ORCID Profile
0000-0002-5895-1947
Current Organisation
Macquarie University
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Other Psychology and Cognitive Sciences | Psychology and Cognitive Sciences not elsewhere classified | Developmental Psychology and Ageing | Mental Health | Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Expanding Knowledge in Psychology and Cognitive Sciences | Health Related to Ageing |
Publisher: Springer Science and Business Media LLC
Date: 02-2021
DOI: 10.1038/S41467-021-21057-Y
Abstract: Aging and Alzheimer’s disease (AD) are associated with progressive brain disorganization. Although structural asymmetry is an organizing feature of the cerebral cortex it is unknown whether continuous age- and AD-related cortical degradation alters cortical asymmetry. Here, in multiple longitudinal adult lifespan cohorts we show that higher-order cortical regions exhibiting pronounced asymmetry at age ~20 also show progressive asymmetry-loss across the adult lifespan. Hence, accelerated thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This organizational principle showed high consistency across cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating s les. Asymmetry-change was further accelerated in AD. Results suggest a system-wide dedifferentiation of the adaptive asymmetric organization of heteromodal cortex in aging and AD.
Publisher: Cambridge University Press (CUP)
Date: 10-08-2021
DOI: 10.1017/S135561772000079X
Abstract: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia. As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years. Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia ( r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status. Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for in iduals with MCI.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2016
DOI: 10.3758/S13423-016-1182-7
Abstract: Lexical competition processes are widely viewed as the hallmark of visual word recognition, but little is known about the factors that promote their emergence. This study examined for the first time whether sleep may play a role in inducing these effects. A group of 27 participants learned novel written words, such as banara, at 8 am and were tested on their learning at 8 pm the same day (AM group), while 29 participants learned the words at 8 pm and were tested at 8 am the following day (PM group). Both groups were retested after 24 hours. Using a semantic categorization task, we showed that lexical competition effects, as indexed by slowed responses to existing neighbor words such as banana, emerged 12 h later in the PM group who had slept after learning but not in the AM group. After 24 h the competition effects were evident in both groups. These findings have important implications for theories of orthographic learning and broader neurobiological models of memory consolidation.
Publisher: Oxford University Press (OUP)
Date: 05-04-2007
DOI: 10.1093/BRAIN/AWM238
Abstract: Beta-amyloid (Abeta) deposition is pathognomic for Alzheimer's disease (AD), but may occur in normal elderly people without apparent cognitive effect. Episodic memory impairment is an early and prominent sign of AD, but its relationship with Abeta burden in non-demented persons and in AD patients is unclear. We examined this relationship using 11C-PIB-PET as a quantitative marker of Abeta burden in vivo in healthy ageing (HA), mild cognitive impairment (MCI) and AD. Thirty-one AD, 33 MCI and 32 HA participants completed neuropsychological assessment and a 11C-PIB-PET brain scan. Multiple linear regression analyses were conducted relating episodic memory performance and other cognitive functions to Abeta burden. Ninety-seven percent of AD, 61% of MCI and 22% of HA cases had increased cortical PIB binding, indicating the presence of Abeta plaques. There was a strong relationship between impaired episodic memory performance and PIB binding, both in MCI and HA. This relationship was weaker in AD and less robust for non-memory cognitive domains. Abeta deposition in the asymptomatic elderly is associated with episodic memory impairment. This finding, together with the strong relationship between PIB binding and the severity of memory impairment in MCI, suggests that in iduals with increased cortical PIB binding are on the path to Alzheimer's disease. The data also suggests that early intervention trials for AD targeted to non-demented in iduals with cerebral Abeta deposition are warranted.
Publisher: Cambridge University Press (CUP)
Date: 25-06-2008
DOI: 10.1017/S1355617708080806
Abstract: The primary impairment in early Alzheimer's disease (AD) is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. AD patients perform poorly on cued-recall paired associate learning (PAL) tasks, which assess the ability of the MTLs to encode relational memory. Since encoding and retrieval processes are confounded within performance indexes on cued-recall PAL, its specificity for AD is limited. Recognition paradigms tend to show good specificity for AD, and are well tolerated, but are typically less sensitive than recall tasks. Associate-recognition is a novel PAL task requiring a combination of recall and recognition processes. We administered a verbal associate-recognition test and cued-recall analogue to 22 early AD patients and 55 elderly controls to compare their ability to discriminate these groups. Both paradigms used eight arbitrarily related word pairs (e.g., pool-teeth) with varying degrees of imageability. Associate-recognition was equally effective as the cued-recall analogue in discriminating the groups, and logistic regression demonstrated classification rates by both tasks were equivalent. These preliminary findings provide support for the clinical value of this recognition tool. Conceptually it has potential for greater specificity in informing neuropsychological diagnosis of AD in clinical s les but this requires further empirical support. ( JINS , 2008, 14 , 591–600.)
Publisher: Cambridge University Press (CUP)
Date: 27-06-2014
DOI: 10.1017/S1041610214001136
Abstract: Autobiographical memory (ABM), personal semantic memory (PSM), and autonoetic consciousness are affected in in iduals with mild cognitive impairment (MCI) but their relationship with Alzheimer's disease (AD) biomarkers are unclear. Forty-five participants (healthy controls (HC) = 31, MCI = 14) completed the Episodic ABM Interview and a battery of memory tests. Thirty-one (HC = 22, MCI = 9) underwent β-amyloid positron emission tomography (PET) and magnetic resonance (MR) imaging. Fourteen participants (HC = 9, MCI = 5) underwent one imaging modality. Unlike PSM, ABM differentiated between diagnostic categories but did not relate to AD biomarkers. Personal semantic memory was related to neocortical β-amyloid burden after adjusting for age and apolipoprotein E ( APOE ) ɛ 4. Autonoetic consciousness was not associated with AD biomarkers, and was not impaired in MCI. Autobiographical memory was impaired in MCI participants but was not related to neocortical amyloid burden, suggesting that personal memory systems are impacted by differing disease mechanisms, rather than being uniformly underpinned by β-amyloid. Episodic and semantic ABM impairment represent an important AD prodrome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 14-05-2007
DOI: 10.1212/01.WNL.0000261919.22630.EA
Abstract: To compare brain beta-amyloid (Abeta) burden measured with [(11)C]Pittsburgh Compound B (PIB) PET in normal aging, Alzheimer disease (AD), and other dementias. Thirty-three subjects with dementia (17 AD, 10 dementia with Lewy bodies [DLB], 6 frontotemporal dementia [FTD]), 9 subjects with mild cognitive impairment (MCI), and 27 age-matched healthy control subjects (HCs) were studied. Abeta burden was quantified using PIB distribution volume ratio. Cortical PIB binding was markedly elevated in every AD subject regardless of disease severity, generally lower and more variable in DLB, and absent in FTD, whereas subjects with MCI presented either an "AD-like" (60%) or normal pattern. Binding was greatest in the precuneus osterior cingulate, frontal cortex, and caudate nuclei, followed by lateral temporal and parietal cortex. Six HCs (22%) showed cortical uptake despite normal neuropsychological scores. PIB binding did not correlate with dementia severity in AD or DLB but was higher in subjects with an APOE-epsilon4 allele. In DLB, binding correlated inversely with the interval from onset of cognitive impairment to diagnosis. Pittsburgh Compound B PET findings match histopathologic reports of beta-amyloid (Abeta) distribution in aging and dementia. Noninvasive longitudinal studies to better understand the role of amyloid deposition in the course of neurodegeneration and to determine if Abeta deposition in nondemented subjects is preclinical AD are now feasible. Our findings also suggest that Abeta may influence the development of dementia with Lewy bodies, and therefore strategies to reduce Abeta may benefit this condition.
Publisher: Oxford University Press (OUP)
Date: 24-09-2010
Abstract: Olfactory dysfunction constitutes one of the earliest signs of Alzheimer's disease (AD) and has been shown in in iduals with amnestic mild cognitive impairment (aMCI). Whether the severity of olfactory impairments in aMCI patients parallels those in AD has not been clearly established. In addition, given reports of asymmetries in neuropathological burden in early AD, functional asymmetries in olfactory performance may enhance early detection if olfactory function is assessed unirhinally. We compared AD, aMCI, and healthy participants on olfactory identification and memory assessed unirhinally. Olfactory identification was most proficient in the healthy participants and least proficient in AD, although this disparity did not depend on nostril side. Nevertheless, when only the worst nostril of each participant was included in the analysis, aMCI patients outperformed their AD counterparts. In contrast, when only the best nostril of each participant was included in the analysis--often regarded as an estimate of birhinal performance--this difference between aMCI and AD dissipated. Olfactory memory did not differ significantly across the groups, perhaps reflecting a floor effect. The findings support the hypothesis that unirhinal olfactory assessment may assist in differentiating between demented and nondemented in iduals.
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Wiley
Date: 09-2008
Abstract: Mild cognitive impairment (MCI) is considered a transitional stage between normal ageing and Alzheimer's disease (AD), but not all MCI cases progress to AD and there has been limited focus on how to identify who will progress. Given claims for a characteristic kind of memory impairment in AD involving deficits in encoding and consolidation of information, we propose that 'memory profiling' of in iduals with MCI may help identify which in iduals will progress. We initially set out to establish whether the same characteristic memory profile was present prior to the onset of AD (preAD). Very few studies provided data that allowed us to examine this, but results tentatively supported an encoding/consolidation profile in preAD. A single study tested the clinically important contrast of preAD versus non-preAD MCI cases and found no difference under any condition or in memory profiles, but interpretation of the findings is limited by short duration of follow-up, ceiling effects, and task limitations in assessing more complex and qualitative aspects of memory. Although existing data lead to equivocal conclusions, we believe that memory profiling is an endeavour worth pursuing, particularly given the increasing number of people with MCI presenting for clinical assessment. We propose that tests designed specifically to measure memory processes should be sensitive to preAD and are required in prospective longitudinal designs to identify these clinically crucial MCI cases.
Publisher: Springer Science and Business Media LLC
Date: 24-09-2021
DOI: 10.1007/S11065-021-09514-3
Abstract: Nonverbal memory tests have great potential value for detecting the impact of lateralized pathology and predicting the risk of memory loss following right temporal lobe resection (TLR) for temporal lobe epilepsy (TLE) patients, but this potential has not been realized. Previous reviews suggest that stimulus type moderates the capacity of nonverbal memory tests to detect right-lateralized pathology (i.e., faces > designs), but the roles of other task-related factors have not been systematically explored. We address these limitations using mixed model meta-regression (k = 158) of right-lateralization effects (right worse than left TLE) testing the moderating effects of: 1) stimulus type (designs, faces, spatial), 2) learning format (single trial, repeated trials), 3) testing delay (immediate or long delay), and 4) testing format (recall, recognition) for three patient scenarios: 1) presurgical, 2) postsurgical, and 3) postsurgical change. For presurgical patients the size of the right-lateralization effect was significantly moderated by stimulus type (faces > designs), testing format (recall > recognition) and its interaction with the learning format (repeated trials more affected by format effect than single trials) of the nonverbal memory tests. For postsurgical patients and presurgical-postsurgical change, test format moderated the size of the right-lateralization effect (recognition > recall) and this explained and overshadowed effects of stimulus type (i.e., faces > designs). This comprehensive review reveals the value of recognition testing in gauging the risk of nonverbal memory decline.
Publisher: SAGE Publications
Date: 2008
Publisher: American Psychological Association (APA)
Date: 10-2018
DOI: 10.1037/PAS0000565
Abstract: The ability to read irregularly spelled words is commonly used to estimate premorbid intelligence, as this ability has been thought to be resistant to early effects of neurodegenerative disorders. However, studies evaluating decline of this skill in Alzheimer's disease (AD) have produced conflicting results. Irregular word reading was assessed three times over 36 months in a large (N = 995) s le, including healthy control, AD, and Mild Cognitive Impairment (MCI) groups. At baseline, MCI and AD groups read correctly an average of 3.01 and 7.39 fewer words, respectively, than healthy controls. The MCI group's performance remained stable during the study, but the AD group declined. Importantly, the observed decline was likely an underestimate, as significant numbers of the AD participants (42.6%) could not complete the task at follow-up. Use of alternate (e.g., demographics-based) methods is advised to augment or replace word pronunciation in estimating premorbid intelligence in in iduals with even mild AD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Publisher: Elsevier BV
Date: 06-2017
Publisher: Springer International Publishing
Date: 10-09-2015
Publisher: Elsevier BV
Date: 10-2009
Publisher: Public Library of Science (PLoS)
Date: 29-11-2022
DOI: 10.1371/JOURNAL.PONE.0272517
Abstract: Behaviour change interventions represent key means for supporting healthy ageing and reducing dementia risk yet brief, scalable behaviour change interventions targeting dementia risk reduction in older adults is currently lacking. Here we describe the aims and design of the three-month Brain Bootc initiative that seeks to target multiple dementia risk and protective factors (healthy eating, physical, social and cognitive inactivity), through the use of multiple behaviour change techniques, including goal-setting for behaviour, information about health consequences and physical prompts to change behaviours that reduce dementia risk among older adults. Our secondary aim is to understand participants’ views of dementia prevention and explore the acceptability and integration of this c aign into daily life. Brain Bootc is a pre-post feasibility trial conducted in Sydney, Australia beginning in January 2021 until late August. Participants aged ≥65 years living independently in the community (n = 252), recruited through social media and flyers, will provide information about their demographics, medical history, alcohol consumption, smoking habits, mental health, physical activity, cognitive activity, and diet to generate a dementia risk profile at baseline and assess change therein at three-month follow-up. During the intervention, participants will receive a resource pack containing their in idual risk profile, educational booklet on dementia risk factors and four physical items designed to prompt physical, social and mental activity, and better nutrition. Outcome measures include change in dementia risk scores, dementia awareness and motivation. A qualitative process evaluation will interview a s le of participants on the acceptability and feasibility of the intervention. This will be the first short-term multi-domain intervention targeting dementia risk reduction in older adults. Findings will generate a new evidence base on how to best support efforts targeting lifestyle changes and to identify ways to optimise acceptability and effectiveness towards brain health for older adults. ACTRN 381046 (registered 17/02/2021) Pre-results.
Publisher: Elsevier BV
Date: 05-2004
Publisher: Springer Science and Business Media LLC
Date: 24-10-2008
DOI: 10.1007/S00213-008-1347-9
Abstract: The nicotinic acetylcholine receptor (nAChR) system plays a regulatory role in a number of cognitive processes. Cholinesterase inhibitors (i.e., galantamine) that potentiate cholinergic neurotransmission improve cognitive function in Alzheimer's disease (AD) however, the relationship between these effects and associated changes in nAChRs are yet to be established in vivo. 2-[18F]Fluoro-A-85380 (2-FA) binds to nAChRs and with positron emission tomography (PET) imaging provides a composite measure of receptor density and ligand affinity. This study aimed to: (1) quantify nAChRs in vivo in 15 drug-naïve patients with mild AD before and after chronic treatment with galantamine, using 2-FA and PET, and (2) examine the relationship between treatment-induced changes in nAChRs and improvements in cognitive function. Participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of approximately 200 MBq of 2-FA on two occasions (before and after 12 weeks, galantamine treatment). A 3-day washout period preceded the second scan. Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). Performance on global measures of cognition significantly improved following galantamine treatment (p < 0.05). This improvement extended to specific cognitive measures of language and verbal learning. No significant differences in nAChR DV(S) before and after galantamine treatment were found. The treatment-induced improvement in cognition was not correlated with regional or global nAChR DV(S), suggesting that changes in nAChRs may not be responsible for the improvements in cognition following galantamine in patients with mild AD.
Publisher: Springer Science and Business Media LLC
Date: 25-10-2017
DOI: 10.1038/S41598-017-14020-9
Abstract: Alzheimer’s Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose in iduals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify in iduals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer’s participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk in iduals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ε4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ε4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of in iduals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.YEBEH.2015.06.016
Abstract: Recent investigations of accelerated long-term forgetting, a condition in which newly acquired memory is normal initially but decays rapidly over days or weeks, indicate that multiple factors might influence whether this phenomenon is seen in patients with epilepsy. Test-based differences such as learning condition or type of memory measure (e.g., recall vs recognition) as well as epilepsy variables (e.g., side, site, or frequency of epileptiform activity) may be important. The present study sought to characterize factors affecting learning and memory for prose passages in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy, with and without hippoc al lesions, 11 patients with extratemporal epilepsy (ETE), and 29 healthy controls. Two matched passages were used to compare effects of initial learning condition (one exposure versus learning-to-criterion) on subsequent patterns of retention. Recall and recognition were tested at different delays (i.e., immediately, 30min, 24h, and 4days). Regression analyses and one-way ANOVAs indicated that having a left-hemisphere epileptic focus had a negative impact on learning, whilst presence of a hippoc al lesion (irrespective of side) was associated with deterioration in recall for intervals up to 24h postencoding. Learning condition affected patterns of memory decay in that the ETE group showed significant decline in recall between 24h and 4days only when stories were learned to criterion. In contrast with recall, no changes over time were evident in recognition memory, as patients with hippoc al lesions were impaired from 30min onward. Epilepsy variables other than side and site of epilepsy/lesion did not influence performance. In conclusion, the left hemisphere is involved in learning of prose material, and the hippoc us is involved in the consolidation of this material mainly for the first 24h. After this, cortical regions outside the hippoc us become important for recall.
Publisher: Cambridge University Press (CUP)
Date: 21-01-2011
DOI: 10.1017/S1041610210002371
Abstract: Background: Olfactory dysfunction is present in early Alzheimer's disease (AD), and has now been reported in people with amnestic mild cognitive impairment (aMCI). Recent evidence suggests that unawareness of an olfactory deficit may predict which MCI patients will subsequently meet AD criteria. However, important methodological limitations challenge this suggestion. While addressing some of the limitations of previous research, this preliminary study explores unawareness of olfactory deficits as a predictive factor of future AD among people with aMCI. Methods: Twenty-five participants with aMCI, 25 AD patients, and 22 healthy elderly participants underwent testing of olfactory identification. Subjective reports regarding perceived decline in olfactory detection and olfactory identification were also obtained. A subset of participants was reassessed 12 months later. Results: Control participants performed better than both aMCI and AD patients on olfactory identification. Almost uniformly, participants did not report decline in either olfactory detection or identification. Prediction of olfactory identification scores from subjective reports of olfactory function was poor, and awareness of olfactory decline bore no relationship to the likelihood of aMCI patients progressing to AD by the 12-month review. Conclusions: Treating awareness of olfactory function as a unitary construct can be misleading, and there is a poor relationship between subjective and objective measures of olfactory ability. Our preliminary data suggest that unawareness of olfactory decline does not improve the identification of patients with MCI who are more likely to be in the prodromal phase of AD. Replication in a larger cohort is needed to support these findings.
Publisher: Elsevier BV
Date: 03-2018
Publisher: Springer Science and Business Media LLC
Date: 02-2018
DOI: 10.1038/S41598-018-20513-Y
Abstract: A single nucleotide polymorphism, rs17070145, in the KIdney and BRAin expressed protein ( KIBRA ) gene has been associated with cognition and hippoc al volume in cognitively normal (CN) in iduals. However, the impact of rs17070145 on longitudinal cognitive decline and hippoc al atrophy in CN adults at greatest risk of developing Alzheimer’s disease is unknown. We investigated the impact rs17070145 has on the rate of cognitive decline and hippoc al atrophy over six years in 602 CN adults, with known brain Aβ-amyloid levels and whether there is an interactive effect with APOE genotype. We reveal that whilst limited independent effects of KIBRA genotype were observed, there was an interaction with APOE in CN adults who presented with high Aβ-amyloid levels across study duration. In comparison to APOE ε4-ve in iduals carrying the rs17070145-T allele, significantly faster rates of cognitive decline (global, p = 0 . 006 verbal episodic memory, p = 0 . 004 ), and hippoc al atrophy ( p = 0 . 04 ) were observed in in iduals who were APOE ε4 + ve and did not carry the rs17070145-T allele. The observation of APOE effects in only non-carriers of the rs17070145-T allele, in the presence of high Aβ-amyloid suggest that carriers of the rs17070145-T allele are conferred a level of resilience to the detrimental effects of high Aβ-amyloid and APOE ε4.
Publisher: Bentham Science Publishers Ltd.
Date: 11-05-2016
DOI: 10.2174/1567205013666160315112151
Abstract: Alzheimer's disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify in iduals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD in iduals. Visual scoring of the buccal cytome demonstrated a significantly lower frequency of basal and karyorrhectic cells in the MCI group compared with controls. A high content, automated assay was developed using laser scanning cytometry to simultaneously measure cell types, nuclear DNA content and aneuploidy, neutral lipid content, putative Tau and amyloid-β (Aβ) in buccal cells. DNA content, aneuploidy, neutral lipids and Tau were similar in all groups. However, there was significantly lower Tau protein in both basal and karyolytic buccal cell types compared with differentiated buccal cells. Aβ, as measured by frequency of cells containing Aβ signal, as well as area and integral of Aβ signal, was significantly higher in the AD group compared with the control group. Buccal cell Aβ was correlated with mini-mental state examination (MMSE) scores (r = -0.436, P=0.001) and several blood-based biomarkers. Combining newly identified biomarkers from buccal cells with those already established may offer a potential route for more specific biomarker panels which may substantially increase the likelihood of better predictive markers for earlier diagnosis of AD.
Publisher: SAGE Publications
Date: 09-2007
DOI: 10.1080/00048670701517926
Abstract: Objectives: The characterization, aetiology, and course of verbal memory deficits in schizophrenia remain ill defined. The impact of antipsychotic medications is also unclear. The purpose of the present paper was to investigate verbal memory performance in established schizophrenia (SZ) and first-episode schizophreniform psychosis (FE). Method: Performances of 32 SZ and 33 FE patients were compared to those of 47 healthy volunteers on measures of verbal working memory, verbal associative learning and story recall. Results: Story recall deficits, but not deficits in working memory or paired associate learning, were demonstrated by both patient groups. Patients treated with typical neuroleptics had more impairment in associative learning with arbitrary word pairings than those treated with atypicals, regardless of patient group. Conclusions: The results are consistent with the notion that some neuropsychological impairment is present at the time of psychosis onset and that this impairment is non-progressive. However, deficits may be specific to subclasses of memory function.
Publisher: Wiley
Date: 12-02-2019
DOI: 10.1111/JNP.12152
Abstract: In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants' memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-08-2016
DOI: 10.1212/WNL.0000000000003094
Abstract: We assessed a blood-based signature, which previously demonstrated high accuracy at stratifying in iduals with high or low neocortical β-amyloid burden (NAB), to determine whether it could also identify in iduals at risk of progression to Alzheimer disease (AD) within 54 months. We generated the blood-based signature for 585 healthy controls (HCs) and 74 participants with mild cognitive impairment (MCI) from the Australian Imaging, Biomarkers and Lifestyle Study who underwent clinical reclassification (blinded to biomarker findings) at 54-month follow-up. The in iduals were split into estimated high and low NAB groups based on a cutoff of 1.5 standardized uptake value ratio. We assessed the predictive accuracy of the high and low NAB groupings based on progression to mild cognitive impairment or AD according to clinical reclassification at 54-month follow-up. Twelve percent of HCs with estimated high NAB progressed in comparison to 5% of HCs with estimated low NAB (odds ratio = 2.4). Forty percent of the participants with MCI who had estimated high NAB progressed in comparison to 5% of the participants with MCI who had estimated low NAB (odds ratio = 12.3). These ratios are in line with those reported for Pittsburgh compound B–PET results. In iduals with estimated high NAB had faster rates of memory decline than those with estimated low NAB. These findings suggest that a simple blood-based signature not only provides estimates of NAB but also predicts cognitive decline and disease progression, identifying in iduals at risk of progressing toward AD at the prodromal and preclinical stages.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2017.08.016
Abstract: Social relevance has an enhancing effect on learning and subsequent memory retrieval. The ability to learn from and remember social interactions may impact on susceptibility to financial exploitation, which is elevated in in iduals with dementia. The current study aimed to investigate learning and memory of social interactions, the relationship between performance and financial vulnerability and the neural substrates underpinning performance in 14 Alzheimer's disease (AD) and 20 behavioural-variant frontotemporal dementia (bvFTD) patients and 20 age-matched healthy controls. On a "trust game" task, participants invested virtual money with counterparts who acted either in a trustworthy or untrustworthy manner over repeated interactions. A non-social "lottery" condition was also included. Participants' learning of trust/distrust responses and subsequent memory for the counterparts and nature of the interactions was assessed. Carer-rated profiles of financial vulnerability were also collected. Relative to controls, both patient groups showed attenuated learning of trust/distrust responses, and lower overall memory for social interactions. Despite poor learning performance, both AD and bvFTD patients showed better memory of social compared to non-social interactions. Importantly, better memory for social interactions was associated with lower financial vulnerability in AD, but not bvFTD. Learning and memory of social interactions was associated with medial temporal and temporoparietal atrophy in AD, whereas a wider network of frontostriatal, insular, fusiform and medial temporal regions was implicated in bvFTD. Our findings suggest that although social relevance influences memory to an extent in both AD and bvFTD, this is associated with vulnerability to financial exploitation in AD only, and is underpinned by changes to different neural substrates. Theoretically, these findings provide novel insights into potential mechanisms that give rise to vulnerability in people with dementia, and open avenues for possible interventions.
Publisher: Informa UK Limited
Date: 03-2007
DOI: 10.1080/02643290601025576
Abstract: The role of semantics in reading aloud remains controversial. To explore this issue, the current study examined the impact of semantic loss on reading-aloud performance in 7 patients with semantic dementia. The results revealed a heterogenous pattern of reading difficulties. Of the patients, 2 selectively made errors on inconsistent words (i.e., surface dyslexia), 4 had a generalized reading deficit with increased errors on consistent words, inconsistent words, and nonwords, while the remaining patient had relatively intact reading-aloud accuracy. All patients had longer reading latencies on real words than controls. The relationship between the reading and semantic deficits in the patients was examined at the item-specific level. This suggested that reading-aloud errors were related to the semantic impairment for inconsistent words but not consistent words. In contrast, semantic loss was related to longer latencies for both consistent and inconsistent words. These findings support models of reading that include a role for semantics in the reading-aloud process.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.BANDL.2016.08.009
Abstract: The cause of stuttering has many theoretical explanations. A number of research groups have suggested changes in the volume and/or function of the striatum as a causal agent. Two recent studies in children and one in adults who stutter (AWS) report differences in striatal volume compared that seen in controls however, the laterality and nature of this anatomical volume difference is not consistent across studies. The current study investigated whether a reduction in striatal grey matter volume, comparable to that seen in children who stutter (CWS), would be found in AWS. Such a finding would support claims that an anatomical striatal anomaly plays a causal role in stuttering. We used voxel-based morphometry to examine the structure of the striatum in a group of AWS and compared it to that in a group of matched adult control subjects. Results showed a statistically significant group difference for the left caudate nucleus, with smaller mean volume in the group of AWS. The caudate nucleus, one of three main structures within the striatum, is thought to be critical for the planning and modulation of movement sequencing. The difference in striatal volume found here aligns with theoretical accounts of stuttering, which suggest it is a motor control disorder that arises from deficient articulatory movement selection and sequencing. Whilst the current study provides further evidence of a striatal volume difference in stuttering at the group level compared to controls, the significant overlap between AWS and controls suggests this difference is unlikely to be diagnostic of stuttering.
Publisher: Oxford University Press (OUP)
Date: 04-12-2016
Abstract: The consequences of losing the ability to move a limb are traumatic. One approach that examines the impact of pathological limb nonuse on the brain involves temporary immobilization of a healthy limb. Here, we investigated immobilization-induced plasticity in the motor imagery (MI) circuitry during hand immobilization. We assessed these changes with a multimodal paradigm, using functional magnetic resonance imaging (fMRI) to measure neural activation, magnetoencephalography (MEG) to track neuronal oscillatory dynamics, and transcranial magnetic stimulation (TMS) to assess corticospinal excitability. fMRI results show a significant decrease in neural activation for MI of the constrained hand, localized to sensorimotor areas contralateral to the immobilized hand. MEG results show a significant decrease in beta desynchronization and faster resynchronization in sensorimotor areas contralateral to the immobilized hand. TMS results show a significant increase in resting motor threshold in motor cortex contralateral to the constrained hand, suggesting a decrease in corticospinal excitability in the projections to the constrained hand. These results demonstrate a direct and rapid effect of immobilization on MI processes of the constrained hand, suggesting that limb nonuse may not only affect motor execution, as evidenced by previous studies, but also MI. These findings have important implications for the effectiveness of therapeutic approaches that use MI as a rehabilitation tool to ameliorate the negative effects of limb nonuse.
Publisher: Informa UK Limited
Date: 04-2012
DOI: 10.1080/13803395.2011.643227
Abstract: The aim of this study was to validate the CogState Brief Battery, which assesses psychomotor, attentional, working memory, and visual learning functions, in healthy older people and in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. In healthy older adults, weak relationships between demographic variables (e.g., education, depression) and cognitive performance were observed. In AD and MCI groups, the magnitude of impairment was greatest for tasks of working memory and memory, with a negative influence of apolipoprotein E ϵ4 status on learning but not working memory. These results suggest that the CogState Brief Battery can be used to screen for AD-related cognitive changes.
Publisher: Wiley
Date: 23-01-2015
DOI: 10.1002/9781118625392.WBECP060
Abstract: Amnestic disorders may involve deficits in the encoding or storage of information in memory, or in retrieval of information from memory. Etiologies vary and include traumatic brain injury, neurodegenerative disease, and psychiatric illness. Different forms of amnesia can be distinguished: anterograde amnesia affects memory for the present, and retrograde amnesia affects memory for the past. Different memory systems may also be affected (working memory, episodic memory or semantic memory). This entry discusses hippoc al amnesia, amnesia caused by Alzheimer's disease (including mild cognitive impairment), memory dysfunction caused by vascular cognitive impairment, Korsakoff's syndrome, posttraumatic amnesia, transient global amnesia, transient epileptic amnesia, and psychogenic amnesia.
Publisher: Wiley
Date: 09-2009
DOI: 10.1002/SYN.20642
Abstract: Extensive experimental and neuropathological evidence supports the general hypothesis that decline in the basal forebrain cholinergic system contributes significantly to age-related cognitive impairment. Postmortem studies suggest reductions in neuronal nicotinic acetylcholine receptors (nAChRs, particularly the alpha(4)beta(2) subtype) with aging. This study aimed to determine the distribution of alpha(4)beta(2)-subtype nAChRs in vivo by 2-FA PET in healthy subjects (aged 21-83) and to establish whether there is an age-related decline in nAChRs. Furthermore, the relationship between PET measures of 2-FA binding and neurobehavioral measures of cognitive function was investigated. All participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of 2-FA (200 MBq). Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). As expected, increasing age was associated with poorer cognitive performance, particularly on tasks assessing episodic memory and attentional processes. No significant age-related differences in regional nAChR DV(S) were found. Furthermore, no significant correlations were found between cognitive measures and nAChR DV(S). These results are consistent with recent studies suggesting the stability of cholinergic markers during senescence. It is plausible that changes in alpha(4)beta(2) nAChRs do occur with advancing age, but are beyond detection by the clinical 2-FA PET approach adopted here. However, this approach may be appropriate for use in pathologies considered to undergo extensive nAChR loss such as Alzheimer's disease and Parkinson's disease.
Publisher: Informa UK Limited
Date: 10-1996
Publisher: Wiley
Date: 03-03-2014
DOI: 10.1016/J.JALZ.2013.11.005
Abstract: High β-amyloid (Aβ) is associated with faster memory decline in healthy in iduals and adults with mild cognitive impairment (MCI). However, longer prospective studies are required to determine if Aβ-related memory decline continues and whether it is associated with increased rate of disease progression. Healthy controls (HCs n = 177) and adults with MCI (n = 48) underwent neuroimaging for Aβ and cognitive assessment at baseline. Cognition was reassessed 18 and 36 months later. Compared with low-Aβ HCs, high-Aβ HC and MCI groups showed moderate decline in episodic and working memory over 36 months. Those with MCI with low Aβ did not show any cognitive decline. Rates of disease progression were increased in the high-Aβ HC and MCI groups. In healthy in iduals, high Aβ likely indicates that Alzheimer's disease (AD)-related neurodegeneration has begun. Once commenced, the rate of decline in cognitive function remains constant across the preclinical and prodromal stages of AD.
Publisher: Oxford University Press (OUP)
Date: 09-07-2020
Abstract: This cross-sectional study aimed to investigate the acceptability and usability of the Cogstate Brief Battery (CBB) in a community-based s le of Australian Indigenous people from the Torres Strait region, based on a user experience framework of human–computer interaction. Two-hundred community participants completed the four subtests of the CBB on an iPad platform, during a free adult health check on two islands in the region, between October and December 2016. Acceptability was defined as completing the learning trial of a task and usability as continuing a task through to completion, determined by examiner acumen and internal Cogstate completion and integrity criteria. These were combined into a single dichotomous completion measure for logistic regression analyses. Performance—measured as reaction times and accuracy of responses—was analyzed using linear regression analyses. CBB completion ranged from 82.0% to 91.5% across the four tasks and the odds of completing decreased with age. After adjusting for age, iPad/tablet familiarity increased the odds of completion for all tasks while level of education and employment increased the odds for some tasks only. These variables accounted for 18.0%–23.8% of the variance in reaction times on speeded tasks. Age and education had the most effect, although semipartial correlations were modest. When administered in a health-screening context, the acceptability and usability of the CBB were greatest in young- to middle-aged participants with some education and iPad/tablet experience. Older and more vulnerable participants may have benefited from additional time and practice on the CBB prior to administration.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.NEUROSCIENCE.2015.01.049
Abstract: Healthy aging is accompanied by neurobiological changes that affect the brain's functional organization and the in idual's cognitive abilities. The aim of this study was to investigate the effect of global age-related differences in the cortical white and gray matter on neural activity in three key large-scale networks. We used functional-structural covariance network analysis to assess resting state activity in the default mode network (DMN), the fronto-parietal network (FPN), and the salience network (SN) of young and older adults. We further related this functional activity to measures of cortical thickness and volume derived from structural MRI, as well as to measures of white matter integrity (fractional anisotropy [FA], mean diffusivity [MD], and radial diffusivity [RD]) derived from diffusion-weighted imaging. First, our results show that, in the direct comparison of resting state activity, young but not older adults reliably engage the SN and FPN in addition to the DMN, suggesting that older adults recruit these networks less consistently. Second, our results demonstrate that age-related decline in white matter integrity and gray matter volume is associated with activity in prefrontal nodes of the SN and FPN, possibly reflecting compensatory mechanisms. We suggest that age-related differences in gray and white matter properties differentially affect the ability of the brain to engage and coordinate large-scale functional networks that are central to efficient cognitive functioning.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.PSYCHRES.2017.11.044
Abstract: Memory impairment in psychosis may be mediated through detrimental effects of hypothalamic-pituitary-adrenal (HPA) axis function. This study prospectively investigated the relationship between cortisol, sulphate dehydroepiandrosterone (DHEA(S) and cortisol: DHEA(S) ratio and memory in 35 first-episode psychosis (FEP) patients during the first 12 weeks of treatment and 23 healthy controls (HC). Morning blood s ling and tests of attention, working memory and verbal memory occurred at baseline and 12-week follow-up. FEP and HC groups did not significantly differ in levels of cortisol, DHEA(S) or their ratio at baseline or over 12-weeks. The FEP group performed significantly below HC on all cognitive measures at baseline and over 12-weeks. Cortisol levels were unrelated to cognition in both groups. At baseline, DHEA(S) was positively associated with attention in HCs, but negatively associated with attention in FEP participants. Change in DHEA(S) was negatively associated with change in memory over 12-weeks in both groups. At 12-weeks, there was a negative correlation between the cortisol: DHEA(S) ratio and attention in both groups. These findings are mostly in contrast to findings in chronic schizophrenia. Investigation at different illness phases and over longer-follow-up periods is required to determine the complex relationship between HPA-axis and memory functioning in psychosis.
Publisher: Elsevier BV
Date: 07-2009
Publisher: Elsevier BV
Date: 09-2016
Publisher: Cambridge University Press (CUP)
Date: 20-11-2013
DOI: 10.1017/S1041610213001956
Abstract: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 in iduals (211 with Alzheimer's disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of in iduals who transitioned to a more severe disease stage compared with those who did not. Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood s le, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging. The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinson's disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%. There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.
Publisher: Wiley
Date: 07-2008
Publisher: American Psychological Association (APA)
Date: 07-2015
DOI: 10.1037/NEU0000156
Abstract: To explore the subjective experience of memory change in groups at risk of dementia (those with mild cognitive impairment MCI or high β-amyloid (Aβ+) burden) to determine the existence of potential phenomenological typologies. We recruited 123 healthy controls (HC) and in iduals with MCI from the Australian Imaging, Biomarker and Lifestyle (AIBL) study. Sixty-7 (HC = 47,MCI = 20) had Aβ scans available for analysis. Semistructured interviews were administered, transcribed, and meaningful phrases extracted from transcripts. Twelve themes were defined and compared across diagnostic status and Aβ status. MCI endorsed more complaints of burdensome coping strategies, increasing frequency, sense of predomination, poor contextualization, progression, dependency, impact on affect, and dismissive attitudes. HCAβ+ acknowledged a progressive memory decline compared to HCAβ-, while MCIAβ+ expressed more burdensome coping strategies, dismissive attitudes, and dependency comparative to either healthy group. Depression was more likely to be related to complaint themes in HCs, while complaint themes were associated with poorer list-learning performance in in iduals with MCI. Complaint themes in those with MCI align with the MCI symptom complex, particularly when accompanied with high Aβ load. Healthy Aβ+ in iduals acknowledged progressive memory change, suggesting they are aware of memory changes not yet detectable via neuropsychological measures. Depressive symptomatology associated with HC complaints, suggesting certain themes are affect-driven, while complaints in MCI are associated with organically driven functional impairment. Qualitative analysis of SMCs can inform the earliest clinical manifestations of Alzheimer's disease. Our findings can inform diagnostic approaches to the clinical evaluation of memory complaints in the nondemented elderly.
Publisher: Wiley
Date: 07-2008
Publisher: Wiley
Date: 16-11-2013
DOI: 10.1016/J.JALZ.2012.07.004
Abstract: Only one study has investigated the relationship between cerebral β-amyloid (Aβ), apolipoprotein E (APOE) ε4 genotype, and cognition. Although significant relationships between cerebral Aβ and cognition were observed in ε4 carriers but not noncarriers, the magnitude of this relationship was not reported. Further, when demographic variables were controlled, the influence of APOE ε4 on the relationship between cerebral Aβ and cognition dissipated. In 144 healthy older adults who had undergone amyloid scanning and APOE ε4 genotyping in the Australian Imaging, Biomarkers, and Lifestyle (AIBL) Flagship Study of Ageing, correlations were conducted to determine the magnitude of relationship between cerebral Aβ and cognition in ε4 carriers and noncarriers. Fisher's Z was used to compare these correlations and Cohen's q determined the magnitude of difference between correlations. Cerebral Aβ was significantly associated with tasks of visual and verbal episodic memory in APOE ε4 carriers. This association was not observed in ε4 noncarriers. The relationship between cerebral Aβ and episodic memory in ε4 carriers was significantly different from that in ε4 noncarriers, and the magnitude of this difference was small to moderate. In APOE ε 4 carriers, there is a moderate negative relationship between cerebral Aβ and episodic memory. This suggests that increased cerebral Aβ may signify the onset of preclinical AD, especially in healthy older adults who are genetically at risk for AD.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2009.10.028
Abstract: Body ownership for an artificial hand and the perceived position of one's own hand can be manipulated in the so-called rubber hand illusion. To induce this illusion, typically an artificial hand is placed next to the participant's body and stroked in synchrony with the real hand, which is hidden from view. Our first aim was to test if the crossmodal congruency task could be used to obtain a measure for the strength of body ownership in the rubber hand illusion. In this speeded location discrimination task participants responded to tactile targets presented to their index or middle finger, while trying to ignore irrelevant visual distracters placed on the artificial hand either on the congruent finger or on the incongruent finger. The difference between performance on congruent and incongruent trials (crossmodal congruency effect, CCE) indicates the amount of multisensory interactions between tactile targets and visual distracters. In order to investigate if changes in body ownership influence the CCE, we manipulated ownership for an artificial hand by synchronous and asynchronous stroking before the crossmodal congruency task (blocked design) in Experiment 1 and during the crossmodal congruency task (interleaved trial-by-trial design) in Experiment 2. Modulations of the CCE by ownership for an artificial hand were apparent in the interleaved trial-by-trial design. These findings suggest that the CCE can be used as an objective measure for body ownership. Secondly, we tested the hypothesis that the lateral spatial distance between the real hand and artificial hand limits the rubber hand illusion. We found no lateral spatial limits for the rubber hand illusion created by synchronous stroking within reaching distances. In conclusion, the sense of ownership seems to be related to modulations of multisensory interactions possibly through peripersonal space mechanisms, and these modulations do not appear to be limited by an increase in distance between artificial hand and real hand.
Publisher: Oxford University Press (OUP)
Date: 03-2009
Publisher: Elsevier BV
Date: 09-2020
Publisher: Springer Science and Business Media LLC
Date: 17-04-2010
Publisher: Frontiers Media SA
Date: 19-12-2018
Publisher: Wiley
Date: 04-02-2016
DOI: 10.1016/J.JALZ.2015.12.013
Abstract: The objective of this study was to determine the utility of subjective memory decline (SMD) to predict episodic memory change and rates of clinical progression in cognitively normal older adults with evidence of high β-amyloid burden (CN Aβ+). Fifty-eight CN Aβ+ participants from the Australian Imaging, Biomarkers, and Lifestyle study responded to an SMD questionnaire and underwent comprehensive neuropsychological assessments. Participant data for three follow-up assessments were analyzed. In CN Aβ+, subjects with high SMD did not exhibit significantly greater episodic memory decline than those with low SMD. High SMD was related to greater rates of progression to mild cognitive impairment or Alzheimer's disease (AD) dementia (hazard ratio = 5.1 95% confidence interval, 1.4-20.0, P = .02) compared with low SMD. High SMD was associated with greater depressive symptomatology and smaller left hippoc al volume. High SMD is a harbinger of greater rates of clinical progression in preclinical AD. Although SMD reflects broader diagnostic implications for CN Aβ+, more sensitive measures may be required to detect early subtle cognitive change.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2015.06.008
Abstract: The ε4 polymorphism of the APOE gene confers a substantially increased risk of developing Alzheimer's disease. However, the influence of the ε4 allele on age-related cognitive functioning is more contentious. Previously, we demonstrated relatively little evidence for a role of the ε4 allele on baseline cognitive performance in older adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing (Foster et al., 2013). We here investigated whether the APOE ε4 allele influenced cognitive status over time when the AIBL cohort was studied longitudinally over a 3-year period. The AIBL neuropsychological test battery was administered at baseline, after 18 months and again after 36 months. Participants comprised 764 Healthy Controls and 131 Mild Cognitively Impaired in iduals enrolled in the AIBL Study of Ageing. We compared in iduals within each group with and without an ε4 allele. Healthy Controls with an ε4 allele manifested a modest acceleration in cognitive decline over 36 months on measures of verbal episodic memory. By contrast, Mild Cognitively Impaired in iduals with an ε4 allele showed increased cognitive decline across a range of cognitive tasks, putatively reflecting early cognitive signs of Alzheimer's disease. Given the long prodromal period that has been noted in late onset Alzheimer's disease, we suggest that these findings are consistent with a prodromal account rather than a phenotypic account of ε4-related cognitive ageing.
Publisher: American Psychological Association (APA)
Date: 11-2008
DOI: 10.1037/A0013050
Abstract: Mild cognitive impairment (MCI) is associated with increased risk of developing Alzheimer's disease (AD), but up to 40% of cases do not develop AD. Examining a case's specific memory profile may help distinguish which MCI cases will progress to AD: An encoding profile is suggestive of incipient AD, whereas a retrieval profile suggests an alternative etiology. Paired associate learning (PAL) tasks are sensitive for preclinical and early detection of AD, but existing tasks do not enable memory profiling. We developed a novel PAL task enabling the differentiation of memory profiles in 19 people with AD, 17 people with amnestic MCI, and 33 normal elderly controls. Unexpectedly, the AD group demonstrated a retrieval profile for PAL using yes-no recognition, although an encoding profile was evident for forced-choice recognition and for the California Verbal Learning Test--Second Edition (Delis, Kramer, Kaplan, & Ober, 2000). There was considerable heterogeneity within the AD and MCI groups as well as intrain idual discordance for memory profiles. The findings challenge the clinical application of memory profiling in the differential diagnosis of AD, and, by extension, question its potential application in the assessment of MCI.
Publisher: Springer Science and Business Media LLC
Date: 10-12-2021
DOI: 10.1038/S41598-021-02827-6
Abstract: To improve understanding of Alzheimer’s disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning it to the other study. Results demonstrated that simulated missing values from one dataset could be accurately imputed, and that imputation of actual missing data in one dataset showed comparable discrimination (p 0.001) for clinical classification to measured data in the other dataset. Further, the increased power of the overall harmonised dataset was demonstrated by observing a significant association between CVLT-II test scores (imputed for ADNI) with PET Amyloid-β in MCI APOE -ε4 homozygotes in the imputed data (N = 65) but not for the original AIBL dataset (N = 11). These results suggest that MissForest can provide a practical solution for data harmonization using imputation across studies to improve power for more nuanced analyses.
Publisher: Wiley
Date: 12-2013
DOI: 10.1002/ANA.24040
Abstract: Biomarkers for Alzheimer disease (AD) can detect the disease pathology in asymptomatic subjects and in iduals with mild cognitive impairment (MCI), but their cognitive prognosis remains uncertain. We aimed to determine the prognostic value of β-amyloid imaging, alone and in combination with memory performance, hippoc al atrophy, and apolipoprotein E ε4 status in nondemented, older in iduals. A total of 183 healthy in iduals (age = 72.0 ± 7.26 years) and 87 participants with MCI (age = 73.7 ± 8.27) in the Australian Imaging, Biomarkers, and Lifestyle study of ageing were studied. Clinical reclassification was performed after 3 years, blind to biomarker findings. β-Amyloid imaging was considered positive if the (11) C-Pittsburgh compound B cortical to reference ratio was ≥1.5. Thirteen percent of healthy persons progressed (15 to MCI, 8 to dementia), and 59% of the MCI cohort progressed to probable AD. Multivariate analysis showed β-amyloid imaging as the single variable most strongly associated with progression. Of combinations, subtle memory impairment (Z score = -0.5 to -1.5) with a positive amyloid scan was most strongly associated with progression in healthy in iduals (odds ratio [OR] = 16, 95% confidence interval [CI] = 3.7-68 positive predictive value [PPV] = 50%, 95% CI = 19-81 negative predictive value [NPV] = 94%, 95% CI = 88-98). Almost all amnestic MCI subjects (Z score ≤ -1.5) with a positive amyloid scan developed AD (OR = ∞ PPV = 86%, 95% CI = 72-95 NPV = 100%, 95% CI = 80-100). Hippoc al atrophy and ε4 status did not add further predictive value. Subtle memory impairment with a positive β-amyloid scan identifies healthy in iduals at high risk for MCI or AD. Clearly amnestic patients with a positive amyloid scan have prodromal AD and a poor prognosis for dementia within 3 years.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2014.11.027
Abstract: Accelerated long term forgetting (ALF), whereby information is rapidly lost over days or weeks has been noted in patients with epileptic conditions. The present study sought to determine which clinical factors underlie such consolidation failure for recent autobiographical experiences in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy (TLE), with and without hippoc al lesions (TLE(+)=12 TLE(-)=9, respectively), 11 patients with extratemporal epilepsy (ETE) and 29 controls (NC). Recall and recognition were tested at different delays (i.e., 30min, 24h and 4 days). During the study interval, most of the patients underwent concurrent ambulatory EEG monitoring. Analyses of variance indicated Group×Delay interval interactions for recall. The TLE(+) group showed significant decline in recall by 24h delay. On recognition Group by Delay interval was not detected but main effect for Group revealed that the ETE group demonstrated ALF on recognition questions over the interval between 24h and 4 days. Regression analyses confirmed that a hippoc al lesion was particularly disruptive to consolidation over the first 24h, and that seizures were associated with memory decline over longer delays. Our findings show that the retention of autobiographical experiences involves multiple mechanisms, which operate over different timeframes.
Publisher: Wiley
Date: 30-05-2019
DOI: 10.1111/TOPS.12350
Abstract: While we often engage in conversational reminiscing with loved ones, the effects of these conversations on our memory performance remain poorly understood. On the one hand, Wegner's transactive memory theory predicts that intimate groups experience benefits from remembering together. On the other hand, research on collaborative recall has shown costs of shared remembering in groups of strangers-at least in terms of number of items recalled-and even in intimate groups there is heterogeneity in outcomes. In the current research, we studied the effects of particular communicative features in determining the outcomes of collaborative recall in intimate groups. We tested 39 older, long-married couples. They completed a non-personal recall task (name all the countries in Europe) and a personal recall task (name all your mutual friends), both separately and together. When they collaborated, we recorded their conversation. We coded for specific "communication variables" and obtained measures of "conversational style." Overall, we found two clusters of communication variables positively associated with collaborative success: (a) cuing each other, responding to cues, and repeating each other and (b) making positive statements about memory performance and persisting with the task. A negative cluster of behaviors-correcting each other, having uneven expertise, and strategy disagreements-was associated with less interactive, more "monologue" style of collaboration, but not with overall recall performance. We discuss our results in terms of the importance of different conversational processes in driving the heterogeneous outcomes of group remembering in intimate groups, suggesting that a focus on recall output alone limits our understanding of conversational remembering.
Publisher: Oxford University Press (OUP)
Date: 08-10-2015
Abstract: Information provided by an informant about a patient with cognitive change is an essential component of clinical history taking. How an informant's report relates to the patient's phenomenological experience of memory loss is yet to be understood. The aim was to examine patterns of relationships between self and informant reports from a phenomenological perspective. Forty-three healthy non-memory complainers (HC-NMC), 37 healthy subjective memory complainers (HC-SMC) and 43 in iduals with mild cognitive impairment (MCI) were administered a semi-structured interview, which measured their concerns of frequency of memory lapses and impact on mood. Informants responded to questionnaires. Self-reported concerns of increasing frequency and impacted mood related to informant concerns in HC-SMCs. MCI with lower informant concern showed a similar pattern to HC-SMCs on complaints of increasing frequency. In those with higher informant concern, self-reports markedly separated from informant concern. The MCI group with greater informant concern performed comparatively poor on verbal and non-verbal memory measures. Our results suggest that the association between self-reported and informant memory concerns is moderated by MCI severity. Self and informant reports of increasing memory lapse frequency aligned in HC-SMC and MCIs with low informant concern, suggesting a similar dyadic experience of memory change. In MCIs with greater informant concern, the pattern changed exposing a changing insight with advancing memory impairment. These in iduals are potentially reflecting a 'forgetting that they forget' phenomenon in elements of their concern.
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.PSCYCHRESNS.2012.02.004
Abstract: As the prevalence of treatment resistant depression (TRD) continues to rise, it remains a clinically important issue to identify neurobiological-, patient- and treatment-related factors that could potentially predict response to treatment. Medial temporal lobe (MTL) structures, in particular the hippoc us and amygdala have been implicated in inferior treatment response. The role of related structures such as the entorhinal cortex and the impact of MTL abnormalities on neurocognitive function, however, have not been systematically examined. The current study investigated MTL abnormalities and neurocognitive characteristics of eventual treatment responders and non-responders to a course of repetitive transcranial magnetic stimulation (rTMS) in order to identify potential predictors of treatment outcome. Prior to rTMS treatment all patients underwent magnetic resonance imaging (MRI) and neuropsychological assessment. MRI analysis was conducted using FreeSurfer 5.0. There was a 50% response rate following up to a 6-week course of daily rTMS treatments. Treatment response was defined as 50% reduction in Hamilton Depression Rating Scale and BDI-II scores from baseline. There was no difference in pre-treatment neurocognitive profiles and MTL volumes between eventual treatment responders and non-responders. Smaller pre-treatment left hippoc us volume showed a trend towards predicting eventual subjective improvement in depressive symptomatology. Although preliminary, our findings suggest that structural abnormalities may have some potential for predicting outcome to rTMS.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.NLM.2008.05.006
Abstract: Neuronal nicotinic acetylcholine receptors (nAChRs) are critical for higher order cognitive processes. Post-mortem studies suggest reductions in nAChRs (particularly the alpha(4)beta(2) subtype) with ageing and in Alzheimer's disease (AD). This study aimed to (1) quantify nAChR distribution in vivo with 2-[18F]fluoro-A-85380 (2-FA) in 15 early AD patients compared to 14 age-matched, healthy controls (HC) and (2) correlate nAChR distribution with cognitive performance in both groups. All participants were non-smokers and underwent cognitive testing along with a dynamic PET scan after injection of 200 MBq of 2-FA. Brain regional 2-FA binding was assessed through a simplified estimation of Distribution Volume (DV(S)). The AD group differed significantly from HC on all cognitive measures employed, with impairments on measures of attention, working memory, language, executive function, visuospatial ability, verbal learning and verbal memory (p<.05). Contrary to post-mortem data this study found no evidence of in vivo nAChR loss in early AD despite significant cognitive impairment. Furthermore, no correlation between nAChR and cognitive performance was found for either group. The findings of the current study suggest preservation of nAChRs early in AD supporting previous studies. It is possible that while the clinical 2-FA PET method described here may be insensitive in detecting changes in early AD, such changes may be detected in more advanced stages of the illness.
Publisher: Informa UK Limited
Date: 04-07-2008
DOI: 10.1080/13825580802099678
Abstract: Associate-recognition has received little attention as a potential clinical tool for detecting early Alzheimer's disease (AD). As an important preliminary stage to investigating the paradigm's diagnostic utility, we designed and administered a verbal associate-recognition task to healthy elderly participants (n = 62) and compared their performance to that on traditional cued-recall PAL. In both test conditions, the stimulus list comprised of a mixture of highly imageable and less imageable word pairs. Overall, performance on the associate-recognition task was superior to that on the cued-recall analogue. This 'recognition advantage' was not attributable to the higher baseline or chance guessing rate in the associate-recognition condition, as the size of the recognition advantage varied across learning trials and stimulus imageability. In comparison to performance on the imageable stimuli, performance on the less imageable stimuli was poor in both associate-recognition and cued-recall conditions. Across the delay, performances were more likely to drop in the cued-recall condition than the associate-recognition condition. These results suggest that verbal associate-recognition may be clinically efficacious and better tolerated in elderly populations than traditional cued-recall paradigms. Although these results are encouraging, further research is required to examine the utility of associate-recognition in clinical populations, particularly early AD.
Publisher: Informa UK Limited
Date: 10-2006
DOI: 10.1080/13554790601026379
Abstract: Face perception is a vital aspect of human social functioning and involves specialized cognitive and neural mechanisms. For ex le, configural face processing involves determining the relationship between the parts of the face, and this process enables us to differentiate between different faces. Here, we report an unusual case in which right anterior temporal lobe atrophy resulted in a profound deficit in the ability to recognize faces. We demonstrate that this patient is not able to process faces via configural information, raising the possibility that the right anterior temporal lobe has a role in configural face processing.
Publisher: Cambridge University Press (CUP)
Date: 18-07-2013
DOI: 10.1017/S1041610213001087
Abstract: To date evidence of the relationship between cognition and Aβ amyloid during the early stages of Alzheimer's Disease (AD) has been inconsistent. This study aimed to describe the nature and magnitude of the relationship between Aβ amyloid and cognitive performance of in iduals without dementia. Composite cognitive measures were developed from the Australian Imaging Biomarkers and Lifestyle study neuropsychological test battery using data from 768 healthy older adults and 133 adults with mild cognitive impairment (MCI). A subgroup of this s le (174 healthy, 53 MCI) underwent neuroimaging for Aβ amyloid. Within the MCI group in iduals with high Aβ amyloid showed selective impairment for memory compared with those with low Aβ amyloid however, this difference was not evident in the healthy group. The current findings provide further evidence of the relationship between Aβ amyloid and cognition, with memory impairment being the primary symptom of the underlying disease during the prodromal phases of AD.
Publisher: MyJove Corporation
Date: 26-07-2013
DOI: 10.3791/50530
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.BRS.2012.06.006
Abstract: Major depressive disorder (MDD) is often resistant to treatment with standard approaches. Repetitive transcranial magnetic stimulation (rTMS) is a new treatment that has proven antidepressant efficacy in treatment resistant MDD (TRD). Preliminary evidence also raises the possibility of rTMS enhancing neuronal plasticity with demonstrated increases in serum levels of brain derived neurotrophic factor (BDNF) found. This is of most relevance to volumetric reductions associated with MDD, particularly in the hippoc us and related structures. Extensive preclinical literature suggests that hippoc al volume reductions from MDD induced suppression of adult neurogenesis can be reversed by different types of classical antidepressant treatments which increase expression of BDNF. The aims of this study were to investigate whether antidepressant response to rTMS has similar therapeutic potential as antidepressant pharmacotherapy in promoting neurogenesis in the HC and surrounding structures and facilitating related neurocognitive improvements. Magnetic resonance imaging and neurocognitive assessments were conducted on 29 patients prior to rTMS treatment (baseline) and at three months post baseline (endpoint). Over time, antidepressant response was associated with a near significant increase in left amygdala volume (6.58%), whilst treatment non-responders showed significant declines in left hippoc us volumes (-2.64%) from baseline. Functionally, there was no cognitive deterioration following rTMS treatment. The results are limited, however, by s le size. These preliminary findings suggest that rTMS may promote neurogenesis or other effects that favour neuronal plasticity and may also be neuroprotective for patients with TRD but these findings need replication in a larger s le.
Publisher: SAGE Publications
Date: 10-06-2013
Abstract: Impaired emotion recognition in dementia is associated with increased patient agitation, behavior management difficulties, and caregiver burden. Emerging evidence supports the presence of very early emotion recognition difficulties in mild cognitive impairment (MCI) however, the relationship between these impairments and psychosocial measures is not yet explored. Emotion recognition abilities of 27 patients with nonamnestic MCI (naMCI), 29 patients with amnestic MCI (aMCI), and 22 control participants were assessed. Self-report measures assessed patient functional disability, while informants rated the degree of burden they experienced. Difficulties in recognizing anger was evident in the amnestic subtype. Although both the patient groups reported greater social functioning disability, compared with the controls, a relationship between social dysfunction and anger recognition was evident only for patients with naMCI. A significant association was found between burden and anger recognition in patients with aMCI. Impaired emotion recognition abilities impact MCI subtypes differentially. Interventions targeted at patients with MCI, and caregivers are warranted.
Publisher: Elsevier BV
Date: 07-2002
DOI: 10.1016/S0006-3223(02)01312-4
Abstract: Our previous work on sulcal-gyral brain morphology in healthy volunteers revealed that males were characterized by greater cortical folding in the left versus right anterior cingulate cortex. Given the evidence showing an absence or reversal of normal anatomical asymmetries in patients with schizophrenia, the current study examined the anterior cingulate cortex sulcal-gyral patterns in patients with schizophrenia. Using high-resolution magnetic resonance imaging, we examined anterior cingulate cortex surface morphology in a group of 55 patients with established schizophrenia and 75 healthy controls. All subjects were male and right-handed. Depending on the presence of a paracingulate sulcus and its antero-posterior extent, three types of anterior cingulate cortex sulcal patterns were identified: "prominent," "present," and "absent." Measures of overall cerebral hemispheric folding were used as independent variables and as covariates to ascertain the specificity of the findings to the anterior cingulate cortex. Examination of anterior cingulate cortex morphology showed that, compared with controls, patients with schizophrenia lacked the leftward anterior cingulate cortex sulcal asymmetry, which was explained by reduced folding in the left anterior cingulate cortex. These differences were over and above differences in cortical folding across the entire left hemisphere. These findings suggest that, in male patients with schizophrenia, there is a disturbance in the neurodevelopment of the left anterior cingulate cortex, as well as a more general aberration of left hemisphere development.
Publisher: Public Library of Science (PLoS)
Date: 04-02-2014
Publisher: Cambridge University Press (CUP)
Date: 09-2018
DOI: 10.1017/S1355617718000541
Abstract: Objectives: The Addenbrooke’s Cognitive Examination (ACE) is a common cognitive screening test for dementia. Here, we examined the relationship between the most recent version (ACE-III) and its predecessor (ACE-R), determined ACE-III cutoff scores for the detection of dementia, and explored its relationship with functional ability. Methods: Study 1 included 199 dementia patients and 52 healthy controls who completed the ACE-III and ACE-R. ACE-III total and domain scores were regressed on their corresponding ACE-R values to obtain conversion formulae. Study 2 included 331 mixed dementia patients and 87 controls to establish the optimal ACE-III cutoff scores for the detection of dementia using receiver operator curve analysis. Study 3 included 194 dementia patients and their carers to investigate the relationship between ACE-III total score and functional ability. Results: Study 1: ACE-III and ACE-R scores differed by ≤1 point overall, the magnitude varying according to dementia type. Study 2: a new lower bound cutoff ACE-III score of 84/100 to detect dementia was identified (compared with 82 for the ACE-R). The upper bound cutoff score of 88/100 was retained. Study 3: ACE-III scores were significantly related to functional ability on the Clinical Dementia Rating Scale across all dementia syndromes, except for semantic dementia. Conclusions: This study represents one of the largest and most clinically erse investigations of the ACE-III. Our results demonstrate that the ACE-III is an acceptable alternative to the ACE-R. In addition, ACE-III performance has broader clinical implications in that it relates to carer reports of functional impairment in most common dementias. ( JINS , 2018, 24 , 854–863)
Publisher: American Psychological Association (APA)
Date: 05-2013
DOI: 10.1037/A0032321
Abstract: It has been proposed that only mild cognitive impairment (MCI) with high Aβ amyloid is indicative of incipient Alzheimer's disease (AD), yet MCI with low Aβ amyloid may reflect other neurodegenerative processes. We aimed to determine the extent to which high Aβ amyloid influenced cognitive function in healthy older adults and adults with MCI. Healthy controls (HC n = 178) and adults with MCI (n = 56) enrolled in the Australian Imaging, Biomarkers, and Lifestyle study, underwent positron emission tomography neuroimaging for Aβ amyloid and completed an extensive neuropsychological battery, assessing the cognitive domains of verbal and visual episodic memory, executive function, visuoconstruction, attention and processing speed, and language at baseline. MCI with low Aβ performed worse than MCI with high Aβ on measures of executive function, attention, visuoconstruction and language. No differences were observed between HC high and low Aβ groups. When compared with HC with low Aβ, both MCI high and low Aβ groups performed worse on measures of episodic memory. However, only the MCI low Aβ group performed worse than HC low Aβ on measures of executive function, attention, visuoconstruction, and language. When compared with HC with low Aβ amyloid, MCI with high Aβ amyloid present with impairments restricted to episodic memory, and the episodic memory impairments in MCI with low Aβ amyloid were accompanied by impairments in executive function, attention, visuoconstruction, and language, suggesting that MCI with high Aβ amyloid reflects prodromal AD, although further longitudinal data is required to confirm this.
Publisher: SERDI
Date: 2019
Abstract: BACKGROUND: The National Institute on Aging and Alzheimer’s Association (NIA-AA) have proposed a new Research Framework: Towards a biological definition of Alzheimer’s disease, which uses a three-biomarker construct: Aß-amyloid, tau and neurodegeneration AT(N), to generate a biomarker based definition of Alzheimer’s disease. OBJECTIVES: To stratify AIBL participants using the new NIA-AA Research Framework using cerebrospinal fluid (CSF) biomarkers. To evaluate the clinical and cognitive profiles of the different groups resultant from the AT(N) stratification. To compare the findings to those that result from stratification using two-biomarker construct criteria (AT and/or A(N)). DESIGN: In iduals were classified as being positive or negative for each of the A, T, and (N) categories and then assigned to the appropriate AT(N) combinatorial group: A-T-(N)- A+T-(N)- A+T+(N)- A+T-(N)+ A+T+(N)+ A-T+(N)- A-T-(N)+ A-T+(N)+. In line with the NIA-AA research framework, these eight AT(N) groups were then collapsed into four main groups of interest (normal AD biomarkers, AD pathologic change, AD and non-AD pathologic change) and the respective clinical and cognitive trajectories over 4.5 years for each group were assessed. In two sensitivity analyses the methods were replicated after assigning in iduals to four groups based on being positive or negative for AT biomarkers as well as A(N) biomarkers. SETTING: Two study centers in Melbourne (Victoria) and Perth (Western Australia), Australia recruited MCI in iduals and in iduals with AD from primary care physicians or tertiary memory disorder clinics. Cognitively healthy, elderly NCs were recruited through advertisement or via spouses of participants in the study. PARTICIPANTS: One-hundred and forty NC, 33 MCI participants, and 27 participants with AD from the AIBL study who had undergone CSF evaluation using Elecsys® assays. INTERVENTION (if any): Not applicable. MEASUREMENTS: Three CSF biomarkers, namely amyloid β1-42, phosphorylated tau181, and total tau, were measured to provide the AT(N) classifications. Clinical and cognitive trajectories were evaluated using the AIBL Preclinical Alzheimer Cognitive Composite (AIBL-PACC), a verbal episodic memory composite, an executive function composite, California Verbal Learning Test – Second Edition Long-Delay Free Recall, Mini-Mental State Examination, and Clinical Dementia Rating Sum of Boxes scores. RESULTS: Thirty-eight percent of the elderly NCs had no evidence of abnormal AD biomarkers, whereas 33% had biomarker levels consistent with AD or AD pathologic change, and 29% had evidence of non-AD biomarker change. Among NC participants, those with biomarker evidence of AD pathology tended to perform worse on cognitive outcome assessments than other biomarker groups. Approximately three in four participants with MCI or AD had biomarker levels consistent with the research framework’s definition of AD or AD pathologic change. For MCI participants, a decrease in AIBL-PACC scores was observed with increasing abnormal biomarkers and increased abnormal biomarkers were also associated with increased rates of decline across some cognitive measures. CONCLUSIONS: Increasing biomarker abnormality appears to be associated with worse cognitive trajectories. The implementation of biomarker classifications could help better characterize prognosis in clinical practice and identify those at-risk in iduals more likely to clinically progress, for their inclusion in future therapeutic trials.
Publisher: Frontiers Media SA
Date: 04-12-2018
Publisher: Elsevier BV
Date: 05-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2006
DOI: 10.1097/01.GME.0000227333.50867.4E
Abstract: To explore whether inhibition of the conversion of testosterone to estradiol modifies the effects of testosterone on cognition in 61 healthy, estrogen-treated postmenopausal women. Seventy-six postmenopausal women using transdermal estrogen for at least 8 weeks, with a serum total testosterone less than 1.2 nmol/L participated in a single-center, double-blind, randomized, placebo-controlled study. All participants received transdermal testosterone, 400 muL of a 0.5% testosterone gel, daily and were randomized to receive either letrozole 2.5 mg/day or an identical placebo tablet. The main outcome measure was cognition, evaluated using a comprehensive battery of standardized neuropsychological tests, at baseline and week 16. Thirty women in each group completed the study. Free testosterone increased from baseline in both groups, with no difference between groups. Free testosterone levels achieved were below the 90th centile for young women in 80% of the participants at week 16. Serum estradiol and sex hormone-binding globulin levels did not differ from baseline or between groups during the study. No clinically significant effects of testosterone treatment were seen for attention and working memory, psychomotor speed, or executive function. Significant improvements were seen for immediate and delayed visual and verbal memory and for simple concentration with testosterone therapy, all of which were unaffected by the aromatase inhibitor. We did not observe any effects of aromatase inhibition on cognition in healthy, estrogen-treated postmenopausal women treated with testosterone. This may be due to insufficient study power or a true lack of effect. However, our findings highlight that the detection of subtle changes in cognition in well women require the development of sensitive instruments and large randomized, controlled trials.
Publisher: Oxford University Press (OUP)
Date: 11-07-2016
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
Publisher: Springer Science and Business Media LLC
Date: 03-2017
Publisher: Elsevier BV
Date: 10-2020
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.
Publisher: Springer Science and Business Media LLC
Date: 06-09-2007
DOI: 10.1007/S11065-007-9032-Z
Abstract: We propose that the earliest neuropsychological detection of Alzheimer's disease (AD) can be informed by current views about the neuropathogenesis of AD and cognitive models of memory and its neurobiological substrates. The primary impairment in early AD is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. On theoretical and empirical grounds, paired associate learning (PAL) appears to be the ideal paradigm for detecting MTL dysfunction in early AD. It has not been embraced as a test of choice, however, and this critical review discusses why the paradigm may have not fulfilled its potential. We suggest that a new PAL variant, 'associate-recognition', may prove to be clinically efficacious.
Publisher: Informa UK Limited
Date: 29-09-2014
DOI: 10.1080/13554794.2014.960429
Abstract: The temporal scale of neuroplasticity following acute alterations in brain structure due to neurosurgical intervention is still under debate. We conducted a longitudinal study with the objective of investigating the postoperative changes in a patient who underwent cerebrovascular surgery and who subsequently lost proprioception in the fingers of her right hand. The results show increased activation in contralesional somatosensory areas, additional recruitment of premotor and posterior parietal areas, and changes in functional connectivity with left postcentral gyrus. These findings demonstrate long-term modifications of cortical organization and as such have important implications for treatment strategies for patients with brain injury.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
Publisher: American Psychological Association (APA)
Date: 11-2008
DOI: 10.1037/A0013357
Abstract: The current research uses a novel methodology to examine the role of semantics in reading aloud. Participants were trained to read aloud 2 sets of novel words (i.e., nonwords such as bink): some with meanings (semantic) and some without (nonsemantic). A comparison of reading aloud performance between these 2 sets of novel words was used to provide an indicator of the importance of semantic information in reading aloud. In Experiment 1, in contrast to expectations, reading aloud performance was not better for novel words in the semantic condition. In Experiment 2, the training of novel words was modified to reflect more realistic steps of lexical acquisition: Reading aloud performance became faster and more accurate for novel words in the semantic condition, but only for novel words with inconsistent pronunciations. This semantic advantage for inconsistent novel words was again observed when a subset of participants from Experiment 2 was retested 6-12 months later (in Experiment 3). These findings provide support for a limited but significant role for semantics in the reading aloud process.
Publisher: SAGE Publications
Date: 2022
DOI: 10.1177/20406223221085111
Abstract: High blood pressure in midlife is an established risk factor for cognitive decline and dementia but less is known about the impact of raised blood pressure on cognition in childhood and early adulthood. We systematically reviewed and quantified the existing evidence base relating to blood pressure in early life and subsequent cognitive performance. Medline, Embase, PsycINFOo, Scopus, and Web of Science were searched from inception to July 2020. We included longitudinal cohort and case–control studies involving participants aged 0–40 years with a baseline and at least one follow-up blood pressure assessment alongside at least one measure of cognition, occurring at the same time as, or subsequent to blood pressure measures. Risk of bias was assessed independently by two reviewers. PROSPERO registration CRD42020214655. Of a total of 5638 records identified, three cohort and two case–control studies were included with ages ranging from 3 to early 30s. Repeated blood pressure measurements averaged over 25 years or cumulative blood pressure in the 25–30 years prior to assessment of cognitive function were associated with poorer cognitive performance in the two largest cohort studies. The smallest cohort study reported no evidence of an association and the results from the two case–control studies were contradictory. All studies were at risk of bias. Overall, the evidence in this area is lacking and study quality is mixed. Our review highlights an urgent need for studies evaluating the potential for a relationship between raised blood pressure and poorer cognition in early life given the potential for possible risk reduction if such a relationship exists.
Publisher: Oxford University Press (OUP)
Date: 21-05-2013
DOI: 10.1093/BRAIN/AWT127
Abstract: In iduals who carry the apolipoprotein E ε4 polymorphism have an increased risk of late-onset Alzheimer's disease. However, because possession of the ε4 allele confers an increased risk for the diagnosis of dementia, it has proven problematic in older in iduals to dissociate the influence of ε4 on cognitive capacity per se as distinct from its influence on clinical diagnostic status. We report a statistical approach that attempts to partial out the influence of diagnostic group membership (Alzheimer's disease, mild cognitive impairment, healthy control) from the influence of apolipoprotein ε4 genetic status on cognitive functioning. The cognitive phenotype hypothesis predicts that ε4-positive in iduals will show cognitive deficits (relative to matched ε4-negative in iduals) independent of the development of Alzheimer's disease. By contrast, the prodromal reclinical Alzheimer's disease hypothesis proposes that the effect of apolipoprotein E status on cognitive performance is a function of the increased risk of dementia in in iduals with the ε4 allele. We evaluated these hypotheses in the Australian Imaging, Biomarkers and Lifestyle cohort (n = 1112). We first determined whether previously reported findings concerning ε4 status and age-related neuropsychological performance could be explained by the inadvertent recruitment of people with mild cognitive impairment into the healthy control group. We then tested each diagnostic group in isolation to identify any neuropsychological patterns that may be attributed to the ε4 allele. Finally, as interactions between the ε4 allele and age have previously been reported in cognitive functioning within healthy elderly populations, we attempted to determine whether the inclusion of mild cognitively impaired in iduals in the s le may drive this relationship. An extensive battery of standardized, well-validated neuropsychological tasks was administered to a final s le of 764 healthy control subjects, 131 in iduals with mild cognitive impairment and 168 in iduals with Alzheimer's disease. The effect of the ε4 allele on cognitive performance was assessed using a statistical mediation analysis and supplemented with Bayesian methods to address a number of the limitations associated with Fisherian/Neyman-Pearsonian significance testing. Our findings support the prodromal reclinical Alzheimer's disease hypothesis and do not support the concept of a distinctive ε4-related cognitive phenotype.
Publisher: Springer Science and Business Media LLC
Date: 13-01-2023
DOI: 10.1038/S41598-022-27190-Y
Abstract: Episodic memory deficits are a common consequence of aging and are associated with a number of neurodegenerative disorders (e.g., Alzheimer’s disease). Given the importance of episodic memory, a great deal of research has investigated how we can improve memory performance. Transcranial electrical stimulation (TES) represents a promising tool for memory enhancement but the optimal stimulation parameters that reliably boost memory are yet to be determined. In our double-blind, randomised, sham-controlled study, 42 healthy adults (36 females 23.3 ± 7.7 years of age) received anodal transcranial direct current stimulation (tDCS), theta transcranial alternating current stimulation (tACS) and sham stimulation during a list-learning task, over three separate sessions. Stimulation was applied over the left temporal lobe, as encoding and recall of information is typically associated with mesial temporal lobe structures (e.g., the hippoc us and entorhinal cortex). We measured word recall within each stimulation session, as well as the average number of intrusion and repetition errors. In terms of word recall, participants recalled fewer words during tDCS and tACS, compared to sham stimulation, and significantly fewer words recalled during tACS compared with tDCS. Significantly more memory errors were also made during tACS compared with sham stimulation. Overall, our findings suggest that TES has a deleterious effect on memory processes when applied to the left temporal lobe.
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2008.02.008
Abstract: Approximately 30% of healthy persons aged over 75 years show Abeta deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between Abeta burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and cognitive tests were performed on 34 elderly participants (age 73+/-6) from the longitudinal Melbourne Healthy Aging Study (MHAS). Subjects were classified as being cognitively 'stable' or 'declining' by an independent behavioural neurologist based on clinical assessment and serial word-list recall scores from the preceding 6-10 years. Decline was calculated from the slope of the word-list recall scores. Abeta burden was quantified using Standardized Uptake Value normalized to cerebellar cortex. Ten subjects were clinically classified as declining. At the time of the PET scans, three of the declining subjects had mild cognitive impairment, one had AD, and six were declining but remained within the normal range for age on cognitive tests. Declining subjects were much more likely to show cortical PiB binding than stable subjects (70% vs. 17%, respectively). Neocortical Abeta burden correlated with word-list recall slopes (r=-0.78) and memory function (r=-0.85) in the declining group. No correlations were observed in the stable group. Abeta burden correlated with incident memory impairment and the rate of memory decline in the non-demented ageing population. These observations suggest that neither memory decline nor Abeta deposition are part of normal ageing and likely represent preclinical AD. Further longitudinal observations are required to confirm this hypothesis.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000335009
Abstract: i Background: /i While dysfunction in emotion recognition is sometimes apparent with aging, and is frequently evident in Alzheimer’s disease, it is unclear whether in iduals who have a high risk of developing dementia exhibit demonstrable changes. i Method: /i A review of the literature pertaining to mild cognitive impairment was undertaken to discern the extent to which emotion recognition deficits are evident in this prodromal period. i Results: /i A search of Medline, Psycinfo and Psyextra databases using specific key words identified only six relevant studies. These studies suggest that the ability to accurately identify facial expressions of affect is compromised. i Conclusions: /i Research in this area is in its infancy. Suggestions are made for furthering our knowledge about this important ability which affects interpersonal relationships, daily functioning, mental well-being and quality of life.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2017
DOI: 10.1038/SREP44368
Abstract: Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer’s disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD in iduals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD in iduals with an AD-like pattern of brain atrophy. These in iduals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate in iduals for clinical trials.
Publisher: Elsevier BV
Date: 2021
Publisher: Informa UK Limited
Date: 15-10-2020
DOI: 10.1080/09658211.2019.1673428
Abstract: The current study examined the influence of collaboration, expertise, and communication on autobiographical memory, by considering gender differences in recall and how they may influence the products and processes of remembering when male-female couples recall events together. Thirty-nine long-married, male-female couples recalled their memories of their wedding day. In Session 1, they recalled it in idually for an experimenter. One week later, in Session 2, they recalled the same event jointly as a collaborative pair. Women reported more details, especially episodic details, than men across both sessions. Notably, collaborative recall included many new details that neither spouse had recalled in idually. Exploratory analyses suggest that women were less influenced by collaboration than were men: women's communication behaviours influenced men's recall, but the reverse was not found for men's communication. Additionally, when couples' in idual recall was more similar in content, men were more likely to decrease their contribution to the collaborative session. We consider these findings in light of transactive memory theory, in which joint meta-memory and the distribution of expertise influence the processes and products of recall in the interdependent system of a couple who extensively share their autobiographical memories.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.NEUROIMAGE.2013.01.001
Abstract: Neuroimaging studies have shown that the neural mechanisms of motor imagery (MI) overlap substantially with the mechanisms of motor execution (ME). Surprisingly, however, the role of several regions of the motor circuitry in MI remains controversial, a variability that may be due to differences in neuroimaging techniques, MI training, instruction types, or tasks used to evoke MI. The objectives of this study were twofold: (i) to design a novel task that reliably invokes MI, provides a reliable behavioral measure of MI performance, and is transferable across imaging modalities and (ii) to measure the common and differential activations for MI and ME with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). We present a task in which it is difficult to give accurate responses without the use of either motor execution or motor imagery. The behavioral results demonstrate that participants performed similarly on the task when they imagined vs. executed movements and this performance did not change over time. The fMRI results show a spatial overlap of MI and ME in a number of motor and premotor areas, sensory cortices, cerebellum, inferior frontal gyrus, and ventrolateral thalamus. MI uniquely engaged bilateral occipital areas, left parahippoc us, and other temporal and frontal areas, whereas ME yielded unique activity in motor and sensory areas, cerebellum, precuneus, and putamen. The MEG results show a robust event-related beta band desynchronization in the proximity of primary motor and premotor cortices during both ME and MI. Together, these results further elucidate the neural circuitry of MI and show that our task robustly and reliably invokes motor imagery, and thus may prove useful for interrogating the functional status of the motor circuitry in patients with motor disorders.
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.
Publisher: Elsevier BV
Date: 2002
DOI: 10.1016/S0028-3932(01)00092-6
Abstract: Medial temporal lobe (MTL) structures are implicated in forming conjunctions between events in order to form enduring relational memories these memories are not evident using direct measures with varieties of amnesic subjects. Extratemporal brain structures are thought to be responsible for preserved memories, which are sometimes detectable using indirect measures. The present study tests this theory of multiple memory systems by examining whether preserved learning can be demonstrated for relational material in MTL-disordered subjects using an indirect measure which minimises conscious mediation of performance. The subjects had undergone anterior temporal lobectomy for relief of temporal lobe epilepsy: left-sided (LATL) cases had a mild verbal amnesia and right-sided (RATL) cases had better verbal memory, forming a comparison group. A direct measure of verbal relational memory was provided by successive trials of cued recall in a specially-constructed paired associate learning task with arbitrarily paired words pairs consisted of either concrete or abstract words. LATL subjects performed worse than RATL subjects, and particularly so with abstract words. Following direct testing, memory for the pairings was measured indirectly using a masked recognition priming technique. RATL subjects showed savings in RT, demonstrating that masked priming can reveal evidence of the formation of conjunctions. Critically, LATL subjects showed no evidence of preserved learning with priming. Thus when MTL structures are damaged, relational memory appears to be affected without exception, consistent with the tenets of multiple memory systems theory.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2007
Publisher: American Psychological Association (APA)
Date: 09-2013
DOI: 10.1037/A0033077
Abstract: Emotion recognition is impaired in dementia and there is some initial evidence to suggest that milder deficits may be present in Mild Cognitive Impairment (MCI) patients, an "at risk" population for transition to dementia. In this study, we investigated the emotion recognition profile of MCI subgroups. Results show emotion recognition deficits exist for the amnestic subtype with impairment in multiple domains, with an emotion-specific deficit for anger recognition. Impaired emotion recognition in aMCI was independent of patient mood and cognitive deficits. The study is the first to examine the nonamnestic subtype. No emotion recognition deficits were found. This finding is surprising given the association between the nonamnestic subtype and frontal systems dysfunction. Impaired emotion recognition could be related to the selective pathophysiology in neural pathways, particularly the temporal lobe and connected limbic and prefrontal regions, implicated in both aMCI and emotion processing. These findings may have implications for early diagnosis, prognosis, and clinical management.
Publisher: Frontiers Media SA
Date: 04-2022
DOI: 10.3389/FPSYG.2022.854051
Abstract: People live and age together in social groups. Across a range of outcomes, research has identified interdependence in the cognitive and health trajectories of ageing couples. Various types of memory decline with age and people report using a range of internal and external, social, and material strategies to compensate for these declines. While memory compensation strategies have been widely studied, research so far has focused only on single in iduals. We examined interdependence in the memory compensation strategies reported by spouses within 58 older couples. Couples completed the Memory Compensation Questionnaire, as well as an open-ended interview about their memory compensation practices. We found that internal, intra-in idual memory compensation strategies were not associated within couples, but external, extra-in idual strategies showed interdependence. In iduals’ scores on material/technological compensation strategies were positively correlated with their partners’. Reported reliance on a spouse was higher for men and increased with age. Our open-ended interviews yielded rich insights into the complex and erse resources that couples use to support memory in day-to-day life. Particularly evident was the extent of interaction and coordination between social and material compensation, such that couples jointly used external compensation resources. Our results suggest that in iduals’ reports of their compensation strategies do not tell the whole story. Rather, we propose that older couples show interdependence in their memory compensation strategies, and adopt complex systems of integrated material and social memory compensation in their day-to-day lives.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-10-2012
Publisher: Wiley
Date: 07-2011
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.JOCN.2006.03.001
Abstract: We describe a 61-year-old woman who gradually developed deficits of balance, gait, and the ability to negotiate movement in space, together with an unusual pattern of cognitive deficits. A series of non-invasive investigations over three years including EEG, CT, MRI, PET and serial neuropsychological review had not provided a diagnosis. Significantly, the four neuropsychological assessments had revealed no progressive decline in cognition. Brain biopsy revealed an abundance of corpora amylacea, and a diagnosis of adult polyglucosan body disease (APBD) was made. This case contributes to the body of knowledge about the cognitive manifestations of this rare disease, and the stability of its functional impact over time.
Publisher: Oxford University Press (OUP)
Date: 2001
Abstract: The sulci and gyri found within the anterior cingulate (AC), and across the cerebrum generally, have been found to vary in location and complexity from one in idual to the next, making it difficult to analyze imaging data accurately and systematically. In this study, we examined the nature of morphometric variance in the AC of the left and right cerebral hemispheres using high-resolution structural magnetic resonance imaging (MRI) acquired from 176 healthy volunteers. Depending on the presence of a paracingulate sulcus (PCS) and its antero-posterior extent, three types of AC patterns were identified: 'prominent', 'present' and 'absent'. Hemispheric comparisons across the whole s le showed the PCS to be more commonly 'prominent' in the left hemisphere and more commonly 'absent' in the right hemisphere. There was a significant gender difference, such that males showed an asymmetric pattern characterized by increased fissurization of the left AC, while females showed greater symmetry, with less fissurization of the left AC. Overall cerebral morphology, namely hemispheric volume and hemispheric fissurization, were also measured and used as independent variables as well as covariates in the analyses in order to ascertain the specificity of the results regarding AC morphology. Results showed that cerebral volume for males was larger on the right than on the left while fissurization showed the reverse asymmetry of greater leftward fissurization. In contrast, females were symmetric in both respects. The findings regarding AC morphology could not be explained by differences in these overall cerebral measures or by differences in age and handedness within the population. The results suggest that in the normal male brain, there exist morphological asymmetries at both the global and local levels that are less apparent in the female brain. The findings have implications for future studies examining the organization, development and functional anatomy of the AC.
Publisher: SAGE Publications
Date: 2008
Publisher: Cambridge University Press (CUP)
Date: 22-05-2013
DOI: 10.1017/S1041610213000665
Abstract: The prognostic value of subjective memory complaints (SMCs) in the diagnosis of dementia of the Alzheimer's type is unclear. While some studies have found an association between SMCs and cognitive decline, many have found a stronger association with depression, which raises questions about their diagnostic utility. We examined the cross-sectional association between SMC severity (as measured using the MAC-Q, a brief SMC questionnaire) and affect, memory, and Alzheimer's disease (AD) biomarkers (β-amyloid deposition and the apolipoprotein E ε4 (APOEε4) allele) in healthy elderly controls (HC M = 78.74 years, SD = 6.7) and in iduals with mild cognitive impairment (MCI M = 72.74 years, SD = 8.8). We analyzed a subset of in iduals drawn from the Australian Imaging Biomarkers and Lifestyle (AIBL) Study of Aging. SMCs were more severe in MCI patients than in HCs. SMC severity was related to affective variables and the interaction between age and group membership (HC/MCI). Within the HC group, SMC severity was related to affective variables only, while severity correlated only with age in the MCI group. SMCs were not related to cognitive variables or AD biomarkers. SMCs were related to solely by poorer mood (greater depressive and anxious symptomatology) in the cognitively healthy elderly however mean levels were subclinical. This finding argues for the assessment of affective symptomatology in conjunction with cognitive assessment in elderly memory complainers. Future AIBL research will focus on assessing other AD biomarkers, such as brain atrophy and Aβ plasma markers, in relation to complaint severity. Once our 36-month follow-up data are collected, we propose to assess whether SMCs can predict future cognitive decline.
Publisher: Frontiers Media SA
Date: 27-08-2019
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.NEUROBIOLAGING.2018.12.014
Abstract: The longevity gene Klotho (KL), specifically the functional KL-VS variant, has previously been associated with cognition and rates of cognitive decline. This study aimed to determine whether KL-VS associations with cognition were observable in preclinical Alzheimer's disease (AD). The study also aimed to determine whether there was a combined influence of KL-VS, neocortical amyloid-β (Aβ) burden, and carriage of the apolipoprotein E (APOE) ε4 allele on cognitive decline. This study involved 581 Aβ-imaged, cognitively normal older adults, enrolled in the Australian Imaging, Biomarkers and Lifestyle Study of Aging. Linear mixed effects models revealed no significant associations between KL-VS and cognitive decline independently or in combination with Aβ burden and APOE ε4 genotype. Overall, previous associations reported between KL-VS and cognitive decline are not observed at the preclinical stages of AD. Furthermore, the results do not support the hypothesis that KL-VS has a modifying effect on Aβ burden and APOE ε4-driven cognitive decline in preclinical AD.
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.
Publisher: Informa UK Limited
Date: 07-1990
Publisher: SAGE Publications
Date: 03-2011
DOI: 10.3109/00048674.2010.547456
Abstract: Objective: Verbal episodic memory deficits are prominent in schizophrenia and have also been found in first episode psychosis (FEP) and in iduals at clinical risk of the disorder. The central role of the hippoc us in verbal memory processing and the consistent findings of hippoc al volume reductions in chronic patients have prompted the suggestion that impaired verbal memory performance may be a biomarker of schizophrenia. However, it is currently unclear as to when, during the early phase of psychosis, verbal memory performance becomes significantly impaired. The current study investigated verbal relational memory in FEP using a novel verbal paired associate task, and tested whether performance was dependent on phase of illness within FEP, where patients with a diagnosis of schizophrenia were considered to be in a more advanced stage than those with schizophreniform disorder. Method: Forty-seven currently psychotic FEP patients and 36 healthy non-psychiatric controls, aged 15–25 years old, completed a test comprising four trials of learning and cued recall of word pairs (denoted AB pairs), an interference phase comprising two trials with new second words (AC pairs), and finally cued recall for the original AB pairings. Results: FEP patients performed similarly to controls on the relational memory task. There was no difference in performance between FEP patients who had a diagnosis of schizophrenia and those with a diagnosis of schizophreniform disorder. Conclusions: Verbal relational memory appears to be intact in FEP. This finding, along with chronic patient literature, suggests that decline in hippoc al and medial temporal lobe functioning occurs during later illness stages. Further research is needed to aid in the development of intervention strategies that may prevent decline in such cognitive domains at this crucial early stage of the illness.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2018
DOI: 10.1007/S11065-018-9368-6
Abstract: Displacement of the cerebellar tonsils in Chiari type I malformation (CMI) can affect functions controlled by the cerebellum and brainstem. While playing an integral role in the control of movement, the cerebellum also has widespread cortical connections, influencing a range of cognitive process. A systematic literature review was conducted to examine the relationship between cognition and CMI, assessing evidence for general or domain-specific cognitive change. The search protocol examined the AMED, CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and Scopus databases. Articles meeting the following criteria were included in this review (i) examined children or adults with a clinically defined diagnosis of CMI, (ii) assessed cognitive function with a prospective examination, (iii) included at least one standardized instrument designed to measure general or specific domains of cognitive function, and (iv) were published in English in a peer-reviewed journal. Twelve articles were identified, including 783 cases aged 3 months to 64 years. General cognition, processing speed, and learning and memory appeared less affected, while language deficits appeared to diminish with age. Executive dysfunction was the most commonly reported cognitive impairment, while attention and working memory, and visuospatial and perceptual skills also appeared vulnerable. Numerous methodological limitations were identified that should be considered in interpreting the impact of CMI and planning future investigations. Overall, there is currently insufficient evidence to describe a valid and reliable profile of cognitive impairment in CMI. Further research is required to confirm these preliminary psychometric results and integrate them with pathophysiological models.
Start Date: 04-2011
End Date: 12-2018
Amount: $21,000,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2013
End Date: 12-2016
Amount: $297,759.00
Funder: Australian Research Council
View Funded Activity