ORCID Profile
0000-0001-7328-9624
Current Organisations
Murdoch University
,
Edith Cowan University
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Publisher: Informa UK Limited
Date: 12-2013
DOI: 10.3109/09540261.2013.870136
Abstract: The Australian Imaging Biomarkers and Lifestyle (AIBL) study is a longitudinal study of 1,112 volunteers from healthy, mild cognitive impairment (MCI) and Alzheimer's disease (AD) populations who are assessed at 18-month intervals in order to enable prospective research into ageing and AD. Using a multidisciplinary battery, AIBL assessments comprise the extensive study of clinical factors and cognitive function, collection of blood and cerebrospinal fluid (CSF) s les for biomarker discovery, structural and β-amyloid (Aβ) neuroimaging, and obtaining information on diet and physical activity patterns of the cohort. Now in its seventh year, AIBL is part of a substantial international effort to prospectively study the relationships between clinical characteristics and putative AD biomarkers in groups who carry different risk factors for AD. The identification of biomarkers would provide a window of opportunity to assess AD risk in in iduals prior to the onset of advanced clinical symptoms, in addition to facilitating testing of therapeutic and lifestyle interventions likely to emerge within the next decade that prevent or delay symptom emergence in those at high risk for developing AD. In this paper, we present key findings from the AIBL study and discuss how they contribute to our understanding of AD pathogenesis and diagnosis.
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: 2017
DOI: 10.1016/J.BPSC.2016.08.006
Abstract: Hypothalamic-pituitary-adrenal axis dysregulation, which is typically assessed by measuring cortisol levels, is associated with cognitive dysfunction, hippoc al atrophy, and increased risk for mild cognitive impairment and Alzheimer's disease (AD). However, little is known about the role of hypothalamic-pituitary-adrenal axis dysregulation in moderating the effect of high levels of amyloid-β (Aβ+) on cognitive decline in the preclinical phase of AD, which is often protracted, and thus offers opportunities for prevention and early intervention. Using data from a 6-year multicenter prospective cohort study, we evaluated the relation between Aβ level, plasma cortisol level, and cognitive decline in 416 cognitively normal older adults. Results revealed that Aβ+ older adults experienced faster decline than Aβ- older adults in all cognitive domains (Cohen's d at 6-year assessment = 0.37-0.65). They further indicated a significant interaction between Aβ and cortisol levels for global cognition (d = 0.32), episodic memory (d = 0.50), and executive function (d = 0.59) scores, with Aβ+ older adults with high cortisol levels having significantly faster decline in these domains compared with Aβ+ older adults with low cortisol levels. These effects were independent of age, sex, APOE genotype, anxiety symptoms, and radiotracer type. In cognitively healthy older adults, Aβ+ is associated with greater cognitive decline and high plasma cortisol levels may accelerate the effect of Aβ+ on decline in global cognition, episodic memory, and executive function. These results suggest that therapies targeted toward lowering plasma cortisol and Aβ levels may be helpful in mitigating cognitive decline in the preclinical phase of 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: Oxford University Press (OUP)
Date: 10-2019
Abstract: To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition. Participants were classified as SuperAgers based on episodic memory performance consistent with younger adults aged 30–44 and no impairment on non-memory tests (n = 179), and were matched with CNFA on age, sex, education, and follow-up time (n = 179). Subdistribution hazard models examined risk of clinical progression to MCI/dementia. Linear mixed models assessed the effect of Aβ on cognition over time. Prevalence of Aβ+ and APOE ε4 was equivalent between SuperAgers and CNFA. SuperAgers had 69%–73% reduced risk of clinical progression to MCI/dementia compared to CNFA (HR: 0.27–0.31, 95% CI: 0.11–0.73, p & .001). Aβ+ was associated with cognitive decline in verbal memory and executive function, regardless of SuperAger/CNFA classification. In the absence of Aβ+, equivalent age-related changes in cognition were observed between SuperAgers and CNFA. SuperAgers displayed resilience against clinical progression to MCI/dementia compared to CNFA despite equivalent risk for Alzheimer’s disease (AD) however, SuperAgers had no greater protection from Aβ+ than CNFA. The deleterious effects of Aβ on cognition persist regardless of baseline cognitive ability. Thus, superior cognitive performance does not reflect resistance against the neuropathological processes associated with AD, and the observed resilience for SuperAgers may instead reflect neuropsychological criteria for cognitive impairment.
Publisher: Oxford University Press (OUP)
Date: 05-2016
DOI: 10.5665/SLEEP.5756
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2016
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: Wiley
Date: 19-10-2017
Publisher: Bentham Science Publishers Ltd.
Date: 17-03-2015
DOI: 10.2174/1567205012666150302154650
Abstract: Previous studies have suggested that mild cognitive impairment (MCI) may be reflective of the early stages of neurodegenerative disorders such as Alzheimer's disease (AD). The hypothesis was that cytokeratin (CK) 14 expression can be used as a biomarker in isolated buccal mucosa to identify in iduals with MCI or AD from the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging. Visual assessment of buccal cell CK14 expression was carried out using immunofluorescence techniques. The frequency of basal buccal cells expressing CK14 was significantly lower in the MCI (P=0.0002) and AD (P<0.05) groups compared with the control group. Receiver-operating characteristic (ROC) curves were carried out for CK14 expression and yielded an area under the curve (AUC) of 0.899 for the MCI (P<0.0001) group and 0.772 for the AD (P=0.004) group. When the CK14 expression data were combined with plasma homocysteine concentration, the AUC was further improved to 0.932 and 0.788 for the MCI (P=0.0001) and AD (P=0.004) groups, respectively. APOE ε4 carriers in the control group had 21% lower CK14 expression compared with control non APOE ε4 carriers, however this difference was not statistically significant. The changes in the buccal cell CK14 expression observed in this pilot study could prove useful as a potential biomarker in identifying in iduals with an increased risk of developing MCI and eventually AD. These promising results need to be replicated in a larger subset of the AIBL cohort and in cohorts of other neurodegenerative disorders to determine changes specific to AD.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.NEUROBIOLAGING.2018.06.005
Abstract: Cognitive decline is considered an inevitable consequence of aging however, estimates of cognitive aging may be influenced negatively by undetected preclinical Alzheimer's disease (AD). This study aimed to determine the extent to which estimates of cognitive aging were biased by preclinical AD. Cognitively normal older adults (n = 494) with amyloid-β status determined from positron emission tomography neuroimaging underwent serial neuropsychological assessment at 18-month intervals over 72 months. Estimates of the effects of age on verbal memory, working memory, executive function, and processing speed were derived using linear mixed models. The presence of preclinical AD and clinical progression to mild cognitive impairment or dementia during the study were then added to these models as covariates. Initially, age was associated with decline across all 4 cognitive domains. With the effects of elevated amyloid-β and clinical progression controlled, age was no longer associated with decline in verbal or working memory. However, the magnitude of decline was reduced only slightly for executive function and was unchanged for processing speed. Thus, considered together, the results of the study indicate that undetected preclinical AD negatively biases estimates of age-related cognitive decline for verbal and working memory.
Publisher: American Psychological Association (APA)
Date: 10-2021
DOI: 10.1037/NEU0000746
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-09-2014
Publisher: Wiley
Date: 22-12-2015
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: Springer Science and Business Media LLC
Date: 09-2016
DOI: 10.1007/S12031-016-0822-8
Abstract: In a group of older adults with very mild dementia, we aimed to characterize the nature and magnitude of cognitive decline as measured by the Cogstate Brief Battery, in relation to Aβ levels and hippoc al volume. Participants were characterized according to their status on the Clinical Dementia Rating (CDR) scale. A total of 308 in iduals who were CDR 0 and had low cerebral Aβ levels (Aβ-), 32 in iduals who were Aβ- and CDR 0.5, and 43 in iduals who were Aβ+ and CDR 0.5 were included in this study. Participants completed the CogState brief battery at baseline, and at 18-, 36-, 54- and 72-month follow-up. Linear mixed model analyses indicated that relative to the Aβ- CDR 0 group, the Aβ+ CDR 0.5 group showed increased rates of memory decline and hippoc al volume loss. However, compared to the Aβ- CDR 0 group, the Aβ- CDR 0.5 group showed no changes in cognitive function or hippoc al volume over 72 months. The results of this study confirm that in in iduals with very mild dementia, who also have biomarker confirmation of Aβ+, changes in cognitive function manifest primarily as deterioration in memory processing, and this is associated with hippoc al volume loss. Conversely, the absence of any cognitive decline or loss in hippoc al volume in in iduals with very mild dementia but who are Aβ- suggests that some other non-AD disease process may underlie any static impairment in cognitive function.
Publisher: Wiley
Date: 05-2010
DOI: 10.1111/J.1471-4159.2010.06634.X
Abstract: The alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) subunit GluR2, which regulates excitotoxicity and the inflammatory cytokine tumour necrosis factor alpha (TNFalpha) have both been implicated in motor neurone vulnerability in amyotrophic lateral sclerosis/motor neurone disease. TNFalpha has been reported to increase cell surface expression of AMPAR subunits to increase synaptic strength and enhance excitotoxicity, but whether this mechanism occurs in motor neurones is unknown. We used primary cultures of mouse motor neurones and cortical neurones to examine the interaction between TNFalpha receptor activation, GluR2 availability, AMPAR-mediated calcium entry and susceptibility to excitotoxicity. Short exposure to a physiologically relevant concentration of TNFalpha (10 ng/mL, 15 min) caused a marked redistribution of both GluR1 and GluR2 to the cell surface as determined by cell surface biotinylation and immunofluorescence. Using fura-2-acetoxymethyl ester microfluorimetry, we showed that exposure to TNFalpha caused a rapid reduction in the peak litude of AMPA-mediated calcium entry in a PI3-kinase and p38 kinase-dependent manner, consistent with increased insertion of GluR2-containing AMPAR into the plasma membrane. This resulted in a protection of motor neurones against kainate-induced cell death. Our data therefore, suggest that TNFalpha acts primarily as a physiological regulator of synaptic activity in motor neurones rather than a pathological drive in amyotrophic lateral sclerosis.
Publisher: Oxford University Press (OUP)
Date: 11-07-2016
Publisher: Elsevier BV
Date: 10-2017
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
Publisher: Cambridge University Press (CUP)
Date: 19-07-2017
DOI: 10.1017/S1041610217001284
Abstract: The brain-derived neurotrophic factor ( BDNF ) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippoc al volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months. Non-demented older adults ( n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood s les were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+. At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF. While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
Publisher: Cambridge University Press (CUP)
Date: 02-10-2019
DOI: 10.1017/S1041610218001072
Abstract: This study investigated the characteristics of subjective memory complaints (SMCs) and their association with current and future cognitive functions. A cohort of 209 community-dwelling in iduals without dementia aged 47–90 years old was recruited for this 3-year study. Participants underwent neuropsychological and clinical assessments annually. Participants were ided into SMCs and non-memory complainers (NMCs) using a single question at baseline and a memory complaints questionnaire following baseline, to evaluate differential patterns of complaints. In addition, comprehensive assessment of memory complaints was undertaken to evaluate whether severity and consistency of complaints differentially predicted cognitive function. SMC and NMC in iduals were significantly different on various features of SMCs. Greater overall severity (but not consistency) of complaints was significantly associated with current and future cognitive functioning. SMC in iduals present distinctive features of memory complaints as compared to NMCs. Further, the severity of complaints was a significant predictor of future cognition. However, SMC did not significantly predict change over time in this s le. These findings warrant further research into the specific features of SMCs that may portend subsequent neuropathological and cognitive changes when screening in iduals at increased future risk of dementia.
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: 06-2008
DOI: 10.1016/J.NEULET.2008.04.056
Abstract: Dietary flavonoids, including the citrus flavanone hesperetin, may have stimulatory effects on cytoprotective intracellular signalling pathways. In primary mouse cortical neurone cultures, but not SH-SY5Y human neuroblastoma cells or human primary dermal fibroblasts (Promocells), hesperetin (100-300nM, 15min) caused significant increases in the level of ERK1/2 phosphorylation, but did not increase CREB phosphorylation. Administration of hesperetin for 18h did not alter gene expression driven by the cyclic AMP response element (CRE), assessed using a luciferase reporter system, but 300nM hesperetin partially reversed staurosporine-induced cell death in primary neurones. Our data show that hesperetin is a neuroprotective compound at concentrations where antioxidant effects are unlikely to predominate. The effects of hesperetin are cell-type dependent and, unlike the flavanol (-)epicatechin, neuroprotection in vitro is not associated with enhanced CREB phosphorylation or CRE-mediated gene expression.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-03-2016
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: Elsevier BV
Date: 03-2018
Publisher: Cambridge University Press (CUP)
Date: 18-09-2015
DOI: 10.1017/S0007114515003335
Abstract: FFQ are commonly used to examine the association between diet and disease. They are the most practical method for usual dietary data collection as they are relatively inexpensive and easy to administer. In Australia, the Cancer Council of Victoria FFQ (CCVFFQ) version 2 and the online Commonwealth Scientific and Industrial Research Organisation FFQ (CSIROFFQ) are used. The aim of our study was to establish the level of agreement between nutrient intakes captured using the online CSIROFFQ and the paper-based CCVFFQ. The CCVFFQ and the online CSIROFFQ were completed by 136 healthy participants. FFQ responses were analysed to give g per d intake of a range of nutrients. Agreement between twenty-six nutrient intakes common to both FFQ was measured by a variety of methods. Nutrient intake levels that were significantly correlated between the two FFQ were carbohydrates, total fat, Na and MUFA. When assessing ranking of nutrients into quintiles, on average, 56 % of the participants (for all nutrients) were classified into the same or adjacent quintiles in both FFQ, with the highest percentage agreement for sugar. On average, 21 % of participants were grossly misclassified by three or four quintiles, with the highest percentage misclassification for fibre and Fe. Quintile agreement was similar to that reported by other studies, and we concluded that both FFQ are suitable tools for iding participants’ nutrient intake levels into high- and low-consumption groups. Use of either FFQ was not appropriate for obtaining accurate estimates of absolute nutrient intakes.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2017
DOI: 10.1038/S41598-017-09577-4
Abstract: Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstrates that the induction of T2D/insulin resistance (IR) can promote the accumulation of Alzheimer’s disease (AD) pathological features. However, the association of T2D with pathological and clinical phenotypes in humans is unclear. Here we investigate the relationship of indices of IR (HOMA-IR) and pancreatic β-cell function (HOMA-B) with cognitive performance across several domains (Verbal/Visual Episodic Memory, Executive Function, Language and a measure of Global cognition) and AD biomarkers (CSF Aβ42, T-tau/P-tau, hippoc al volume and neocortical Aβ-amyloid burden). We reveal that HOMA-IR (p 0.001) incrementally increases across diagnostic groups, becoming significantly elevated in the AD group compared with cognitively normal (CN) adults. In CN adults, higher HOMA-IR was associated with poorer performance on measures of verbal episodic memory (p = 0.010), executive function (p = 0.046) and global cognition (p = 0.007), as well as with higher CSF T-tau (p = 0.008) and P-tau (p = 0.014) levels. No association was observed with CSF Aβ or imaging modalities. Together our data suggest that IR may contribute to reduced cognitive performance and the accumulation of CSF tau biomarkers in cognitively normal adults.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
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: Elsevier BV
Date: 09-2018
Publisher: Public Library of Science (PLoS)
Date: 02-10-2015
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: Wiley
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 26-02-2013
DOI: 10.1038/TP.2012.150
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: Springer Science and Business Media LLC
Date: 20-11-2012
DOI: 10.1038/TP.2012.118
Publisher: Elsevier BV
Date: 08-2023
Publisher: Springer Science and Business Media LLC
Date: 29-07-2014
DOI: 10.1038/MP.2014.79
Abstract: The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. In idual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each in idual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.JAD.2017.12.101
Abstract: Relationships between depression and Alzheimer's disease (AD) may become clearer if studied in preclinical AD where dementia is not present. The aim of this study was to evaluate prospectively, relationships between brain amyloid-β (Aβ), depressive symptoms and screen positive depression in cognitively normal (CN) older adults. Depressive symptoms were measured with the Geriatric Depression Inventory (GDS-15) in CN adults from the Australian Imaging Biomarkers and Lifestyle (AIBL) study without depression at baseline and classified as having abnormally high (Aβ+ n = 136) or low (Aβ- n = 449) Aβ according to positron emission tomography at 18-month intervals over 72 months. Incident cases of screen positive depression were not increased in Aβ+ CN adults although small increases in overall depressive symptoms severity (d = - 0.25 95% CI, - 0.45, - 0.05) and apathy-anxiety symptoms (d = - 0.28 95% CI - 0.48, - 0.08) were. As the AIBL s le is an experimental s le, no in iduals had severe medical illnesses or significant psychiatric disorders. Additionally, in iduals who had evidence of screen-positive depression at screening were excluded from enrolment in the AIBL study. Thus, the current data can be considered only as providing a foundation for understanding relationships between Aβ and depression in preclinical AD. These results suggest that the presence of a depressive disorder or even increased depressive symptoms are themselves unlikely to be a direct consequence of increasing Aβ. New depressive disorders presenting in CN older adults could therefore be investigated for aetiologies beyond AD.
Publisher: Wiley
Date: 14-03-2013
DOI: 10.1016/J.JALZ.2012.12.006
Abstract: A practical biomarker is required to facilitate the preclinical diagnosis of Alzheimer's disease (AD). Plasma amyloid beta (Aβ)1-40, Aβ1-42, Aβn-40, and Aβn-42 peptides were measured at baseline and after 18 months in 771 participants from the Australian Imaging Biomarkers and Lifestyle (AIBL) study of aging. Aβ peptide levels were compared with clinical pathology, neuroimaging and neuropsychological measurements. Although inflammatory and renal function covariates influenced plasma Aβ levels significantly, a decrease in Aβ1-42/Aβ1-40 was observed in patients with AD, and was also inversely correlated with neocortical amyloid burden. During the 18 months, plasma Aβ1-42 decreased in subjects with mild cognitive impairment (MCI) and in those transitioning from healthy to MCI. Our findings are consistent with a number of published plasma Aβ studies and, although the prognostic value of in idual measures in any given subject is limited, the diagnostic contribution of plasma Aβ may demonstrate utility when combined with a panel of peripheral biomarkers.
Publisher: Wiley
Date: 11-05-2017
Publisher: Springer Science and Business Media LLC
Date: 05-07-2018
DOI: 10.1007/S13668-018-0229-Y
Abstract: The purposes of this review were to examine literature published over the last 5 years and to evaluate the role of nutrition in cognitive function and brain ageing, focussing on the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. Results suggest that higher adherence to a healthy dietary pattern is associated with preservation of brain structure and function as well as slower cognitive decline, with the MIND diet substantially slowing cognitive decline, over and above the MeDi and DASH diets. Whilst results to-date suggest adherence to a healthy diet, such as the MeDi, DASH, or MIND, is an important modifiable risk factor in the quest to develop strategies aimed at increasing likelihood of healthy brain ageing, further work is required to develop dietary guidelines with the greatest potential benefit for public health a research topic of increasing importance as the world's population ages.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.JNEUROIM.2014.05.005
Abstract: Inflammation is a hallmark of Alzheimer's disease (AD). Whether directly involved in the pathogenesis, or a downstream consequence of neuronal death, the blood neutrophil-lymphocyte ratio (NLR) is reported to be a putative, non-invasive peripheral biomarker for AD. The aim of this study was to re-evaluate the diagnostic utility of longitudinal measures of the NLR. The NLR was stable across all time-points and weakly correlated with neocortical amyloid burden (R=0.21 at baseline, 0.27 at 18 months, 0.20 at 36 months and 0.10 at 54 months). Cross-sectionally, the NLR was significantly elevated in AD participants as compared to HC participants at baseline (p<0.0001), 18 months (p 0.05 at all time-points except for 18 months p 0.05) adjusted for age, sex and APOEε4 allele status. Comparing the NLR between cognitive transition groups over time (transition towards an AD type dementia), there was no significant difference in the NLR levels between those participants, who did not transition and those participants who did transition, or those in the stable AD group after adjusting for age, sex and APOEε4 allele status (p>0.05). Despite inflammation being a hallmark in AD and previous reports showing that the NLR can discriminate HC from AD patients, our results suggest that the sensitivity of the NLR itself is not robust enough for diagnostic utility. We identified significant relationships cross sectionally (p 0.5). The NLR also had limited association with cognitive decline, although in our cohort, the number of participants transitioning was relatively small. In conclusion, the NLR may reflect AD-related inflammatory processes in the periphery, but age and sex are dominant covariates which need to be controlled for in population-based screening.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2018
DOI: 10.1038/S41398-018-0293-5
Abstract: Accumulating research has linked Mediterranean diet (MeDi) adherence with slower cognitive decline and reduced Alzheimer’s disease (AD) risk. However, no study to-date has examined the relationship between MeDi adherence and accumulation of cerebral Aβ-amyloid (Aβ a pathological hallmark of AD) in older adults. Cognitively normal healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing completed the Cancer Council of Victoria Food Frequency Questionnaire at baseline, which was used to construct a MeDi score for each participant (score range 0–9 higher score indicating higher adherence). Cerebral Aβ load was quantified by Pittsburgh Compound B positron emission tomography at baseline, 18 and 36 months: Only in iduals categorised as “Aβ accumulators”, and thus considered to be on the AD pathway, were included in the analysis ( N = 77). The relationship between MeDi adherence, MeDi components, and change in cerebral Aβ load (baseline to 36 months) was evaluated using Generalised Linear Modelling, accounting for age, gender, education, Apolipoprotein E ε4 allele status, body mass index and total energy intake. Higher MeDi score was associated with less Aβ accumulation in our cohort (β = −0.01 ± 0.004, p = 0.0070). Of the in idual MeDi score components, a high intake of fruit was associated with less accumulation of Aβ (β = −0.04 ± 0.01, p = 0.00036). Our results suggest MeDi adherence is associated with reduced cerebral AD pathology accumulation over time. When our results are considered collectively with previous data linking the MeDi to slower cognitive decline, it is apparent that MeDi adherence warrants further investigation in the quest to delay AD onset.
Publisher: Informa UK Limited
Date: 2012
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.BBR.2019.01.013
Abstract: Higher cardiorespiratory fitness has been associated with better cognitive function in older adults yet, this relationship demonstrates a degree of variability across the older adult population. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health. One such genetic factor is the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, which has previously been shown to moderate the relationship between self-reported physical activity and memory performance. In this study we aim to investigate the interaction between BDNF Val66Met polymorphism and objectively-measured cardiorespiratory fitness on performance on tasks assessing verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60-80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. Higher-fit in iduals performed better on a task assessing visuospatial memory, compared with lower-fit in iduals. Furthermore, an interaction between BDNF Val66Met and fitness was observed in terms of visuospatial memory performance on a continuous paired associate learning task whereby lower-fit Met carriers performed 1 standard deviation worse than higher-fit Met carriers. No differences were observed between the higher-fit and lower-fit Val/Val homozygotes. Future intervention studies should evaluate the effect of structured exercise on cognitive health between BDNF Val66Met carriers and Val/Val homozygotes.
Publisher: American Medical Association (AMA)
Date: 04-2018
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.JSAMS.2019.06.013
Abstract: High-intensity exercise is a potential therapeutic tool to postpone or prevent the onset of cognitive decline. However, there is a lack of sufficient evidence regarding the longitudinal effects of structured resistance training on cognitive function in healthy adults. The purpose of this study was to investigate the effect of two ecologically valid, intense 12-week resistance training programs on cognitive function in late middle-aged adults. Single-site parallel randomised controlled trial at the Department of Exercise Science strength and conditioning laboratory. Groups allocated by minimisation randomisation. Forty-five healthy adults (age range=41-69 years) were enrolled and randomised into (A) high-load, long rest resistance training (n=14), or (B) moderate-load, short rest resistance training (n=15) twice per week for 12 weeks, or a non-exercising control (n=16). Follow-up within seven days. Data were collected September 2016-December 2017. Cognitive function assessed using the CogState computerised battery. Assessors were blinded to participant group allocation. Secondary outcomes were maximal muscle strength and body composition. Forty-four participants were analysed in 2018. Delayed verbal memory performance was improved (p=0.02) in resistance training groups (g=0.67-0.79) when compared to the control group, with no differences between training groups. Likewise, increases in maximal muscle strength were observed (p<0.01) in resistance training groups when compared to the control group, with no differences between training groups. No differences in body composition were observed. There were no adverse events or side-effects of the intervention. 12 weeks of intense resistance training improves delayed verbal memory irrespective of training design (i.e., high-load vs. moderate-load). This study is registered at www.anzctr.org.au ACTRN12616000690459.
Publisher: Frontiers Media SA
Date: 18-02-2015
Publisher: Springer Science and Business Media LLC
Date: 26-02-2018
DOI: 10.1038/S41398-018-0094-X
Abstract: The glymphatic system is postulated to be a mechanism of brain Aβ-amyloid clearance and to be most effective during sleep. Ablation of the astrocytic end-feet expressed water-channel protein, Aquaporin-4, in mice, results in impairment of this clearance mechanism and increased brain Aβ-amyloid deposition, suggesting that Aquaporin-4 plays a pivotal role in glymphatic function. Currently there is a paucity of literature regarding the impact of AQP4 genetic variation on sleep, brain Aβ-amyloid burden and their relationship to each other in humans. To address this a cross-sectional observational study was undertaken in cognitively normal older adults from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Genetic variants in AQP4 were investigated with respect to self-reported Pittsburgh Sleep Quality Index sleep parameters, positron emission tomography derived brain Aβ-amyloid burden and whether these genetic variants moderated the sleep-Aβ-amyloid burden relationship. One AQP4 variant, rs72878776, was associated with poorer overall sleep quality, while several SNPs moderated the effect of sleep latency (rs491148, rs9951307, rs7135406, rs3875089, rs151246) and duration (rs72878776, rs491148 and rs2339214) on brain Aβ-amyloid burden. This study suggests that AQP4 genetic variation moderates the relationship between sleep and brain Aβ-amyloid burden, which adds weight to the proposed glymphatic system being a potential Aβ-amyloid clearance mechanism and suggests that AQP4 genetic variation may impair this function. Further, AQP4 genetic variation should be considered when interpreting sleep-Aβ relationships.
Publisher: Cold Spring Harbor Laboratory
Date: 06-09-2018
DOI: 10.1101/408955
Abstract: Higher cardiorespiratory fitness has been associated with enhanced cognitive function in older adults yet, this relationship demonstrates a degree of variability. Thus, it is hypothesised that variation in genetic factors may influence the relationship between fitness and cognitive health. In this study we evaluate whether the BDNF Val66Met polymorphism moderates the relationship between cardiorespiratory fitness and verbal and visuospatial memory. Data from ninety-nine cognitively normal men and women aged 60 – 80 years were used. Fitness was assessed by peak oxygen consumption, and verbal and visuospatial memory were evaluated using well-validated measures. Participants were categorised into: lower-fit Met carriers, higher-fit Met carriers, lower-fit Val/Val, or higher-fit Val/Val. A significant interaction was observed between BDNF Val66Met and fitness on visuospatial memory performance whereby lower-fit Met carriers performed 1SD lower than higher-fit Met carriers ( p =0.04). We observed higher levels of fitness mitigated the deleterious effect of BDNF Met allele carriage on visuospatial memory. Future intervention studies should evaluate the effect of structured exercise on cognitive health between BDNF Val66Met carriers and Val/Val homozygotes.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Springer Science and Business Media LLC
Date: 02-10-2012
DOI: 10.1038/TP.2012.91
Publisher: Springer Science and Business Media LLC
Date: 20-02-2015
Publisher: American Chemical Society (ACS)
Date: 16-02-2018
DOI: 10.1021/ACS.JPROTEOME.7B00788
Abstract: Over the last two decades, EDTA-plasma has been used as the preferred s le matrix for human blood proteomic profiling. Serum has also been employed widely. Only a few studies have assessed the difference and relevance of the proteome profiles obtained from plasma s les, such as EDTA-plasma or lithium-heparin-plasma, and serum. A more complete evaluation of the use of EDTA-plasma, heparin-plasma, and serum would greatly expand the comprehensiveness of shotgun proteomics of blood s les. In this study, we evaluated the use of heparin-plasma with respect to EDTA-plasma and serum to profile blood proteomes using a scalable automated proteomic pipeline (ASAP
Publisher: Informa UK Limited
Date: 15-05-2017
DOI: 10.1080/00207454.2016.1182527
Abstract: Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062 p < .05 and F = 3.2670 p < .05, respectively). Our cross-sectional findings suggest that the positive effect of HDL-C on verbal memory may be present much earlier than previously reported and provide further support for the role of HDL-C in healthy brain ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.
Publisher: MyJove Corporation
Date: 18-11-2012
DOI: 10.3791/4196
Publisher: Springer Science and Business Media LLC
Date: 14-08-2013
DOI: 10.1038/MP.2012.107
Abstract: Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-β (Aβ) and Aβ brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aβ and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ε4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aβ levels were measured in fasting blood s les. A subgroup (n=116) underwent (11)C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aβ1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aβ from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aβ1-42/1-40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.
Publisher: Springer Science and Business Media LLC
Date: 08-2019
DOI: 10.1007/S00421-019-04202-W
Abstract: There is growing evidence for a preventative effect of resistance training on cognitive decline through physiological mechanisms yet, the effect of resistance training on resting growth factors and homocysteine levels is incompletely understood. This study aimed to investigate the effect of intense resistance training, for 12 weeks, on changes in peripheral growth factors and homocysteine in late middle-aged adults. 45 healthy adults were enrolled into the single-site parallel groups' randomized-controlled trial conducted at the Department of Exercise Science, Strength and Conditioning Laboratory, Murdoch University. Participants were allocated to the following conditions: (1) high-load resistance training (n = 14), or (2) moderate-load resistance training (n = 15) twice per week for 12 weeks or (3) non-exercising control group (n = 16). Data were collected from September 2016 to December 2017. Fasted blood s les were collected at baseline and within 7 days of trial completion for the analysis of resting serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1, vascular endothelial growth factor, and plasma homocysteine levels. No differences in baseline to post-intervention change in serum growth factors or plasma homocysteine levels were observed between groups. A medium effect was calculated for BDNF change within the high-load condition alone (+ 12.9%, g = 0.54). High-load or moderate-load resistance training twice per week for 12 weeks has no effect on peripheral growth factors or homocysteine in healthy late middle-aged adults. Australian New Zealand Clinical Trials Registry: ACTRN12616000690459.
Publisher: Elsevier BV
Date: 10-2018
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: 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: Cambridge University Press (CUP)
Date: 22-04-2016
DOI: 10.1017/S0007114516001203
Abstract: Curcumin therapy in animals has produced positive cognitive and behavioural outcomes results of human trials, however, have been inconsistent. In this study, we report the results of a 12-month, randomised, placebo-controlled, double-blind study that investigated the ability of a curcumin formulation to prevent cognitive decline in a population of community-dwelling older adults. In iduals ( n 96) ingested either placebo or 1500 mg/d Biocurcumax TM for 12 months. A battery of clinical and cognitive measures was administered at baseline and at the 6-month and 12-month follow-up assessments. A significant time×treatment group interaction was observed for the Montreal Cognitive Assessment (repeated-measures analysis time×treatment F =3·85, P ·05). Subsequent analysis revealed that this association was driven by a decline in function of the placebo group at 6 months that was not observed in the curcumin treatment group. No differences were observed between the groups for all other clinical and cognitive measures. Our findings suggest that further longitudinal assessment is required to investigate changes in cognitive outcome measures, ideally in conjunction with biological markers of neurodegeneration.
Publisher: Wiley
Date: 2017
Publisher: Human Kinetics
Date: 10-2019
Abstract: Objectives : To examine the associations between physical activity duration and intensity, cardiorespiratory fitness, and executive function in older adults. Methods : Data from 99 cognitively normal adults (age = 69.10 ± 5.1 years n = 54 females) were used in the current study. Physical activity (intensity and duration) was measured with the International Physical Activity Questionnaire, and fitness was measured by analysis of maximal aerobic capacity, VO 2 peak. Executive function was measured comprehensively, including measures of Shifting, Updating, Inhibition, Generativity, and Nonverbal Reasoning. Results : Higher levels of cardiorespiratory fitness were associated with better performance on Generativity ( B = .55 95% confidence interval [.15, .97]). No significant associations were found between self-reported physical activity intensity/duration and executive functions. Discussion : To our knowledge, this study is the first to identify an association between fitness and Generativity. Associations between physical activity duration and intensity and executive function requires further study, using objective physical activity measures and longitudinal observations.
Publisher: Wiley
Date: 12-08-2019
Publisher: Informa UK Limited
Date: 30-08-2019
DOI: 10.1080/13825585.2018.1513449
Abstract: The high prevalence of sleep disruption among older adults may have implications for cognitive aging, particularly for higher-order aspects of cognition. One domain where sleep disruption may contribute to age-related deficits is prospective memory-the ability to remember to perform deferred actions at the appropriate time in the future. Community-dwelling older adults (55-93 years, N = 133) undertook assessment of sleep using actigraphy and participated in a laboratory-based prospective memory task. After controlling for education, sleep disruption (longer awakenings) was associated with poorer prospective memory. Additionally, longer awakenings mediated the relationship between older age and poorer prospective memory. Other metrics of sleep disruption, including sleep efficiency and wake after sleep onset, were not related to prospective memory, suggesting that examining the features of in idual wake episodes rather than total wake time may help clarify relationships between sleep and cognition. The mediating role of awakening length was partially a function of greater depression and poorer executive function (shifting) but not retrospective memory. This study is among the first to examine the association between objectively measured sleep and prospective memory in older adults. Furthermore, this study is novel in suggesting sleep disruption might contribute to age-related prospective memory deficits perhaps, with implications for cognitive aging more broadly. Our results suggest that there may be opportunities to prevent prospective memory decline by treating sleep problems.
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/7935406
Abstract: Cortical cholinergic deficiency is prominent in Alzheimer’s disease (AD), and published findings of diminished pupil flash response in AD suggest that this deficiency may extend to the visual cortical areas and anterior eye. Pupillometry is a low-cost, noninvasive technique that may be useful for monitoring cholinergic deficits which generally lead to memory and cognitive disorders. The aim of the study was to evaluate pupillometry for early detection of AD by comparing the pupil flash response (PFR) in AD ( N = 14 ) and cognitively normal healthy control (HC, N = 115 ) participants, with the HC group stratified according to high ( N = 38 ) and low ( N = 77 ) neocortical amyloid burden (NAB). Constriction phase PFR parameters were significantly reduced in AD compared to HC (maximum acceleration p 0.05 , maximum velocity p 0.0005 , average velocity p 0.005 , and constriction litude p 0.00005 ). The high-NAB HC subgroup had reduced PFR response cross-sectionally, and also a greater decline longitudinally, compared to the low-NAB subgroup, suggesting changes to pupil response in preclinical AD. The results suggest that PFR changes may occur in the preclinical phase of AD. Hence, pupillometry has a potential as an adjunct for noninvasive, cost-effective screening for preclinical AD.
Publisher: Oxford University Press (OUP)
Date: 08-12-2017
Abstract: The extent to which increasing age is associated with impairment in cognitive function, termed cognitive aging, may have been overestimated in prior studies. The inclusion of in iduals with severe or uncontrolled systemic medical illness or prodromal neurodegenerative disease in normal aging s les is likely to bias estimates toward lower cognitive performance and inflate estimates of variability. Unbiased estimates of cognitive aging in 658 adults aged 60-84, who underwent rigorous screening to ensure their general and cognitive health, were computed. The first study screened the psychometric properties of a battery of neuropsychological tests in order to identify those with optimal properties to evaluate cognitive aging. The second study used the selected tests to compare baseline performance within 5-year age bands from 60 to 84. The first study identified a battery of 12 tests that provided reliable measures of memory, psychomotor speed, attention, and executive function and were appropriate for investigating age-related cognitive changes. The second study observed moderate to large age-related impairment for performance on tests of complex psychomotor function, category fluency, verbal learning, and verbal and visual memory. No, or only small, age effects were observed for working memory, phonemic fluency, learning of visual information, and reaction time. These data suggested that while increasing age is associated with impairment in cognitive function, this impairment is less severe and is evident only on more complex neuropsychological tests than estimated previously in s les selected using less rigorous criteria to ensure cognitive health.
Publisher: Human Kinetics
Date: 08-2020
Abstract: The purpose of this investigation was to assess the acute changes in growth factors associated with cognitive health following two ecologically valid, intense resistance exercise sessions. Twenty-nine late-middle-aged adults performed one session of either (a) moderate-load resistance exercise or (b) high-load resistance exercise. Venous blood was collected prior to warm-up, immediately following exercise and 30 min following exercise. Serum was analyzed for brain-derived neurotrophic factor, insulin-like growth factor 1, and vascular endothelial growth factor. Session intensity was determined by blood lactate concentration and session rating of perceived exertion. Postexercise blood lactate was greater following moderate-load when compared with high-load resistance exercise. Subjective session intensity was rated higher by the session rating of perceived exertion following moderate-load when compared with high-load resistance exercise. No differences were observed in serum growth factor levels between groups. Ecologically valid and intense moderate-load or high-load exercise methods do not alter serum growth factor levels in late-middle-aged adults.
Publisher: Cambridge University Press (CUP)
Date: 14-12-2016
DOI: 10.1017/S0007114515004687
Abstract: Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer’s disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (A β ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in A β metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that A β metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence A β metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin’s relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 04-2016
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JAGP.2016.08.007
Abstract: To examine how β-amyloid (Aβ), APOE and BDNF genotypes, and cortisol relate to depressive and anxiety symptoms in cognitively normal older women and men. Cross-sectional data were analyzed from 423 older adults from the Australian Imaging Biomarkers and Lifestyle study. Analyses of covariance evaluated associations between Aβ, APOE and BDNF genotype, and cortisol in relation to severity of depressive and anxiety symptoms. Among Aβ+ older adults, APOE ε4 carriage was associated with greater severity of anxiety symptoms (d = 0.55) and in the full s le, APOE ε4 carriage was linked to greater severity of depressive (d = 0.26) and anxiety (d = 0.21) symptoms. Among Aβ+ women, ε4 carriers reported greater anxiety symptoms than non-ε4 carriers (d = 0.83), and female BDNF rs6265 Val66 Met allele carriers reported greater depressive symptoms (d = 0.29). Sex moderated the relationship between Aβ, APOE genotype, and BDNF genotype in predicting severity of anxiety and depressive symptoms in cognitively normal older adults.
Publisher: Springer Science and Business Media LLC
Date: 19-11-2015
DOI: 10.1186/S13195-015-0157-7
Abstract: Cerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer’s disease (AD), are known to be sensitive to variation based on pre-analytical s le processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility. Standardized lumbar puncture using small calibre atraumatic spinal needles and CSF collection using gravity fed collection followed by syringe aspirated extraction was performed in a s le of elderly in iduals participating in a large long-term observational research trial. Analyte assay concentrations were compared. For the 44 total paired s les of gravity collection and aspiration, reproducibility was high for biomarker CSF analyte assay concentrations (concordance correlation [95%CI]: beta-amyloid1-42 (Aβ42) 0.83 [0.71 - 0.90]), t-tau 0.99 [0.98 - 0.99], and phosphorylated tau (p-tau) 0.82 [95 % CI 0.71 - 0.89]) and Bonferroni corrected paired s le t-tests showed no significant differences (group means (SD): Aβ42 366.5 (86.8) vs 354.3 (82.6), p = 0.10 t-tau 83.9 (46.6) vs 84.7 (47.4) p = 0.49 p-tau 43.5 (22.8) vs 40.0 (17.7), p = 0.05). The mean duration of collection was 10.9 minutes for gravity collection and minute for aspiration. Our results demonstrate that aspiration of CSF is comparable to gravity droplet collection for AD biomarker analyses but could considerably accelerate throughput and improve the procedural tolerability for assessment of CSF biomarkers.
Publisher: MDPI AG
Date: 06-08-2020
DOI: 10.3390/LIFE10080141
Abstract: In response to double-stranded breaks (DSBs) in chromosomal DNA, H2AX (a member of histone H2A family) becomes phosphorylated to form γH2AX. Although increased levels of γH2AX have been reported in the neuronal nuclei of Alzheimer’s disease (AD) patients, the understanding of γH2AX responses in buccal nuclei of in iduals with mild cognitive impairment (MCI) and AD remain unexplored. In the current study, endogenous γH2AX was measured in buccal cell nuclei from MCI (n = 18) or AD (n = 16) patients and in healthy controls (n = 17) using laser scanning cytometry (LSC). The γH2AX level was significantly elevated in nuclei of the AD group compared to the MCI and control group, and there was a concomitant increase in P-trend for γH2AX from the control group through MCI to the AD group. Receiver-operating characteristic curves were carried out for different γH2AX parameters γH2AX in nuclei resulted in the greatest area under the curve value of 0.7794 (p = 0.0062) with 75% sensitivity and 70% specificity for the identification of AD patients from control. In addition, nuclear circularity (a measure of irregular nuclear shape) was significantly higher in the buccal cell nuclei from the AD group compared with the MCI and control groups. Additionally, there was a positive correlation between the nuclear circularity and γH2AX signals. The results indicated that increased DNA damage is associated with AD.
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: Elsevier BV
Date: 11-2021
Publisher: Wiley
Date: 24-08-2022
DOI: 10.1111/JNC.15681
Abstract: Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) in stable healthy control (HC), healthy controls who will convert to MCI/AD (HC-Conv) and AD patients (AD). Compared to HC we observed an increased cholesterol/ApoA-I ratio in AD and HC-Conv, as well as an increased ApoD/ApoA-I ratio and a decreased ApoA-II/ApoA-I ratio in AD. Higher cholesterol/ApoA-I ratio was also associated with lower cortical grey matter volume and higher ventricular volume, while higher ApoA-II/ApoA-I and ApoJ/ApoA-I ratios were associated with greater cortical grey matter volume (and for ApoA-II also with greater hippoc al volume) and smaller ventricular volume. Additionally, in a clinical status-independent manner, the ApoE/ApoA-I ratio was significantly lower in APOE ε4 carriers and lowest in APOE ε4 homozygous. Together, these data indicate that in AD patients the composition of HDL is altered, which may affect HDL functionality, and such changes are associated with altered regional brain volumetric data.
Publisher: Cambridge University Press (CUP)
Date: 10-04-2015
DOI: 10.1017/S0007114515000926
Abstract: Alzheimer's disease (AD), the most common form of dementia, is a chronic, progressive neurodegenerative disease that manifests clinically as a slow global decline in cognitive function, including deterioration of memory, reasoning, abstraction, language and emotional stability, culminating in a patient with end-stage disease, totally dependent on custodial care. With a global ageing population, it is predicted that there will be a marked increase in the number of people diagnosed with AD in the coming decades, making this a significant challenge to socio-economic policy and aged care. Global estimates put a direct cost for treating and caring for people with dementia at $US604 billion, an estimate that is expected to increase markedly. According to recent global statistics, there are 35·6 million dementia sufferers, the number of which is predicted to double every 20 years, unless strategies are implemented to reduce this burden. Currently, there is no cure for AD while current therapies may temporarily ameliorate symptoms, death usually occurs approximately 8 years after diagnosis. A greater understanding of AD pathophysiology is paramount, and attention is now being directed to the discovery of biomarkers that may not only facilitate pre-symptomatic diagnosis, but also provide an insight into aberrant biochemical pathways that may reveal potential therapeutic targets, including nutritional ones. AD pathogenesis develops over many years before clinical symptoms appear, providing the opportunity to develop therapy that could slow or stop disease progression well before any clinical manifestation develops.
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: Springer Science and Business Media LLC
Date: 31-03-2020
DOI: 10.1186/S13195-020-00595-5
Abstract: β-amyloid (Aβ) positron emission tomography (PET) imaging is currently the only Food and Drug Administration-approved method to support clinical diagnosis of Alzheimer’s disease (AD). However, numerous research studies support the use of cerebrospinal fluid (CSF) biomarkers, as a cost-efficient, quick and equally valid method to define AD pathology. Using automated Elecsys® assays (Roche Diagnostics) for Aβ (1–42) (Aβ42), Aβ (1–40) (Aβ40), total tau (tTau) and phosphorylated tau (181P) (pTau), we examined CSF s les from 202 participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing cohort, to demonstrate the concordance with pathological AD via PET imaging. Ratios Aβ42/Aβ40, tTau/Aβ42 and pTau/Aβ42 had higher receiver operator characteristic—area under the curve (all 0.94), and greater concordance with Aβ-PET (overall percentage agreement ~ 90%), compared with in idual biomarkers. Strong concordance between CSF biomarkers and Aβ-PET status was observed overall, including for cognitively normal participants, further strengthening the association between these markers of AD neuropathological burden for both developmental research studies and for use in clinical trials.
Publisher: Wiley
Date: 25-04-2017
DOI: 10.1002/GPS.4489
Abstract: Several studies have reported that non-demented older adults with clinical depression show changes in amyloid-β (Aβ) levels in blood, cerebrospinal fluid and on neuroimaging that are consistent with those observed in patients with Alzheimer's disease. These findings suggest that Aβ may be one of the mechanisms underlying the relation between the two conditions. We sought to determine the relation between elevated cerebral Aβ and the presence of depression across a 54-month prospective observation period. Cognitively normal older adults from the Australian Imaging Biomarkers and Lifestyle study who were not depressed and had undergone a positron emission tomography scan to classify them as either high Aβ (n = 81) or low Aβ (n = 278) participated. Depressive symptoms were assessed using the Geriatric Depression Scale - Short Form at 18-month intervals over 54 months. Whilst there was no difference in probable depression between groups at baseline, incidence was 4.5 (95% confidence interval [CI] 1.3-16.4) times greater within the high Aβ group (9%) than the low Aβ group (2%) by the 54-month assessment. Results of this study suggest that elevated Aβ levels are associated with a 4.5-fold increased likelihood of developing clinically significant depressive symptoms on follow-up in preclinical Alzheimer's disease. This underscores the importance of assessing, monitoring and treating depressive symptoms in older adults with elevated Aβ. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ARR.2019.01.003
Abstract: Several prospective cohort studies have reported an association between higher levels of physical activity and decreased risk of cognitive decline and dementia, years later. To support physical activity as a preventative measure against dementia, including Alzheimer's disease (AD the most common form of dementia), evidence regarding the underlying mechanisms is vital. Here, we review previous work examining the role of physical activity in modulating levels of AD pathological hallmarks, beta-amyloid (Aβ) and tau (in the brain, cerebrospinal fluid and blood). Robust evidence from transgenic animal studies suggests that physical activity (voluntary wheel running) and exercise (forced wheel running) are implicated in lowering levels of brain Aβ and tau. Nevertheless, evidence from human studies, utilising measurements from positron emission tomography and cerebrospinal fluid biomarkers, is less consistent. Rigorous randomised controlled trials utilising long exercise interventions are vital to further understand the relationship between physical activity and Alzheimer's disease.
Publisher: Springer Science and Business Media LLC
Date: 31-03-2015
DOI: 10.1038/TP.2015.39
Abstract: In idual biological differences may contribute to the variability of outcomes, including cognitive effects, observed following electroconvulsive treatment (ECT). A narrative review of the research literature on carriage of the apolipoprotein E ɛ4 allele ( APOE-ɛ4 ) and the protein biomarker beta amyloid (Aβ) with ECT cognitive outcome was undertaken. ECT induces repeated brain seizures and there is debate as to whether this causes brain injury and long-term cognitive disruption. The majority of ECT is administered to the elderly (over age 65 years) with drug-resistant depression. Depression in the elderly may be a symptom of the prodromal stage of Alzheimer’s disease (AD). Carriage of the APOE-ɛ4 allele and raised cerebral Aβ are consistently implicated in AD, but inconsistently implicated in brain injury (and related syndromes) recovery rates. A paucity of brain-related recovery, genetic and biomarker research in ECT responses in the elderly was found: three studies have examined the effect of APOE-ɛ4 allele carriage on cognition in the depressed elderly receiving ECT, and two have examined Aβ changes after ECT, with contradictory findings. Cognitive changes in all studies of ECT effects were measured by a variety of psychological tests, making comparisons of such changes between studies problematic. Further, psychological test data-validity measures were not routinely administered, counter to current testing recommendations. The methodological issues of the currently available literature as well as the need for well-designed, hypothesis driven, longitudinal studies are discussed.
Publisher: Wiley
Date: 18-08-2017
DOI: 10.1016/J.JALZ.2016.06.2364
Abstract: "Walkable" neighborhoods offer older adults opportunities for activities that may benefit cognition-related biological mechanisms. These have not previously been examined in this context. We objectively assessed neighborhood walkability for participants (n = 146) from the Australian Imaging, Biomarkers and Lifestyle study with apolipoprotein E (APOE) genotype and two 18-month-apart brain volumetric and/or amyloid β burden assessments. Linear mixed models estimated associations of neighborhood walkability with levels and changes in brain imaging outcomes, the moderating effect of APOE ε4 status, and the extent to which associations were explained by physical activity. Cross-sectionally, neighborhood walkability was predictive of better neuroimaging outcomes except for left hippoc al volume. These associations were to a small extent explained by physical activity. APOE ε4 carriers showed slower worsening of outcomes if living in walkable neighborhoods. These findings indicate associations between neighborhood walkability and brain imaging measures (especially in APOE ε4 carriers) minimally attributable to physical activity.
Publisher: Wiley
Date: 24-07-2018
DOI: 10.1002/GPS.4761
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.NEUBIOREV.2016.01.004
Abstract: Traumatic brain injury (TBI) increases the risk of neurodegenerative disorders many years post-injury. However, molecular mechanisms underlying the relationship between TBI and neurodegenerative diseases, such as Alzheimer's disease (AD), remain to be elucidated. Nevertheless, previous studies have demonstrated a link between TBI and increased amyloid-β (Aβ), a protein involved in AD pathogenesis. Here, we review animal studies that measured Aβ levels following TBI. In addition, from a pool of initially identified 1209 published papers, we examined data from 19 eligible animal model studies using a meta-analytic approach. We found an acute increase in cerebral Aβ levels ranging from 24h to one month following TBI (overall log OR=2.97 ± 0.40, p<0.001). These findings may contribute to further understanding the relationship between TBI and future dementia risk. The methodological inconsistencies of the studies discussed in this review suggest the need for improved and more standardised data collection and study design, in order to properly elucidate the role of TBI in the expression and accumulation of Aβ.
Publisher: Wiley
Date: 26-12-2013
DOI: 10.1016/J.JALZ.2012.10.006
Abstract: Alzheimer's disease (AD) is an epidemic facing the entire world. Increased knowledge gained during the past 25 years indicates that AD falls along a clinical and neuropathological spectrum represented as a continuum that extends from preclinical disease in which there are no symptoms, through early symptomatic phases, and finally to AD dementia. The Alzheimer's research community recognizes that imaging, body fluids, and cognitive biomarkers contribute to enhanced diagnostic confidence for AD. There has also been emerging consensus regarding the use of AD biomarkers in clinical trials. The use of biomarkers in clinical trials and practice is h ered by the lack of standardization. In response to the emerging need for standardization, an international meeting of AD researchers was held in Melbourne, Australia, in March 2012 to bring together key researchers, clinicians, industry, and regulatory stakeholders with the aim of generating consensus on standardization and validation of cognitive, imaging, and fluid biomarkers, as well as lifestyle parameters used in research centers worldwide.
No related grants have been discovered for Stephanie Rainey-Smith.