ORCID Profile
0000-0001-7927-2540
Current Organisations
Murdoch University
,
University of Western Australia
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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: Oxford University Press (OUP)
Date: 05-2016
DOI: 10.5665/SLEEP.5756
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2016
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.NEUROBIOLAGING.2014.04.033
Abstract: (11)C-Pittsburgh compound B (PiB) is a positron emission tomography (PET) tracer designed to bind to amyloid-β (Aβ) plaques, one of the hallmarks of Alzheimer's disease (AD). The potential of PiB as an early marker of AD led to the increasing use of PiB in clinical research studies and development of several F-18-labeled Aβ radiotracers. Automatic quantification of PiB images requires an accurate parcellation of the brain's gray matter (GM). Typically, this relies on a coregistered magnetic resonance imaging (MRI) to extract the cerebellar GM, compute the standardized uptake value ratio (SUVR), and provide parcellation and segmentation for quantification of regional and global SUVR. However, not all subjects can undergo MRI, in which case, an MR-less method is desirable. In this study, we assess 3 PET-only quantification methods: a mean atlas, an adaptive atlas, and a multi-atlas approaches on a database of 237 subjects having been imaged with both PiB PET and MRI. The PET-only methods were compared against MR-based SUVR quantification and evaluated in terms of correlation, average error, and performance in classifying subjects with low and high Aβ deposition. The mean atlas method suffered from a significant bias between the estimated neocortical SUVR and the PiB status, resulting in an overall error of 5.6% (R(2) = 0.98), compared with the adaptive and multi-atlas approaches that had errors of 3.06% and 2.74%, respectively (R(2) = 0.98), and no significant bias. In classifying PiB-negative from PiB-positive subjects, the mean atlas had 10 misclassified subjects compared with 0 for the adaptive and 1 for the multi-atlas approach. Overall, the adaptive and the multi-atlas approaches performed similarly well against the MR-based quantification and would be a suitable replacements for PiB quantification when no MRI is available.
Publisher: Wiley
Date: 19-10-2017
Publisher: Bentham Science Publishers Ltd.
Date: 24-02-2015
DOI: 10.2174/1567205012666150204125732
Abstract: This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer's disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small s le size in both studies. The current study examines APPr in MC versus NC in a larger s le. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study. APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson's correlation coefficient (r). APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505 p<0.05) and Precuneus (r=-0.510 p<0.05). APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2013
DOI: 10.1038/MP.2012.162
Abstract: Western countries are experiencing aging populations and increased longevity thus, the incidence of dementia and Alzheimer's disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes.
Publisher: AMPCo
Date: 14-03-2021
DOI: 10.5694/MJA2.50972
Publisher: Elsevier BV
Date: 08-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-09-2014
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: 05-2021
Publisher: Wiley
Date: 07-2019
Publisher: Elsevier BV
Date: 04-2013
Publisher: Elsevier BV
Date: 10-2017
Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
Publisher: Springer Science and Business Media LLC
Date: 22-09-2020
DOI: 10.1186/S13195-020-00681-8
Abstract: Electrophysiological studies show that reductions in power within the alpha band are associated with the Alzheimer’s disease (AD) continuum. Physical activity (PA) is a protective factor that has proved to reduce AD risk and pathological brain burden. Previous research has confirmed that exercise increases power in the alpha range. However, little is known regarding whether other non-modifiable risk factors for AD, such as increased age or APOE ε4 carriage, alter the association between PA and power in the alpha band. The relationship between PA and alpha band power was examined in a s le of 113 healthy adults using magnetoencephalography. Additionally, we explored whether ε4 carriage and age modulate this association. The correlations between alpha power and gray matter volumes and cognition were also investigated. We detected a parieto-occipital cluster in which PA positively correlated with alpha power. The association between PA and alpha power remained following stratification of the cohort by genotype. Younger and older adults were investigated separately, and only younger adults exhibited a positive relationship between PA and alpha power. Interestingly, when four groups were created based on age (younger-older adult) and APOE (E3/E3-E3/E4), only younger E3/E3 (least predicted risk) and older E3/E4 (greatest predicted risk) had associations between greater alpha power and higher PA. Among older E3/E4, greater alpha power in these regions was associated with improved memory and preserved brain structure. PA could protect against the slowing of brain activity that characterizes the AD continuum, where it is of benefit for all in iduals, especially E3/E4 older adults.
Publisher: Elsevier BV
Date: 07-2021
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: Informa UK Limited
Date: 12-2018
DOI: 10.1111/AP.12372
Publisher: Wiley
Date: 07-2019
Publisher: Springer Science and Business Media LLC
Date: 21-04-2022
DOI: 10.1007/S11357-022-00558-8
Abstract: The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippoc al volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippoc al volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippoc al volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive in iduals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippoc al volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes.
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: 07-2018
Publisher: Frontiers Media SA
Date: 28-03-2022
DOI: 10.3389/FNAGI.2022.771214
Abstract: Previous studies have indicated that physical activity may be beneficial in reducing the risk for Alzheimer's disease (AD), although the underlying mechanisms are not fully understood. The goal of this study was to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers (i.e., measured using a novel high-performance mass spectrometry-based assay), in apolipoprotein E (APOE) ε4 carriers and noncarriers. We evaluated 143 cognitively normal older adults, all of whom had brain amyloid deposition assessed using positron emission tomography and had their physical activity levels measured using the International Physical Activity Questionnaire (IPAQ). We observed an inverse correlation between brain amyloidosis and plasma beta-amyloid (Aβ) 1−42 but found no association between brain amyloid and plasma Aβ 1−40 and amyloid precursor protein (APP) 669−711 . Additionally, higher levels of physical activity were associated with lower plasma Aβ 1−40 , Aβ 1−42 , and APP 669−711 levels in APOE ε4 noncarriers. The ratios of Aβ 1−40 /Aβ 1−42 and APP 669−711 /Aβ 1−42 , which have been associated with higher brain amyloidosis in previous studies, differed between APOE ε4 carriers and non-carriers. Taken together, these data indicate a complex relationship between physical activity and brain amyloid deposition and potential blood-based AD biomarkers in cognitively normal older adults. In addition, the role of APOE ε4 is still unclear, and more studies are necessary to bring further clarification.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2012
DOI: 10.1038/TP.2012.118
Publisher: Wiley
Date: 11-05-2017
Publisher: S. Karger AG
Date: 29-09-2023
DOI: 10.1159/000526297
Abstract: b i Introduction: /i /b Evidence suggests that maintaining a higher level of cardiorespiratory fitness (CRF) later in life can offer some protection against brain volume loss as we age. By contrast, mild traumatic brain injury (mTBI) could accelerate age-related cortical atrophy. The current study sought to examine whether variations in the CRF level modified the association between mTBI history and brain volumetric measures in a s le of older adults. b i Methods: /i /b Seventy-nine community-dwelling older adults (mean age 68.7 ± 4.3 years, 54.4% female) were assessed for their mTBI history: 25 participants (32%) reported sustaining at least one lifetime mTBI. Participants also underwent a CRF assessment and magnetic resonance imaging (MRI) to obtain global and region-of-interest volumes. b i Results: /i /b Analysis of covariance, controlling for age, sex, education, and apolipoprotein i (APOE) /i ε4 allele carriage, revealed that participants with a history of mTBI had a significantly larger total mean grey matter volume (582.21 ± 12.46 cm sup /sup ) in comparison to participants with no mTBI history (571.08 ± 17.21 cm sup /sup , i = /i 0.01 after correction for multiple comparisons). However, no differences between groups based on mTBI history were found for total white matter volume or in any other cortical or subcortical structures examined. A subsequent moderation analysis found that CRF was predominantly non-influential on the association between mTBI history and the MRI-quantified measures of brain volume. b i Conclusion: /i /b While unexpected, the findings suggest that a history of mTBI can lead to grey matter alterations in the ageing brain. However, concurrent variations in the CRF level did not influence the differences in brain volume found based on mTBI exposure status.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2020
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: 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: 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: 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: 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: Elsevier BV
Date: 02-2021
Publisher: Cambridge University Press (CUP)
Date: 22-09-2022
DOI: 10.1017/S1355617721001132
Abstract: Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity VO 2peak ) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults. Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention. The intervention was found to increase fitness in the exercise groups, as compared with the control group ( F = 9.88, p = .001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe ( β = 0.29, p = 0.036, r = 0.27), right supplementary motor area ( β = 0.30, p = 0.031, r = 0.29), and both right ( β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus ( β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups. At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in in idual cardiorespiratory fitness was positively associated with frontal GM volume in our s le of older adults. These results provide evidence of in idual variability in exercise-induced fitness on brain structure.
Publisher: Research Square Platform LLC
Date: 23-09-2020
DOI: 10.21203/RS.3.RS-78125/V1
Abstract: BACKGROUND: Physical inactivity has been consistently linked to increased risk of cognitive decline however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. In addition, we investigated in idual variability in exercise response by examining effects of relevant genetic factors and changes in cardiorespiratory fitness on cognitive change. METHODS: This multi-arm randomised clinical trial investigated the effects of 6-months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12-months post-intervention. Ninety-nine cognitively normal men and women (aged 60 – 80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e., high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. Apolipoprotein e4 genotype and brain-derived neurotrophic factor Val66Met carriage were identified. RESULTS: There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. We observed an association between changes in global cognition and executive function and changes in cardiorespiratory fitness from pre- to post-intervention: this relationship was strongest in brain-derived neurotrophic factor non-Met carriers. CONCLUSIONS We did not observe a direct effect of exercise on cognition. Nevertheless, our data suggests genetics may moderate the relationship between fitness and cognitive change following exercise, and this should be examined further in larger trials. TRIAL REGISTRATION: This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered 3 rd May 2017 - retrospectively registered. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372780
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.BBR.2022.114108
Abstract: Lifestyle factors such as physical activity and optimal sleep are associated with better cognition and lower levels of Alzheimer's disease (AD) biomarkers, including brain beta-amyloid (Aβ) burden. We utilised cross-sectional data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study to determine whether self-reported physical activity (measured via the International Physical Activity Questionnaire) moderates the relationship between self-reported sleep (measured via the Pittsburgh Sleep Quality Index), cognition, and brain Aβ. Participants were 349 community-dwelling cognitively normal older adults (75.3 ± 5.7 years), all of whom underwent comprehensive cognitive assessment. Data from a subset of participants (n = 201) were used for analyses with brain Aβ burden (measured by positron emission tomography) as the outcome. Physical activity moderated the relationship between sleep duration and episodic memory (β = -0.10, SE =0.03, p = .005), and sleep efficiency and episodic memory (β = -0.09, SE =0.04, p = .011), such that greater amounts of physical activity mitigated the impact of suboptimal sleep duration and efficiency on episodic memory. Physical activity also moderated the relationship between sleep duration and brain Aβ (β = -0.13, SE =0.06, p = .031), and overall sleep quality and brain Aβ (β = 0.13, SE =0.06, p = .027). Our findings suggest that physical activity may play an important role in the relationship between sleep and cognitive function, and brain Aβ.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2020
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: Wiley
Date: 07-2014
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: Annual Reviews
Date: 09-05-2022
DOI: 10.1146/ANNUREV-CLINPSY-072720-014213
Abstract: Is the field of cognitive aging irretrievably concerned with decline and deficits, or is it shifting to emphasize the hope of preservation and enhancement of cognitive function in late life? A fragment of an answer comes from research attempting to understand the reasons for in idual variability in the extent and rate of cognitive decline. This body of work has created a sense of optimism based on evidence that there are some health behaviors that lify cognitive performance or mitigate the rate of age-related cognitive decline. In this context, we discuss the role of physical activity on neurocognitive function in late adulthood and summarize how it can be conceptualized as a constructive approach both for the maintenance of cognitive function and as a therapeutic for enhancing or optimizing cognitive function in late life. In this way, physical activity research can be used to shape perceptions of cognitive aging.
Publisher: Elsevier BV
Date: 09-2016
Publisher: Elsevier BV
Date: 10-2018
Publisher: Springer Science and Business Media LLC
Date: 27-01-2023
DOI: 10.1186/S13195-023-01170-4
Abstract: Wide evidence suggests that physical activity (PA) confers protection against Alzheimer’s disease (AD). On the other hand, the apolipoprotein E gene ( APOE ) ε4 allele represents the greatest genetic risk factor for developing AD. Extensive research has been conducted to determine whether frequent PA can mitigate the increased AD risk associated with APOE ε4. However, thus far, these attempts have produced inconclusive results. In this context, one possible explanation could be that the influence of the combined effect of PA and APOE ε4 carriage might be dependent on the specific outcome measure utilised. Main body. In order to bridge these discrepancies, the aim of this theoretical article is to propose a novel model on the interactive effects of PA and APOE ε4 carriage on well-established mechanisms underlying AD. Available literature was searched to investigate how PA and APOE ε4 carriage, independently and in combination, may alter several molecular pathways involved in AD pathogenesis. The reviewed mechanisms include amyloid beta (Aβ) and tau deposition and clearance, neuronal resilience and neurogenesis, lipid function and cerebrovascular alterations, brain immune response and glucose metabolism. Finally, combining all this information, we have built an integrative model, which includes evidence-based and theoretical synergistic interactions across mechanisms. Moreover, we have identified key knowledge gaps in the literature, providing a list of testable hypotheses that future studies need to address. We conclude that PA influences a wide array of molecular targets involved in AD neuropathology. A deeper understanding of where, when and, most importantly, how PA decreases AD risk even in the presence of the APOE ε4 allele will enable the creation of new protocols using exercise along pharmaceuticals in combined therapeutic approaches.
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: 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: 07-2017
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: Cold Spring Harbor Laboratory
Date: 02-01-2022
DOI: 10.1101/2022.01.01.474700
Abstract: As in iduals get older, the structural integrity of brain regions becomes progressively diminished. Neurotrophic function might aid in preventing such losses through increased synaptogenesis and neurogenesis, particularly in the hippoc us, a brain structure relevant for cognitive function. However, the carriage of certain genetic alleles for genes involved in neurotrophic function might restrain the effectiveness of neurotrophin signalling, hindering neuroprotection. Yet, research on the contribution of single nucleotide polymorphisms (SNPs) within genes coding for neurotrophins and their receptors to hippoc al volumes is scarce, with the exception of rs6265 within the brain-derived neurotrophic factor gene. Therefore, the aim of this study was to identify SNPs within genes involved neurotrophic function that are associated with hippoc al volume in a s le of 23,776 cognitively normal older adults from the UK Biobank. We found that, in in iduals older than 50, homozygote carriage of the major alleles rs4839435-A within nerve growth factor gene and rs56405676-T within the neurotrophic receptor tyrosine kinase 2 gene, were associated with increase hippoc al volumes, compared to carriage of 1 or 2 copies of the minor alleles. However, only rs56405676-T was significantly associated with greater hippoc al volumes in in iduals older than 60. Hence this study might serve to identify populations at higher risk of hippoc al attrition and cognitive decline.
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: Elsevier BV
Date: 07-2020
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: Sciencedomain International
Date: 10-01-2014
Publisher: Springer Science and Business Media LLC
Date: 02-2021
DOI: 10.1186/S13195-021-00774-Y
Abstract: Physical inactivity has been consistently linked to increased risk of cognitive decline however, studies examining the impact of exercise interventions on cognition have produced inconsistent findings. Some observational studies suggest exercise intensity may be important for inducing cognitive improvements however, this has yet to be thoroughly examined in older adult cohorts. The objective of the current study was to evaluate the effect of systematically manipulated high-intensity and moderate-intensity exercise interventions on cognition. This multi-arm pilot randomised clinical trial investigated the effects of 6 months of high-intensity exercise and moderate-intensity exercise, compared with an inactive control, on cognition. Outcome measures were assessed at pre- (baseline), post- (6 months), and 12 months post-intervention. Ninety-nine cognitively normal men and women (aged 60–80 years) were enrolled from October 2016 to November 2017. Participants that were allocated to an exercise group (i.e. high-intensity or moderate-intensity) engaged in cycle-based exercise two times per week for 6 months. Cognition was assessed using a comprehensive neuropsychological test battery. Cardiorespiratory fitness was evaluated by a graded exercise test. There was a dose-dependent effect of exercise intensity on cardiorespiratory fitness, whereby the high-intensity group experienced greater increases in fitness than the moderate-intensity and control groups. However, there was no direct effect of exercise on cognition. We did not observe a direct effect of exercise on cognition. Future work in this field should be appropriately designed and powered to examine factors that may contribute to in idual variability in response to intervention. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered on 3 May 2017—retrospectively registered. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372780
Publisher: Wiley
Date: 07-2015
Publisher: Wiley
Date: 12-2022
DOI: 10.1002/ALZ.064392
Abstract: Physical inactivity is one of the greatest modifiable risk factors for dementia and research shows physical activity can delay cognitive decline in older adults. However, much of this research has used subjective physical activity data and a single follow‐up cognitive assessment. Further studies using objectively measured physical activity and comprehensive cognitive data measured at multiple timepoints are required. Participants were 199 community‐dwelling cognitively normal older adults (68.7 5.9 years) from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Actigraphy was used to measure physical activity at baseline, yielding measures of intensity (peak counts), total activity (total counts) and energy expenditure (kilocalories k/cal). Cognitive function was assessed using a cognitive battery administered every 18‐months from baseline (3‐11 years follow‐up), yielding composite scores for episodic memory, executive function, attention and processing speed, and global cognition. Higher baseline energy expenditure predicted improvements in episodic memory and maintained global cognition over time ( β = 0.011, SE = 0.005, p = 0.031 β = 0.009, SE = 0.004, p = 0.047, respectively). Both physical activity intensity and total activity predicted global cognition, such that those with higher peak and total counts had better cognition over time ( β = 0.012, SE = 0.004, p = 0.005 β = 0.012, SE = 0.004, p = 0.005, respectively). Finally, higher total activity predicted improved episodic memory over time ( β = 0.011, SE = 0.005, p = .022). These results suggest that physical activity is associated with preserved cognitive function over time, and that activity intensity may play an important role. This research further highlights the importance of early intervention to prevent cognitive decline and may aid in informing lifestyle interventions for dementia prevention.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Wiley
Date: 07-0007
Publisher: MDPI AG
Date: 31-08-2022
Abstract: One of the most recognisable features of ageing is a decline in brain health and cognitive dysfunction, which is associated with perturbations to regular lipid homeostasis. Although ageing is the largest risk factor for several neurodegenerative diseases such as dementia, a loss in cognitive function is commonly observed in adults over the age of 65. Despite the prevalence of normal age-related cognitive decline, there is a lack of effective methods to improve the health of the ageing brain. In light of this, exercise has shown promise for positively influencing neurocognitive health and associated lipid profiles. This review summarises age-related changes in several lipid classes that are found in the brain, including fatty acyls, glycerolipids, phospholipids, sphingolipids and sterols, and explores the consequences of age-associated pathological cognitive decline on these lipid classes. Evidence of the positive effects of exercise on the affected lipid profiles are also discussed to highlight the potential for exercise to be used therapeutically to mitigate age-related changes to lipid metabolism and prevent cognitive decline in later life.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2020
DOI: 10.1186/S13195-020-00608-3
Abstract: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer’s disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one s le may strengthen our understanding of this complex phenomenon. The relationship between PA and functional connectivity (FC) was examined in a s le of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition, and mood was also investigated. A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all in iduals (across the whole s le, in ε4 carriers, and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group, decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory). PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all in iduals, especially ε4 carriers.
Publisher: American Medical Association (AMA)
Date: 10-2012
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: 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: 12-2020
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.
Start Date: 2016
End Date: 2020
Funder: National Health and Medical Research Council
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