Search

Physical activity and exercise can improve cognitive function and reduce the risk for dementia. Other lifestyle factors, including sleep, are associated with cognitive function and dementia risk, and exercise is an effective therapeutic strategy for improving sleep. Based on these associations, it has been hypothesised that sleep might be an important mediator for the effects of exercise on cognition. Here, we review the current literature to evaluate whether sleep and physical activity are independently or jointly associated with cognitive function. The extant literature in this area is minimal, and the causal relationships between physical activity, sleep and cognition have not been examined. A small number of cross-sectional studies in this area suggest that physical activity may attenuate some of the negative impact that poor sleep has on cognition, and also that sleep may be a mechanism through which physical activity improves cognitive abilities. Further research may enable the development of individually tailored intervention programs to result in the greatest cognitive benefit, ultimately delaying the onset of Alzheimer’s disease.

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer’s disease dementia (AD)) as an ‘Inception cohort’ who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an ‘Enrichment cohort’ (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. Results: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. Conclusion: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

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.

Background There is a paucity of interventional research that systematically assesses the role of exercise intensity and cardiorespiratory fitness, and their relationship with executive function in older adults. To address this limitation, we have examined the effect of a systematically manipulated exercise intervention on executive function. Methods Ninety-nine cognitively normal participants (age = 69.10 ± 5.2 years; n = 54 female) were randomized into either a high-intensity cycle-based exercise, moderate-intensity cycle-based exercise, or no-intervention control group. All participants underwent neuropsychological testing and fitness assessment at baseline (preintervention), 6-month follow-up (postintervention), and 12-month postintervention. Executive function was measured comprehensively, including measures of each subdomain: Shifting, Updating/ Working Memory, Inhibition, Verbal Generativity, and Nonverbal Reasoning. Cardiorespiratory fitness was measured by analysis of peak aerobic capacity; VO2peak. Results First, the exercise intervention was found to increase cardiorespiratory fitness (VO2peak) in the intervention groups, in comparison to the control group (F =10.40, p≤0.01). However, the authors failed to find mean differences in executive function scores between the high-intensity, moderate intensity, or inactive control group. On the basis of change scores, cardiorespiratory fitness was found to associate positively with the executive function (EF) subdomains of Updating/Working Memory (β = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (β = 0.30, p = 0.03, r = 0.28) for intervention, but not control participants. Conclusion At the aggregate level, the authors failed to find evidence that 6-months of high-intensity aerobic exercise improves EF in older adults. However, it remains possible that individual differences in experimentally induced changes in cardiorespiratory fitness may be associated with changes in Updating/ Working Memory and Verbal Generativity.

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.

Exercise has been shown to benefit brain structure and function, particularly in aging populations. However, the mechanisms by which exercise exerts its effects, especially in humans, are not fully understood. This review argues that one reason for this knowledge gap is that exercise likely operates through multiple levels of mechanisms. Furthermore, the mechanisms of exercise may vary depending on factors such as age and health state. We discuss the state of evidence at each of three levels of analysis (molecular/cellular, brain structure/function, and mental states and higher-order behaviors) and highlight consistencies across these levels, inconsistencies within them, and knowledge gaps. Lastly, based on these, we speculate about which mechanisms of exercise may be universal across age groups and populations versus those that might be distinct to specific age ranges or populations.

Introduction: 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 sample of older adults. Methods: 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. Results: Analysis of covariance, controlling for age, sex, education, and apolipoprotein (APOE) ε4 allele carriage, revealed that participants with a history of mTBI had a significantly larger total mean grey matter volume (582.21 ± 12.46 cm3) in comparison to participants with no mTBI history (571.08 ± 17.21 cm3, p = 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. Conclusion: 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.

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 individual 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 amplify 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.

BackgroundGrey matter atrophy occurs as a function of ageing and is accelerated in dementia. Previous research suggests physical activity attenuates grey matter loss; however, there appears to be individual variability in this effect. Understanding factors that can affect the relationship between physical activity and brain volume may enable prediction of individual response, and aid in identifying those that gain the greatest neural benefits from physical activity. The current study examined the relationship between objectively-measured physical activity and brain volume; and whether this relationship is moderated by age, sex, or a priori candidate genetic factors.MethodsData from 10,083 men and women (50 years and over) of the UK Biobank were used to examine: 1) the relationship between objectively-measured physical activity and brain volume; and 2) whether the relationship between objectively-measured physical activity and brain volume is moderated by age, sex, brain-derived neurotrophic factor (BDNF) Val66Met, or apolipoprotein (APOE) ε4 allele carriage. All participants underwent a magnetic resonance imaging scan to quantify grey matter volumes, physical activity monitoring via accelerometry, and genotyping.ResultsPhysical activity was associated with total grey matter volume (B = 0.14, p = 0.001, q = 0.005) and right hippocampal volume (B = 1.45, p = 0.008, q = 0.016). The physical activity*sex interaction predicted cortical grey matter (B = 0.22, p = 0.003, q = 0.004), total grey matter (B = 0.30, p < 0.001, q = 0.001), and right hippocampal volume (B = 3.60, p = 0.001, q = 0.002). Post-hoc analyses revealed males received benefit from higher physical activity levels, in terms of greater cortical grey matter volume (B = 0.13, p = 0.01), total grey matter volume (B=0.23, p < 0.001), and right hippocampal volume (B = 3.05, p = 0.008). No moderating effects of age, APOE ε4 allele carriage, or BDNF Val66Met genotype were observed.DiscussionOur results indicate that in males, but not females, an association exists between objectively-measured physical activity and grey matter volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of sex-effects on the relationship between physical activity and brain volume.

Objective: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; VO2peak) 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.Methods: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.Results:The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = 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.Conclusions: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 individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.

Background: Although higher cardiorespiratory fitness (CRF) has been linked to better executive function, the mechanisms by which this occurs remain a matter of speculation. One hypothesis is that higher CRF is associated with elevated top-down control in which brain regions processing task-relevant information are up-regulated and brain regions processing task-irrelevant information are down-regulated. Methods: We tested this top-down hypothesis in 50 young adults (μ age = 25.22 ± 5.17 years) by measuring CRF via a graded maximal exercise test and performing functional Magnetic Resonance Imaging (fMRI) during a color-word Stroop task. We used task-evoked functional connectivity, quantified from a psychophysiological interaction analysis (PPI), to test our hypotheses that (a) higher CRF would be associated with greater connectivity between control centers (i.e., prefrontal and parietal areas) and visual feature centers (i.e., occipital areas) that are involved with processing task-relevant stimulus dimensions (i.e., color), and (b) higher CRF would be associated with lower connectivity between control centers and visual feature centers that are involved with processing task-irrelevant dimensions of the stimuli (i.e., word processing areas). Results: Controlling for sex and BMI, we found, consistent with our second hypothesis, that higher CRF was associated with reduced functional connectivity between parietal and occipital areas involved in the task-irrelevant dimension of the task (i.e., word form areas). There were no associations between CRF and functional connectivity with the prefrontal cortex or evidence of heightened connectivity between attentional control and visual feature centers. Conclusions: These results suggest that CRF associations with executive functioning might be explained by CRF-mediated differences between brain regions involved with attentional control (parietal regions) and the down-regulation of regions involved with processing task-irrelevant stimulus features (occipital regions).

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, VO2peak. 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.

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 samples 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.

"A multilayered action plan is needed for a substantial, timely and sustained investment in dementia prevention"

Background The highly encouraging findings from the Finnish Geriatric Intervention Study (known as FINGER) led to the global initiative for dementia risk reduction known as world-wide FINGERS (WW FINGERS). As part of the collaboration, our Australian AU-ARROW trial will follow the general protocol of the FINGER trial, and will also be aligned with the U.S. arm of the study, US-POINTER, though will have minor cultural and dietary modifications to determine the validity of the intervention in an Australian setting. Method AU-ARROW is a randomised, single-blind 2-year clinical trial that will recruit 600 participants aged 60-79 satisfying specific inclusion/exclusion criteria, including normal cognition and one or more cardiovascular risk factors that place them at greater risk of cognitive decline. Participants will be distributed across two sites (a) Macquarie University Health Clinics, Sydney, NSW and (b) Sarich Neuroscience Research Institute, Edith Cowan University, Perth, WA, and will be randomised equally into either the innovative multi-modal intervention group or the study control group, who will receive general lifestyle advice and annual health check-ups, without treatment. Multi-modal intervention consists of aerobic exercise, resistance training and stretching; dietary advice with monitoring to encourage adherence to the MIND diet; cognitive training sessions via the Brain HQ computerised online training system; and medical monitoring and regular health education sessions. Heart rate trackers, diet and exercise log books, and the monitoring of Brain HQ sessions will all help with adherence. Primary outcome measure is improvement in global cognitive score, measured using neurocognitive tests identical to those in the US-POINTER protocol. Additional neurocognitive tests, physical function improvements, detailed diet monitoring and sleep monitoring will provide added data. The unique extra value of AU-ARROW trial consists of the testing for Alzheimer’s disease (AD) blood biomarkers in all participants; as well as the AD Aβ amyloid-specific ligand-PET imaging, brain MRI and retinal biomarker tests that half of the participants will undergo. These tests will provide comprehensive data which have the ultimate purpose of increasing knowledge of the preclinical stages of AD, and help not only to develop preclinical AD diagnostic tests but also efficacy of AU-ARROW’s intervention.

Background 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. Methods The relationship between PA and alpha band power was examined in a sample 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. Results 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. Conclusion PA could protect against the slowing of brain activity that characterizes the AD continuum, where it is of benefit for all individuals, especially E3/E4 older adults.

BACKGROUND: 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. METHODS: The relationship between PA and alpha band power was examined in a sample 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. RESULTS: 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. CONCLUSION: PA could protect against the slowing of brain activity that characterizes the AD continuum, where it is of benefit for all individuals, especially E3/E4 older adults.

Introduction For decades, researchers have tried to understand the moderating effect of APOE e4 carriage on the relationship between physical activity (PA), brain health and dementia risk. However, this field has produced inconsistent findings. Method We conducted a systematic review of the literature, searching for observational and interventional studies examining the effect of APOE e4 carriage on the relationships between PA, dementia risk and different markers of brain health. Results Observational studies using dementia risk as a primary outcome measure generally found that in shorter follow-up periods (up to 10 years) both APOE e4 carriers and non-carriers benefit from PA, although longer follow-ups showed mixed results. In neuroimaging studies, mainly carriers or both groups showed benefits. Additionally, the association between PA and amyloid burden was more evident among carriers. Overall, studies with greater samples of active APOE e4 carriers are more likely to report benefits within this group in terms of lower dementia risk and reduced brain pathology. Discussion Although we have identified some patterns for the modulating effect of APOE e4 on PA and dementia or brain pathology, the available data is, overall, inconclusive. Heterogeneity in study design, methodology, and outcomes blur the ability to detect clear associations.

Background: 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 sample may strengthen our understanding of this complex phenomenon. Method: The relationship between PA and functional connectivity (FC) was examined in a sample 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. Results: A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, 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). Conclusions: PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, especially ϵ4 carriers., This study was funded by the Spanish Ministry of Economy and Competitiveness under the Grant PSI2015-68793-C3-1-R [D601] and by the project B2017/BMD-3760 from NEUROCENTRO. Complimentary, it was supported by a predoctoral fellowship from La Caixa Foundation to JFL, a postdoctoral fellowship from the Spanish Ministry of Economy and Competitiveness to PC (FJCI-2015-26755), a grant from the Spanish Ministry of Science, Innovation and Universities to JVR (FJCI-2017-33396), and a predoctoral grant by the Spanish Ministry of Economy (BES-2016-076869) to FRT.

Prospective memory (PM) can deteriorate with age and adversely influence health behaviours. Research suggests that personality is related to PM in healthy young adults, but we know little about the role of personality in the PM amongst older adults. Community-dwelling older adults (N = 152) completed the NEO Five-Factor Inventory-3 and PM measures. After adjusting for demographics and general cognition, higher neuroticism and lower levels of openness were independently associated with lower objectively-measured time- and event-based PM. Lower conscientiousness was the only personality predictor of self-reported everyday PM failures. Findings indicate that personality plays a role in PM functioning in the laboratory and daily life.

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 individuals 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 individual 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.

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) sample, 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 individuals with even mild AD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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 individual 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.

Numerous animal studies have reported exercise reduces the accumulation of Alzheimer's disease pathology, including amyloid-β (Aβ) and tau. Furthermore, we previously reported a relationship between higher levels of physical activity (PA) and lower brain Aβ burden in a human population. The recent advent of tau positron emission tomography (PET) tracers enables us to extend our investigations into the evaluation of the relationship between PA and brain tau burden. Utilizing data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, we have examined the cross-sectional relationship between habitual PA and PET-quantified tau burden. Forty-three cognitively healthy older adults were categorized into low-moderate PA (LMPA; n = 16) or high PA (HPA; n = 27), based on self-reported PA levels. Tau PET imaging with the AV1451 tracer was conducted on all participants. The LMPA group had significantly higher neocortical tau burden (presented as a z-score; 1.22±1.98), compared to the HPA group (z-score: - 0.28±1.18). The difference between the LMPA and HPA groups was also evident when examining regional tau burden in the temporoparietal cortex and the prefrontal cortex. Our results suggest an association between self-reported PA level and brain tau burden. Future longitudinal and interventional studies utilizing larger samples sizes are vital to further investigate the nature of the relationship between tau and PA.

Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group in Western Australia which was involved in the discovery and sequencing of the amyloid-β peptide (also known as Aβ or A4 peptide) extracted from cerebral amyloid plaques. This review discusses the journey from the discovery of the Aβ peptide in Alzheimer’s disease (AD) brain to the establishment of pre-clinical AD using PET amyloid tracers, a method now serving as the gold standard for developing peripheral diagnostic approaches in the blood and the eye. The latter developments for early diagnosis have been largely achieved through the establishment of the Australian Imaging Biomarker and Lifestyle research group that has followed 1,100 Australians for 11 years. AIBL has also been instrumental in providing insight into the role of the major genetic risk factor apolipoprotein E ɛ4, as well as better understanding the role of lifestyle factors particularly diet, physical activity and sleep to cognitive decline and the accumulation of cerebral Aβ.

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.

Accumulating evidence suggests a diet high in protein and fiber may confer some protection against Alzheimer's disease (AD). However, no human studies to-date have assessed the relationship between protein and fiber intake, and plasma and brain amyloid-β (Aβ). Consequently, this cross-sectional study, investigated the association of self-reported dietary intakes of protein and fiber, with plasma and brain Aβ burden (n = 541, and n = 162 respectively), in a well-characterized cohort of cognitively normal older adults, drawn from the larger Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. We observed 12.59 and 8.43 higher odds of 'high' brain Aβ burden (PiB PET SUVR≥1.5) if protein intake fell in the lowest and middle tertile, respectively, compared to the highest tertile (p = 0.008; p = 0.013). Thus, in this cohort, the more protein consumed, the less likelihood of 'high' Aβ burden in the brain. No other significant associations were observed. The results of this study highlight the potentially protective impact of high dietary protein intake on brain Aβ burden in older adults, before objective memory decline is apparent. While longitudinal validation is required, these findings may assist in the development of dietary approaches aimed at preventing or delaying AD onset.

Brain-derived neurotrophic factor (BDNF) has been shown to increase in an intensity dependent manner in response to aerobic exercise. However, previous research investigating the use of resistance exercise to increase BDNF levels has been less conclusive, likely due to the low intensity nature of traditional resistance exercise programs. This study examined the influence of acute resistance exercise to-fatigue on serum BDNF levels and blood lactate.Acute crossover study.Eleven untrained to intermediately trained males (age: 25.0±1.3 year) and five untrained females (age: 23.2±1.1 year) were recruited to undertake two bouts of resistance exercise. Strength (five sets of five repetitions, 180s recovery) and hypertrophy (three sets of ten repetitions, 60s recovery) based resistance exercise was implemented to-fatigue to examine the effect on serum BDNF and blood lactate levels immediately post-, and 30min post-exercise.An interaction (p0.01; ES=0.52) was observed between conditions immediately post-exercise, with hypertrophy resulting in significantly greater BDNF levels when compared with strength exercise. Changes in lactate and BDNF from baseline to post- exercise were positively correlated following hypertrophy exercise (r=0.70; p0.01), but not correlated following strength exercise (r=0.18; p=0.56).The use of a to-fatigue hypertrophy based resistance exercise protocol provides the necessary stimulus to increase peripheral serum BDNF. Mechanistically, the presence of lactate does not appear to drive the BDNF response during resistance exercise.

Personality factors have been associated with Alzheimer’s disease (AD) and dementia, but they have not been examined against markers of regional brain glucose metabolism (a primary measure of brain functioning) in older adults without clinically diagnosed cognitive impairment. The relationship between personality factors derived from the five-factor model and cerebral glucose metabolism determined using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-d-glucose (18F-FDG-PET) was examined in a cohort of 237 non-demented, community-dwelling older adults aged 60–89 years (M ± SD = 73.76 ± 6.73). Higher neuroticism and lower scores on extraversion and conscientiousness were significantly associated with decreased glucose metabolism in brain regions typically affected by AD neuropathological processes, including the hippocampus and entorhinal cortex. Furthermore, while there were significant differences between apolipoprotein E (APOE) ε4 allele carriers and non-carriers on 18F-FDG-PET results in the neocortex and other brain regions (p

Mild traumatic brain injury (mTBI) accounts for a large majority of traumatic brain injuries sustained globally each year. Older adults, who are already susceptible to age-related declines to neurocognitive health, appear to be at an increased risk of both sustaining an mTBI and experiencing slower or impaired recovery. There is also growing evidence that mTBI is a potential risk factor for accelerated cognitive decline and neurodegeneration. Lifestyle-based interventions are gaining prominence as a cost-effective means of maintaining cognition and brain health with age. Consequently, inter-individual variations in exercise, sleep, and dietary patterns could influence the trajectory of post-mTBI neurocognitive recovery, particularly in older adults. This review synthesises the current animal and human literature centred on the mechanisms through which lifestyle-related habits and behaviours could influence acute and longer-term neurocognitive functioning following mTBI. Numerous neuroprotective processes which are impacted by lifestyle factors have been established in animal models of TBI. However, the literature is characterised by a lack of translation to human samples and limited appraisal of the interaction between ageing and brain injury. Further research is needed to better establish the therapeutic utility of applying lifestyle-based modifications to improve post-mTBI neurocognitive outcomes in older adults.

Age-related decrease in testosterone levels is a potential risk factor for cognitive decline in older men. However, observational studies and clinical trials have reported inconsistent results on the effects of testosterone on individual cognitive domains. Null findings may be attributed to factors that studies have yet to consider. In particular, individual variations in polyglutamine (CAG) length in the androgen receptor (AR) gene could alter androgenic activity in brain regions associated with cognitive processes including memory and executive functions. However, the role of AR CAG repeat length as a moderator of the relationship between testosterone levels and cognition has not been investigated. Therefore, we aimed to examine the relationship between baseline calculated free testosterone (cFT) levels, change in cFT levels over 18 months and CAG repeat length on cognitive performance in memory, executive function, language, attention and processing speed domains. These relationships were examined in 304 cognitively normal older male participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. In the attention and processing speed domain, a short CAG repeat length appears to exacerbate the effects of low baseline cFT levels that are also lower than expected at follow-up. These results highlight that individual variations in AR CAG repeat length should be considered in future studies and clinical trials that examine the complex relationship between testosterone and cognition.

STUDY OBJECTIVES: To evaluate the association between self-reported sleep quality and levels of brain β-amyloid (Aβ) burden, and to determine the effect of the apolipoprotein E (APOE) e4 allele on any associations found. METHODS: This study is a cross-sectional analysis of 184 cognitively healthy men and women aged over 60 y. We measured sleep quality factors: specifically, sleep duration, latency (time taken to fall asleep), disturbances, efficiency, daytime dysfunction, and overall sleep quality, using the Pittsburgh Sleep Quality Index. All participants underwent Aβ positron emission tomography imaging for the quantification of brain Aβ burden and were APOE genotyped. Linear regression analyses were used to evaluate the relationship between sleep quality factors and brain Aβ burden, adjusting for age, body mass index, cardiovascular disease, and symptoms of depression, with APOE e4 carriage entered as a moderator. RESULTS: Of the sleep factors, longer sleep latency was associated with higher levels of brain Aβ (B = 0.003 [standard error = 0.001], P = 0.02). APOE e4 allele (carrier/noncarrier) did not moderate the relationship between sleep latency and brain Aβ burden. CONCLUSIONS: Our findings suggest a relationship between brain Aβ burden and sleep latency, independent of APOE e4 genotype.