsevier BV
Date: 12-1999
DOI: 10.1016/S0925-4927(99)00036-0
Abstract: Brain magnetic resonance imaging (MRI) scans on 98 elderly subjects, 62 with a diagnosis of schizophrenia and 36 healthy controls, were independently and blindly rated by two investigators using the visual rating methods of Fazekas et al. (Fazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A., 1987. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. American Journal of Neuroradiology 8, 421-426) and Victoroff et al. (Victoroff, J., Mack, W.J., Grafton, S.T., Schreiber, S.S., Chui, H.C., 1994. A method to improve interrater reliability of visual inspection of brain MRI scans in dementia. Neurology 44, 2267-2276) for periventricular, deep white matter and subcortical gray matter signal hyperintensities (SHs) on T2-weighted images. The hyperintense signal volumes were measured by manual delineation of the signals on a workstation using Analyze software (computerised method). The subjects also underwent a detailed neuropsychological assessment. There was a high correlation between two experienced raters for both visual ratings, and the correspondence between the two methods was high. The inter-rater reliability for the computerised method was modest but significant, and the association between the visual and computerised methods was good except for ratings for SHs in subcortical nuclei. The Fazekas and computerised methods, and to a lesser degree the Victoroff method, had modest but significant correlations with some neuropsychological test measures. In conclusion, we did not demonstrate a clear superiority in reliability or validity for one demanding computerised method of rating SHs. Visual ratings should therefore be considered adequate for most clinical and research purposes, but such ratings should be accompanied by adequate training and the provision of standard reference images.
Combined cerebral blood flow effects of a cholinergic agonist (milameline) and a verbal recognition task in early Alzheimer`s disease
Publisher: Wiley
Date: 10-2006
DOI: 10.1111/J.1440-1819.2006.01567.X
Abstract: RU 35926/CI-979 (milameline) is a partial muscarinic agonist with promnestic effects in animal models. Preliminary animal studies suggest that this agent has the capacity to reverse cholinergic dysfunction and that it may impact on regional cerebral blood flow (rCBF). A total of 10 subjects with Alzheimer's disease (AD) of mild severity underwent high resolution split-dose single photon emission computed tomography (SPECT) during performance of a verbal recognition and control task, both before and after 18 weeks treatment with melameline or placebo. SPECT images were coregistered with in idual's magnetic resonance imaging scans allowing extraction of rCBF values from multiple anatomical regions of interest (ROI). The effect of milameline was examined in eight in iduals who were found after unblinding to be taking active drug. Effects of milameline were most apparent in the frontal regions, basal ganglia and thalamus. In the group as a whole, the greatest increase in rCBF due to milameline treatment was observed in the left globus pallidus. Response to milameline treatment was associated with increases in rCBF in the cingulate gyrus bilaterally, and less so for the left thalamus. Milameline-related increases in rCBF values were exaggerated by the verbal recognition task. Milameline has a demonstrable effect on cerebral blood flow in mild AD. Consistent with emerging animal data, the effects on rCBF appear most prominent in frontal and subcortical regions in AD subjects. The effects on rCBF appear to be augmented by the performance of a cognitively demanding task, raising the possibility that such tasks could assist in building an awareness of the functional neuropsychopharmacology of drugs designed for cognitive enhancement.
The heritability of volumes of brain structures and its relationship to age: A review of twin and family studies
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.ARR.2013.10.003
Abstract: Total brain volume (BV) and the volumes of brain substructures are influenced by genes, the magnitude of which changes with age. One approach to the examination of genetic influences on the volumes of brain structures is to determine their heritability using twin and family studies. We reviewed published cross-sectional studies which examined heritability in healthy subjects at different ages. We identified 32 studies, which examined a total of 77 brain volumetric measures. The findings of our review showed that BVs are under significant genetic influence at all ages, although different brain regions showed different heritability levels. Furthermore, the cross-sectional approach of our review found that heritability factor for the majority of BVs declined with age, such as in the total brain and cerebrum, followed by subsequent increment of environmental influences. Overall, this study identified for the first time a cross-sectional pattern for brain structures' heritability changes with age, and suggests the potential for longitudinal investigations in the future.
Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI.
Publisher: Oxford University Press (OUP)
Date: 09-08-2023
Abstract: Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention. We investigated the association between white matter hyperintensity burden and DNA methylation in blood at ∼450 000 cytosine-phosphate-guanine (CpG) sites in 9732 middle-aged to older adults from 14 community-based studies. Single CpG and region-based association analyses were carried out. Functional annotation and integrative cross-omics analyses were performed to identify novel genes underlying the relationship between DNA methylation and white matter hyperintensities. We identified 12 single CpG and 46 region-based DNA methylation associations with white matter hyperintensity burden. Our top discovery single CpG, cg24202936 (P = 7.6 × 10−8), was associated with F2 expression in blood (P = 6.4 × 10−5) and co-localized with FOLH1 expression in brain (posterior probability = 0.75). Our top differentially methylated regions were in PRMT1 and in CCDC144NL-AS1, which were also represented in single CpG associations (cg17417856 and cg06809326, respectively). Through Mendelian randomization analyses cg06809326 was putatively associated with white matter hyperintensity burden (P = 0.03) and expression of CCDC144NL-AS1 possibly mediated this association. Differentially methylated region analysis, joint epigenetic association analysis and multi-omics co-localization analysis consistently identified a role of DNA methylation near SH3PXD2A, a locus previously identified in genome-wide association studies of white matter hyperintensities. Gene set enrichment analyses revealed functions of the identified DNA methylation loci in the blood–brain barrier and in the immune response. Integrative cross-omics analysis identified 19 key regulatory genes in two networks related to extracellular matrix organization, and lipid and lipoprotein metabolism. A drug-repositioning analysis indicated antihyperlipidaemic agents, more specifically peroxisome proliferator-activated receptor-alpha, as possible target drugs for white matter hyperintensities. Our epigenome-wide association study and integrative cross-omics analyses implicate novel genes influencing white matter hyperintensity burden, which converged on pathways related to the immune response and to a compromised blood–brain barrier possibly due to disrupted cell–cell and cell–extracellular matrix interactions. The results also suggest that antihyperlipidaemic therapy may contribute to lowering risk for white matter hyperintensities possibly through protection against blood–brain barrier disruption.
The prevalence of cognitive impairment no dementia in community-dwelling elderly: a pilot study.
Publisher: SAGE Publications
Date: 09-2004
DOI: 10.1080/J.1440-1614.2004.01451.X
Abstract: Objective: To determine the prevalence of ‘cognitive impairment no dementia’ (CIND) and ‘amnestic mild cognitive impairment’ (aMCI) in a population s le of 70–79-year-olds and the risk factors for CIND. Method: Cross sectional population survey. Setting: Sutherland Shire, Sydney, Australia. Subjects: 150 community-dwelling 70–79-year-olds were screened by telephone, 42 of whom were assessed at home. Measures: Demographics, subjective ratings of physical and emotional health and memory, cardiovascular risk factors, medications, the Mini-Mental State Examination, Boston Naming Test, Trail Making Tests A and B, Block Design, Rey Auditory Verbal Learning Test (RAVLT), Visual Reproduction, Logical Memory, letter and category fluency, the National Adult Reading Test (NART), the Geriatric Depression Scale (GDS) and the ‘state’ section of the State-Trait Anxiety Inventory (STAI-S). Results: From the 400 subjects contacted initially, 150 consented to be interviewed and 131 eligible subjects were recruited. Of a 1-in-3 random s le of 42 subjects assessed at home, 14 (33.3%) subjects met criteria for CIND, 1 (2.4%) had possible dementia and the 27 remaining (64.3%) were cognitively normal. Four (9.5%) met criteria for aMCI. Subjects with CIND were older, had lower ranking occupations and were less likely to be currently working than those classified as cognitively normal. Ten subjects with CIND did not meet criteria for aMCI because they lacked subjective memory impairment (n = 3) or had cognitive deficits other than memory (n = 7). All subjects with aMCI met criteria for CIND. Conclusions: One-third of in iduals in this population s le met criteria for CIND. CIND is a broader definition than aMCI. Further research is needed to determine the longitudinal course and clinical utility of these definitions of cognitive impairment.
A Randomised, Double-Blind, Sham-Controlled Trial of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis for Treatment-Resistant Obsessive-Compulsive Disorder
Publisher: Cold Spring Harbor Laboratory
Date: 27-10-2020
DOI: 10.1101/2020.10.24.20218024
Abstract: 1 Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ±10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham ( p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ±1.9 points ( Χ 2 (11) = 39.8, p = 3.8 × 10 −5 ), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ±3.9 points ( p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s in idualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippoc us and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippoc al, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS for in iduals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.
Diastolic Blood Pressure Variability in Later Life May Be a Key Risk Marker for Cognitive Decline
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2022
DOI: 10.1161/HYPERTENSIONAHA.121.18799
Abstract: There is an increasing awareness of the need to understand the interaction between long-term blood pressure patterns and their impact on the brain and cognition. Our aim was to investigate the relationship between repeated blood pressure measures and change in cognitive performance over 12 years and imaging data at 12 years using a longitudinal population study. The data consisted of 2 cohorts, one midlife and one later life. Using linear regression, we examined the relationship between blood pressure (systolic, diastolic, change in blood pressure between visits, and visit-to-visit variability), change in cognitive performance and imaging at 12 years. Data on cognitive change were available in 1054 at midlife, baseline age 42.7 (SD 1.5) and 1233 in later life, 62.5 (1.5) years. Imaging data were available in 168 and 233, respectively. After adjustment for multiple comparisons greater diastolic blood pressure variability in later life was associated with a −1.95 point decline (95% CI, −2.89 to −1.01) on an attention-based task and a −0.42 point (95% CI, −0.68 to −0.15) decline in performance on a psychomotor task. A higher SD in diastolic pressure across follow-up was associated with greater white matter hyperintensity volume (%increase per 10 mm Hg increase in the SD [1.50 (95% CI, 1.16–1.94]). In a largely normotensive/mildly hypertensive population, our analyses reported no relationships between blood pressure and cognition in midlife but a potential role for diastolic blood pressure variability in later life as a risk marker for cognitive decline. This may indicate an at-risk period or a means to identify an at-risk population at the age where diastolic pressure is starting to decline.
STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease
Publisher: Wiley
Date: 18-11-2016
Association of SORL1 gene variants with hippocampal and cerebral atrophy and Alzheimer's disease.
Publisher: Bentham Science Publishers Ltd.
Date: 31-07-2014
DOI: 10.2174/1567205011666140618101408
Abstract: Sortilin-related receptor, Sorl1, is a neuronal receptor that interacts with the amyloid precursor protein to regulate amyloidogenesis. Variants in the gene encoding Sorl1 are associated with Alzheimer's disease (AD), as well as its neuroimaging markers. To investigate the relationship between SORL1 gene variants with ADrelated brain morphologies and AD, testing for sex-specific effects. The s le comprised 292 in iduals aged ≥ 75 years participating in the longitudinal Sydney Older Persons Study. A sub-s le also underwent a brain MRI scan (n=102, 53 males 49 females). The relationships of three SORL1 single nucleotide polymorphisms (SNPs): rs4935774, rs2298813, rs1133174 with brain MRI measures, and AD were determined. Significant associations of SORL1 variants with cross-sectional brain MRI measures and AD were observed only when the s le was stratified by sex. The most common haplotype (H1), comprising rs4935774-T, rs2298813-G, and rs1133174-G alleles (T/G/G) was associated with whole brain atrophy in both males and females (p=0.012 & p=0.013 respectively). Only SNP rs1133174 was in idually associated with hippoc al atrophy in males (p= 0.039) and females (p=0.025). Of the 292 participants, 111 had either probable or possible AD. A significant association of H1 with AD (p = 0.017) was observed in females. A nominally significant association of SNP rs1133174 with AD (p = 0.051) was also observed in the whole cohort. The results provide evidence that the association of polymophisms in the sortilin-related receptor gene (SORL1) with AD and its MRI biomarkers of brain and hippoc al atrophy are moderated by sex.
Total and regional gray matter volume is not related to APOE*E4 status in a community sample of middle-aged individuals.
Publisher: Oxford University Press (OUP)
Date: 05-2008
Abstract: The APOE*E4 allele has been associated with greater gray matter atrophy and with Alzheimer's disease. The aim of this study was to investigate whether the relationship between cerebral gray matter atrophy and APOE*E4 genotype was also present in a community-dwelling, nondemented 60- to 64-year-old cohort. Hippoc al and amygdalar volumes were manually traced and analyzed on 331 cranial T1-weighted magnetic resonance imaging (MRI) scans to detect differences associated with APOE*E4 genotype. Voxel-based morphometric (VBM) analyses were applied to detect regional gray matter volume differences. No total, hippoc al, or amygdalar gray matter volume difference was detected between APOE*E4 carriers and noncarriers. In nondemented 60- to 64-year-olds, there was no association between APOE genotype and gray matter volume using both region-of-interest analysis and VBM.
Magnetic resonance spectroscopy in AD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-03-2001
DOI: 10.1212/WNL.56.5.592
Abstract: Proton MR spectroscopy (MRS) studies have found both decreased N-acetylaspartate (NAA) and increased myo-inositol in the occipital, temporal, parietal, and frontal regions of patients with AD, even at the early stages of the disease. This diffuse NAA decline is independent of regional atrophy and probably reflects a decrease in neurocellular viability. Reports of such metabolite changes are now emerging in the mild cognitive impairment prodrome and in investigation of the medial temporal lobe. In vivo quantitation of neural choline in AD has been inconclusive because of poor test-retest repeatability. Less robust evidence using phosphorous MRS has shown significant phosphocreatine decline and increments in the cell membrane phosphomonoesters in the early, and possibly asymptomatic, stages of the disease. These phosphorous metabolite disturbances normalize with disease progression. Phosphodiester concentration has been found to correlate strongly with AD plaque counts. MRS of AD has therefore introduced new pathophysiologic speculations. Studies of automated MRS for AD diagnosis have reported high sensitivity and moderate specificity, but are yet to test prospective s les and should be extended to include at least two MRS regions of interest. MRS has promise for predicting cognitive status and monitoring pharmacologic efficacy, and can assess cortical and subcortical neurochemical change.
Neuroanatomical Correlates of Cognitive Performance in Late Life
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000333372
Abstract: i Background/Aim: /i While a number of studies examined the neuroanatomical correlates of cognitive function in older adults, the results have been inconsistent. Examination of a large epidemiologically acquired s le with high-resolution magnetic resonance imaging has the potential to enhance the evidence in this field. i Methods: /i The participants were 326 non-demented elderly adults undergoing a battery of neuropsychological tests and brain magnetic resonance imaging scans. Regression analyses were performed to examine the correlation between voxel-based grey matter (GM) volume and four cognitive domain scores. i Results: /i Positive correlations were observed between specific GM volumes and cognitive domains, i.e. bilateral temporal lobes and hippoc i with language bilateral temporal, parietal, and occipital lobes with processing speed and bilateral frontal, temporal, parietal, and occipital lobes with executive function. The positive correlation between verbal memory performance and GM volume in the bilateral medial temporal lobes was not significant after correction for age. i Conclusion: /i Our findings suggest that the location of GM correlates of cognitive tests is largely consistent with the conventional understanding of the neuroanatomical basis of cognition. However, the lack of hemispheric predominance in these GM correlates, and the extensively positive correlation between GM volume and cognitive performance, perhaps reflects the characteristics of the ageing brain.
Brain atrophy in ageing: Estimating effects of blood glucose levels vs. other type 2 diabetes effects
Publisher: Elsevier BV
Date: 02-2018
The Study of Mental and Resistance Training (SMART) Study-Resistance Training and/or Cognitive Training in Mild Cognitive Impairment: A Randomized, Double-Blind, Double-Sham Controlled Trial
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.JAMDA.2014.09.010
Abstract: Mild cognitive impairment (MCI) increases dementia risk with no pharmacologic treatment available. The Study of Mental and Resistance Training was a randomized, double-blind, double-sham controlled trial of adults with MCI. Participants were randomized to 2 supervised interventions: active or sham physical training (high intensity progressive resistance training vs seated calisthenics) plus active or sham cognitive training (computerized, multidomain cognitive training vs watching videos/quizzes), 2-3 days/week for 6 months with 18-month follow-up. Primary outcomes were global cognitive function (Alzheimer's Disease Assessment Scale-cognitive subscale ADAS-Cog) and functional independence (Bayer Activities of Daily Living). Secondary outcomes included executive function, memory, and speed/attention tests, and cognitive domain scores. One hundred adults with MCI [70.1 (6.7) years 68% women] were enrolled and analyzed. Resistance training significantly improved the primary outcome ADAS-Cog [relative effect size (95% confidence interval) -0.33 (-0.73, 0.06) P < .05] at 6 months and executive function (Wechsler Adult Intelligence Scale Matrices P = .016) across 18 months. Normal ADAS-Cog scores occurred in 48% (24/49) after resistance training vs 27% (14/51) without resistance training [P < .03 odds ratio (95% confidence interval) 3.50 (1.18, 10.48)]. Cognitive training only attenuated decline in Memory Domain at 6 months (P < .02). Resistance training 18-month benefit was 74% higher (P = .02) for Executive Domain compared with combined training [z-score change = 0.42 (0.22, 0.63) resistance training vs 0.11 (-0.60, 0.28) combined] and 48% higher (P < .04) for Global Domain [z-score change = .0.45 (0.29, 0.61) resistance training vs 0.23 (0.10, 0.36) combined]. Resistance training significantly improved global cognitive function, with maintenance of executive and global benefits over 18 months.
Measuring mania metabolites: a longitudinal proton spectroscopy study of hypomania
Publisher: Wiley
Date: 07-08-2007
DOI: 10.1111/J.1600-0447.2007.01060.X
Abstract: Using single-voxel proton spectroscopy we aimed to investigate changes in metabolite levels in key brain regions during hypomania and euthymia in patients with bipolar disorder (BD). Nine patients with a diagnosis of BD and nine age, sex, education, and handedness-matched comparison subjects underwent magnetic resonance proton spectroscopy (H(1)-MRS) using a 1.5 T magnet. Patients were assessed whilst hypomanic and euthymic. Metabolite (N-acetyl asparTate, NAA myo-inositol, mI choline, Cho) levels in the basal ganglia (BG), anterior cingulate cortex (AC), and frontal cortex (FC) were compared both between groups and within the patient group. Multivariate analysis revealed significant complex relationships between metabolite levels and brain regions with significant differences observed both between bipolar patients (hypomanic and euthymic) and controls, and across the two mood states. Hypomanic patients had lower mean metabolite levels when averaged across the AC and FC regions, compared with the controls. They also had a smaller difference in mean metabolite levels between the BG and FC than the control group. Euthymic patients were also found to have a smaller difference in the level of NAA between the BG and AC than the control group. This exploratory study of BD demonstrates significant differences in metabolite levels that vary both with respect to brain region and mood state. Not withstanding the confounding effects of medication and the limitation of small s le size the findings are important as they demonstrate that a longitudinal approach is a useful design especially in the context of a long-term phasic illness.
P3–088: Staging of microstructural white matter damage in early Alzheimer's disease
Publisher: Wiley
Date: 07-2013
Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Publisher: Springer Science and Business Media LLC
Date: 29-05-2018
DOI: 10.1038/S41467-018-04362-X
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486 age 16–102) and find 148 genome-wide significant independent loci ( P 5 × 10 −8 ) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent s les. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
Depersonalization disorder
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2010
P1‐388: Incidence of MCI and Dementia Over Six Years in an Australian Population Sample
Publisher: Wiley
Date: 07-2016
Pseudodementia twelve years on.
Publisher: BMJ
Date: 03-1990
Abstract: This paper reports a longitudinal study of 19 patients diagnosed as having pseudodementia more than a decade earlier. In only one patient was the earlier diagnosis changed to definite dementia and, in this patient, there were strong indicators that such a diagnosis should have been made initially. In a second patient, dementia could not be excluded. The remaining patients did not show evidence of a dementing illness and the courses of the illnesses resembled the primary psychiatric disorders responsible for the pseudodementia. The results validate the clinical utility of the term "pseudodementia".
Cerebral Blood Volume in T2-Weighted White Matter Hyperintensities Using Exogenous Contrast Based Perfusion MRI
Publisher: American Psychiatric Association Publishing
Date: 02-2004
Natural Plant-Derived Acetylcholinesterase Inhibitors: Relevance for Alzheimer's Disease
Publisher: Wiley
Date: 09-2017
Use of medications with anticholinergic properties and cognitive function in a young-old community sample
Publisher: Wiley
Date: 06-2009
DOI: 10.1002/GPS.2157
Abstract: To examine whether anticholinergic medications have effects on the level of cognitive function or cognitive decline in persons in their early to mid 60s. A randomly selected community-based s le of 2058 persons aged 60-64 at baseline was interviewed twice over four years. Anticholinergic medication use was determined from self-report medication data using the Anticholinergic Drug Scale. Cognition was assessed with the California Verbal Learning Test I (one trial), Digits Backwards, the Symbol Digit Modalities Test, the Mini-Mental State Exam and simple and choice reaction time. Persons meeting criteria for Mild Cognitive Impairment were identified in a clinical substudy. Mixed models adjusting for age, sex, self-rated depression and physical health, and total number of medications were used to analyse the data. There was a significant main effect of anticholinergic group averaged across time for the Symbol Digits Modalities Test with poorer performance among anticholinergic medication users. Main effects for the other cognitive tests and mild cognitive impairment were non-significant. No time by anticholinergic group interactions were significant. This study suggests that exposure to anticholinergic medication is associated with lower level of complex attention in the young-old, but not with greater cognitive decline over time. Although the clinical significance of this is not clear, caution should be taken when prescribing medications with anticholinergic effects to older persons.
Cognitive correlates of 1H MRS measures in the healthy elderly brain
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.BRAINRESBULL.2005.01.015
Abstract: Ageing is associated with cognitive decline, with some studies indicating that this decline can be mostly accounted for by slowing of information processing speed. Whilst it is likely that this is associated with age-related changes in fronto-subcortical neuronal circuits, such changes are not visible on routine neuroimaging. We examined the integrity of this brain region using proton magnetic resonance spectroscopy (1H MRS) and hypothesised that functional changes measured by 1H MRS would be associated with cognitive performance. Fifty-nine healthy elderly subjects (age 58-85 years) underwent single-voxel 1H MRS in frontal white matter and occipito-parietal gray matter, and a comprehensive neuropsychological battery. The results showed a significant correlation between frontal white matter NAA/H2O and a composite measure of neuropsychological performance representing speed of information processing, attentional function and visual memory, controlling for age and sex. This research highlights the importance of the relationship between regional brain changes and cognitive function in the ageing brain, and suggests that MRS may be a sensitive marker of subclinical change in cognition.
O3–09–03: Reaction‐time measures predict incident dementia over 4 years: The Sydney Memory and Ageing Study
Publisher: Wiley
Date: 07-2013
Hippocampal Volumes in Adults With Bipolar Disorder
Publisher: American Psychiatric Association Publishing
Date: 2010
Abstract: Functional neuroimaging studies have implicated the hippoc us formation in the pathophysiology of bipolar disorder, but findings from volumetric studies have been less consistent. The authors aim to further investigate the existence of volumetric abnormalities in the hippoc us of in iduals with bipolar disorder. In addition to methodological inconsistencies, many previous studies have been lacking clinical robustness with respect to characterizing bipolar patients and comparison subjects. Hence, the present study matched the groups closely across a number of demographic parameters. Using MRI, hippoc al volumes of 24 bipolar patients were compared to 24 sex-, age-, and education-matched comparison subjects, and these findings were further investigated in relation to both illness and treatment factors. A significantly larger (8.5%) right hippoc us was seen in bipolar patients than in comparison subjects, and this difference was not associated with a history of psychosis, familial illness, or lithium treatment, after controlling for potential confounds. Patients reporting fewer affective episodes did however have significantly larger left hippoc us volumes than comparison subjects. The authors found that the left hippoc us was larger in a group of adult bipolar subjects relative to the healthy comparison group. The reason for this is unclear, but in this s le, it was not associated with family history, psychotic features, or medication exposure. A negative association was found between left hippoc al volume and number of episodes or duration of illness, suggesting the hippoc us might be larger in the early phase of bipolar disorder but becomes smaller with time.
Mortality and Institutionalization in Early Survivors of Stroke: The Effects of Cognition, Vascular Mild Cognitive Impairment, and Vascular Dementia
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.JSTROKECEREBROVASDIS.2009.09.006
Abstract: We explored th effects of vascular mild cognitive impairment (VaMCI), vascular dementia (VaD), and other predictors on mortality and institutionalization in early survivors of ischemic stroke without previous dementia who had been admitted to a stroke unit. A total of 202 consecutive consenting eligible ischemic stroke survivors and a matched s le of 97 community controls were followed for up to 10 years. Data for 167 patients who underwent detailed assessment 3-6 months after stroke were analyzed to determine predictors of outcomes. Cumulative mortality rates for patients (and controls) were 27% (4%) for the first 5 years and rose to 83% (10%) by 10 years. Predictors of mortality were older age, any cognitive impairment, less independent function, and less education. Nursing home admission rates were 24% at 5 years and 32% at 10 years for patients and 0 for controls over 8.9 years. Predictors of institutionalization were less independent function and older age. Patients with ischemic stroke who survive the first week have moderate, lower-than-expected mortality rates in the first 5 years that increase thereafter. VaMCI, VaD, and functional decline are predictors of mortality, while functional decline and older age predict institutionalization.
Cell therapy plus voluntary running rescues memory dysfunction in a rodent model of brain ageing
Publisher: Wiley
Date: 07-2011
Can the clinical dementia rating Scale identify mild cognitive impairment and predict cognitive and functional decline?
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000447057
Abstract: b i Background: /i /b The Clinical Dementia Rating Scale (CDR) is used to rate dementia severity. Its utility in diagnosing mild cognitive impairment (MCI) and its predictive value remain unknown. b i Aims: /i /b The aim of this study was to examine the association between CDR scores and expert MCI diagnosis, and to determine whether baseline CDR scores were predictive of cognitive or functional decline and progression to dementia over 6 years. b i Methods: /i /b At baseline, the s le comprised 733 non-demented participants aged 70-90 years from the longitudinal Sydney Memory and Ageing Study. Global and sum of boxes CDR scores were obtained at baseline. Participants also received comprehensive neuropsychological and functional assessment as well as expert consensus diagnoses at baseline and follow-up. b i Results: /i /b At baseline, CDR scores had high specificity but low sensitivity for broadly defined MCI. The balance of sensitivity and specificity improved for narrowly defined MCI. Longitudinally, all baseline CDR scores predicted functional change and dementia, but CDR scores were not predictive of cognitive change. b i Conclusion: /i /b CDR scores do not correspond well with MCI, except when MCI is narrowly defined, suggesting that the CDR taps into the more severe end of MCI. All CDR scores usefully predict functional decline and incident dementia.
Early life affects late-life health through determining DNA methylation across the lifespan: A twin study
Publisher: Elsevier BV
Date: 03-2022
Vanadium oxide supported on non-stoichiometric strontium hydroxyapatite catalysts for the oxidative dehydrogenation of n-octane
Publisher: Elsevier BV
Date: 12-2014
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
Publisher: Springer Science and Business Media LLC
Date: 04-2023
DOI: 10.1038/S41591-023-02268-W
Abstract: Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults ( N = 1,748 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort ( N = 2,862 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippoc al PVS, and of basal ganglia PVS and hippoc al PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.
Differential expression of synaptic and interneuron genes in the aging human prefrontal cortex
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.NEUROBIOLAGING.2018.06.011
Abstract: Altered inhibition-excitation balance is implicated in brain aging. We hypothesized that expression of 14 genes encoding proteins localized to synapses or interneurons would show age-related changes relative to 1 another in postmortem tissue from the prefrontal cortex of 37 in iduals (18-78 years) and that synaptic or interneuron markers would be differentially correlated with human brain volumes across aging. The majority of genes examined were differentially expressed with age, most being downregulated. Expression of 3 interneuron-related genes was significantly negatively associated with age (calbindin, somatostatin, cholecystokinin), whereas 3 synapse-related genes showed significant age-related expression change (PSD95, GAP43, VGLUT1). On covarying for 2 glial markers (GFAP, IBA1), all 3 interneuron genes and 1 synaptic gene (Growth-associated protein 43) remained significant. Two genes were significantly associated with total brain volume (calbindin, complexin 2) and a marker of synaptic density (synaptophysin) was significantly associated with cortical gray matter volume. Age-related change in expression of genes involved in maintenance of inhibition-excitation balance and regulation of prefrontocortical network dynamics suggests these pathways may contribute to brain aging.
O3‐03‐06: How to define the cognitive impairment in Mild Cognitive Impairment: Comparison of different neuropsychological classification methods using data from the Sydney Memory and Ageing Study
Publisher: Wiley
Date: 07-2009
Psychological well-being in individuals with mild cognitive impairment
Publisher: Informa UK Limited
Date: 05-2014
DOI: 10.2147/CIA.S58866
Antidepressant Effects of ECT may be related to Hippocampal Neurogenesis
Publisher: Elsevier BV
Date: 03-2015
Alpha-synuclein transmission and mitochondrial toxicity in primary human foetal enteric neurons in vitro
Publisher: Springer Science and Business Media LLC
Date: 12-09-2014
DOI: 10.1007/S12640-013-9420-5
Abstract: Parkinson's disease (PD) is a multicentred neurodegenerative disorder characterised by the accumulation and aggregation of alpha-synuclein (α-syn) in several parts of the central nervous system. However, it is well established that PD can generate symptoms of constipation and other gastrointestinal problems and α-syn containing lesions have been identified in intestinal nerve cells. In this study, we show that α-syn can be taken up and accumulate in primary human foetal enteric neurons from the gastrointestinal tract and can be transferred between foetal enteric neurons. Impaired proteosomal/lysosomal degradation can promote the uptake and accumulation of α-syn in enteric neurons. Enteric neurons exposed to α-syn can also lead to impaired mitochondrial complex I activity, reduced mitochondrial function, and NAD(+) depletion culminating in cell death via energy restriction. These findings demonstrate neuron-to-neuron transmission of α-syn in enteric neurons, providing renewed evidence for Braak's hypothesis and the aetiology of PD.
Screening plasma for biomarkers of mild cognitive impairment and Alzheimer's disease by quantitative proteomic methods
Publisher: Wiley
Date: 07-2010
Frequency and clinical, neuropsychological and neuroimaging correlates of apathy following stroke - The Sydney Stroke Study
Publisher: Cambridge University Press (CUP)
Date: 05-10-2005
DOI: 10.1017/S0033291705006173
Abstract: Background. The frequency and clinical, neuropsychological and neuroimaging correlates of apathy in patients who have had a stroke are inadequately defined. Method. A total of 167 consecutive patients admitted to the stroke units of two university hospitals after an ischaemic stroke and 109 controls received extensive medical, psychiatric and neuropsychological assessments a subset received a magnetic resonance imaging (MRI) scan. The groups were matched for sex and age. Patients were assessed 3–6 months after their stroke. The s le for this study comprised 135 patients and 92 controls who completed the Apathy Evaluation Scale (AES). Results. Apathy was present in 26·7% of stroke patients compared to 5·4% of controls. Apathetic stroke patients were older, more functionally dependent and had lower Mini-Mental State Examination (MMSE) scores than those without apathy. Apathy was not associated with risk factors for cerebrovascular disease or stroke severity. There was a weak but significant correlation between apathy and self-reported depression but not with clinician-rated depression. Neuropsychologically, after correction for age, premorbid intelligence (IQ) and depression, apathy was associated with reduced attention and speed of information processing. On neuroimaging there were trends for associations of apathy with the extent of hyperintensities in the right hemisphere and right fronto-subcortical circuit, but not with total stroke volume or number of strokes. Conclusions. Apathy is common following a cerebrovascular event. Presence of apathy may be related to older age and right fronto-subcortical pathway pathology, rather than stroke severity. It is associated with functional impairment and cognitive deficits.
White matter hyperintensities in the forties: Their prevalence and topography in an epidemiological sample aged 44-48
Publisher: Wiley
Date: 08-05-2009
DOI: 10.1002/HBM.20586
A rating scale for neuroleptic malignant syndrome
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.PSYCHRES.2005.05.003
Abstract: The development of a rating scale for neuroleptic malignant syndrome (NMS) is described. The clinical and laboratory features of NMS were categorised into six domains after a thorough literature review and examination of patients. The reliability of this scale was established on 25 NMS patients and 50 control subjects based on chart reviews. A factor analysis supported a six-factor solution. The validity of the scale was indicated by the relationship of the severity rating to duration of illness and outcome. The inter-rater reliability of the scale was established prospectively in 10 subjects. The scale offers a measure of severity of NMS in the clinical setting so as to support the clinical diagnosis, monitor patients and determine their progress. The scale may be applicable not only to NMS or suspected NMS but also to NMS-like syndromes such as lethal catatonia.
Diagnostic Criteria for Vascular Cognitive Disorders
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2014
P4‐153: Subjective Cognitive Decline and Progression to Dementia Due to AD and Non‐AD in Memory Clinic and Community‐Based Cohorts
Publisher: Wiley
Date: 07-2016
Altered functional connectivity strength in informant‐reported subjective cognitive decline: A resting‐state functional magnetic resonance imaging study
Publisher: Wiley
Date: 2018
Cerebral small vessel disease and the risk of Alzheimer’s disease: A systematic review
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.ARR.2018.06.002
Abstract: Cerebral small vessel disease (CSVD) comprises a variety of disorders affecting small arteries and microvessels of the brain, manifesting as white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and deep brain infarcts. In addition to its contribution to vascular dementia (VaD), it has also been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). A systematic review of the literature available on Medline, Embase and Pubmed was undertaken, whereby CSVD was ided into WMHs, CMBs and deep brain infarcts. Biomarkers of AD pathology in the cerebrospinal fluid or plasma, or positron emission tomographic imaging for amyloid and/or tau deposition were used for AD pathology. A total of 4117 articles were identified and 41 articles met criteria for inclusion. These consisted of 17 articles on vascular risk factors for clinical AD, 21 articles on Aβ pathology and 15 articles on tau pathology, permitting ten meta-analyses. CMBs or lobar CMBs were associated with pooled relative risk (RR) of AD at 1.546, (95%CI 0.842-2.838, z = 1.41 p = 0.160) and 1.526(95%CI 0.760-3.063, z = 1.19, p = 0.235) respectively, both non-significant. Microinfarcts were associated with significantly increased AD risk, with pooled odds ratio OR at 1.203(95%CI 1.014-1.428, 2.12 p = 0.034). Aβ pathology was significantly associated with WMHs in AD patients but not in normal age-matched controls. The pooled β (linear regression) for total WMHs with CSF Aβ42 in AD patients was -0.19(95%CI -0.26-0.11, z = 4.83 p = 0.000) and the pooled r (correlation coefficient) for WMHs and PiB in the normal population was -0.10 (95%CI -0.11-0.30, 0.93 p = 0.351). CMBs were significantly associated with Aβ pathology in AD patients. The pooled standardized mean difference (SMD) was -0.453, 95%CI -0.697- -0.208, z = 3.63 p = 0.000. There was no significant relationship between the incidence of lacunes and levels of CSFAβ, with a pooled β of 0.057 (95%CI -0.050-0.163, z = 1.05 p = 0.295). No significant relationship was found between CMBs and the levels of CSFt-tau/CSFp-tau in AD patients (-0.014, 95%CI -0.556-0.529, z = 0.05 p = 0.960 -0.058, 95%CI -0.630-0.515, z = 0.20 p = 0.844) and cortical CMBs and CSF p-tau in the normal population (0.000, 95%CI -0.706-0.706, z = 0.00 p = 0.999). Some CSVD markers were significantly associated with clinical AD pathology and may be associated with Aβ/tau pathology. WMHs and microinfarcts were associated with increased risk of AD. It remains unclear whether they precede or follow AD pathology.
The ageing brain: A symposium
Publisher: SAGE Publications
Date: 12-2001
Dementia: new projections and time for an updated response.
Publisher: SAGE Publications
Date: 11-2005
Spatially constrained fuzzy hyper-prototype clustering with application to brain tissue segmentation
Publisher: IEEE
Date: 12-2010
CORRIGENDUM
Publisher: Cambridge University Press (CUP)
Date: 12-03-2007
Ethical issues of a doctors' strike.
Publisher: BMJ
Date: 03-1986
DOI: 10.1136/JME.12.1.53
Abstract: To study the ocular and extra-ocular features, clinical presentation, and treatment of prickly pear glochids. This retrospective study included 23 eyes of 21 patients with ocular prickly pear spines who were seen between August and October 2011 in the outpatient ophthalmic clinic at Prince Rashid Bin Al Hassan military hospital in Jordan. Medical records of patients including age, gender, history of exposure to prickly pear plants, and ocular examination were reviewed. All glochids were localized and removed with forceps under topical anesthesia with the patient at the slit l . Patients were followed up after one week. The mean age of patients was 37.1 years with a male to female ratio of 1.6: 1. Involvement of the right eye was seen in 61.9% patients, left eye in 28.6% patients, and bilateral involvement in 9.5% patients. Glochids were most commonly found in the upper subtarsal conjunctival space (47.6%) followed by inferior palpebral conjunctiva in 23.8% eyes. The most common complaint was eye irritation in 95.2% patients. Pain was a complaint in 57.1% patients. Superior corneal epithelial erosions or ulcer were found in 33.3% patients, inferior corneal epithelial erosions in 19.1% patients, and diffuse epithelial erosions in 9.5% patients. Glochids were found in other parts of the body in 38.1% patients. Although prickly pear glochid ocular surface injury is not uncommon in the region during summer, it should be considered in patient with eye pain during that period. Farmers who are in close contact with prickly pears should use protective eyeglasses and gloves.
Editorial introductions
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
P3‐071: A GENOME‐WIDE META‐ANALYSIS OF PLASMA CLUSTERIN LEVELS IN THE CHARGE CONSORTIUM
Publisher: Wiley
Date: 07-2014
A Review of Tobacco, Alcohol, Adiposity, and Activity as Predictors of Cognitive Change
Publisher: Informa UK Limited
Date: 03-2012
Risk Profiles of Subtypes of Mild Cognitive Impairment: The Sydney Memory and Ageing Study
Publisher: Wiley
Date: 05-12-2011
DOI: 10.1111/J.1532-5415.2011.03774.X
Abstract: To compare the risk profiles of mild cognitive impairment (MCI) subtypes in a population-based elderly s le. Cross-sectional study. The population-based Sydney Memory and Ageing Study. Seven hundred fifty-seven English-speaking, community-dwelling in iduals without dementia aged 70 to 90. Comprehensive neuropsychological assessments were used to diagnose MCI and its subtypes, categorized as amnestic (aMCI) or nonamnestic (naMCI) and as single- (sdMCI) or multiple- (mdMCI) domain. Risk profiles were derived from sociodemographic lifestyle and cardiac, physical, mental, and general health data. Whole-s le and sex-specific comparisons between aMCI and naMCI and between mdMCI and sdMCI were made using age- (and sex-) adjusted multiple regressions comprising initially significant univariate factors. Risk factors for MCI were presence of the apolipoprotein E (APOE) ε4 allele, heart disease, high homocysteine, poor odor identification ability, low visual acuity, and lower mental activity. The odds of having naMCI rather than aMCI were lower with greater levels of social activity and greater if taking antihypertensives, the latter particularly in men. The odds of naMCI were greater in men taking antidepressants or with a longer 6-meter walk time and in women with hypertension. The odds of having mdMCI rather than sdMCI were greater in participants with a history of depression or having the APOE ε4 allele. Greater odds of mdMCI were also associated with lower mental activity, particularly for women. For men, the odds of mdMCI were greater with the APOE ε4 allele and lower if diagnosed with high cholesterol. MCI subtypes exhibit distinctive, sex-dependent risk profiles. This is consistent with MCI subtypes having different etiologies and outcomes and supports the idea that subtyping MCI may offer predictive validity and clinical application.
DNA Gyrase Is the Target for the Quinolone Drug Ciprofloxacin in Arabidopsis thaliana
Publisher: Elsevier BV
Date: 02-2016
Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: A pilot investigation
Publisher: Wiley
Date: 16-05-2005
DOI: 10.1111/J.1440-1819.2005.01382.X
Abstract: In an open study, four subjects with a stable deficit syndrome of schizophrenia received high frequency repetitive transcranial magnetic stimulation (15 Hz at 90% of motor threshold, 1800 pulses each session, daily for 20 sessions over 4 weeks) over the left dorsolateral prefrontal cortex. Subjects showed a significant reduction in negative symptoms and improvement in function, with no change in positive symptoms. This improvement was maintained at the 1 month follow up. Repetitive transcranial magnetic stimulation as a treatment of the deficit syndrome of schizophrenia is feasible, safe and may be beneficial. A systematic study in randomized control trials would be appropriate.
NUMBER OF FACE-TO-FACE CONTACTS PREDICTS VARIANCE IN COGNITIVE FUNCTION IN HEALTHY OLDER ADULTS
Publisher: Wiley
Date: 07-2018
P2–035: Development of a targeted mass spectrometry method for accurate quantification of human sirtuins in biological samples
Publisher: Wiley
Date: 07-2013
Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume
Publisher: Springer Science and Business Media LLC
Date: 26-09-2018
DOI: 10.1038/S41467-018-06234-W
Abstract: The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly in iduals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes ( ρ genetic = −0.59, p -value = 3.14 × 10 −6 ), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.
Lifetime cigarette smoking is associated with striatal volume measures
Publisher: Wiley
Date: 11-03-2012
DOI: 10.1111/J.1369-1600.2010.00301.X
Abstract: Nicotine, the primary addictive component of tobacco, affects the mammalian brain. Smokers' brains have smaller cortical grey matter volumes and/or lower densities compared with non-smokers'. Differences in subcortical structures like the striatum are however, less clear. A high concentration of nicotinic receptors makes the striatum a potential target for nicotine. In addition, striatal nuclei are essential components of the reward/reinforcement pathway involved in addiction. The aim of this study was to explore the relationship between striatal nuclei (caudate, putamen and nucleus accumbens area) volumes and lifetime smoking in a large community-based s le of 'young-old' in iduals. Brain volumes were measured using a semi-automated method in 315 participants aged 64-70 years who were selected from a larger randomly s led cohort and who consented to a magnetic resonance imaging scan. Multiple regression analysis was used to assess the relationship between striatal volumes and cigarette smoking measures while controlling for age, sex, intracranial and total brain volumes and general physical and mental health measures. Greater lifetime use of cigarettes (measured in pack-years) was associated with smaller left nucleus accumbens area volume (P = 0.018) and larger left putamen volume (P = 0.025). Greater putaminal volume was also associated with a lower age at smoking initiation (P = 0.004). In this generally healthy cohort, lifetime use of cigarettes is significantly associated with striatal volume measures. These changes could indicate predisposing factors for nicotine addiction, or an effect of chronic nicotine exposure or a combination of both.
The twilight of dementia
Publisher: Elsevier BV
Date: 11-2010
Hippocampal sulcal cavities: Prevalence, risk factors and relationship to memory impairment
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.BRAINRES.2010.10.089
Abstract: While hippoc al volumes have been extensively examined in neuropsychiatric disorders and ageing, small areas of signal variation within the hippoc us commonly observed on MRI, described as hippoc al sulcal cavities (HSCs), have received less attention. We review the published literature on HSCs to examine their prevalence, putative aetiological factors such as hypertension, and possible cognitive correlates. HSCs were reported in 77% (66% weighted mean) of patients with memory disorders and 48% (47% weighted mean) of controls, and the prevalence increased with age in healthy subjects (r=0.64, p=0.047). A number of studies reported hypertension as a risk factor, and related their presence to poorer memory function. Further work is needed to fully understand the clinical significance of these lesions.
MAINTAIN YOUR BRAIN : A RANDOMISED CONTROLLED TRIAL OF AN INTERNET-BASED MULTI-COMPONENT LIFESTYLE INTERVENTION TO PREVENT COGNITIVE DECLINE AND DEMENTIA
Publisher: Wiley
Date: 07-2017
Genetic influences on five measures of processing speed and their covariation with general cognitive ability in the elderly: The older Australian twins study
Publisher: Springer Science and Business Media LLC
Date: 27-05-2012
DOI: 10.1007/S10519-011-9474-1
Abstract: Processing speed (PS) is one of the basic elements of cognitive functions and has been regarded as a "common mechanism" which mediates general cognitive decline in aging. The present study of Australian twins (117 monozygotic pairs, 98 dizygotic pairs, and 42 single twins aged 65 years and over), estimated the genetic influences in five measures of PS: Digit Symbol Coding (DS), Trail Making Test A (TMTA), Stroop color naming and word reading (Stroop), Simple Reaction Time (SRT) and Complex Reaction Time (CRT) and their covariation with general cognitive ability (GCA): reasoning, problem-solving, and memory. Additive genetic factors explained 62% of the variance in DS, 42% in TMTA, 57% in Stroop, and 48% and 35% in SRT and CRT, respectively. Quantitative genetic modeling showed that all of the covariation between the five PS measures and GCA could be explained by one common genetic factor, while the covariation between the PS measures was partly explained by non-shared environmental as well as genetic influences. The genetic correlation among the PS measures was strongest for DS and TMTA, and between the PS measures and GCA was strongest for DS. These findings suggest that the different PS measures, as well as GCA were to a large extent influenced by the same set of genes and that the relationship between PS and GCA is entirely due to shared-genetic influences.
Age-related cortical thinning in cognitively healthy individuals in their 60s: The PATH Through Life study
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.NEUROBIOLAGING.2015.12.009
Abstract: Although it is recognized that the human cortex thins with age, longitudinal estimates of thinning patterns specific to healthy young-old age (<75 years) in iduals are lacking. Importantly, many neurodegenerative disorders first manifest between midlife and old age, and normative estimates may provide a reference for differential change associated with such disorders. Here, we provide longitudinal estimates of cortical thinning observed over 12 years in a large group (n = 396) of healthy in iduals, aged 60-66 years at baseline scan, who were scanned with magnetic resonance imaging (1.5T) on 4 occasions. Longitudinal age-related thinning was observed across most of the cortices, with a mean change of -0.3% per year. We measured significant thinning in heteromodal association cortex, with less thinning in regions expected to atrophy later in life (e.g., primary sensory cortex). Men showed more extensive thinning than women. Our comparison of cross-sectional and longitudinal estimates adds to growing evidence that cross-sectional designs may underestimate age-related changes in cortical thickness.
Follow-up of mild cognitive impairment and related disorders over four years in adults in their sixties: The PATH through life study
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000154646
Abstract: i Aims: /i The study aimed to estimate incidence rates of mild cognitive impairment and related disorders, and conversion to dementia. i Methods: /i The data are drawn from the PATH Through Life Study. Baseline assessment in 2001–2002 included 2,551 participants 60–64 years old with 2,222 participating in a 4-year follow-up. Those screened positive with a cognitive assessment received clinical assessment for diagnoses of mild cognitive disorders (MCD) or dementia using established clinical criteria. Prevalence and incidence rates for the cohort were estimated with predictive regression models. i Results: /i Annual incidence of dementia was 0.25%. Prevalence of mild cognitive impairment was 4.2%, age-associated memory impairment was 2.4%, age-associated cognitive decline was 7.6%, mild neurocognitive disorders occurred in 12.9% and other cognitive disorders in 7.3%. Prevalence of any diagnosis of any MCD (Any-MCD) was 29.5% and the annual incidence rate for Any-MCD was 5.7%. Agreement for specific diagnoses between waves 1 and 2 was fair to poor (0–47.0%), but agreement for Any-MCD over 4 years was 89.0%. i Conclusion: /i MCD diagnoses do not predict dementia at a 4-year follow-up in young-old adults. Prevalence rates for MCD vary greatly depending on the criteria and time of assessment.
A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease
Publisher: Wiley
Date: 02-05-2014
Cognition, function, and prevalent dementia in centenarians and near‐centenarians: An individual participant data (IPD) meta‐analysis of 18 studies
Publisher: Wiley
Date: 12-2022
DOI: 10.1002/ALZ.12828
Abstract: There are limited data on prevalence of dementia in centenarians and near‐centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. Participant‐level data were obtained from 18 community‐based studies ( N = 4427) in 11 countries that included in iduals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta‐analysis was performed. The mean age was 98.3 years (SD = 2.67) 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95 .92–0.98) was protective, as was hypertension (odds ratio [OR] 0.51 .35–0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia‐free survival in C/NC remain to be understood.
Dementia prevention: The discordance between observational and intervention studies and the search for more evidence
Publisher: Wiley
Date: 02-2009
Utility of intraindividual reaction time variability to predict white matter hyperintensities: A potential assessment tool for clinical contexts?
Publisher: Cambridge University Press (CUP)
Date: 08-08-2013
DOI: 10.1017/S1355617713000830
Abstract: Intrain idual variability (IIV) refers to reaction time (RT) variation across the trials of a given cognitive task. Little research has contrasted different measures of IIV or assessed how many RT trials are required to provide a robust measure of the construct. We, therefore, investigated three measures of IIV (raw SD , coefficient of variation, and intrain idual SD statistically removing time-on-task effects) in relation to frontal white matter hyperintensities (obtained through structural MRI) in 415 cognitively normal community-dwelling adults aged 44 to 48 years. Results indicated the three IIV measures did not differ greatly in predictions of white matter hyperintensities, although it is possible that time-on-task effects were influential. As few as 20 trials taking approximately 52 s to administer provided a reliable prediction of frontal white matter hyperintensities. We conclude that future work should evaluate the comparative utility of different IIV measures in relation to persons exhibiting clear neuropathology. ( JINS , 2013, 19 , 1–6)
Neuropsychiatry and neurophilosophy
Publisher: Cambridge University Press (CUP)
Date: 06-2007
WHAT HAPPENS TO THE HIPPOCAMPUS 12-MONTHS AFTER TRAINING? LONGITUDINAL LINEAR MIXED EFFECTS MODEL ANALYSIS OF MILD COGNITIVE IMPAIRMENT IN THE SMART TRIAL
Publisher: Wiley
Date: 07-2017
Validated Alzheimer’s Disease Risk Index (ANU-ADRI) is associated with smaller volumes in the default mode network in the early 60s
Publisher: Springer Science and Business Media LLC
Date: 14-12-2019
An epigenome-wide association study meta-analysis of educational attainment
Publisher: Springer Science and Business Media LLC
Date: 31-10-2017
DOI: 10.1038/MP.2017.210
The Vascular Behavioral and Cognitive Disorders criteria for vascular cognitive disorders: a validation study
Publisher: Wiley
Date: 17-05-2019
DOI: 10.1111/ENE.13960
Abstract: The Vascular Behavioral and Cognitive Disorders (VASCOG) criteria for vascular cognitive disorders were published in 2014, but their concurrent and predictive validity have not been examined. Participants (N = 165, aged 49-86 years) were from Sydney Stroke Study, a longitudinal study of post-stroke cognitive impairment and dementia. Diagnoses using the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN), the Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for vascular dementia (VaD) were made by consensus at multidisciplinary case conferences. Diagnoses for mild vascular cognitive disorder (mVCD) and VaD using VASCOG, DSM-5 and the Vascular Impairment of Cognition Classification Consensus Study (VICCCS) criteria were made by two study authors. Agreement levels between criteria sets were examined using Cohen's kappa (κ). The ability of VaD diagnoses to predict mortality over 10 years and of mVCD to predict dementia over 5 years was investigated. The VASCOG criteria yielded rates of mVCD slightly lower than for DSM-5 and VICCCS. VaD rates were similar for all criteria, although slightly lower for DSM-IV. Agreement between the VASCOG, VICCCS and DSM-5 criteria was excellent for VaD and mVCD (κ = 0.83-1.0), but lower for VaD between VASCOG and the other criteria (κ = 0.47-0.63). VaD-based mortality predictions were similar for the VASCOG, VICCCS and DSM-5 criteria, and higher than those for other criteria. The prediction of incident dementia within 5 years from mVCD was slightly lower with VASCOG criteria than with DSM-5 and VICCCS criteria. The VASCOG criteria have greater sensitivity, modest concurrent validity and better predictive validity than older criteria for VaD, but are comparable to DSM-5 and VICCCS criteria. Their operationalization and inclusion of a mild VCD category make them useful for clinical and research applications.
The heritability of amyloid burden in older adults: the Older Australian Twins Study.
Publisher: BMJ
Date: 17-12-2021
Abstract: To determine the proportional genetic contribution to the variability of cerebral β-amyloid load in older adults using the classic twin design. Participants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females mean age: 71.14 (5.15) years) were drawn from the Older Australian Twins Study. Participants underwent detailed clinical and neuropsychological evaluations, as well as MRI, diffusion tensor imaging (DTI) and amyloid PET scans. Fifty-eight participants (17 MZ pairs, 12 DZ pairs) had PET scans with 11 Carbon-Pittsburgh Compound B, and 148 participants (44 MZ pairs, 30 DZ pairs) with 18 Fluorine-NAV4694. Cortical amyloid burden was quantified using the centiloid scale globally, as well as the standardised uptake value ratio (SUVR) globally and in specific brain regions. Small vessel disease (SVD) was quantified using total white matter hyperintensity volume on MRI, and peak width of skeletonised mean diffusivity on DTI. Heritability ( h 2 ) and genetic correlations were measured with structural equation modelling under the best fit model, controlling for age, sex, tracer and scanner. The heritability of global amyloid burden was moderate (0.41 using SUVR 0.52 using the centiloid scale) and ranged from 0.20 to 0.54 across different brain regions. There were no significant genetic or environmental correlations between global amyloid burden and markers of SVD. Amyloid deposition, the hallmark early feature of Alzheimer’s disease, is under moderate genetic influence, suggesting a major environmental contribution that may be amenable to intervention.
Novel genetic loci associated with hippocampal volume
Publisher: Springer Science and Business Media LLC
Date: 18-01-2017
DOI: 10.1038/NCOMMS13624
Abstract: The hippoc al formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippoc al volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippoc al structure here we perform a genome-wide association study (GWAS) of 33,536 in iduals and discover six independent loci significantly associated with hippoc al volume, four of them novel. Of the novel loci, three lie within genes ( ASTN2 , DPP4 and MAST4 ) and one is found 200 kb upstream of SHH . A hippoc al subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippoc al volume are also associated with increased risk for Alzheimer’s disease ( r g =−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippoc al volume and risk for neuropsychiatric illness.
The application of lipidomics to biomarker research and pathomechanisms in Alzheimer's disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
Neuroleptic-induced respiratory dyskinesia.
Publisher: American Psychiatric Association Publishing
Date: 05-1995
DOI: 10.1176/JNP.7.2.223
Abstract: Respiratory dyskinesia is a common but under-recognized side effect of chronic neuroleptic administration. It manifests as irregular respiration, dyspnea, grunting or gasping, and abnormal chest or esophageal movements. It occurs almost exclusively in association with other tar e effects of neuroleptics, such as tar e dyskinesia and tar e akathisia. Complications of the disorder include respiratory alkalosis and aspiration pneumonia. The authors describe 5 patients with respiratory dyskinesia whose cases highlight the important clinical features of neuroleptic-induced respiratory dyskinesia and the manner in which some cases may be misdiagnosed. They also review the literature on this syndrome and discuss the likely pathophysiological mechanisms.
The development of the concept of akathisia: a historical overview
Publisher: Elsevier BV
Date: 07-1995
DOI: 10.1016/0920-9964(94)00058-G
Abstract: This paper traces the history of 'akathisia' and related syndromes, and examines the important studies that have helped shape our current understanding of the concept. Even though the term has come to be used synonymously with drug-induced akathisia, its origin was in the pre-neuroleptic era, and it is still often used to describe syndromes not related to medication. The literature clearly distinguishes restless legs syndrome (RLS) from akathisia. The complexity of the akathisia syndrome has increasingly become manifest, and a number of sub-types have been described. Recent attempts have been made to operationalize its diagnostic criteria and understand its pathophysiology. Akathisia due to non-neuroleptic drugs, in particular the serotonin-specific reuptake inhibitors (SSRIs), has also received much attention. The development of newer psychopharmacotherapeutic drugs, with different side-effects profiles, has made this focus pertinent and timely.
The 10-Item Kessler Psychological Distress Scale (K10) as a Screening Instrument in Older Individuals
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JAGP.2013.01.009
Abstract: To provide population-based Kessler Psychological Distress Scale (K10) normative data for older adults and cut scores for screening. Adults age ≥65 years who participated in either the 1997 or 2007 Australian National Surveys of Mental Health and Well-being (N = 3,697). The proportion of respondents who reported psychological distress, and the correspondence of K10 scores with diagnosis of mental disorder, disability, and service use. Scores on the K10 corresponded well with rates of mental disorder. Higher K10 scores were associated with increased levels of internalizing disorder, comorbidity, functional disability, and service use. Receiver operating characteristic curve analysis revealed an area under the curve score of 0.86, suggesting good predictive power. For screening purposes, a cut score of 15 was found to be associated with the best balance between sensitivity (0.77) and specificity (0.78). Similar levels of predictive power were observed across various subgroups of the population. Score ranges for groups who met criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition affective or anxiety disorder showed that for those age 65-75, a score of 20 or greater and a score of 17 or greater for those older than 75 years warrant heightened clinical interest. The K10 exhibits sensitivity to internalizing disorders as they occur across the lifespan and can be used with confidence when assessing psychological distress in old-age community dwellers. The significant association between higher K10 scores and disability suggests that the presence of psychological distress, regardless of diagnostic status, requires clinician attention.
Editorial
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
Repetitive transcranial magnetic stimulation as treatment for anxiety disorders
Publisher: Informa UK Limited
Date: 10-2008
DOI: 10.1586/14737175.8.10.1449
Abstract: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and generally well-tolerated method of focally stimulating brain regions. It has been shown to be efficacious in the treatment for depression, but only to a limited degree. It has also been investigated for the treatment of some anxiety disorders, particularly obsessive-compulsive disorder, post-traumatic stress disorder and panic disorder. While anecdotal reports and open studies have suggested a therapeutic role for rTMS in anxiety disorders, controlled studies, which have varied greatly in terms of rTMS administration, have not shown it to be superior to placebo. Furthermore, reports in animal models of anxiety have not been consistent. Therefore, to date, there is no convincing evidence for the clinical role of rTMS in anxiety disorders. Further research is needed, drawing on advances in our understanding of pathological neurocircuitry in anxiety disorders and the mechanisms of action by which rTMS may alter that neurocircuitry. With advances in neuroimaging technology, this understanding is likely to be more accessible than it has been in the past.
Is a lack of disgust something to fear? A functional magnetic resonance imaging facial emotion recognition study in euthymic bipolar disorder patients
Publisher: Wiley
Date: 06-2007
DOI: 10.1111/J.1399-5618.2007.00485.X
Abstract: To determine the neural responses invoked in the recognition of facial fear and disgust in euthymic bipolar patients as compared with healthy subjects. This study examined 10 female euthymic bipolar patients, and 10 suitably matched healthy subjects using functional magnetic resonance imaging (fMRI) while subjects were engaged in an explicit facial emotion recognition task involving fear, disgust and neutral expressions. The activation paradigm involved nominating the facial expression using specified response keys. Behavioural data were collected and analysed and both within-group (Fear versus Neutral Disgust versus Neutral) and random-effects between-group analyses were performed on fMRI data using BrainVoyager (Brain Innovations, Maastricht, the Netherlands). Patients were equally accurate in identifying facial expressions as healthy subjects but were slower to respond, especially with respect to fear and disgust. Responses to fear and disgust (within-group analyses) resulted in activation of anticipated brain regions such as amygdala and insula, respectively. However, between-group random effects analysis revealed differential responses to both disgust and fear in both healthy subjects and euthymic bipolar patients such that euthymic bipolar patients responded largely to fear and healthy subjects responded more so to disgust. This partitioning of responsiveness was reflected by differential activation involving the hippoc us and amygdala. Greater responsiveness to fear with hippoc al activation in patients perhaps reflects recollection of traumatic events associated with past experiences of illness or simply the use of a more mnemonic (hippoc al) as opposed to affective (amygdala) approach when performing the task. It is possible that in bipolar disorder, prefrontal-subcortical network dysfunction that relegates neural processing to limbic regions is impaired and that clinically euthymic bipolar patients, although able to accurately and effectively identify emotions such as fear and disgust, are limited in their ability to interpret their salience. The implications of these findings are discussed.
Cognitive generation of affect in bipolar depression: an fMRI study
Publisher: Wiley
Date: 30-01-2004
DOI: 10.1111/J.0953-816X.2003.03159.X
Abstract: In iduals with bipolar disorder manifest the full spectrum of emotions ranging from depression to mania. In attempting to understand the functional substrates of mood we attempted to identify brain regions associated with the cognitive generation of affect in bipolar depressed patients. We therefore examined ten depressed female subjects with bipolar affective disorder, and ten age-matched and sex-matched healthy comparison subjects using functional magnetic resonance imaging (fMRI) while viewing alternating blocks of captioned pictures designed to evoke negative, positive or no affective change. The activation paradigm involved the presentation of the same visual materials over three experiments alternating (experiment 1) negative and reference (experiment 2) positive and reference and (experiment 3) positive and negative captioned pictures. The stimuli produced activation in both patients and comparison subjects in brain regions previously implicated in the generation and modulation of affect, in particular the prefrontal and anterior cingulate cortices. The activation in patients, when compared with healthy subjects, involved additional subcortical regions, in particular the amygdala, thalamus, hypothalamus and medial globus pallidus. Patients and comparison subjects displayed differential sensitivity to affective change with negative (experiment 1) and positive (experiment 2) affect induction producing converse patterns of activation. We conclude that bipolar depressed patients perhaps recruit additional subcortical limbic systems for emotional evaluation and this may reflect state-related or trait-related dysfunction. The differential patterns of activation inform us about bipolar depression and have potential diagnostic and therapeutic significance.
Alternating and postictal psychoses: Review and a unifying hypothesis
Publisher: Oxford University Press (OUP)
Date: 15-03-2007
Obsessive-compulsive behaviour: a disorder of decision-making.
Publisher: SAGE Publications
Date: 09-2005
DOI: 10.1080/J.1440-1614.2005.01680.X
Abstract: Objective: Compulsive in iduals are habitually indecisive, and indecision reaches its pathological apex in obsessive–compulsive disorder (OCD). With the increasing interest in the neurobiology of decision-making, it may be useful to conceptualize OCD as a disorder of decision-making. Method: A selective review of the neurobiological studies of the decision-making process was performed, and the convergence with the understanding of the neurobiology of OCD examined. Results: The dorsolateral, orbitofrontal and anterior cingulate cortices are engaged in multiregion neural subsystems that interact with each other to retain information online, manipulate options, make choices and maintain goals. These interact with the limbic regions, especially the amygdala, in relation to history of reward and emotional valence relating to a choice, and the basal ganglia for behavioural execution. Abnormalities in these regions also characterize OCD and related disorders, therefore leading to problems in making some decisions that are affect-laden by nature or association. Conclusion: Conceptualizing OCD as a disorder of decision-making leads to new approaches for its investigation, and novel strategies for both physical and behavioural– cognitive treatments.
The Brain Effects of Laser Acupuncture in Healthy Individuals: An fMRI Investigation
Publisher: Public Library of Science (PLoS)
Date: 07-09-2010
White matter hyperintensities: lateralization effects.
Publisher: Cambridge University Press (CUP)
Date: 12-2006
Western diet is associated with a smaller hippocampus: A longitudinal investigation
Publisher: Springer Science and Business Media LLC
Date: 08-09-2015
Brain dysfunction in anorexia nervosa: cause or consequence of under-nutrition?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
Contributions to dementia research by Australian Psychiatry
Publisher: SAGE Publications
Date: 25-03-2017
Investigating the Genetics of Hippocampal Volume in Older Adults without Dementia
Publisher: Public Library of Science (PLoS)
Date: 27-01-2015
Neuropsychiatry
Publisher: SAGE Publications
Date: 08-1993
DOI: 10.3109/10398569309081339
Abstract: The relative emphasis on “biological” or “psychological” formulations in our understanding of “mental” disorders has varied at different periods in history. The early traditions of Western medicine, as represented by ancient Greek and Roman physicians, recognised that mental disturbance could be produced by physical disorders. The famous 17th century neurologist Thomas Willis, who coined the term “neurology”, believed in a neurological basis of psychiatric disorder. This opinion was explicitly stated in the mid-19th century text on mental disorders by Griesinger [1]. In fact, in die latter half of the 19th century, neuropsychiatry was synonymous with general psychiatry. A number of developments led to this situation. The study of aphasia had resulted in a burgeoning interest in brain structure-function relationships. The recognition of general paresis as an acquired disease with an identifiable aetiology had resulted in therapeutic optimism. Further, neurologists of this period were interested in retaining the territory of mental disorder as a source of patients.
Global, regional, and national burden of Alzheimer's disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
Publisher: Elsevier BV
Date: 2019
Neuropsychological outcome from psychosurgery for obsessive-compulsive disorder
Publisher: SAGE Publications
Date: 06-1995
DOI: 10.1080/00048679509075924
Abstract: Seventeen obsessive-compulsive disorder patients treated with psychosurgery were administered a comprehensive neuropsychological test battery. Their performance on neuropsychological testing was compared with that of an age and severity matched s le of 17 OCD sufferers who had not received psychosurgery. The psychosurgery and control groups did not differ in intellectual or memory functioning, consistent with earlier findings that psychosurgery does not reduce global ability estimates. The psychosurgery group performed more poorly than the control group on an adaptation of the Wisconsin Card Sorting Test, demonstrating the possible impact of frontal lobe lesions on the abilities underpinning the formation and shifting of response sets.
Mediating Effects of Processing Speed and Executive Functions in Age-Related Differences in Episodic Memory Performance: A Cross-Validation Study
Publisher: American Psychological Association (APA)
Date: 11-2012
DOI: 10.1037/A0030053
Abstract: Age differences in episodic memory (memory) have been attributed to a general reduction in processing speed (the "speed mediation hypothesis"), but also to declines in the efficiency of executive functions operations ("executive decline hypothesis"). To test predictions from these competing models, we examined the mediating effects of processing speed (speed) and executive functions (executive) on age and episodic memory in three older adult cohorts. The first s le comprised 842 in iduals from the Sydney Memory and Aging Study (MAS). The second and third s les included 476 in iduals from the Older Australian Twins Study (OATS), with each twin from a pair randomly assigned to form two s les. A series of regression analyses was performed on each of the three s les independently, so as to obtain the sizes and statistical significances of the indirect effects of age on each of the memory variables, mediated by each of the Executive and Speed composites. Sex was a control variable for all analyses. Analyses were repeated with current depression as an additional control variable. Data from the MAS s le suggested that both Speed and Executive composites were significant mediators, with the former having a stronger mediation effect. A similar pattern was found in the two OATS s les. These findings are consistent with those of previous studies in which speed had a stronger mediating effect than executive on age-related variation in memory. They provide further support for the speed mediation hypothesis, although not negating the executive decline hypothesis.
White matter hyperintensities and within-person variability in community-dwelling adults aged 60-64 years
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2007.02.006
Abstract: Estimates of white matter hyperintensities (WMH) derived from T2-weighted MRI were investigated in relation to cognitive performance in 469 healthy community-dwelling adults aged 60-64 years. Frontal lobe WMH but not WMH from other brain regions (temporal, parietal, and occipital lobes, anterior and posterior horn, periventricular body) were associated with elevated within-person reaction time (RT) variability (trial to trial fluctuations in RT performance) but not performance on several other cognitive tasks including psychomotor speed, memory, and global cognition. The findings are consistent with the view that elevated within-person variability is related to neurobiological disturbance, and that attentional mechanisms supported by the frontal cortex play a key role in this type of variability.
Replicable Expansion and Differentiation of Neural Precursors from Adult Canine Skin
Publisher: Elsevier BV
Date: 08-2017
P2‐287: PREVALENCE OF MILD COGNITIVE IMPAIRMENT (MCI) IN DIVERSE ETHNO‐CULTURAL AND GEOGRAPHICAL REGIONS INTERNATIONALLY: THE COSMIC COLLABORATION
Publisher: Wiley
Date: 07-2014
Structural MRI Biomarkers of Mild Cognitive Impairment from Young Elders to Centenarians
Publisher: Bentham Science Publishers Ltd.
Date: 12-02-2016
DOI: 10.2174/1567205013666151218150534
Abstract: Underpinnings of mild cognitive impairment (MCI) change with increasing age. We hypothesize that MRI signatures of mild cognitive impairment (MCI) would be different at a higher age compared to younger elders. 244 participants (71-103 years) from the Sydney Memory and Ageing Study and the Sydney Centenarian Study were categorized as amnestic MCI (aMCI), non-amnestic MCI (naMCI) or cognitively normal (CN). Brain "atrophy" and white matter hyper-intensities (WMHs) associated with MCI subtypes and age effects were examined by general linear models, controlling for confounding factors. Reduced logistic regressions were performed to determine structures that best discriminated aMCI from CN in in iduals <85 and those ≥85 years. aMCI was associated with smaller volumes of overall cortex, medial temporal structures, anterior corpus callosum, and select frontal and parietal regions compared to CN such associations did not significantly change with age. Structures that best discriminated aMCI from CN differed however in the <85 and ≥85 age groups: cortex, putamen, parahippoc al, precuneus and superior frontal cortices in <85 years, and the hippoc us, pars triangularis and temporal pole in ≥85 years. Differences between naMCI and CN were small and non-significant in the s le. WMHs were not significantly associated with MCI subtypes. Structural MRI distinguishes aMCI, but not naMCI, from CN in elderly in iduals. The structures that best distinguish aMCI from CN differ in those <85 from those ≥85, suggesting different neuropathological underpinnings of cognitive impairment in the very old.
Genetics of ageing-related changes in brain white matter integrity - a review.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.ARR.2012.10.003
Abstract: White matter (WM) plays a vital role in the efficient transfer of information between grey matter regions. Modern imaging techniques such as diffusion tensor imaging (DTI) have enabled the examination of WM microstructural changes across the lifespan, but there is limited knowledge about the role genetics plays in the pattern and aetiology of age-related WM microstructural changes. Family and twin studies suggest that the heritability of WM integrity measures changes over the lifespan, with the common DTI measure, fractional anisotropy (FA), showing moderate to high heritability in adults. However, few heritability studies have been undertaken in older adults. Linkage studies in middle-aged adults suggest that specific regions on chromosomes 3 and 15 may harbour genetic variants for WM integrity. A number of studies have investigated candidate genes, with the APOE ɛ4 polymorphism being the most frequently studied. Although these candidate gene studies suggest associations of particular genes with WM integrity measures in some specific brain regions, the findings remain inconsistent due to differences in their methodologies, s les and the outcome measures used. The APOE ɛ4 allele has been associated with decreased WM integrity (FA) in the cingulum, corpus callosum and parahippoc al gyrus. Only one genome-wide association study of global WM integrity measures in older adults has been published, and reported suggestive single nucleotide polymorphisms await replication. Overall, genetic age-related WM integrity studies are lacking and a concerted effort to examine the genetic determinants of age-related decline in WM integrity is clearly needed to improve our understanding of the ageing brain.
The paradox of psychosurgery to treat mental disorders
Publisher: Cambridge University Press
Date: 21-07-2011
Cognition and mortality in older people: the Sydney Memory and Ageing Study
Publisher: Oxford University Press (OUP)
Date: 26-10-2015
Abstract: Both cognitive ability and cognitive decline have been shown to predict mortality in older people. As dementia, a major form of cognitive decline, has an established association with shorter survival, it is unclear the extent to which cognitive ability and cognitive decline predict mortality in the absence of dementia. To determine whether cognitive ability and decline in cognitive ability predict mortality in older in iduals without dementia. The Sydney Memory and Ageing Study is an observational population-based cohort study. Participants completed detailed neuropsychological assessments and medical examinations to assess for risk factors such as depression, obesity, hypertension, diabetes, hypercholesterolaemia, smoking and physical activity. Participants were regularly assessed at 2-year intervals over 8 years. A community s le in Sydney, Australia. One thousand and thirty-seven elderly people without dementia. Overall, 236 (22.8%) participants died within 8 years. Both cognitive ability at baseline and decline in cognitive ability over 2 years predicted mortality. Decline in cognitive ability, but not baseline cognitive ability, was a significant predictor of mortality when depression and other medical risk factors were controlled for. These relationships also held when excluding incident cases of dementia. The findings indicate that decline in cognition is a robust predictor of mortality in older people without dementia at a population level. This relationship is not accounted for by co-morbid depression or other established biomedical risk factors.
The impact of type 2 diabetes and body mass index on cerebral structure is modulated by brain reserve
Publisher: Wiley
Date: 20-09-2019
DOI: 10.1111/ENE.13780
Abstract: Body mass index (BMI), hyperglycaemia and type 2 diabetes and their interactive effects are associated with brain volume atrophy in ageing. It remains to be established if these risk factors are particularly concerning in in iduals with high or low brain volumes. Demographics, venous blood and magnetic resonance imaging data were collected for 494 healthy community-living adults aged 53-78 (mean 65) years, as part of the Personality and Total Health Through Life study. Associations between BMI, blood glucose, diabetes status and brain volume (whole brain, grey matter, white matter and subcortical structures) were investigated using quantile regression. Quantile regression revealed vulnerability to BMI × glucose interactions particularly in lower volumes and significant main effects for type 2 diabetes particularly in higher volumes. Diabetes was most strongly associated with brain volumes. The association between BMI, blood glucose and diabetes was not consistent across the full range of brain volumes. Explicit investigation of the upper and lower boundaries of brain volume distributions was valuable. We found evidence of protective reserve from higher brain volumes and that a combination of high BMI and higher blood glucose was particularly concerning for in iduals with lower brain volumes.
Neuroleptic-induced defecation in rats as a model for neuroleptic dysphoria
Publisher: Elsevier BV
Date: 04-1993
DOI: 10.1016/0165-1781(93)90053-J
Abstract: Two groups of 32 rats were challenged in a well-habituated environment with haloperidol (0.5 mg/kg), haloperidol (0.1 mg/kg), domperidone (0.1 mg/kg), or saline to study the effect of these drugs on defecation--an index of emotionality--and voluntary movements in the 2 hours after the injection. The haloperidol-treated rats in the high-dose condition had significantly more bolus counts in the 2 hours after the injection than were observed in the groups treated with domperidone (a peripheral dopamine D2 receptor antagonist) or placebo. All movements were greatly reduced in the haloperidol-treated rats and, in this group, the ones with more bolus counts did not differ in their activity levels from those with fewer bolus counts. There was a trend for the rats that were less mobile at 10 minutes after the injection to produce more boli in the 2-hour period. Our study, therefore, replicates the findings of Sanberg (1980) and Russell et al. (1987a, 1987b) that haloperidol increases "emotional" defecation in rats in well-habituated environments, but the same model does not replicate the motor component of neuroleptic-induced akathisia seen in human subjects.
Halting Antipsychotic Use in Long-Term care (HALT): A single-arm longitudinal study aiming to reduce inappropriate antipsychotic use in long-term care residents with behavioral and psychological symptoms of dementia
Publisher: Cambridge University Press (CUP)
Date: 07-03-2017
DOI: 10.1017/S1041610217000084
Abstract: Inappropriate use of antipsychotic medications to manage Behavioral and Psychological Symptoms of Dementia (BPSD) continues despite revised guidelines and evidence for the associated risks and side effects. The aim of the Halting Antipsychotic Use in Long-Term care (HALT) project is to identify residents of long-term care (LTC) facilities on antipsychotic medications, and undertake an intervention to deprescribe (or cease) these medicines and improve non-pharmacological behavior management. LTC facilities will be recruited across Sydney, Australia. Resident inclusion criteria will be aged over 60 years, on regular antipsychotic medication, and without a primary psychotic illness or very severe BPSD, as measured using the Neuropsychiatric Inventory (NPI). Data collection will take place one month and one week prior to commencement of deprescribing and 3, 6 and 12 months later. During the period prior to deprescribing, training will be provided for care staff on how to reduce and manage BPSD using person-centered approaches, and general practitioners of participants will be provided academic detailing. The primary outcome measure will be reduction of regular antipsychotic medication without use of substitute psychotropic medications. Secondary outcome measures will be NPI total and domain scores, Cohen-Mansfield Agitation Inventory scores and adverse events, including falls and hospitalizations. While previous studies have described strategies to minimize inappropriate use of antipsychotic medications in people with dementia living in long-term care, sustainability and a culture of prescribing for BPSD in aged care remain challenges. The HALT project aims to evaluate the feasibility of a multi-disciplinary approach for deprescribing antipsychotics in this population.
Drug-induced movement disorders in institutionalised adults with mental retardation: clinical characteristics and risk factors.
Publisher: SAGE Publications
Date: 06-1992
DOI: 10.1177/000486749202600208
Abstract: Fifty-three institutionalised adults with mental retardation, the majority (73.5%) moderate to severe, were examined for drug-induced movement disorders. Using a global AIMS score of 2 or more, 16 (34%) of the 47 subjects who had been exposed to neuroleptics had tar e dyskinesia (TD). Three of these had developed the dyskinesia upon withdrawal of neuroleptics. The dyskinetic movements were mainly seen in the lingual, perioral and other facial muscles. Two (33%) out of 6 subjects with no history of exposure to neuroleptics also had similar dyskinetic movements. The total neuroleptic dose significantly, and age marginally, but not sex, brain damage or level of mental retardation, emerged as risk factors for TD. Two (3.7%) subjects had definite akathisia and 16 (30.8 %) significant extrapyramidal side effects. This study supports the findings of previous studies of considerable neurological adverse effects of neuroleptics in this patient group and cautions against their injudicious use. It provides further evidence for some putative risk factors for TD and is noteworthy for its lack of support for the contentious issue of brain damage as a risk factor.
Schizophrenia with onset after age 50 years
Publisher: Royal College of Psychiatrists
Date: 11-1999
Abstract: Schizophrenia occurring for the first time in late life may be a distinct entity or part of a continuum. Can late-onset schizophrenia (LOS) and early-onset schizophrenia (EOS) be differentiated by their phenomenology and risk factors to their development? Convenience s les of 27 DSM–III–R defined LOS subjects, 30 EOS subjects and 34 control subjects were systematically assessed. Premorbidly, both groups of subjects with schizophrenia had personality traits that were different from controls but not from each other. The EOS subjects had more family members with a history of psychiatric illness or schizophrenia and less hearing impairment than the other two groups, which did not differ from each other. Clinically, LOS and EOS subjects were similar, except that EOS subjects had more negative symptom scores, tended to have more delusions of guilt/sin and of being controlled and more formal thought disorder, and had significantly poorer instrumental activities of daily living. Phenomenology and risk factors do not distinguish discrete LOS.
Genetic effects on information processing speed are moderated by age – converging results from three samples
Publisher: Wiley
Date: 08-04-2014
DOI: 10.1111/GBB.12132
Abstract: Information processing is a cognitive trait forming the basis of complex abilities like executive function. The Trail Making Test (TMT) is a well-established test of information processing with moderate to high heritability. Age of the in idual also plays an important role. A number of genetic association studies with the TMT have been performed, which, however, did not consider age as a moderating factor. We report the results of genome-wide association studies (GWASs) on age-independent and age-dependent TMT performance in two population-representative community s les (Munich Antidepressant Response Signature, MARS: N1 = 540 Ludwig Maximilians University, LMU: N2 = 350). Age-dependent genome-wide findings were then evaluated in a third s le of healthy elderly subjects (Sydney Memory and Ageing Study, Sydney MAS: N3 = 448). While a meta-analysis on the GWAS findings did not reveal age-independent TMT associations withstanding correction for multiple testing, we found a genome-wide significant age-moderated effect between variants in the DSG1 gene region and TMT-A performance predominantly reflecting visual processing speed (rs2199301, P(meta-analysis) = 1.3 × 10(-7)). The direction of the interaction suggests for the minor allele a beneficial effect in younger adults turning into a detrimental effect in older adults. The detrimental effect of the missense single nucleotide polymorphism rs1426310 within the same DSG1 gene region could be replicated in Sydney MAS participants aged 70-79, but not in those aged 80 years and older, presumably a result of survivor bias. Our findings demonstrate opposing effects of DSG1 variants on information processing speed depending on age, which might be related to the complex processes that DSG1 is involved with, including cell adhesion and apoptosis.
Microstructural white matter changes, not hippocampal atrophy, detect early amnestic mild cognitive impairment
Publisher: Public Library of Science (PLoS)
Date: 14-03-2013
Complex mental activity and the aging brain: Molecular, cellular and cortical network mechanisms
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.BRAINRESREV.2007.07.007
Abstract: There is strong evidence to suggest that high levels of complex mental activity can improve clinical outcome from brain injury. What are the neurobiological mechanisms underlying this observation? This paper proposes that complex mental activity induces a spectrum of biological changes on brain structure and function which can be best understood in a multiscalar spatiotemporal framework. Short-term molecular changes may include induction of BDNF, NGF and endopeptidase genes and elevation of the high-energy phosphocreatine-creatine resting state equilibrium. Animal models have implicated these processes in the reduction and even reversal of neurodegenerative changes secondary to mental work. These mechanisms can therefore be described as neuroprotective. Medium-term cellular changes are erse and include neurogenesis, synaptogenesis, angiogenesis and formation of more complex dendritic branching patterns. Importantly, these effects parallel behavioral improvement, and thus a neurogenerative class of mechanisms is implicated. Finally, in the post-lesion context, computation principles such as efficiency, small world connectivity and functional adaptation are identified as important, with supportive clinical evidence from neuroimaging studies. Thus, dynamic compensatory cortical network mechanisms may also be relevant, yet take some time to evolve. This paper will explore the neurobiological and clinical implications of this framework, in particular in the context of age-related brain disease.
Memory training alters hippocampal neurochemistry in healthy elderly
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-07-2003
DOI: 10.1097/01.WNR.0000077548.91466.05
Abstract: Accumulating epidemiological evidence supports the notion of brain reserve, but there has been no investigation of neurobiological change associated with brief mental activation training in humans. Healthy older in iduals were therefore investigated with magnetic resonance spectroscopy (MRS) in different brain regions before and after 5 weeks of focused memory training. Recall of a test-word list of > 23 items was achieved accompanied by elevation of creatine and choline signals in the hippoc us. Those at risk for neural dysfunction, as indicated by lower neurometabolites at baseline, demonstrated the largest MRS increases after training. Biochemical changes related to cellular energy and cell-membrane turnover were found to increase after structured memory exercises and were limited to the medial temporal lobe.
Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants
Publisher: Oxford University Press (OUP)
Date: 10-2013
DOI: 10.1017/S1461145713000539
Abstract: Computer-administered cognitive training (CT) tasks are a common component of cognitive remediation treatments. There is growing evidence that transcranial direct current stimulation (tDCS), when given during cognitive tasks, improves performance. This randomized, controlled trial explored the potential synergistic effects of CT combined with tDCS in healthy participants. Altogether, 60 healthy participants were randomized to receive either active or sham tDCS administered during training on an adaptive CT task (dual n-back task), or tDCS alone, over 10 daily sessions. Cognitive testing (working memory, processing speed, executive function, reaction time) was conducted at baseline, end of the 10 sessions, and at 4-wk follow-up to examine potential transfer effects to non-trained tasks. Altogether, 54 participants completed the study. Over the 10 ‘online’ sessions, participants in the active tDCS+CT condition performed more accurately on the CT task than participants who received sham tDCS+CT. The performance enhancing effect, however, was present only during tDCS and did not result in greater learning (i.e. improvement over sessions) on the CT task. These results confirm prior reports of enhancement of cognitive function during tDCS stimulation. At follow-up, the active tDCS+CT group, but not the sham tDCS+CT group, showed greater gains on a non-trained test of attention and working memory than the tDCS-only group (p 0.01). Although this gain can mainly be attributable to training, this result suggests that active tDCS may have a role in further enhancing outcomes.
Schizophrenia with onset after age 50 years
Publisher: Royal College of Psychiatrists
Date: 11-1999
Abstract: Late-onset schizophrenia (LOS) may have a basis in age-related coarse brain disease, but empirical support for this is conflicting. Is LOS characterised by more neurological disease than early-onset schizophrenia (EOS)? DSM–III–R–defined LOS subjects ( n =27) were compared with 30 EOS and 34 volunteer control subjects on neurological status, neuropsychological test performance and brain magnetic resonance imaging (MRI) LOS and EOS groups had more ‘soft’ neurological signs and drug-induced movement abnormalities, and performed more poorly on tests assessing speed of information processing, memory and frontal executive functioning. On MRI, the LOS and EOS groups had greater lateral ventricular size than the control group. The LOS subjects also had more signal hyperintensities in periventricular white matter and subcortical nuclei than controls. LOS and EOS subjects were very similar on neuropsychological, neurological and structural neuroimaging parameters, except that there were more MRI periventricular hyperintensities in LOS subjects.
A critique of the extant criteria for vascular cognitive disorders and a proposal
Publisher: Wiley
Date: 07-2012
Cardiovascular risk factors and life events as antecedents of depressive symptoms in middle and early-old age: Path through life study
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2009
Frontal cortical volumes and cognitive performance in young-old adults in the PATH through life study
Publisher: Elsevier BV
Date: 07-2009
The effects of age and sex on cortical sulci in the elderly
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.NEUROIMAGE.2010.02.016
Abstract: A large number of structural brain studies using magnetic resonance imaging (MRI) have reported age-related cortical changes and sex difference in brain morphology. Most studies have focused on cortical thickness or density, with relatively few studies of cortical sulcal features, especially in the elderly. In this paper, we report global sulcal indices (g-SIs) of both cerebral hemispheres and the average sulcal span in six prominent sulci, as observed in T1-weighted scans obtained from a large community cohort of 319 non-demented in iduals aged between 70 and 90 years (mean=78.06+/-4.75 male/female=149/170), using automated methods. Our results showed that for both hemispheres, g-SIs had significant negative correlations with age in both men and women. Using an interactive effect analysis, we found that g-SIs for men declined faster with age than that for women. The widths of all six sulcal spans increased significantly with age, with largest span increase occurring in the superior frontal sulcus. Compared to women, men had significantly wider sulcal spans for all sulci that were examined. Our findings suggest that both age and sex contribute to significant cortical gyrification differences and variations in the elderly. This study establishes a reference for future studies of age-related brain changes and neurodegenerative diseases in the elderly.
Sex differences in regional gray matter in healthy individuals aged 44-48 years: a voxel-based morphometric study.
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.NEUROIMAGE.2007.03.063
Abstract: The study examined sex-related differences in regional gray matter (GM) in 44-48 year old healthy in iduals. T1-weighted MRI scans were acquired in 411 subjects aged 44-48 from a random community s le and optimized voxel-based morphometry was applied to detect regional GM difference between men and women, correcting for effects of age, years of education, handedness, and total intracranial volume (TIV). Men had larger brain volumes and higher white matter (WM) to TIV ratios compared with women. Women had higher GM to TIV ratios than men. After controlling for age, years of education, handedness, and TIV, there were no significant differences between men and women in the total GM volumes. Regional sex dimorphism was present, with men having more GM volume in midbrain, left inferior temporal gyrus, right occipital lingual gyrus, right middle temporal gyrus, and both cerebellar hemispheres. Women showed more GM in dorsal anterior, posterior and ventral cingulate cortices, and right inferior parietal lobule. Our results suggest sex dimorphism in GM in middle aged healthy in iduals, which is not likely to be explained by brain pathology. These differences may provide the structural brain basis for sex differences in certain cognitive functions.
Molecular Targets of Tannic Acid in Alzheimer's Disease
Publisher: Bentham Science Publishers Ltd.
Date: 18-07-2017
DOI: 10.2174/1567205014666170206163158
Abstract: Tannic acid (TA) is a naturally occurring plant-derived polyphenol found in several herbaceous and woody plants, including legumes, sorghum, beans, bananas, persimmons, rasberries, wines and a broad selection of teas. Clinically, TA has strong antioxidant/free radical scavenging, antiinflammatory, anti-viral/bacterial, and anti-carcinogenic properties. While the aetiology of Alzheimer's disease (AD) remains unclear, this complex multifactorial neurodegenerative disorder remains the most common form of dementia, and is a growing public health concern worldwide. The neuroprotective effects of TA against AD have been shown in several in vitro and in vivo models of AD. Apart from its potent antioxidant and anti-inflammatory roles, evidence suggests that TA is also a natural inhibitor of β-secretase (BACE1) activity and protein expression. BACE1 is the primary enzyme responsible for the production and deposition of Aβ peptide. TA also destabilises neurotoxic amyloid beta (Aβ) fibrils in vitro. Apart from its effects on the Aβ cascade, TA can also inhibit the in vitro aggregation of tau peptide, a core component of intracellular neurofibrillary tangles (NFTs). This review summarizes the relevance of TA and TA-related vegetable extracts (tannins) in the pathogenesis of AD and its enzymatic targets. It also highlights the significance of TA as an important lead compound against AD.
Genome-wide average DNA methylation is determined in utero
Publisher: Oxford University Press (OUP)
Date: 06-03-2018
DOI: 10.1093/IJE/DYY028
P3‐151: Change in adiposity measures and cognition in Australian aging women
Publisher: Wiley
Date: 07-2010
Central nervous system medication use in older adults with intellectual disability: Results from the successful ageing in intellectual disability study
Publisher: SAGE Publications
Date: 27-05-2016
Abstract: Information on the rates and predictors of polypharmacy of central nervous system medication in older people with intellectual disability is limited, despite the increased life expectancy of this group. This study examined central nervous system medication use in an older s le of people with intellectual disability. Data regarding demographics, psychiatric diagnoses and current medications were collected as part of a larger survey completed by carers of people with intellectual disability over the age of 40 years. Recruitment occurred predominantly via disability services across different urban and rural locations in New South Wales and Victoria. Medications were coded according to the Monthly Index of Medical Specialties central nervous system medication categories, including sedatives/hypnotics, anti-anxiety agents, antipsychotics, antidepressants, central nervous system stimulants, movement disorder medications and anticonvulsants. The Developmental Behaviour Checklist for Adults was used to assess behaviour. Data were available for 114 people with intellectual disability. In all, 62.3% of the s le was prescribed a central nervous system medication, with 47.4% taking more than one. Of those who were medicated, 46.5% had a neurological diagnosis (a seizure disorder or Parkinson’s disease) and 45.1% had a psychiatric diagnosis (an affective or psychotic disorder). Linear regression revealed that polypharmacy was predicted by the presence of neurological and psychiatric diagnosis, higher Developmental Behaviour Checklist for Adults scores and male gender. This study is the first to focus on central nervous system medication in an older s le with intellectual disability. The findings are in line with the wider literature in younger people, showing a high degree of prescription and polypharmacy. Within the s le, there seems to be adequate rationale for central nervous system medication prescription. Although these data do not indicate non-adherence to guidelines for prescribing in intellectual disability, the high rate of polypharmacy and its relationship to Developmental Behaviour Checklist for Adults scores reiterate the importance of continued medication review in older people with intellectual disability.
Electroconvulsive treatment of neuroleptic malignant syndrome: a review and report of cases.
Publisher: SAGE Publications
Date: 10-1999
DOI: 10.1080/J.1440-1614.1999.00630.X
Abstract: Objective: Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse effect of neuroleptic medication, with no satisfactory treatment currently available. Electroconvulsive therapy (ECT) has been anecdotally reported to be effective in its treatment. We review 45 published case reports of ECT for NMS and describe nine new cases, to examine its effectiveness, the likelihood of adverse reactions, and the theoretical implications of such treatment. Method: The authors used Medline to identify reports in the English literature where ECT was used in cases of suspected NMS. In addition, the charts of patients referred to the second author for treatment of NMS were reviewed and cases in which ECT used were identified. Results: The case reports suggest that ECT is effective in many in iduals with NMS, even when drug therapy has failed. The response is usually apparent after a few treatments, generally up to six. The response is not predictable on the basis of age, gender, psychiatric diagnosis or any particular feature of NMS including catatonia. Electroconvulsive therapy is a relatively safe treatment in NMS, although the risk of cardiovascular complications should be considered. Malignant hyperthermia due to the anaesthesia associated with ECT has not been reported in patients with NMS, and succinylcholine has been used safely with the exception of one report of fever and raised creatine kinase levels and another report of hyperkalemia. Conclusions: Electroconvulsive therapy is the preferred treatment in severe NMS, cases where the underlying psychiatric diagnosis is psychotic depression or catatonia, and in cases where lethal catatonia cannot be ruled out. The effectiveness of ECT for the treatment of NMS has theoretical implications for the relationship between NMS and catatonia, and the possible pathophysiological mechanisms that underlie these disorders.
APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline.
Publisher: Oxford University Press (OUP)
Date: 12-05-2020
Abstract: We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 in iduals aged 54–103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step in idual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.
Chapter 18 Disruption of the neural correlates of working memory using high- and low-frequency repetitive transcranial magnetic stimulation: a negative study
Publisher: Elsevier
Date: 2003
Metal and complementary molecular bioimaging in Alzheimer's disease
Publisher: Frontiers Media SA
Date: 15-07-2014
Quantification of hemorphins in Alzheimer's disease brains
Publisher: Wiley
Date: 02-02-2004
DOI: 10.1002/JNR.20020
Abstract: The hemorphins are a family of opioid receptor-binding peptides originating from the beta-chain of hemoglobin and have been found at high levels within the central and peripheral nervous systems. In addition to opioid receptor binding, hemorphins have been shown to have a number of effects on the renin-angiotensin system, including inhibition of angiotensin-converting enzyme and angiotensin IV receptor binding. However, relatively few studies have examined the role of hemorphins in neurological diseases. Here we report the first study of hemorphins in Alzheimer's disease (AD) brains. Quantitative MALDI-TOF mass spectrometry was employed to assess levels of LVV and VV hemorphin-6 and -7 in 10 control and 10 AD brain tissue s les. LVV hemorphin-6 and total hemorphin levels were elevated in AD temporal neocortex but not in hippoc us, occipital lobe, or frontal lobe. The elevation of hemorphins is probably indicative of a vascular abnormality resulting from cerebral amyloid angiopathy associated with both neurodegenerative disease and aging.
Debate on neurosurgery
Publisher: Royal College of Psychiatrists
Date: 2004
DOI: 10.1192/BJP.184.1.85
The determinants and longitudinal course of post-stroke mild cognitive impairment
Publisher: Cambridge University Press (CUP)
Date: 11-2009
DOI: 10.1017/S1355617709990579
Abstract: While post-stroke dementia has been extensively investigated, the large number of patients with mild cognitive impairment (MCI) following stroke has received less attention, and reports on the longitudinal course of such impairment are inconsistent in their findings. We examined patients with MCI ( n = 45) or no cognitive impairment (NCI) ( n = 59), based on consensus criteria following detailed neuropsychological assessments and magnetic resonance imaging (MRI) scans, and compared them with healthy control subjects ( n = 84), all of whom were assessed at two time points, 3 years apart. The MCI at baseline in this group was judged to be vascular in etiology (vaMCI). Incident dementia was diagnosed in 24.4% of vaMCI and 8.5% of NCI subjects and no control subjects over 3 years, giving a rate of conversion of approximately 8% per year in post-stroke vaMCI. The vaMCI group showed greater decline in logical memory than the NCI group. Within the vaMCI group, those who developed dementia had great decline in language and executive function. Compared with NCI patients, those with vaMCI had more vascular risk factors and more white matter hyperintensities on MRI at baseline, but did not differ in their brain or hippoc al volumes. Neither MRI volumetric measures nor interval cerebrovascular events predicted decline in function. The major determinant of decline and categorical transition was impaired performance at baseline, suggesting that those with mild impairment post-stroke are more vulnerable to subsequent decline. ( JINS , 2009, 15 , 915–923.)
Deep brain stimulation of the antero-medial globus pallidus interna for Tourette syndrome
Publisher: Public Library of Science (PLoS)
Date: 19-08-2014
P2‐307: THE EFFECT OF ALCOHOL CONSUMPTION AND APOLIPOPROTEIN E (APOE) 4 STATUS ON INCIDENT DEMENTIA OVER 4‐YEARS IN THE SYDNEY MEMORY AND AGEING STUDY
Publisher: Wiley
Date: 07-2014
The Identification and Management of Drug-Induced Akathisia
Publisher: Springer Science and Business Media LLC
Date: 07-1995
COSMIC: COhort Studies of Memory in an International Consortium
Publisher: Wiley
Date: 07-2013
Longitudinal study of cerebral blood flow in Alzheimer's disease using single photon emission tomography
Publisher: Elsevier BV
Date: 02-1997
The independent influences of age and education on functional brain networks and cognition in healthy older adults
Publisher: Cold Spring Harbor Laboratory
Date: 25-06-2017
DOI: 10.1101/154898
Abstract: Healthy ageing is accompanied by a constellation of changes in cognitive processes and alterations in functional brain networks. The relationships between brain networks and cognition during ageing in later life are moderated by demographic and environmental factors, such as prior education, in a poorly understood manner. Using multivariate analyses, we identify three latent patterns (or modes) linking resting-state functional connectivity to demographic and cognitive measures in 101 cognitively-normal elders. The first mode ( p =0.00043) captures an opposing association between age and core cognitive processes such as attention and processing speed on functional connectivity patterns. The functional subnetwork expressed by this mode links bilateral sensorimotor and visual regions through key areas such as the parietal operculum. A strong, independent association between years of education and functional connectivity loads onto a second mode ( p =0.012), characterised by the involvement of key hub-regions. A third mode ( p =0.041) captures weak, residual brain-behaviour relations. Our findings suggest that circuits supporting lower-level cognitive processes are most sensitive to the influence of age in healthy older adults. Education, and to a lesser extent, executive functions, load independently onto functional networks - suggesting that the moderating effect of education acts upon networks distinct from those vulnerable with ageing. This has important implications in understanding the contribution of education to cognitive reserve during healthy ageing.
Response to Yucel and MacQueen's letter to the editor [2]
Publisher: Wiley
Date: 2006
DOI: 10.1002/HIPO.20197
Dissociable Cellular and Genetic Mechanisms of Cortical Thinning at Different Life Stages
Publisher: Research Square Platform LLC
Date: 27-05-2022
DOI: 10.21203/RS.3.RS-1686228/V1
Abstract: Mechanisms underpinning neurotypical age-related variations in cortical thickness in the human brain remain insufficiently specified. Here we used cell-specific marker genes, followed by gene ontology and enrichment analyses, to quantify the association between gene-expression levels and inter-regional age-related variations in neurotypical cortical thinning using multicohort neuroimaging data from 14,248 in iduals ages 4-89 years. We found that early-life ( years), mid-life (20-60 years), and late-life ( years) were associated with distinct patterns of association between inter-regional profiles of cortical thickness and expression profiles of markers genes for CA1 and S1 pyramidal cells, astrocytes, and microglia. Gene ontology and enrichment analyses indicated each of the three life-stages was associated with different biological processes and cellular components these related to synaptic modeling in early life, neurotransmission in mid-life, and neurodegeneration in late-life. These findings provide mechanistic insights on age-related cortical thinning during typical development and ageing.
Plasma protein profiling of Mild Cognitive Impairment and Alzheimer’s disease using iTRAQ quantitative proteomics
Publisher: Springer Science and Business Media LLC
Date: 17-01-2014
Abstract: With the promise of disease modifying treatments, there is a need for more specific diagnosis and prognosis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Plasma biomarkers are likely to be utilised to increase diagnostic accuracy and specificity of AD and cognitive decline. Isobaric tags (iTRAQ) and proteomic methods were used to identify potential plasma biomarkers of MCI and AD. Relative protein expression level changes were quantified in plasma of 411 cognitively normal subjects, 19 AD patients and 261 MCI patients. Plasma was pooled into 4 groups including normal control, AD, amnestic single and multiple domain MCI (aMCI), and nonamnestic single and multiple domain MCI (nMCI). Western-blotting was used to validate iTRAQ data. Integrated function and protein interactions were explored using WEB based bioinformatics tools (DAVID v6.7 and STRING v9.0). In at least two iTRAQ replicate experiments, 30 proteins were significantly dysregulated in MCI and AD plasma, relative to controls. These proteins included ApoA1, ApoB100, complement C3, C4b-binding protein, afamin, vitamin D-binding protein precursor, isoform 1 of Gelsolin actin regulator, Ig mμ chain C region (IGHM), histidine-rich glycoprotein and fibrinogen β and γ chains. Western-blotting confirmed that afamin was decreased and IGHM was increased in MCI and AD groups. Bioinformatics results indicated that these dysregulated proteins represented a ersity of biological processes, including acute inflammatory response, cholesterol transport and blood coagulation. These findings demonstrate that expression level changes in multiple proteins are observed in MCI and AD plasma. Some of these, such as afamin and IGHM, may be candidate biomarkers for AD and the predementia condition of MCI.
Differential longitudinal changes in structural complexity and volumetric measures in community-dwelling older individuals
Publisher: Elsevier BV
Date: 07-2020
Effects of pre‐operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study
Publisher: Wiley
Date: 09-08-2021
DOI: 10.1111/ANAE.15560
Abstract: We aimed to determine the impact of pre‐operative isolation on postoperative pulmonary complications after elective surgery during the global SARS‐CoV‐2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre‐defined sub‐group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS‐CoV‐2 infection. Patients who isolated pre‐operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS‐CoV‐2 incidence and high‐income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre‐operative testing use of COVID‐19‐free pathways or community SARS‐CoV‐2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.
The effect of exercise training on cognitive function in older adults with mild cognitive impairment: A meta-analysis of randomized controlled trials
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.JAGP.2013.02.018
Abstract: Investigations of exercise and cognition have primarily focused on healthy or demented older adults, and results have been equivocal in in iduals with mild cognitive impairment (MCI). Our aim was to evaluate efficacy of exercise on cognition in older adults with MCI. We conducted a meta-analysis of random controlled trials (RCTs) of exercise effects on cognitive outcomes in adults with MCI. Searches were conducted in Medline, EMBASE, CINAHL, PEDro, SPORTSDICUS, PsychInfo, and PubMed. Adults aged over 65 years with MCI or Mini-Mental State Exam mean score 24-28 inclusive. Study quality was assessed using the PEDro scale data on participant and intervention characteristics and outcomes were extracted, followed by meta-analysis. Fourteen RCTs (1,695 participants age 65-95 years) met inclusion criteria. Quality was modest and under-powering for small effects prevalent. Overall, 42% of effect sizes (ESs) were potentially clinically relevant (ES >0.20) with only 8% of cognitive outcomes statistically significant. Meta-analysis revealed negligible but significant effects of exercise on verbal fluency (ES: 0.17 [0.04, 0.30]). No significant benefit was found for additional executive measures, memory, or information processing. Overall results were inconsistent with benefits varying across exercise types and cognitive domains. There is very limited evidence that exercise improves cognitive function in in iduals with MCI, although published research is of moderate quality and inconclusive due to low statistical power. Questions remain regarding the magnitude, generalization, persistence, and mechanisms of benefits. Large-scale, high-quality RCTs are required to determine if exercise improves cognition or reduces dementia incidence in those with MCI.
Stimulus intensity in transcranial magnetic stimulation (TMS) studies [3]
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2001
Screening for cognitive impairment with the Montreal Cognitive Assessment in Chinese patients with acute mild stroke and transient ischaemic attack: a validation study
Publisher: BMJ
Date: 07-2016
SARS‐CoV‐2 infection and venous thromboembolism after surgery: an international prospective cohort study
Publisher: Wiley
Date: 24-08-2021
DOI: 10.1111/ANAE.15563
Abstract: SARS‐CoV‐2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri‐operative or prior SARS‐CoV‐2 were at further increased risk of venous thromboembolism. We conducted a planned sub‐study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS‐CoV‐2 diagnosis was defined as peri‐operative (7 days before to 30 days after surgery) recent (1–6 weeks before surgery) previous (≥7 weeks before surgery) or none. Information on prophylaxis regimens or pre‐operative anti‐coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS‐CoV‐2 2.2% (50/2317) in patients with peri‐operative SARS‐CoV‐2 1.6% (15/953) in patients with recent SARS‐CoV‐2 and 1.0% (11/1148) in patients with previous SARS‐CoV‐2. After adjustment for confounding factors, patients with peri‐operative (adjusted odds ratio 1.5 (95%CI 1.1–2.0)) and recent SARS‐CoV‐2 (1.9 (95%CI 1.2–3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS‐CoV‐2 (1.7 (95%CI 0.9–3.0)). Overall, venous thromboembolism was independently associated with 30‐day mortality (5.4 (95%CI 4.3–6.7)). In patients with SARS‐CoV‐2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri‐operative or recent SARS‐CoV‐2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS‐CoV‐2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
Mild Cognitive impairment as a predictor of falls in community-dwelling older people
Publisher: Elsevier BV
Date: 10-2012
Critical periods for cognitive reserve building activities for late life global cognition and cognitive decline: the Sydney memory and aging cohort study
Publisher: Informa UK Limited
Date: 28-02-2023
P3‐128: Plasma Apolipoproteins and Physical And Cognitive Health in Very Old Individuals
Publisher: Wiley
Date: 07-2016
Personality Development in Traditional Maori Society and the Impact of Modernization
Publisher: Informa UK Limited
Date: 08-1990
DOI: 10.1080/00332747.1990.11024512
Abstract: This paper is an attempt to integrate the available research, clinical data and literary information concerning the developmental experiences of the New Zealand Maori. The Maori developmental pattern in the traditional society is compared with that of the Caucasian, mostly Anglo-Saxon, New Zealander (Pakeha), highlighting the contrasting elements while at the same time accommodating considerable overlap between the two postulated developmental patterns. The Maori personality development is seen as being characterized by an indulgent and permissive infancy, a withdrawal of this succorance during childhood, which is characterized by prominent peer-orientation, and a reintegration into adult society during adolescence with gradual maturation of social roles subsequently. The disruption of this pattern as a result of urbanization and Westernization is discussed, along with its adverse consequences. The recent initiatives by the Maori community to preserve the old traditions take the developmental issues into consideration, and although it is too early to judge their success or otherwise, they look quite promising.
Lithium and dementia [2]
Publisher: American Medical Association (AMA)
Date: 03-2018
Increased neurofibrillary tangles in the brains of older pedestrians killed in traffic accidents
Publisher: S. Karger AG
Date: 2006
DOI: 10.1159/000093066
Abstract: i Background/Aims: /i Older people are over-represented in pedestrian fatalities, and it has been suggested that the presence of cognitive impairment or dementia in these in iduals may contribute to their accidents. Using neuropathological methods, we aimed to compare the prevalence of dementia pathology in fatally injured older pedestrians with similarly aged ambulatory subjects who died from other causes. i Methods: /i The brains of 52 pedestrians (65–93 years) and 52 controls (65–92 years) were assessed for neurofibrillary tangles (NFT), neuritic plaques, Lewy bodies and vascular lesions using established neuropathological criteria. i Results: /i The examination for Alzheimer’s disease (AD) pathology showed that 43% of the pedestrians had NFT scores of III–VI using Braak and Braak staging, compared with 23% of the controls (p 0.05, Fisher’s exact test), indicating incipient, possible or probable AD. There were no differences in the prevalence of pathology for vascular dementia or dementia with Lewy bodies. i Conclusion: /i These results suggest that cognitive decline associated with AD, even in the earliest stages of the disease, may be a factor in fatal traffic accidents for older pedestrians. Special measures for pedestrian safety are necessary in areas with high densities of older citizens and especially for those diagnosed as having a mild cognitive impairment or AD.
Organisational aspects and assessment practices of Australian memory clinics: an Australian Dementia Network (ADNeT) Survey
Publisher: BMJ
Date: 02-2021
DOI: 10.1136/BMJOPEN-2020-038624
Abstract: Conducting a national survey of clinicians and administrators from specialised dementia assessment services (memory clinics) in Australia to examine their current organisational aspects and assessment procedures and inform clinical tool harmonisation as part of the Australian Dementia Network—memory clinics project. A cross-sectional survey. Public and private memory clinics across Australia. 150 in idual clinicians completed the survey between May and August 2019. Responses could be given anonymously. Most clinics were publicly funded services (83.2%) and in metropolitan regions (70.9%). Descriptive data on organisational aspects of memory clinics (eg, waiting times, staffing) the three most commonly used assessment tools per assessment type (eg, self-report) and cognitive domain (eg, attention). Since the last national survey in 2009, the number of memory clinics across Australia has increased substantially but considerable variability has remained with respect to funding structure, staffing and assessment procedures. The average clinic employed 2.4 effective full-time staff (range 0.14–14.0). The reported waiting time for an initial assessment ranged from 1 week to 12 months with a median of 7 weeks. While most clinics (97%) offered follow-up assessments for their clients, only a few (31%) offered any form of cognitive intervention. We identified over 100 different cognitive assessment tools that were used at least ‘sometimes’, with widespread use of well-established core screening tools and a subset of common neuropsychological tests. This paper presents a current snapshot of Australian memory clinics, showing considerable heterogeneity with some common core elements. These results will inform the development of national memory clinic guidelines. Furthermore, our data make a valuable contribution to the international comparison of clinical practice standards and advocate for greater harmonisation to ensure high-quality dementia care.
Transcriptome Signature of Depression
Publisher: Elsevier BV
Date: 2017
Relationship Between Sulcal Characteristics and Brain Aging
Publisher: Frontiers Media SA
Date: 12-11-2018
Plasma protein profiling of mild cognitive impairment and Alzheimer's disease
Publisher: Wiley
Date: 07-2013
Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial
Publisher: Royal College of Psychiatrists
Date: 2012
DOI: 10.1192/BJP.BP.111.097634
Abstract: Preliminary evidence suggests transcranial direct current stimulation (tDCS) has antidepressant efficacy. To further investigate the efficacy of tDCS in a double-blind, sham-controlled trial (registered at www.clinicaltrials.gov : NCT00763230). Sixty-four participants with current depression received active or sham anodal tDCS to the left prefrontal cortex (2 mA, 15 sessions over 3 weeks), followed by a 3-week open-label active treatment phase. Mood and neuropsychological effects were assessed. There was significantly greater improvement in mood after active than after sham treatment ( P .05), although no difference in responder rates (13% in both groups). Attention and working memory improved after a single session of active but not sham tDCS ( P .05). There was no decline in neuropsychological functioning after 3–6 weeks of active stimulation. One participant with bipolar disorder became hypomanic after active tDCS. Findings confirm earlier reports of the antidepressant efficacy and safety of tDCS. Vigilance for mood switching is advised when administering tDCS to in iduals with bipolar disorder.
Behavioral and psychological symptoms associated with dementia subtype and severity
Publisher: Cambridge University Press (CUP)
Date: 12-11-2010
DOI: 10.1017/S1041610209991220
Abstract: Background: There is a growing body of research exploring differences in behavioral and psychological symptoms of dementia (BPSD) between Alzheimer's disease (AD) and vascular dementia (VaD), yet these differences are inconsistent and it is uncertain whether this inconsistency might be due to the confounding effect of differing severities of dementia. Methods: BPSD, measured with the Behavior Problems Check List (BPCL) and Revised Memory and Behavior Problems Check List (RMBPCL) and CDR-measured severity of dementia were examined using archival data of in iduals with AD (N = 377) or VaD (including multi-infarct and other vascular causes N = 74) presenting to a Sydney memory disorders clinic over a 20-year period. Results: There was no significant difference in scores for AD and VaD patients on the BPCL or on the RMBPCL when controlling for sex and severity of dementia. However, severity of BPSD increased with increasing severity of dementia. Conclusions: BPSD severity is no different in AD and VaD at the time of initial assessment in a memory disorders clinic population of mild to moderate dementia. However, BPSD increases with severity of dementia in this group.
Exceptional Longevity and Polygenic Risk for Cardiovascular Health
Publisher: MDPI AG
Date: 18-03-2019
Abstract: Studies investigating exceptionally long-lived (ELL) in iduals, including genetic studies, have linked cardiovascular-related pathways, particularly lipid and cholesterol homeostasis, with longevity. This study explored the genetic profiles of ELL in iduals (cases: n = 294, 95–106 years controls: n = 1105, 55–65 years) by assessing their polygenic risk scores (PRS) based on a genome wide association study (GWAS) threshold of p 5 × 10−5. PRS were constructed using GWAS summary data from two exceptional longevity (EL) analyses and eight cardiovascular-related risk factors (lipids) and disease (myocardial infarction, coronary artery disease, stroke) analyses. A higher genetic risk for exceptional longevity (EL) was significantly associated with longevity in our s le (odds ratio (OR) = 1.19–1.20, p = 0.00804 and 0.00758, respectively). Two cardiovascular health PRS were nominally significant with longevity (HDL cholesterol, triglycerides), with higher PRS associated with EL, but these relationships did not survive correction for multiple testing. In conclusion, ELL in iduals did not have significantly lower polygenic risk for the majority of the investigated cardiovascular health traits. Future work in larger cohorts is required to further explore the role of cardiovascular-related genetic variants in EL.
Plasma apolipoproteins and physical and cognitive health in very old individuals
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.NEUROBIOLAGING.2017.02.017
Abstract: Apolipoproteins play a crucial role in lipid metabolism with implications in cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We quantified 7 apolipoproteins in plasma in 1067 in iduals aged 56-105 using immunoassays and explored relationships with APOE polymorphism ε2/3/4, vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH, and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends. Centenarians had the highest ApoE levels and the lowest frequency of APOE ε4 allele relative to younger groups. Apolipoprotein levels trended lower in APOE ε4 homozygotes and heterozygotes compared with noncarriers, with ApoE and ApoJ being significantly lower. Levels of all apolipoproteins except ApoH were higher in females. Sex- and age-related differences were apparent in the association of apolipoproteins with cognitive performance, as only women had significant negative associations of ApoB, ApoE, ApoH, and ApoJ in mid-life, whereas associations at older age were nonsignificant or positive. Our findings suggest levels of some apolipoproteins, especially ApoE, are associated with lifespan and cognitive function in exceptionally long-lived in iduals.
Avoiding skin burns with transcranial direct current stimulation: preliminary considerations
Publisher: Oxford University Press (OUP)
Date: 06-10-2010
A Naturalistic Study of the Acceptability and Effectiveness of Internet-Delivered Cognitive Behavioural Therapy for Psychiatric Disorders in Older Australians
Publisher: Public Library of Science (PLoS)
Date: 12-08-2013
Plasma beta-amyloid correlates with cognition and brain volumetrics in mild cognitive impairment [Abstract P1-242]
Publisher: Wiley
Date: 07-2013
Effect of white matter hyperintensities on cortical cerebral blood volume using perfusion MRI
Publisher: Elsevier BV
Date: 04-2004
Classifying neurocognitive disorders: the DSM-5 approach
Publisher: Springer Science and Business Media LLC
Date: 30-09-2014
DOI: 10.1038/NRNEUROL.2014.181
Abstract: Neurocognitive disorders--including delirium, mild cognitive impairment and dementia--are characterized by decline from a previously attained level of cognitive functioning. These disorders have erse clinical characteristics and aetiologies, with Alzheimer disease, cerebrovascular disease, Lewy body disease, frontotemporal degeneration, traumatic brain injury, infections, and alcohol abuse representing common causes. This ersity is reflected by the variety of approaches to classifying these disorders, with separate groups determining criteria for each disorder on the basis of aetiology. As a result, there is now an array of terms to describe cognitive syndromes, various definitions for the same syndrome, and often multiple criteria to determine a specific aetiology. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) provides a common framework for the diagnosis of neurocognitive disorders, first by describing the main cognitive syndromes, and then defining criteria to delineate specific aetiological subtypes of mild and major neurocognitive disorders. The DSM-5 approach builds on the expectation that clinicians and research groups will welcome a common language to deal with the neurocognitive disorders. As the use of these criteria becomes more widespread, a common international classification for these disorders could emerge for the first time, thus promoting efficient communication among clinicians and researchers.
APOE genotype and MRI markers of cerebrovascular disease: Systematic review and meta-analysis
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-07-2013
Mental Health and Illness of the New Zealand Maori
Publisher: SAGE Publications
Date: 06-1990
METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: An initiative of the Joint Programme for Neurodegenerative Disease Research.
Publisher: Wiley
Date: 08-2016
Cognitive leisure activities, but not watching TV, for future brain benefits [5]
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-08-2006
Is the reduction of mental phenomena an attainable goal?
Publisher: American Psychiatric Association Publishing
Date: 05-1999
DOI: 10.1176/JNP.11.2.274
Posterior compensatory network in cognitively intact elders with hippocampal atrophy
Publisher: Wiley
Date: 11-02-2015
DOI: 10.1002/HIPO.22395
Abstract: Functional compensation in late life is poorly understood but may be vital to understanding long-term cognitive trajectories. To study this we first established an empirically derived threshold to distinguish hippoc al atrophy in those with Mild Cognitive Impairment (MCI n = 34) from those with proficient cognition (PRO n = 22), using data from a population-based cohort. Next, to identify compensatory networks we compared cortical activity patterns during a graded spatial working memory (SWM) task in only cognitively proficient in iduals, either with (PROATR ) or without hippoc al atrophy (PRONIL ). Multivariate Partial Least Squares analyses revealed that these groups engaged spatially distinct SWM-related networks. In those with hippoc al atrophy and under conditions of basic-SWM demand, expression of a posterior compensatory network (PCN) comprised calcarine and posterior parietal cortex strongly correlated with superior SWM performance (r = -0.96). In these in iduals, basic level SWM response times were faster and no less accurate than in those with no hippoc al atrophy. Cognitively proficient older in iduals with hippoc al atrophy may, therefore, uniquely engage posterior brain areas when performing simple spatial working memory tasks.
Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
Publisher: Springer Science and Business Media LLC
Date: 06-12-2019
DOI: 10.1038/S41380-019-0605-Z
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small s le sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 in iduals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippoc us, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of in idual CpGs revealed genome-wide significant associations with hippoc al volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippoc al volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins
Publisher: Cold Spring Harbor Laboratory
Date: 07-05-2020
DOI: 10.1101/2020.05.05.075606
Abstract: The critical role of blood lipids in a broad range of health and disease states is well recognised, while an understanding of the complex genetic regulation of lipid homeostasis is emerging. Traditional blood lipids (LDL-C, HDL-C and triglycerides) are known to be substantially regulated by genetic variation. Less well explored is the interplay of genetics and environment within the broader blood lipidome. Here we use the twin model to examine heritability of the plasma lipidome among healthy older aged twins and explore gene expression and epigenetic (DNA methylation) associations of these lipids. Heritability of 209 plasma lipids quantified by liquid chromatography coupled mass spectrometry (LC-MS) was assessed in 75 monozygotic and 55 dizygotic twin pairs enrolled in the Older Australian Twins Study (OATS), aged 69-93 years. Only 27/209 lipids (13.3%) were significantly heritable under the classical ACE twin model ( h 2 = 0.28-0.59). Ceramides (Cer) and triglycerides (TG) were most heritable, while sphingomyelins (SM) and most phospholipids, especially lysophospholipids, were not significantly heritable. Lipid levels correlated with 3731 transcripts. Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, which were not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for a proportion of variability in some non-heritable lipids, especially lysophosphatidylcholine (LPC). We found a complex interplay of genetic and environmental influences on the ageing plasma lipidome, with most of the variation controlled by unique environmental influences.
Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression
Publisher: Cambridge University Press (CUP)
Date: 23-12-2002
DOI: 10.1017/S0033291702006839
Abstract: Background. The efficacy and safety of bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, placebo-controlled study. Method. Nineteen medication-resistant depressed subjects were randomly assigned to 3 weeks of active or sham rTMS. Effects on mood and neuropsychological function were assessed. Results. Both groups improved significantly in mood over the 3 weeks, but there was no significant difference between active and sham treatments. There were no significant neuropsychological effects. Conclusions. Bilateral rTMS was not superior to sham in treating resistant depression in this pilot study, but caused no neuropsychological impairment.
Schizophrenia-Like Psychosis and Epilepsy: The Status of the Association
Publisher: American Psychiatric Association Publishing
Date: 03-1998
Abstract: Current knowledge of the relationship between epilepsy and schizophrenia-like psychosis is examined, and the proposed pathogenetic mechanisms are evaluated. The author provides an overview of the published literature on epilepsy and schizophrenia-like psychosis. The schizophrenia-like psychoses of epilepsy are inadequately categorized by the current classifications. Their categorization into ictal, postictal, and interictal psychoses is clinically useful, but it does not imply distinct pathophysiology for each. The recent interest in postictal psychoses has opened an important avenue for research. Brief interictal psychoses, involving alternation between epilepsy and psychosis and accompanied by forced normalization, are uncommon. Many aspects of the relationship with chronic interictal psychosis remain controversial. The majority of investigators support a special but not exclusive relationship with mediobasal temporal lobe epilepsy, and left temporal bias receives only limited support. The chronic psychosis resembles schizophrenia phenomenologically. Some suggested risk factors are severe and intractable epilepsy, epilepsy of early onset, secondary generalization of seizures, certain anticonvulsant drugs, and temporal lobectomy. Different neuropathological studies suggest the presence of cortical dysgenesis or diffuse brain damage. There are many mechanisms by which epilepsy may be associated with schizophrenia-like psychosis. It is likely that structural brain abnormalities, e.g., cortical dysgenesis or diffuse brain lesions, underlie both epilepsy and psychosis, and that the seizures modify the presentation of the psychosis, and vice versa, thus producing a clinical picture of both an affinity and an antagonism between the two disorders.
Psychotic disorder and traumatic brain injury.
Publisher: Springer Science and Business Media LLC
Date: 05-2003
DOI: 10.1007/S11920-003-0042-0
Abstract: Traumatic brain injury (TBI) can result in serious and disabling neuropsychiatric disorders, such as cognitive deficits and personality change, as well as severe and chronic psychosis. This review focuses on the relationship between TBI and schizophrenia-like psychosis (SLP) including its epidemiology, diagnostic criteria, clinical presentation, psychopathology, risk factors, and pathophysiology. The relationships between post-traumatic epilepsy and SLP, and brain trauma and schizophrenia, are also discussed. The risk of SLP does increase after TBI. The clinical presentation has considerable overlap with primary schizophrenic disorder, with a prominence of persecutory and other delusions and auditory hallucinations, as well as a lack of negative symptoms. The onset is often gradual, with a subacute or chronic course. More severe and diffuse brain injury, especially of the temporal and frontal lobes, is the most prominent risk factor. Genetic load may also play a role, but presence of epilepsy could be a protective factor. Further large and systematic longitudinal studies are needed.
Sirtuin expression during aging and in Alzheimer's disease
Publisher: Wiley
Date: 07-2012
Development and validation of a rating scale for perivascular spaces on 3T MRI
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.JNS.2019.116621
Abstract: To develop and validate a novel perivascular space rating scale, based on single axial slices in the basal ganglia and the centrum semiovale on T1-weighted and FLAIR images obtained on a 3T MRI scanner. 414 community dwelling older adults age 70-90 were assessed. The number of perivascular spaces in the slices 2 mm (basal ganglia) and 37 mm (centrum semiovale) above the anterior commissure were counted. The construct validity of the scale was tested by examining associations with age, sex, vascular risk factors and neuroimaging markers of small vessel disease white matter hyperintensities, lacunes and cerebral microbleeds. Associations with cross sectional global and domain specific cognition were also examined. The rating scale had excellent inter-rater reliability (intraclass correlation coefficient in basal ganglia 0.82 and centrum semiovale 0.96), good intra-rater reliability (ICC in basal ganglia 0.72 and centrum semiovale 0.87) and reasonable concurrent validity with an existing perivascular spaces scale (Spearman rho = 0.49, p < .001). There was a median of four basal ganglia and zero centrum semiovale perivascular spaces. Basal ganglia perivascular spaces were more common in men and associated with the other neuroimaging markers. Perivascular spaces in either location were not independently associated with global or domain specific cognitive impairment. The new rating scale is easy to use, quick, has good psychometric properties and performs better than existing scales in a community dwelling older cohort. Further studies are needed to validate the scale in more erse cohorts with greater cerebrovascular burden.
P1-465: Amyloid burden is independent of cerebrovascular burden, but hypertension promotes amyloid accumulation over time
Publisher: Wiley
Date: 07-2018
Systemic inflammation is associated with MCI and its subtypes: The Sydney Memory and Aging Study
Publisher: S. Karger AG
Date: 2010
DOI: 10.1159/000322092
Abstract: i Background/Aims: /i Raised low-grade systemic inflammation has been associated with dementia, and preliminary studies suggest an association with mild cognitive impairment (MCI). This study examines the relationship between systemic inflammation and MCI subtypes. i Methods: /i We measured the inflammatory markers C-reactive protein, interleukins (IL)-1β, -6, -8, -10 and -12, plasminogen activator inhibitor-1 (PAI-1), serum amyloid A (SAA), tumor necrosis factor-α (TNF-α) and vascular adhesion molecule-1 (VCAM-1) in the Sydney Memory and Ageing Study (MAS) cohort, a longitudinal study of 1,037 Australians aged 70–90 years. i Results: /i After adjusting for possible confounding variables, levels of TNF-α and SAA were higher in participants with MCI compared to cognitively normal in iduals, and some sex differences were apparent. Nonamnestic multiple domain MCI was associated with higher levels of IL-1β and IL-12, TNF-α and SAA compared to cognitively normal, amnestic MCI (single and multiple domain) and nonamnestic single domain MCI. PAI-1 levels were higher in cognitively normal and nonamnestic multiple domain MCI than in amnestic multiple domain MCI. i Conclusion: /i Our findings suggest an association between specific inflammatory markers and MCI subtypes, highlight sex differences in the association with MCI, and point to a discrete impact of systemic inflammation on cognition.
Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.MAD.2018.06.002
Abstract: Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses. Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts. Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males). In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls.
Bilateral deep brain stimulation of the nucleus accumbens for comorbid obsessive compulsive disorder and Tourette's syndrome
Publisher: BMJ
Date: 12-09-2012
The relationship of neuropsychological function to instrumental activities of daily living in mild cognitive impairment
Publisher: Wiley
Date: 16-09-2011
DOI: 10.1002/GPS.2612
Abstract: While activities of daily living are by definition preserved in mild cognitive impairment (MCI), there is evidence of poorer instrumental activities of daily living (IADL) functioning in MCI compared to normal ageing. The aims of the present study were to examine differences in IADL between in iduals with MCI and cognitively normal elderly, and to examine the relationships of IADL with cognitive functions. The s le of 762 community-living participants aged 70-90 were assessed with a comprehensive neuropsychological test battery and with the informant-completed Bayer-Activities of Daily Living Scale (B-ADL). Compared to cognitively normal in iduals, the MCI group was rated as having more difficulties on the B-ADL and performed worse on cognitive tests. Factor analysis of the B-ADL items yielded two factors, which were labelled 'high cognitive demand' (HCD) and 'low cognitive demand' (LCD). In iduals with MCI scored worse than cognitively normal participants on the HCD factor but similarly on the LCD factor. Men were rated as having more difficulties on the HCD, but not the LCD, factor compared to women. The HCD factor score correlated significantly with all five cognitive domains measured, but the LCD factor correlated significantly only with attention rocessing speed and to a lesser extent with executive function. Having more difficulties in IADL, especially those with higher demand on cognitive capacities, was found to be associated with MCI and overall cognitive functioning. This has implications for the definition of MCI, as lack of functional impairment is generally used as a criterion for diagnosis.
GWAS for executive function and processing speed suggests involvement of the CADM2 gene
Publisher: Springer Science and Business Media LLC
Date: 14-04-2015
DOI: 10.1038/MP.2015.37
Erratum: 1H MRS in stroke patients with and without cognitive impairment (Neurobiology of Aging (2005) 26 (873-882) DOI: 10.1016/j. neurobiolaging.2004.07.008)
Publisher: Elsevier BV
Date: 03-2006
Study protocol for the BRAIN Training Trial: A randomised controlled trial of Balance, Resistance, and INterval training on cognitive function in older adults with mild cognitive impairment
Publisher: BMJ
Date: 12-2022
DOI: 10.1136/BMJOPEN-2022-062059
Abstract: Epidemiological evidence suggests that both poor cardiovascular fitness and low muscle mass or strength markedly increase the rate of cognitive decline and incident dementia in older adults. Results from exercise trials for the improvement of cognition in older adults with mild cognitive impairment (MCI) have reported mixed results. This is possibly due to insufficient exercise intensities. The aim of the Balance, Resistance, And INterval (BRAIN) Training Trial is to determine the effects of two forms of exercise, high-intensity aerobic interval training (HIIT) and high-intensity power training (POWER) each compared with a sham exercise control group on cognition in older adults with MCI. One hundred and sixty community-dwelling older (≥ 60 years) people with MCI have been randomised into the trial. Interventions are delivered supervised 2–3 days per week for 12 months. The primary outcome measured at baseline, 6 and 12 months is performance on a cognitive composite score measuring the executive domain calculated from a combination of computerised (NeuroTrax) and paper-and-pencil tests. Analyses will be performed via repeated measures linear mixed models and generalised linear mixed models of baseline, 6-month and 12-month time points, adjusted for baseline values and covariates selected a priori. Mixed models will be constructed to determine the interaction of GROUP × TIME. Ethical approval was obtained from the University of Sydney (HREC Ref.2017/368), University of Queensland (HREC Ref. 2017/HE000853), University of British Columbia (H16-03309), and Vancouver Coastal Health Research Institute (V16-03309) Human Research Ethics. Dissemination will be via publications, conference presentations, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT and POWER on subclinical markers of disease. ACTRN12617001440314 Australian New Zealand Clinical Trials Registry.
Brain reserve and cognitive decline: A non-parametric systematic review
Publisher: Cambridge University Press (CUP)
Date: 02-05-2006
DOI: 10.1017/S0033291706007744
Abstract: Background. A previous companion paper to this report (Valenzuela & Sachdev, Psychological Medicine 2006, 36 , 441–454) suggests a link between behavioural brain reserve and incident dementia however, the issues of covariate control and ascertainment bias were not directly addressed. Our aim was to quantitatively review an independent set of longitudinal studies of cognitive change in order to clarify these factors. Method. Cohort studies of the effects of education, occupation, and mental activities on cognitive decline were of interest. Abstracts were identified in MEDLINE (1966–September 2004), CURRENT CONTENTS (to September 2004), PsychINFO (1984–September 2004), Cochrane Library Databases and reference lists from relevant articles. Eighteen studies met inclusion criteria. Key information was extracted by both reviewers onto a standard template with a high level of agreement. Cognitive decline studies were integrated using a non-parametric method after converting outcome data onto a common effect size metric. Results. Higher behavioural brain reserve was related to decreased longitudinal cognitive decline after control for covariates in source studies (ϕ=1·70, p ·001). This effect was robust to correction for both multiple predictors and multiple outcome measures and was the result of integrating data derived from more than 47000 in iduals. Conclusions. This study affirms that the link between behavioural brain reserve and incident dementia is most likely due to fundamentally different cognitive trajectories rather than confound factors.
Characterizing mild cognitive disorders in the young-old over 8 years: Prevalence, estimated incidence, stability of diagnosis, and impact on IADLs
Publisher: Wiley
Date: 07-03-2013
DOI: 10.1016/J.JALZ.2012.11.013
Abstract: Few studies report incidence of mild cognitive impairment (MCI) and other mild cognitive disorders (MCD) in cohorts in their 60s, at an age when diagnoses are less stable. The authors' goal was to estimate the incidence and prevalence of MCI and MCD, characterize subgroups with stable vs nonstable diagnoses, and evaluate the impact of diagnosis on daily life in a young-old cohort. A community-based cohort age 60 to 64 years in 1999 (n = 2551) was monitored for 8 years and assessed every 4 years. A two-stage s ling design was used to identify MCI and MCD through a neuropsychological and neurological assessment. A panel of physicians blind to previous diagnoses reviewed each case using published criteria. The prevalence of MCDs in the cohort aged 68 to 72 years at the last follow-up was approximately 10%. An estimated 141 subjects (7.7%) progressed to MCI and 183 subjects (10.0%) progressed to MCD between years 4 and 8. Only eight participants received a dementia diagnosis at any wave, five of whom progressed from MCDs. More than 45% of diagnoses were unstable during the 8 years of follow-up. Stable diagnoses were associated with lower Mini-Mental State Examination scores, history of neurological disorder, higher cardiovascular risk, and depression at baseline. MCDs were associated with impairments in instrumental activities of daily living and higher rates of reporting memory problems prior to diagnosis. MCDs in in iduals in their 60s occur in at least 10% of the population and are likely to be heterogeneous in terms of their etiology and long-term prognosis, but may cause a significant impact in everyday life.
Parental history of dementia and the risk of dementia: A cross‐sectional analysis of a global collaborative study
Publisher: Wiley
Date: 24-05-2023
DOI: 10.1111/PCN.13561
Abstract: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. For this cross‐sectional study, we harmonized and pooled data for 17,194 older adults from nine population‐based cohorts of eight countries. These studies conducted face‐to‐face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15–1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31–2.26), but not with the risk of non‐AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15–1.97) and AD (OR = 1.80, 95% CI = 1.33–2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28–3.55 in males OR = 1.68, 95% CI = 1.16–2.44 for females). Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying in iduals at higher risk of AD and stratifying the risk for AD in clinical trials.
Cortical Thinning at Midlife: The PATH Through Life Study
Publisher: Springer Science and Business Media LLC
Date: 23-07-2016
DOI: 10.1007/S10548-016-0509-Z
Abstract: Cortical thinning is a part of normal ageing. Recent studies suggest that accelerated cortical thinning in vulnerable regions may be a useful biomarker for neuropathologies including Alzheimer's disease (AD). Longitudinal studies, which have largely focused on older adults, have provided estimates of normative rates and patterns of age-related cortical thinning. Very little, however, is known about healthy cortical thinning at midlife. Here we provide longitudinal estimates of age-related cortical thinning observed over 8 years, in a large (n = 404) group of healthy in iduals aged 44-49 years at baseline, who were scanned with MRI (1.5T) on up to three occasions. Age-related cortical thinning was assessed across the whole cortex. We measured a mean annual decrease in cortical thickness of 0.26 % on the left and 0.17 % on the right hemisphere, and largely affecting frontal and cingulate cortices. Medial and lateral temporal regions were generally spared. Studying regions that are specifically vulnerable to-or spared from-healthy age-related cortical thinning at midlife may be important for the early identification of neurodegeneration, including AD.
Response to: English Language Proficiency, Hearing Impairment, and Functional Change in Mild Cognitive Impairment
Publisher: Elsevier BV
Date: 11-2017
Incidental findings on cerebral MRI in twins: the Older Australian Twins Study
Publisher: Springer Science and Business Media LLC
Date: 04-07-2018
DOI: 10.1007/S11682-017-9747-2
Abstract: Incidental findings on structural cerebral magnetic resonance imaging (MRI) are common in healthy subjects, and the prevalence increases with age. There is a paucity of data regarding incidental cerebral findings in twins. We examined brain MRI data acquired from community-dwelling older twins to determine the prevalence and concordance of incidental cerebral findings, as well as the associated clinical implications. Participants (n = 400) were drawn from the Older Australian Twins Study. T1-weighted and T2-weighted fluid-attenuated inversion recovery (FLAIR) cerebral MRI scans were systematically reviewed by a trained, blinded clinician. Incidental findings were recorded according to pre-determined categories, and the diagnosis confirmed by an experienced neuroradiologist. Periventricular and deep white matter hyperintensities (WMH) were scored visually. WMH heritability was calculated for those with the twin pair included in the study (n = 320 in iduals monozygotic (MZ) = 92 twin pairs, dizygotic (DZ) = 68 twin pairs). Excluding infarcts and WMH, a total of 47 (11.75%) incidental abnormalities were detected. The most common findings were hyperostosis frontalis interna (8 participants 2%), meningiomas, (6 participants 1.5%), and intracranial lipomas (5 participants 1.25%). Only 3% of participants were referred for follow-up. Four twin pairs, all monozygotic, had lesions concordant with their twin. Periventricular WMH was moderately heritable (0.61, CI 0.43-0.75, p = 7.21E-08) and deep WMH highly heritable (0.80, CI 0.66-0.88, p = 1.76E-13). As in the general population, incidental findings on cerebral MRI in older twins are common, although concordance rates are low. Such findings can alter the clinical outcome of participants, and should be anticipated by researchers when designing trials involving cerebral imaging.
White matter hyperintensities are related to physical disability and poor motor function
Publisher: BMJ
Date: 03-2005
Reduced activation to implicit affect induction in euthymic bipolar patients: An fMRI study
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.JAD.2006.06.005
Abstract: To examine whether euthymic bipolar patients engage similar or contrasting brain regions as healthy subjects when responding to implicit affect induction. The study examined 10 euthymic patients with bipolar I disorder, and 10 age- and gender-matched healthy subjects using event-related functional magnetic resonance imaging (fMRI) while subjects engaged in a modified word-based memory task designed to implicitly evoke negative, positive or no affective change. The activation paradigm involved nominating whether a target word was contained within a previously presented word list using specified response keys. The fMRI task produced significantly greater activation in healthy subjects as compared to patients in response to both negative and positive affect in the anterior and posterior cingulate, medial prefrontal cortex, middle frontal and right parahippoc al gyri. Only negative affect produced significantly greater activation in the postcentral gyrus, inferior parietal lobule, thalamus and putamen and only positive affect achieved the same in the precentral, superior temporal and lingual gyri, precuneus, cuneus, caudate, pons, midbrain and cerebellum. There were no brain regions in which responses were greater in patients as compared to healthy subjects. There were no statistically significant differences between the groups with respect to speed or accuracy. Diminished prefrontal, cingulate, limbic and subcortical neural activity in euthymic bipolar patients as compared to healthy subjects is suggestive of emotional compromise that is independent of cognitive and executive functioning. This finding is of clinical importance and has implications both for the diagnosis and treatment of bipolar disorder. Future studies should aim to replicate these findings and examine the development of bipolar disorder, investigating in particular the effects of medication.
UBO Detector - A cluster-based, fully automated pipeline for extracting white matter hyperintensities.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.NEUROIMAGE.2018.03.050
Abstract: We present 'UBO Detector', a cluster-based, fully automated pipeline for extracting and calculating variables for regions of white matter hyperintensities (WMH) (available for download at cheba.unsw.edu.au/group/neuroimaging-pipeline). It takes T1-weighted and fluid attenuated inversion recovery (FLAIR) scans as input, and SPM12 and FSL functions are utilised for pre-processing. The candidate clusters are then generated by FMRIB's Automated Segmentation Tool (FAST). A supervised machine learning algorithm, k-nearest neighbor (k-NN), is applied to determine whether the candidate clusters are WMH or non-WMH. UBO Detector generates both image and text (volumes and the number of WMH clusters) outputs for whole brain, periventricular, deep, and lobar WMH, as well as WMH in arterial territories. The computation time for each brain is approximately 15 min. We validated the performance of UBO Detector by showing a) high segmentation (similarity index (SI) = 0.848) and volumetric (intraclass correlation coefficient (ICC) = 0.985) agreement between the UBO Detector-derived and manually traced WMH b) highly correlated (r
Predicting Cognitive, Functional, and Diagnostic Change over 4 Years Using Baseline Subjective Cognitive Complaints in the Sydney Memory and Ageing Study
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.JAGP.2014.09.001
Abstract: There is limited understanding of the usefulness of subjective cognitive complaint(s) (SCC) in predicting longitudinal outcome because most studies focus solely on memory (as opposed to nonmemory cognitive) complaints, do not collect data from both participants and informants, do not control for relevant covariates, and have limited outcome measures. Therefore the authors investigate the usefulness of participant and informant SCCs in predicting change in cognition, functional abilities, and diagnostic classification of mild cognitive impairment or dementia in a community-dwelling s le over 4 years. Nondemented participants (N = 620) in the Sydney Memory and Ageing Study aged between 70 and 90 years completed 15 memory and 9 nonmemory SCC questions. An informant completed a baseline questionnaire that included 15 memory and 4 nonmemory SCC questions relating to the participant. Neuropsychological, functional, and diagnostic assessments were carried out at baseline and again at 4-year follow-up. Cross-sectional and longitudinal analyses were carried out to determine the association between SCC indices and neuropsychological, functional, and diagnostic data while controlling for psychological measures. Once participant characteristics were controlled for, participant complaints were generally not predictive of cognitive or functional decline, although participant memory-specific complaints were predictive of diagnostic conversion. Informant-related memory questions were associated with global cognitive and functional decline and with diagnostic conversion over 4 years. Informant memory complaint questions were better than participant complaints in predicting cognitive and functional decline as well as diagnoses over 4 years.
P4‐099: Validated dementia risk factor composite is associated with lower hippocampal volumes and cortical thickness
Publisher: Wiley
Date: 07-2015
Schizophrenia-like psychosis following traumatic brain injury: A chart-based descriptive and case-control study
Publisher: Cambridge University Press (CUP)
Date: 02-2001
DOI: 10.1017/S0033291701003336
Abstract: Background. Head injury has been reported to increase the likelihood of the development of schizophrenia-like psychosis (SLP), but its features and risk factors have been insufficiently investigated. Method. Between 1987 and 1997, we examined 45 referred patients with SLP following brain trauma. These subjects were matched with 45 head-injured subjects without SLP on age (current and at injury) and gender, and their case records reviewed systematically. The groups were compared and logistic regression analyses performed. Results. The psychoses had a mean age of onset of 26·3 years, a mean latency of 54·7 months after head injury, usually a gradual onset and a subacute or chronic course. Prodromal symptoms were common and depression often present at onset. Paranoid delusions and auditory hallucinations were the predominant features, with formal thought disorder, catatonic features and negative symptoms being uncommon. The SLP group had more widespread brain damage on neuroimaging, especially in the left temporal and right parietal regions, and were more impaired cognitively. Fewer (non-significantly) SLP subjects had epilepsy which was more likely to be well-controlled in this group. On regression analysis, a positive family history of psychosis and duration of loss of consciousness were the best predictors of SLP. Conclusions. Head injury-related psychosis is usually paranoid-hallucinatory and subacute or chronic in its presentation. A genetic predisposition to schizophrenia and severity of injury with significant brain damage and cognitive impairment may be vulnerability factors.
Neurogenesis and precursor cell differences in the dorsal and ventral adult canine hippocampus
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.NEULET.2015.03.017
Abstract: During evolution a unique anterior-posterior flexure posited the canine dentate gyrus in two distinct dorsal and ventral positions. We therefore sought to explore neurogenesis and neurogenic cell-related difference along the canine hippoc al dorsal-ventral axis. Post mortem histological analysis revealed 49.1% greater doublecortin (DCX)-positive cells and a 158.5% greater percentage of double labeled DCX-positive/neuronal nuclei (NeuN) positive cells in the dorsal subgranular zone compared to the ventral. We then show neural precursor cells isolated from fresh hippoc al tissue are capable of proliferating long term, and after differentiation, express neuronal and glial markers. Dorsal hippoc al isolates produced a 120.0% higher frequency of sphere-forming neural precursor cells compared to ventral hippoc al tissue. Histological DCX and neurosphere assay results were highly correlated. Overall, we provide the first evidence that the dorsal canine hippoc us has a markedly higher rate of adult neurogenesis than the ventral hippoc us, possibly related to a greater frequency of contributory neural precursor cells.
Pluripotent stem cells & neurodegenerative and ischaemic brain diseases: Basic science to clinical applications
Publisher: BENTHAM SCIENCE PUBLISHERS
Date: 19-05-2012
The relationship between inflammatory markers and voxel-based gray matter volumes in nondemented older adults
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.NEUROBIOLAGING.2015.10.008
Abstract: Ageing is characterized by chronically elevated inflammatory markers (IMs). Peripheral IM levels have been found in negative correlations with brain structural measures including global and lobar volumes and the hippoc us. This study investigated the relationship between 10 peripheral IMs and voxel-based gray matter (GM) volumes in nondemented older adults (n = 463). Two proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-1β) and 2 vascular IMs (vascular cellular adhesion molecule-1 and plasminogen activator inhibitor-1) were negatively correlated with regional GM volumes. TNF-α and interleukin-1β were both significantly correlated with GM volumes in the left occipitotemporal area, left superior occipital gyrus, and left inferior parietal lobule TNF-α was also significantly correlated with the bilateral medial prefrontal cortices and approached significance for the correlations with the bilateral hippoc i. Significant GM correlations with vascular cellular adhesion molecule-1 were located in the bilateral anterior cingulate cortices, and with plasminogen activator inhibitor-1 in the cerebellum and right hippoc us. The neuroanatomical correlation patterns of 2 proinflammatory cytokines and 2 vascular IMs might be reflective of the effects of neurodegenerative and vascular pathological processes in the ageing brain.
Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium
Publisher: Cold Spring Harbor Laboratory
Date: 09-09-2018
DOI: 10.1101/409649
Abstract: Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery s le comprised 22,822 in iduals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
Education, atrophy, and cognitive change in an epidemiological sample in early old age
Publisher: Elsevier BV
Date: 03-2009
Memory complaints in a community sample aged 60-64 years: associations with cognitive functioning, psychiatric symptoms, medical conditions, APOE genotype, hippocampus and amygdala volumes, and white-matter hyperintensities.
Publisher: Cambridge University Press (CUP)
Date: 11-2004
DOI: 10.1017/S0033291704003162
Abstract: Background. Previous research has found that depression is a major cause of memory complaints. However, there is evidence that memory complaints also weakly predict cognitive decline and dementia. The present study examined a range of possible determinants of memory complaints, covering psychiatric and personality factors, medical history, cognitive test performance, and biological risk factors for dementia (APOE genotype, hippoc us and amygdala volumes, and white-matter hyperintensities). Method. A community survey was carried out with 2546 persons aged 60–64 years living in Canberra and Queanbeyan, Australia. Participants were asked about memory problems which interfered with daily life and whether medical help had been sought. A randomly selected subs le of 476 persons was given a brain MRI scan. Results. Participants with memory complaints were found to have poorer memory test performance, more depression and anxiety symptoms, have higher scores on personality traits involving negative affect, and to have worse physical health. Multivariate analyses showed that measures of cognitive performance did not make a unique contribution to the prediction of memory complaints above that of the other categories of predictors. Those with memory complaints did not differ on any of the biological risk factors for dementia. Conclusion. In a community s le aged 60–64 years, memory complaints were most closely related to psychiatric symptoms, personality characteristics and poor physical health. There was no evidence of brain changes indicating early dementia.
Depression-Dependent Exacerbation of Tardive Dyskinesia
Publisher: Royal College of Psychiatrists
Date: 08-1989
Abstract: A middle-aged woman with a recurrent depressive illness showed worsening of her tar e dyskinesia during the depressive phases, with improvement on remission.
Neuropsychiatry: Where are we and where do we go from here?
Publisher: Medknow
Date: 2013
The longitudinal course of post-stroke apathy over five years
Publisher: American Psychiatric Association Publishing
Date: 2013
DOI: 10.1176/APPI.NEUROPSYCH.12040080
Abstract: The prevalence of apathy is high after stroke, but its subsequent course remains unclear. We sought to determine the longitudinal course and predictors of apathy after stroke. Eligible patients admitted after a stroke and healthy control participants who were rated at least once on the Apathy Evaluation Scale were assessed over 5 years. Rates and levels of apathy in patients rose over 5 years. Significant risk factors for apathy were dementia, interval cerebrovascular events, poor physical functioning, and high depression scores. Apathy is common after stroke and becomes more prevalent with time, especially in those who show evidence of cognitive and functional decline.
Case-control study of neuroleptic malignant syndrome
Publisher: American Psychiatric Association Publishing
Date: 08-1997
Abstract: The authors performed a case-control study of neuroleptic malignant syndrome to identify potential risk factors. Twenty-five patients with neuroleptic malignant syndrome were matched with 50 comparison subjects on age, sex, primary psychiatric diagnosis, and time of admission to the hospital. The records of all subjects were reviewed independently by two researchers for information on postulated risk factors. Exploratory direct comparisons of the two groups were followed by a conditional logistic regression analysis. Patients with neuroleptic malignant syndrome were more likely to be agitated or dehydrated before the development of neuroleptic malignant syndrome, often needed restraint or seclusion, and received larger doses of neuroleptics soon after hospitalization. Previous treatment with ECT increased vulnerability. The prevalence of neuroleptic malignant syndrome may be reduced by avoiding large doses of neuroleptics over short periods in the management of acute psychosis and by paying adequate attention to the patient's hydration and electrolyte status.
Do extrapyramidal features in Alzheimer patients treated with acetylcholinesterase inhibitors predict disease progression?
Publisher: Informa UK Limited
Date: 07-2007
DOI: 10.1080/13607860601086439
Abstract: The objective of the study is to explore the longitudinal course of patients with Alzheimer's disease (AD) with and without extrapyramidal signs (EPS) taking donepezil. A cohort of 106 community-dwelling patients with probable AD receiving donepezil in Sydney, Australia (n = 52) and Manchester, UK (n = 54) was followed over 12 months. Cognition was measured by the Mini-Mental State Exam (MMSE) and the Alzheimer Disease Assessment Scale-Cognitive test (ADAS-Cog) and function by the Alzheimer Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL). A further follow-up at five years was conducted to examine mortality and institutionalisation. At baseline, EPS were correlated with MMSE (r = -0.467, p < 0.01), ADAS-Cog (r = 0.485, p < 0.01) and ADCS-ADL (r = -0.526, p < 0.01) scores. Patients with EPS had lower MMSE (F = 9.95, df = 1, p = 0.002) and ADCS-ADL (F = 9.41, df = 1, p = 0.003) scores than patients without EPS. Over one year no time main effects or time x group interaction effects were observed for either dependent variable. At five years patients with EPS were found to have a hazard of institution or death 2.2 times higher than those without EPS (p = 0.018 95% CI: 1.2, 4.4). There was a positive association between EPS and cognitive and functional impairment. However, EPS did not predict more rapid cognitive or functional decline of patients taking donepezil or response to donepezil. The presence of EPS was a risk factor both for institutionalisation and for death.
Prediction of cognitive decline after stroke using proton magnetic resonance spectroscopy
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.JNS.2006.08.014
Abstract: Structural MRI measures have been used to predict cognitive decline in elderly subjects, but few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) for this purpose, particularly after stroke. We studied the potential of (1)H-MRS to predict cognitive decline in patients with stroke or TIA and healthy ageing controls over 12 months and 3 years. Structural MRI and single-voxel (1)H-MRS in the frontal white matter and the occipito-parietal gray matter were performed at the index assessment (3-6 months post-stroke) in 49 stroke/TIA patients and 60 controls. Neuropsychological testing was performed at the index assessment and repeated at 12 months in 30 stroke/TIA patients and 49 controls, and at 3 years in 25 patients and 48 controls. In stroke/TIA patients, frontal NAA/Cr predicted cognitive decline over 12 months and 3 years, and in elderly control subjects frontal NAA predicted cognitive decline over 12 months only. In stroke/TIA patients, the (1)H-MRS measures were better predictors of cognitive decline than structural measures. (1)H-MRS may be useful in assessing early cognitive impairment after stroke/TIA and in normal ageing.
Tourette syndrome, co-morbidities and quality of life
Publisher: SAGE Publications
Date: 13-07-2016
Abstract: Tourette syndrome is often associated with attention deficit hyperactivity disorder, obsessive compulsive disorder and other co-morbidities, the presence of which can reduce health-related quality of life. The relationship between the number and type of co-morbidities and tic severity upon health-related quality of life has been insufficiently examined in Tourette syndrome populations and not at all in the Australian context. We hypothesised that an increased number of co-morbid diagnoses would be inversely related to health-related quality of life and that the presence of attention deficit hyperactivity disorder and obsessive compulsive disorder in particular would negatively impact health-related quality of life. In all, 83 people with a previously established diagnosis of Tourette syndrome, who responded to a letter of invitation sent to the Tourette Syndrome Association of Australia past-member database, formed the study s le. Participants completed the Gilles de la Tourette Syndrome-Quality of Life Scale and a short form of the National Hospital Interview Schedule to assess tics and related behaviours. Participants with pure-Tourette syndrome had significantly better health-related quality of life than those with Tourette syndrome and three or more co-morbid diagnoses. Few differences were observed between the pure-Tourette syndrome and Tourette syndrome and one or two co-morbid diagnoses groups. Analysis of the impact of in idual co-morbid disorders and Tourette syndrome symptoms on health-related quality of life indicated that attention deficit hyperactivity disorder exerted a significant negative effect, as did the presence of complex tics, especially coprolalia and copropraxia. When these variables were examined in multiple regression analysis, number of co-morbidities and the presence of coprophenomena emerged as significant predictors of health-related quality of life. While tics are the defining feature of Tourette syndrome, it appears to be the presence of co-morbidities, attention deficit hyperactivity disorder, in particular, and coprophenomena that have the greater impact on health-related quality of life. This has implications for symptom-targeting in the treatment of Tourette syndrome since all available treatments are symptomatic and not disease modifying.
Neuroplasticity in depressed individuals compared with healthy controls
Publisher: Springer Science and Business Media LLC
Date: 16-05-2013
DOI: 10.1038/NPP.2013.126
Genetics of hand grip strength in mid to late life
Publisher: Springer Science and Business Media LLC
Date: 02-2015
Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia
Publisher: Springer Science and Business Media LLC
Date: 27-04-2022
Cortical gyrification and its relationships with cortical volume, cortical thickness, and cognitive performance in healthy mid-life adults
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.BBR.2015.03.018
Abstract: Across species, greater cortical gyrification, or folding of the cortex, has been shown to be associated with higher cognitive abilities and is thought to reflect an evolutionary process aimed at maximizing the number of cerebral computational units while minimizing the energy and communication costs of larger brains. Relatively little is known about the significance of in idual variation in gyrification in humans and how it relates to other aspects of cerebral structure and function. In the current study, we examined relationships between cortical gyrification and (i) cortical volume, (ii) cortical thickness, and (iii) executive functions. Participants were middle-aged healthy adults (44-48 years old, n=396) in a community-based s le. T1-weighted 3D structural magnetic resonance imaging scans were acquired in a Fast Field Echo sequence. Cortical gyrification, volume, and thickness were measured through the semi-automated software FreeSurfer. Results showed that cortical gyrification was strongly and positively related to cortical volume, but was negatively related to cortical thickness in many regions of the cortex. In addition, frontal gyrification was positively related to performance in working memory and mental flexibility tasks. These results support the view that greater cortical gyrification is related both to bigger brain volumes and better cognitive function, but not to greater cortical thickness. The results provide evidence of functional relevance of cortical gyrification development, and show that it can be a useful index to investigate structure-cognition relationships.
The Association of Sedentary Behaviour and Cognitive Function in People Without Dementia: A Coordinated Analysis Across Five Cohort Studies from COSMIC
Publisher: Springer Science and Business Media LLC
Date: 16-09-2020
DOI: 10.1007/S40279-019-01186-7
Abstract: Besides physical activity as a target for dementia prevention, sedentary behaviour is hypothesized to be a potential target in its own right. The rising number of persons with dementia and lack of any effective treatment highlight the urgency to better understand these modifiable risk factors. Therefore, we aimed to investigate whether higher levels of sedentary behaviour are associated with reduced global cognitive functioning and slower cognitive decline in older persons without dementia. We used five population cohorts from Greece, Australia, USA, Japan, and Singapore (HELIAD, PATH, SALSA, SGS, and SLAS2) from the Cohort Studies of Memory in an International Consortium. In a coordinated analysis, we assessed the relationship between sedentary behaviour and global cognitive function with the use of linear mixed growth model analysis (mean follow-up range of 2.0–8.1 years). Baseline datasets combined 10,450 older adults without dementia with a mean age range between cohorts of 66.7–75.1 years. After adjusting for multiple covariates, no cross-sectional association between sedentary behaviour and cognition was found in four studies. One association was detected where more sedentary behaviour was cross-sectionally linked to higher cognition levels (SLAS2, B = 0.118 (0.075 0.160), P 0.001). Longitudinally, there were no associations between baseline sedentary behaviour and cognitive decline ( P 0.05). Overall, these results do not suggest an association between total sedentary time and lower global cognition in older persons without dementia at baseline or over time. We hypothesize that specific types of sedentary behaviour may differentially influence cognition which should be investigated further. For now, it is, however, too early to establish undifferentiated sedentary time as a potential effective target for minimizing cognitive decline in older adults without dementia.
A controlled study of sensory tics in Gilles de 1a Tourette syndrome and obsessive-compulsive disorder using a structured interview.
Publisher: BMJ
Date: 02-1997
Abstract: To determine the prevalence and characteristics of sensory tics in the Gilles de la Tourette syndrome (GTS), and a matched population of patients with obsessive-compulsive disorder (OCD) using a structured assessment. 50 subjects each of GTS, OCD, and healthy controls were studied to determine the prevalence and phenomenology of sensory tics, and diagnose tic disorders, OCD, and affective disorders according to DSM-III-R criteria. The severity of tics and obsessive-compulsive symptoms were quantified using the Tourette syndrome global scale (TSGS) and Yale-Brown obsessive-compulsive scale (Y-BOCS) respectively. The GTS group (28%) had significantly-greater life-time prevalence of sensory tics than the OCD (10%) and healthy (8%) groups (P < 0.05). The sensory tics in both the GTS and OCD groups were predominantly located in rostral anatomical sites. Multiple sensory tics occurred in some patients with GTS or OCD, but not in healthy subjects. Within the OCD group, those who had sensory tics had significantly higher TSGS scores (P < 0.0001), and a higher prevalence of GTS (P < 0.005). Sensory tics seem to be a common and distinctive feature of GTS and that subpopulation of patients with OCD predisposed to tic disorders. Neurophysiologically, a possible explanation for sensory tics is that they represent the subjectively experienced component of neural dysfunction below the threshold for motor and vocal tic production.
In Vivo Hippocampal Measurement and Memory: A Comparison of Manual Tracing and Automated Segmentation in a Large Community-Based Sample
Publisher: Public Library of Science (PLoS)
Date: 16-04-2009
Golfers' cramp: Clinical characteristics and evidence against it being an anxiety disorder
Publisher: Wiley
Date: 1992
Abstract: The clinical characteristics of 20 golfers suffering from golfers' cr or the "yips" are described. The typical description is that of a middle-aged golfer who has played competitive golf since his teens and develops the problem during a tournament in the form of a jerk, spasm, or freezing of movement while putting or chipping, with the rest of the game being relatively unaffected. The problem generally takes a chronic fluctuating course, and a number of 'trick' strategies are partially or fully successful. In this study, the subjects were compared with a matched group of 20 unaffected golfers on a number of indices of psychopathology no significant differences emerged. The more severely affected golfers also did not differ significantly from the mildly affected ones, except on the subjective report of anxiety. These data support the argument that golfers' cr is not an anxiety disorder or a neurosis. The important role of anxiety and arousal in its manifestation is, nevertheless, recognized and its pathophysiology speculated upon.
Homocysteine as a risk factor for cognitive impairment in stroke patients
Publisher: S. Karger AG
Date: 2003
DOI: 10.1159/000068481
Abstract: i Background: /i Elevated total homocysteine (tHcy) levels are associated with an increased risk of cerebrovascular disease. It is uncertain whether tHcy is also an independent risk factor for cognitive impairment. i Methods: /i We examined 95 stroke subjects 3 months after their strokes, and 55 healthy comparison subjects, with a detailed neuropsychological assessment, and MRI brain scans in a proportion (n = 97). Baseline measurements of tHcy, serum folate and B sub /sub , creatinine and plasma fibrinogen levels were obtained. i Results: /i tHcy levels were higher in the stroke subjects by a mean 34%. These levels were significantly correlated with the first factor of a principal component analysis of the neuropsychological data, after controlling for age, folate, B sub /sub and creatinine levels. The correlation of Hcy levels was particularly significant with frontal-executive functioning and attention. tHcy levels were significantly correlated with number of infarcts and total stroke volume in the stroke group, but not with T sub /sub -weighted deep white matter hyperintensity scores, after correction for age. In the control group, tHcy levels were significantly correlated with ventricle-to-brain ratios as measures of brain atrophy. i Conclusion: /i This study provides evidence that high tHcy levels are associated with cognitive impairment, in particular that of frontal-executive function. The major component of this association is accounted for by small and large strokes, but non-vascular neurotoxic effects of tHcy also appear to play a role. tHcy must receive greater attention as a risk factor for cognitive impairment.
Socio-Economic Position and Type 2 Diabetes Risk Factors: Patterns in UK Children of South Asian, Black African-Caribbean and White European Origin
Publisher: Public Library of Science (PLoS)
Date: 07-03-2012
Microstructural white matter changes in cognitively normal individuals at risk of cognitive decline
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-07-2012
Increased Anterior Cingulate Cortex Volume in Bipolar I Disorder
Publisher: SAGE Publications
Date: 11-2007
DOI: 10.1080/00048670701634978
Abstract: Objective: Functional neuroimaging studies have implicated the anterior cingulate cortex (ACC) in the pathophysiology of bipolar disorder (BD), but findings from volumetric studies have been less consistent, therefore the purpose of the present study was to further investigate the existence of volumetric abnormalities in the ACC cortex of in iduals with BD. In addition to methodological inconsistencies many previous studies have been lacking robustness clinically with respect to characterizing bipolar patients and comparison subjects. Hence, the present study matched the groups closely across a number of demographic parameters. Methods: Using magnetic resonance imaging, ACC volumes of 24 bipolar patients were compared to 24 gender-, age-, and education-matched control subjects, and these findings were further investigated in relation to both illness and treatment factors. Results: A significantly larger (26%) right ACC in bipolar patients than control subjects was seen, and this difference was not associated with a history of psychosis, familiality, or lithium treatment, after controlling for potential confounds. Patients reporting fewer affective episodes did, however, have significantly larger ACC volumes than controls, suggesting ACC volumetric changes early in the course of BD. Conclusions: An increase in the size of the ACC may have important implications for the neurobiology of BD. It is suggested that attempts to control affective instability during the early stages of the illness necessitates greater ACC mediation via its role in conflict resolution and hence this is reflected in the increased size of the ACC early in the course of the illness.
Diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease: a review.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2008
Progression of white matter hyperintensities in elderly individuals over 3 years
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-01-2007
DOI: 10.1212/01.WNL.0000251302.55202.73
Abstract: The aims of this study were to examine white matter hyperintensities (WMHs) in the brains of elderly in iduals, the rate of progression, the anatomic regions most vulnerable, and the predictors of change. We examined 51 healthy volunteers (mean age 71 years) with T2-weighted brain MRI on the same scanner 3 years apart. WMH volumes were determined by an automated method, and the anatomic location of change was determined for both deep WMHs (DWMHs) and periventricular WMHs (PVWMHs). The total brain WMH volume increased by 39.6%, i.e., 13.2% per year, with the change in DWMH being 43.8% and 29.7% in PVWMH. The increase was significant in all regions except the occipital lobe and cerebellum. Age, sex, and cerebrovascular risk factors were not significant predictors of WMH progression. The main predictor of progression was baseline level of WMH. The number of WMH lesions increased by a mean of 1.78, and the progression was mainly accounted for by an increase in very large (>16 mm) lesions. Eight subjects showed a slight decrease in WMH. White matter hyperintensities are progressive in most elderly in iduals with an increasing rate of progression as the burden of lesions increases. The rate of progression is greater in deep white matter and in the anterior brain regions. Risk factors for progression are not well understood, and genetic and other environmental factors must be examined. Quantitation of white matter hyperintensities may serve as a surrogate marker of the progression of small vessel disease.
Sydney Memory and Ageing Study: An epidemiological cohort study of brain ageing and dementia
Publisher: Informa UK Limited
Date: 12-2013
DOI: 10.3109/09540261.2013.860890
Abstract: Non-demented community-dwelling older adults aged 70-90 years (n = 1,037) randomly recruited from the electoral roll completed neuropsychological and medical assessments over six years. The overall prevalence of mild cognitive impairment (MCI) at baseline was 36.7%. Risk factors for MCI include APOE ε4 allele carrier status, high homocysteine, heart disease, poor odour identification, low visual acuity and low mental activity, but notable age and sex differences were observed. Neuropsychiatric symptoms were rare depression was the most common and was associated with cognitive impairment in at least one domain as well as subsequent dementia 2 years later. Poorer cognitively demanding functional abilities were associated with cognitive impairment. Biomarkers for cognitive impairment and decline were identified. Inflammatory markers and plasma apolipoprotein levels were associated with poorer performance in the attention rocessing speed domain. Measures of white matter lesions, white matter integrity, sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline. Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline. Compared to previous reports, our prevalence rates of MCI were higher but rates of progression to dementia and reversion to normal were similar, as were risk factors for progression to dementia.
Short-term Trajectories of Poststroke Cognitive Function
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-04-2023
DOI: 10.1212/WNL.0000000000207281
Abstract: Past studies on poststroke cognitive function have focused on the average performance or change over time, but few have investigated patterns of cognitive trajectories after stroke. This project used latent class growth analysis (LCGA) to identify clusters of patients with similar patterns of cognition scores over the first-year poststroke and the extent to which long-term cognitive outcome is predicted by the clusters (“trajectory groups”). Data were sought from the Stroke and Cognition consortium. LCGA was used to identify clusters of trajectories based on standardized global cognition scores at baseline (T 1 ) and at the 1-year follow-up (T 2 ). One-step in idual participant data meta-analysis was used to examine risk factors for trajectory groups and association of trajectory groups with cognition at the long-term follow-up (T 3 ). Nine hospital-based stroke cohorts with 1,149 patients (63% male mean age 66.4 years [SD 11.0]) were included. The median time assessed at T 1 was 3.6 months poststroke, 1.0 year at T 2 , and 3.2 years at T 3 . LCGA identified 3 trajectory groups, which were characterized by different mean levels of cognition scores at T 1 (low-performance, −3.27 SD [0.94], 17% medium-performance, −1.23 SD [0.68], 48% and high-performance, 0.71 SD [0.77], 35%). There was significant improvement in cognition for the high-performance group (0.22 SD per year, 95% CI 0.07–0.36), but changes for the low-performance and medium-performance groups were not significant (−0.10 SD per year, 95% CI −0.33 to 0.13 0.11 SD per year, 95% CI −0.08 to 0.24, respectively). Factors associated with the low- (vs high-) performance group include age (relative risk ratio [RRR] 1.18, 95% CI 1.14–1.23), years of education (RRR 0.61, 95% CI 0.56–0.67), diabetes (RRR 3.78, 95% CI 2.08–6.88), large artery vs small vessel strokes (RRR 2.77, 95% CI 1.32–5.83), and moderate/severe strokes (RRR 3.17, 95% CI 1.42–7.08). Trajectory groups were predictive of global cognition at T 3 , but its predictive power was comparable with scores at T 1 . The trajectory of cognitive function over the first-year poststroke is heterogenous. Baseline cognitive function ∼3.6 months poststroke is a good predictor of long-term cognitive outcome. Older age, lower levels of education, diabetes, large artery strokes, and greater stroke severity are risk factors for lower cognitive performance over the first year.
Longitudinal Changes During Aging Using Proton Magnetic Resonance Spectroscopy
Publisher: Oxford University Press (OUP)
Date: 03-2006
Abstract: We aimed to examine the longitudinal change in proton magnetic resonance spectroscopy ((1)H-MRS) visible metabolites (N-acetyl aspartate [NAA], creatine [Cr], choline [Cho], and myo-Inositol [mI]) in brains of elderly in iduals over 3 years and relate them to cognitive function. Neurologically and psychiatrically normal volunteers (n = 40) were examined at baseline and 3 years later with (1)H-MRS in two voxels (frontal white matter n = 29, and occipitoparietal gray matter n = 36) and with detailed neuropsychological assessments. Longitudinal analyses were performed with age, educational level, sex, and white matter hyperintensities (WMH) in voxels as covariates. Frontal mI was significantly increased over time in male participants, but all other metabolites were stable over time. Neuropsychological performance was not significantly changed over 3 years, and there was no relationship between change in metabolite levels and change in neuropsychological function. MRS-visible metabolites are stable in elderly persons over 3 years, with the exception of mI which shows an increase. Increasing mI may be a marker of aging or a preclinical neurodegenerative process. MRS changes do not correlate with change in neurocognitive function during aging.
Genetic variants associated with longitudinal changes in brain structure across the lifespan
Publisher: Springer Science and Business Media LLC
Date: 04-2022
DOI: 10.1038/S41593-022-01042-4
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 in iduals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Cerebral Blood Flow in Community-Based Older Twins Is Moderately Heritable: An Arterial Spin Labeling Perfusion Imaging Study
Publisher: Frontiers Media SA
Date: 02-07-2019
P1‐081: Neuropsychiatric symptoms and cognitive decline over two years in a community sample with and without mild cognitive impairment
Publisher: Wiley
Date: 07-2012
P1‐080: Rates of dementia amongst an exceptionally old cohort of Australians: The Sydney Centenarian Study
Publisher: Wiley
Date: 07-2012
P2‐242: THE NEURO‐NORMS CALCULATOR FOR OLDER ADULTS: DEMOGRAPHICALLY ADJUSTED NORMATIVE DATA AND STATISTICAL ANALYSIS OF NEUROPSYCHOLOGICAL TEST PERFORMANCE
Publisher: Wiley
Date: 07-2014
Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease
Publisher: Wiley
Date: 28-10-2010
DOI: 10.1002/ANA.22274
Abstract: Frontotemporal lobar degeneration (FTLD) is the most common cause of early-onset dementia. Pathological ubiquitinated inclusion bodies observed in FTLD and motor neuron disease (MND) comprise trans-activating response element (TAR) DNA binding protein (TDP-43) and/or fused in sarcoma (FUS) protein. Our objective was to identify the causative gene in an FTLD-MND pedigree with no mutations in known dementia genes. A mutation screen of candidate genes, luciferase assays, and quantitative polymerase chain reaction (PCR) was performed to identify the biological role of the putative mutation. Neuropathological characterization of affected in iduals and western blot studies of cell lines were performed to identify the pathological mechanism of the mutation. We identified a nonpolymorphic mutation (c.672*51G>T) in the 3'-untranslated region (UTR) of the Sigma nonopioid intracellular receptor 1 (SIGMAR1) gene in affected in iduals from the FTLD-MND pedigree. The c.672*51G>T mutation increased gene expression by 1.4-fold, corresponding with a significant 1.5-fold to 2-fold change in the SIGMAR1 transcript or Sigma-1 protein in lymphocyte or brain tissue. Brains of SIGMAR1 mutation carriers displayed a unique pathology with cytoplasmic inclusions immunopositive for either TDP-43 or FUS but not Sigma-1. Overexpression of SIGMAR1 shunted TDP-43 and FUS from the nucleus to the cytoplasm by 2.3-fold and 5.2-fold, respectively. Treatment of cells with Sigma-1 ligands significantly altered translocation of TDP-43 by up to 2-fold. SIGMAR1 is a causative gene for familial FTLD-MND with a unique neuropathology that differs from other FTLD and MND cases. Our findings also suggest Sigma-1 drugs as potential treatments for the TDP-43/FUS proteinopathies.
Dissociable Cellular and Genetic Mechanisms of Cortical Thinning at Different Life Stages
Publisher: Cold Spring Harbor Laboratory
Date: 22-03-2022
DOI: 10.1101/2022.03.21.484899
Abstract: Mechanisms underpinning age-related variations in cortical thickness in the human brain remain poorly understood. We investigated whether inter-regional age-related variations in cortical thinning (in a multicohort neuroimaging dataset from the ENIGMA Lifespan Working Group totalling 14,248 in iduals, aged 4-89 years) depended on cell-specific marker gene expression levels. We found differences amidst early-life ( years), mid-life (20-60 years), and late-life ( years) in the patterns of association between inter-regional profiles of cortical thickness and expression profiles of marker genes for CA1 and S1 pyramidal cells, astrocytes, and microglia. Gene ontology and enrichment analyses indicated that each of the three life-stages was associated with different biological processes and cellular components: synaptic modeling in early life, neurotransmission in mid-life, and neurodegeneration in late-life. These findings provide mechanistic insights into age-related cortical thinning during typical development and aging.
Novel genetic loci underlying human intracranial volume identified through genome-wide association
Publisher: Springer Science and Business Media LLC
Date: 03-10-2016
DOI: 10.1038/NN.4398
Neuropsychiatry
Publisher: Cambridge University Press
Date: 18-09-2008
Vascular contributions to cognitive impairment and dementia: Research consortia that focus on etiology and treatable targets to lessen the burden of dementia worldwide
Publisher: Wiley
Date: 2019
Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture
Publisher: Springer Science and Business Media LLC
Date: 23-09-2020
DOI: 10.1038/S41467-020-18534-1
Abstract: Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P -threshold ( P optimal ) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and in iduals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.
Obsessive-compulsive behaviour: a disorder of decision-making
Publisher: SAGE Publications
Date: 09-2005
Book Review: Neuropsychiatry: The Clinical Neuropsychiatry of Multiple Sclerosis. Second Edition
Publisher: SAGE Publications
Date: 07-2009
The coming age of brain stimulation in neuropsychiatry?
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2007
P4‐012: GENOME‐WIDE SIGNIFICANT RESULTS IDENTIFIED FOR PLASMA APOLIPOPROTEIN H LEVELS
Publisher: Wiley
Date: 07-2014
Prevalence of mild cognitive impairment in 60-to 64-year-old community-dwelling individuals: The personality and total health through life 60+ study
Publisher: S. Karger AG
Date: 2005
DOI: 10.1159/000082351
Abstract: This epidemiological study aimed at determining the prevalence of mild cognitive impairment (MCI) in 60- to 64-year-old in iduals using different diagnostic criteria. Community dwelling in iduals (n = 2,551) in the age range of 60–64 years were recruited randomly through the electoral roll. They were screened using the MMSE and a short cognitive battery, and those who screened positive underwent detailed medical and cognitive assessments. Extant MCI-related diagnoses were established by consensus. Predictive regression models on the sub-s le were used to determine population prevalence for the diagnoses. Of the 224 subjects who screened positive for MCI, 112 underwent a detailed assessment and 74% met the criteria for at least one recognised diagnosis of mild cognitive deficit (MCI and related diagnoses). By predictive regression modelling, the prevalence of any MCI diagnosis was 13.7% (95% CI 9.1–30.2) in the population of 60- to 64-year-olds. The estimated prevalence rates for specific diagnoses were: MCI 3.7%, ageing-associated cognitive decline 3.1%, Clinical Dementia Rating score (0.5) 2.8%, age-associated memory impairment 1%, other cognitive disorders 0.9%, and mild neurocognitive disorder 0.6%. Agreement on ‘caseness’ between various proposed diagnoses was at best fair and generally poor. Memory and other cognitive problems not meeting the threshold for dementia are relatively common in 60- to 64-year-old in iduals living in the community. The prevalence rate varies up to six-fold according to the diagnostic criteria applied, with limited overlap between diagnoses. There is an urgent need for standardization of the criteria.
Brief internet-delivered cognitive behavioral therapy for anxiety in older adults
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.JANXDIS.2012.04.002
Abstract: This study examined the efficacy of an Internet-delivered cognitive-behavior therapy program developed for older adults. Twenty-two participants with elevated scores (≥8) on the Generalized Anxiety Disorder 7-Item Scale (GAD-7) participated in the course, which consisted of five lessons, homework tasks, additional resources, a moderated discussion forum, and weekly telephone support from a Clinical Psychologist. Ninety-five percent of the s le met diagnostic criteria for an anxiety disorder at pre-treatment. All participants completed the five lessons within the allotted eight weeks. Three-month follow-up data was collected from 95% of participants. Reductions in symptoms of anxiety and stress, with large within-group effect sizes (Cohen's d) were found on the GAD-7 (d=1.03) and the Depression, Anxiety and Stress Scales - 21 Items (d=0.98) at follow-up. Participants reported high levels of satisfaction with the program. These encouraging results provide tentative support for the online treatment of older adults with anxiety.
Cerebral small vessel disease genomics and its implications across the lifespan
Publisher: Springer Science and Business Media LLC
Date: 08-12-2020
DOI: 10.1038/S41467-020-19111-2
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older in iduals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk in iduals and for genetically-informed prioritization of drug targets for prevention trials.
People with mild cognitive impairment are at increased risk of serious injury
Publisher: Swansea University
Date: 05-09-2018
Abstract: IntroductionData-linkage studies using administrative hospital data have shown that people with dementia have double the rate of injury-related hospitalisations and poorer health outcomes than those without. No previous research has explored whether people with mild cognitive impairment are also at increased risk of serious injury requiring hospitalisation. Objectives and ApproachA major barrier to the use of administrative hospital data for undertaking research focusing on people with MCI is that MCI cannot be reliably identified from ICD-10 coded administrative data. To overcome this limitation, hospitalisation and death data was linked to data from participants (community-dwelling 70-90 year olds) enrolled in the population-based longitudinal Sydney Memory and Ageing Study (MAS). MAS participants underwent comprehensive neuropsychological assessments at baseline, then 2, 4 and 6 years’ follow-up to accurately determine cognitive status at each time-period. Linkage to hospital records allowed identification of injury-related hospitalisations and outcomes for the 2-year period following each assessment. ResultsThere were 335 injury-related hospitalisations for the 867 participants 222 (25.6%) participants had at least one injury-related hospitalisation. After adjusting for age-and-sex, participants in a state of MCI had 1.7 (95%CI 1.2-2.4) times higher odds of an injury-related hospitalisation than participants in a state of normal cognition, whilst participants with dementia had 2.3 (95%CI 1.2-4.4) times higher odds. There was no difference in odds between participants with MCI and dementia. Of the 116 hospitalisations for people with MCI, the majority (79.3%) were due to falls. Non-fracture head injuries (25.9%), upper limb and trunk fractures (13.8% respectively) were the most common injury type. There were no differences in injury type, mean length of stay, or 30-day mortality between people with normal cognition, MCI and dementia. Conclusion/ImplicationsOlder people with objectively defined MCI are at higher risk of injury, predominantly as a result of falls, than their cognitively intact peers. Falls-risk screening and fall prevention initiatives may be indicated for people with MCI. Further research is required to determine which cognitive domains contribute to this increased risk.
Arterial stiffness, the brain and cognition: A systematic review
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.ARR.2014.02.002
Abstract: Arterial stiffness is a known predictor of cardiovascular disease, and has also been associated with markers of cerebral small vessel disease as well as poor cognitive function and cognitive decline. The consistency of these associations and their relationship to each other are unclear. We conducted a systematic review of the evidence associating arterial stiffness with cognitive function and cognitive decline, and with makers of cerebral small vessel disease, specifically lacunar infarcts and white matter hyperintensities. Thirteen cross-sectional studies examining arterial stiffness and white matter hyperintensities or lacunar infarctions reported a positive association between increased arterial stiffness and radiological findings of cerebral small vessel disease. Two longitudinal studies examining the relationship between arterial stiffness and white matter hyperintensities found increased pulse wave velocity to be an independent predictor of white matter hyperintensity volume. Fifteen cross-sectional and seven longitudinal studies examining arterial stiffness and cognition were identified. Fourteen of the fifteen cross-sectional studies associated increased arterial stiffness with lower cognitive function, and six of the seven longitudinal studies found arterial stiffness to be predictive of cognitive decline. Arterial stiffness is associated with cerebral small vessel disease and decreased cognitive function. However methodological limitations such as differing covariates between studies and an over-reliance on the MMSE to measure cognition are a concern across much of the literature.
Impact of load-related neural processes on feature binding in visuospatial working memory
Publisher: Public Library of Science (PLoS)
Date: 24-08-2011
High (15 Hz) and low (1 Hz) frequency transcranial magnetic stimulation have different acute effects on regional cerebral blood flow in depressed patients
Publisher: Cambridge University Press (CUP)
Date: 31-07-2003
DOI: 10.1017/S0033291703007955
Abstract: Background. High and low frequency repetititve transcranial magnetic stimulation (rTMS) are both effective in treating depression but have contrary effects on motor cortical activity. This study aimed to understand further the mechanisms of action of high and low frequency rTMS by examining their acute effects on regional cerebral blood flow (rCBF) in depressed patients. Method. Eighteen depressed subjects underwent brain single photon emission computerized tomography (SPECT) scanning using split-dose 99m Tc-HMPAO, and were examined during sham and active rTMS to the left prefrontal cortex, at 15 Hz or 1 Hz ( N =9 each). Relative rCBF changes were examined by statistical parametric mapping and by regions of interest analysis. Results. High (15 Hz) frequency rTMS resulted in relative rCBF increases in the inferior frontal cortices, right dorsomedial frontal cortex, posterior cingulate and parahippoc us. Decreases occurred in the right orbital cortex and subcallosal gyrus, and left uncus. Low (1 Hz) frequency rTMS led to increased relative rCBF in the right anterior cingulate, bilateral parietal cortices and insula and left cerebellum. High frequency rTMS led to an overall increase, whereas low frequency rTMS produced a slight decrease, in the mean relative rCBF in the left dorsolateral prefrontal cortex. Conclusions. High (15 Hz) and low (1 Hz) frequency rTMS led to different frontal and remote relative rCBF changes, which suggests different neurophysiological and possibly neuropsychiatric consequences of a change in frequency of rTMS.
Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: Opportunities and challenges
Publisher: SAGE Publications
Date: 10-07-2022
Clozapine-induced neuroleptic malignant syndrome: Review and report of new cases
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-1995
DOI: 10.1097/00004714-199510000-00010
Abstract: The published case reports of clozapine-induced neuroleptic malignant syndrome (NMS) are reviewed, to which the authors add three, and possibly four, new cases seen in Australia, occurring in and estimated 1,250 patients exposed to the drug. The review suggests that typical NMS does occur with clozapine and that its incidence may be as common as with the classic neuroleptics. The features of clozapine-induced NMS may be somewhat different, with fewer extrapyramidal side effects and a lower rise in creatine kinase levels. The occurrence of NMS with clozapine raises important issues with regard to our understanding of the pathophysiology of the syndrome.
High psychiatric morbidity in patients with medically unexplained symptoms
Publisher: BMJ
Date: 05-2001
Performance-Based Assessment of Instrumental Activities of Daily Living: Validation of the Sydney Test of Activities of Daily Living in Memory Disorders (STAM)
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.JAMDA.2016.08.007
Abstract: The distinction between dementia and mild cognitive impairment (MCI) relies upon the evaluation of independence in instrumental activities of daily living (IADL). Self- and informant reports are prone to bias. Clinician-based performance tests are limited by long administration times, restricted access, or inadequate validation. To close this gap, we developed and validated a performance-based measure of IADL, the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). Prospective cohort study (Sydney Memory and Ageing Study). Eastern Suburbs, Sydney, Australia. 554 community-dwelling in iduals (54% female) aged 76 and older with normal cognition, MCI, or dementia. Activities of daily living were assessed with the STAM, administered by trained psychologists, and the informant-based Bayer-Activities of Daily Living Scale (B-ADL). Depressive symptoms were measured with the Geriatric Depression Scale (15-item version). Cognitive function was assessed with a comprehensive neuropsychological test battery. Consensus diagnoses of MCI and dementia were made independently of STAM scores. The STAM showed high interrater reliability (r = 0.854) and test-retest reliability (r = 0.832). It discriminated significantly between the diagnostic groups of normal cognition, MCI, and dementia with areas under the curves ranging from 0.723 to 0.948. A score of 26.5 discriminated between dementia and nondementia with a sensitivity of 0.831 and a specificity of 0.864. Correlations were low with education (r = 0.230) and depressive symptoms (r = -0.179), moderate with the B-ADL (r = -0.332), and high with cognition (ranging from r = 0.511 to r = 0.594). The mean time to complete the STAM was 16 minutes. The STAM has good psychometric properties. It can be used to differentiate between normal cognition, MCI, and dementia and can be a helpful tool for diagnostic classification both in clinical practice and research.
Vascular dysfunction—The disregarded partner of Alzheimer's disease
Publisher: Wiley
Date: 2019
DOI: 10.1016/J.JALZ.2018.07.222
Abstract: Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker‐based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood‐brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for % of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.
White matter hyperintensities and impaired choice stepping reaction time in older people
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.NEUROBIOLAGING.2010.12.009
Abstract: White matter hyperintensities (WMHs) are associated with impaired mobility in older people, but no studies have identified neuropsychological and sensorimotor mediating factors for this association. Our objective was to determine whether neuropsychological and sensorimotor functions mediate the association of WMHs and choice stepping reaction time (CSRT) under standard and dual-task conditions using structural equation modeling. Two hundred fifty-four older community dwellers (77.8 ± 4.5 years) underwent structural magnetic resonance imaging, CSRT tests, neuropsychological and sensorimotor assessments. WMH volumes were quantified using an automated method. WMH volumes were significantly associated with neuropsychological tests and dual task CSRT performance. All neuropsychological and sensorimotor variables were also significantly associated with standard and dual task CSRT. The structural equation modeling revealed that impaired sensorimotor function was the only factor influencing impaired stepping performances in the standard condition. In the dual task condition, the association between WMHs and CSRT was mediated through slowed cognitive processing and not through reduced sensorimotor functioning. The conclusion was that WMHs are associated with slowed performance on a dual task CSRT task and this relationship is explained primarily by underlying neuropsychological impairments.
Longitudinal changes in sulcal morphology associated with late-life aging and MCI
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.NEUROIMAGE.2013.02.047
Abstract: The present study investigated changes in sulcal morphology associated with late-life aging and mild cognitive impairment (MCI). Participants were 219 community-dwelling 70-90 year-olds from the Sydney Memory and Ageing Study all had MRI scans and were classified as having normal cognition (NC) or MCI at each of waves 1 and 2, two years apart. Automated methods were used to calculate a global sulcal index (g-SI), widths of five prominent sulci, and regional cortical thickness. There were significant longitudinal declines in g-SI and increases in sulcal width among the entire s le, but the rate of change differed among cognitive subgroups. Participants with MCI at both waves (persisting MCI) showed accelerated sulcal widening, particularly for the superior frontal and superior temporal sulci. The sulcal morphology of participants who reverted from MCI to NC was more consistent with stable NC than persisting MCI. Overall cortical thickness decreased between waves similarly across the subgroups. While changes in sulcal morphology are characteristic of normal late-life aging, they are accelerated in in iduals with MCI (in contrast to changes in cortical thickness). Sulcal measures also differentiate between persistent MCI and MCI that reverts to NC, and may thus help in predicting the prognosis of MCI patients.
The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume
Publisher: Elsevier BV
Date: 04-2016
Secondary Schizophrenia
Publisher: Cambridge University Press
Date: 04-02-2009
Abstract: Schizophrenia may not be a single disease, but the result of a erse set of related conditions. Modern neuroscience is beginning to reveal some of the genetic and environmental underpinnings of schizophrenia however, an approach less well travelled is to examine the medical disorders that produce symptoms resembling schizophrenia. This book is the first major attempt to bring together the diseases that produce what has been termed & apos secondary schizophrenia& apos . International experts from erse backgrounds ask the questions: does this medical disorder, or drug, or condition cause psychosis? If yes, does it resemble schizophrenia? What mechanisms form the basis of this relationship? What implications does this understanding have for aetiology and treatment? The answers are a feast for clinicians and researchers of psychosis and schizophrenia. They mark the next step in trying to meet the most important challenge to modern neuroscience – understanding and conquering this most mysterious of human diseases.
White matter hyperintensities in mid-adult life
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
Evaluation of a research diagnostic algorithm for DSM-5 neurocognitive disorders in a population-based cohort of older adults
Publisher: Springer Science and Business Media LLC
Date: 04-03-2017
The organisation of the elderly connectome
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.NEUROIMAGE.2015.04.009
Abstract: Investigations of the human connectome have elucidated core features of adult structural networks, particularly the crucial role of hub-regions. However, little is known regarding network organisation of the healthy elderly connectome, a crucial prelude to the systematic study of neurodegenerative disorders. Here, whole-brain probabilistic tractography was performed on high-angular diffusion-weighted images acquired from 115 healthy elderly subjects (age 76-94 years 65 females). Structural networks were reconstructed between 512 cortical and subcortical brain regions. We sought to investigate the architectural features of hub-regions, as well as left-right asymmetries, and sexual dimorphisms. We observed that the topology of hub-regions is consistent with a young adult population, and previously published adult connectomic data. More importantly, the architectural features of hub connections reflect their ongoing vital role in network communication. We also found substantial sexual dimorphisms, with females exhibiting stronger inter-hemispheric connections between cingulate and prefrontal cortices. Lastly, we demonstrate intriguing left-lateralized subnetworks consistent with the neural circuitry specialised for language and executive functions, whilst rightward subnetworks were dominant in visual and visuospatial streams. These findings provide insights into healthy brain ageing and provide a benchmark for the study of neurodegenerative disorders such as Alzheimer's disease (AD) and frontotemporal dementia (FTD).
Transcranial direct current stimulation - what is the evidence for its efficacy and safety?
Publisher: Faculty Opinions Ltd
Date: 27-07-2009
DOI: 10.3410/M1-58
Cross-sectional and prospective inter-relationships between depressive symptoms, vascular disease and cognition in older adults
Publisher: Cambridge University Press (CUP)
Date: 29-10-2019
DOI: 10.1017/S0033291718002994
Abstract: It has been proposed that vascular disease is the mechanism linking depression and cognition, but prospective studies have not supported this hypothesis. This study aims to investigate the inter-relationships between depressive symptoms, cognition and cerebrovascular disease using a well-characterised prospective cohort. Data came from waves 1 (2005–2007) and 2 (2007–2009) of the Sydney Memory and Ageing Study ( n = 462 mean age = 78.3 years). At wave 1, there was an association between depressive symptoms and white matter hyperintensity (WMH) volume [ b = 0.016, t (414) = 2.34, p = 0.020]. Both depressive symptoms [ b = −0.058, t (413) = −2.64, p = 0.009] and WMH volume [ b = −0.011, t (413) = −3.77, p 0.001], but not stroke/transient ischaemic attack (TIA) [ b = −0.328, t (413) = −1.90, p = 0.058], were independently associated with lower cognition. Prospectively, cerebrovascular disease was not found to predict increasing depressive symptoms [stroke/TIA: b = −0.349, t (374.7) = −0.76, p = 0.448 WMH volume: b = 0.007, t (376.3) = 0.875, p = 0.382]. Depressive symptoms predicted increasing WMH severity [ b = 0.012, t (265.9) = −3.291, p = 0.001], but not incident stroke/TIA (odds ratio = 0.995 CI 0.949–1.043 p = 0.820). When examined in separate models, depressive symptoms [ b = −0.027, t (373.5) = −2.16, p = 0.032] and a history of stroke/TIA [ b = −0.460, t (361.2) = −4.45, p 0.001], but not WMH volume [ b = 0.001, t (362.3) = −0.520, p = 0.603], predicted declines in cognition. When investigated in a combined model, a history of stroke/TIA remained a predictor of cognitive decline [ b = −0.443, t (360.6) = −4.28, p 0.001], whilst depressive symptoms did not [ b = −0.012, t (359.7) = −0.96, p = 0.336]. This study is contrasted with previous prospective studies which indicate that depressive symptoms predict cognitive decline independently of vascular disease. Future research should focus on further exploring the vascular mechanisms underpinning the relationship between depressive symptoms and cognition.
Heritability of brain volumes in older adults: the Older Australian Twins Study
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.NEUROBIOLAGING.2013.10.079
Abstract: The relative contributions of genetic and environmental factors to brain structure change throughout the lifespan. Brain structures have been reported to be highly heritable in middle-aged in iduals and younger however, the influence of genes on brain structure is less studied in older adults. We performed a magnetic resonance imaging study of 236 older twins, with a mean age of 71.4 ± 5.7 years, to examine the heritability of 53 brain global and lobar volumetric measures. Total brain volume (63%) and other volumetric measures were moderately to highly heritable in late life, and these genetic influences tended to decrease with age, suggesting a greater influence of environmental factors as age advanced. Genetic influences were higher in men and on the left hemisphere compared with the right. In multivariate models, common genetic factors were observed for global and lobar total and gray matter volumes. This study examined the genetic contribution to 53 brain global and lobar volumetric measures in older twins for the first time, and the influence of age, sex, and laterality on these genetic contributions, which are useful information for a better understanding of the process of brain aging and helping in iduals to have a healthy aging.
How high a dose of stimulant medication in adult attention deficit hyperactivity disorder?
Publisher: SAGE Publications
Date: 08-2000
DOI: 10.1080/J.1440-1614.2000.00732.X
Abstract: Objective: This paper examines clinical and neuroscientific evidence to address the question whether high doses of stimulant drugs offer additional advantages in the treatment of adult attention deficit hyperactivity disorder (ADHD) and at what cost. It attempts to arrive at a reasonable upper limit of dosage for clinical purposes. Method: The study involves a selective review of the treatment studies of ADHD in children and adults and an examination of the pharmacokinetic and pharmaco-dynamic data on psychostimulants in humans and animals. Results and Conclusions: The clinical and experimental data justify the use of chronic low-dose stimulant treatment of ADHD in adults, with the recommended upper limit of dose being 1 mg/kg for methylphenidate and 0.5 mg/kg for dex hetamine. There is no empirical evidence of greater improvement with higher doses and any beneficial effect is likely to be compromised by the adverse effects, some of which can be very serious. The recommended doses should be exceeded only after careful consideration and objective documentation of beneficial and adverse consequences. Monitoring of drug levels in blood may be of some value for compliance or pharmacokinetic considerations, as there is a direct relationship between blood and brain levels as well as dopamine transporter occupancy. These recommendations are tentative and further clinical research is warranted.
CSF AND BLOOD BIOMARKERS OF EARLY-ONSET ALZHEIMER’S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Publisher: Wiley
Date: 07-2018
Gray matter atrophy patterns of mild cognitive impairment subtypes
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.JNS.2011.12.011
Abstract: Mild cognitive impairment (MCI) is a heterogeneous neurocognitive disorder that can be classified into various subtypes. The present study aims to examine the gray matter (GM) atrophy patterns of MCI subtypes in comparison with a cognitively healthy group. Participants, including 135 MCI subjects and 120 cognitively healthy controls, were drawn from the Sydney Memory and Ageing Study. The MCI subjects were first categorized into amnestic (aMCI) and non-amnestic (naMCI) subtypes, which were then ided into single-domain (aMCI-SD and naMCI-SD) and multiple-domain subtypes (aMCI-MD and naMCI-MD). Furthermore, naMCI-SD was ided into three subgroups (language, processing speed, and executive function) according to in idual cognitive impairment. Voxel-wise GM volumes were then compared between MCI subtypes and controls. The aMCI group had significantly lower GM volumes in the bilateral hippoc i and temporal cortices than the controls. This was mainly due to GM reduction of aMCI-MD but not aMCI-SD, as the latter did not show any significant GM reduction. GM reduction of naMCI and its two sub isions was shown in widespread brain regions compared to controls. GM volumes of the multiple-domain subtypes (aMCI-MD and naMCI-MD) were lower than their single-domain counterparts (aMCI-SD and naMCI-SD) in the frontal and temporal lobes, respectively. Moreover, the language subgroup of naMCI-SD showed GM reduction in the frontal and temporal lobes compared to controls. MCI subtypes displayed specific patterns of GM atrophy that appear to be related to their various clinical presentations, which implies that underlying mechanisms of MCI subtypes are different.
Renin-Angiotensin system genetic polymorphisms and brain white matter lesions in older australians.
Publisher: Oxford University Press (OUP)
Date: 12-03-2014
DOI: 10.1093/AJH/HPU035
Abstract: White matter lesions (WMLs), seen as hyperintensities on T2-weighted magnetic resonance imaging brain scans, are common in the brains of healthy older in iduals. They are thought to be related to cerebral small vessel disease and to have a genetic component to their aetiology, and hypertension is thought to be an important risk factor. Genetic polymorphisms in hypertension-related genes may therefore be associated with the formation of WMLs. In this study, a s le of 445 Australians aged 60-65 years was drawn from a larger longitudinal epidemiological study, the Personality and Total Health Through Life Project. The associations of single nucleotide polymorphisms (SNPs) in the genes encoding angiotensinogen (AGT, rs699), angiotensin-converting enzyme (ACE, rs4362), and angiotensin II receptor type 1 (AGTR1, rs5182) with WMLs were examined. No in idual SNPs showed a significant association with WMLs for the whole s le. When the cohort was stratified by sex, ACE rs4362 and AGT rs699 showed significant associations with WMLs in men only (P = 0.01 and P = 0.03, respectively), and remained significant after controlling for hypertension. Although the AGTR1 SNP did not show any association with WMLs, the interaction of the AGT rs699 and AGTR1 rs5182 SNPs with WMLs was significant before (P = 0.03) and after adjustment for hypertension (P = 0.045). The results provide evidence for association of polymorphisms in the renin-angiotensin system genes with WMLs, independent of hypertension. Male-only associations with WMLs were found for the AGT rs699 and ACE rs362 polymorphisms. Moreover, for the entire s le an interaction between AGT and AGTR1 rs5182 genotypes on WMLs was observed.
Cholesterol Is Associated With Stroke, but Is Not a Risk Factor
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2004
The Precursor to Glutathione (GSH), γ-Glutamylcysteine (GGC), Can Ameliorate Oxidative Damage and Neuroinflammation Induced by Aβ40 Oligomers in Human Astrocytes
Publisher: Frontiers Media SA
Date: 08-08-2019
Negative symptoms, cognitive dysfunction, tardive akathisia and tardive dyskinesia.
Publisher: Wiley
Date: 06-1996
DOI: 10.1111/J.1600-0447.1996.TB10677.X
Abstract: This study examined the relationship of neuropsychological deficits and negative symptoms with tar e akathisia in chronic schizophrenic patients. Consecutive volunteers (n = 100) were recruited from Community Health Centres with a DSM-III-R diagnosis of schizophrenic disorder, chronic and on stable medication. Subjects were subgrouped into tar e akathisia (TA), tar e dyskinesia (TD) and control groups using four sets of criteria. Detailed single examinations were performed using the following measures: sociodemographic, illness-related and treatment-related variables, Negative Symptom Rating Scale (NSRS), Abnormal Involuntary Movement Scale (AIMS), Rating Scale for Extrapyramidal Side-Effects (EPSE), Akathisia Rating Scale, Barnes Akathisia Rating Scale, and a brief neuropsychological test battery. Group comparisons and logistic regression analyses were performed in order to test the significance of findings. TA ratings showed a significant association with NSRS subscale scores, and with some neuropsychological test scores (Symbol Digits Modalities Test, and to a lesser extent Trail Making Test and Finger Tapping Test). TD scores showed a consistent association with age, and a less consistent association with gender, and their association with NSRS subscale scores and neuropsychological dysfunction was positive but less significant. Higher EPSE scores predicted TA and limb truncal (LT) dyskinesia. In conclusion, TA showed a more significant association with some clinical indices of organic brain dysfunction than the oral-lingual-buccal-facial dyskinetic syndrome. Prospective studies are necessary to determine whether organicity is a vulnerability factor for TA. Both our data and the published literature suggest that the movement disorder seen in TA and TD is but one feature of complex syndromes that include motor and cognitive features.
Caudate nucleus volumes in stroke and vascular dementia
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.PSCYCHRESNS.2009.04.002
Abstract: We aimed to assess the volume of the nucleus caudatus as a neuroanatomical substrate of fronto-subcortical circuits, in stroke patients with/without dementia, and the relationship to potential determinants of neural circuit integrity such as white matter hyperintensities (WMH) and stroke volume. Stroke only (Stroke) (n=19) and stroke with Vascular Dementia (VaD) (n=16) and healthy control (n=20) subjects, matched on demographic variables, underwent extensive neuropsychiatric assessments and manual MRI-based volumetric measurements for intracranial area (ICA), stroke volume, and bilateral caudate volume. WMH on MRI were quantified using an automated algorithm. Multivariate analysis of covariance (controlling for age and ICA), revealed that across the three groups, caudate volumes were significantly different. There was a significant difference in bilateral caudate nucleus volume between subjects by diagnosis (Stroke, VaD, control). The control group was largest in overall mean volume of the diagnostic groups, followed by the Stroke group (86% of controls), and finally, the VaD group (72%). There was a partial correlation between total caudate volume and the total volume of deep WMH including periventricular regions and brainstem, controlling for ICA and for total stroke volume. Stroke patients with VaD have smaller caudate nuclei compared to those without dementia and healthy controls, with the stroke-only patients being intermediate in their caudate volume status. There was preliminary evidence of negative correlation of caudate volume with volume of deep WMH and total stroke volume, suggesting cerebrovascular disease contributes to caudate atrophy,which, in turn may disrupt fronto-subcortical circuits.
Iranian Brain Imaging Database: A Neuropsychiatric Database of Healthy Brain
Publisher: Negah Scientific Publisher
Date: 2021
Abstract: Introduction: The Iranian Brain Imaging Database (IBID) was initiated in 2017, with 5 major goals: provide researchers easy access to a neuroimaging database, provide normative quantitative measures of the brain for clinical research purposes, study the aging profile of the brain, examine the association of brain structure and function, and join the ENIGMA consortium. Many prestigious databases with similar goals are available. However, they were not done on an Iranian population, and the battery of their tests (e.g. cognitive tests) is selected based on their specific questions and needs. Methods: The IBID will include 300 participants (50% female) in the age range of 20 to 70 years old, with an equal number of participants (#60) in each age decade. It comprises a battery of cognitive, lifestyle, medical, and mental health tests, in addition to several Magnetic Resonance Imaging (MRI) protocols. Each participant completes the assessments on two referral days. Results: The study currently has a cross-sectional design, but longitudinal assessments are considered for the future phases of the study. Here, details of the methodology and the initial results of assessing the first 152 participants of the study are provided. Conclusion: IBID is established to enable research into human brain function, to aid clinicians in disease diagnosis research, and also to unite the Iranian researchers with interests in the brain.
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