Suboptimal self-reported sleep efficiency and duration are associated with faster accumulation of brain amyloid beta in cognitively unimpaired older adults.

INTRODUCTION: This study investigated whether self-reported sleep quality is associated with brain amyloid beta (Aß) accumulation. METHODS: Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self-reported sleep data, and positron emission tomography-determined brain Aß measured over a minimum of three time points (range 33.3-72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) ε4 allele status, and time, adjusting for sex and baseline age. RESULTS: Sleep duration <6 hours, in APOE ε4 carriers, and sleep efficiency <65%, in the whole sample and APOE ε4 non-carriers, is associated with faster accumulation of brain Aß. DISCUSSION: These findings suggest a role for self-reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer's disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights: In cognitively unimpaired older adults self-report sleep is associated with brain amyloid beta (Aß) accumulation.Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype.Sleep duration <6 hours is associated with faster brain Aß accumulation in APOE ε4 carriers.Sleep efficiency < 65% is associated with faster brain Aß accumulation in APOE ε4 non-carriers.Personalized sleep interventions should be studied for potential to slow Aß accumulation.

The impact of exercise on blood-based biomarkers of Alzheimer's disease in cognitively unimpaired older adults.

Physical activity is a promising preventative strategy for Alzheimer's disease: it is associated with lower dementia risk, better cognition, greater brain volume and lower brain beta-amyloid. Blood-based biomarkers have emerged as a low-cost, non-invasive strategy for detecting preclinical Alzheimer's disease, however, there is limited literature examining the effect of exercise (a structured form of physical activity) on blood-based biomarkers. The current study investigated the influence of a 6-month exercise intervention on levels of plasma beta-amyloid (Aß42, Aß40, Aß42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) chain in cognitively unimpaired older adults, and as a secondary aim, whether blood-based biomarkers related to cognition. Ninety-nine community-dwelling older adults (69.1 ± 5.2) were allocated to an inactive control, or to moderate or high intensity exercise groups where they cycled twice weekly for six months. At baseline and six months (post-intervention), fasted blood was collected and analysed using single molecule array (SIMOA) assays, and cognition was assessed. Results demonstrated no change in levels of any plasma biomarker from pre- to post-intervention. At baseline, higher NfL was associated with poorer cognition (ß = -0.33, SE = 0.13, adjusted p = .042). Exploratory analyses indicated higher cardiorespiratory fitness was associated with higher NfL and GFAP levels in apolipoprotein E (APOE) ε4 non-carriers compared to ε4 carriers (NfL, ß = -0.43, SE = 0.19, p = .029; GFAP, ß = -0.41, SE = 0.20, p = .044), though this association was mediated by body mass index (BMI). These results highlight the importance of considering BMI in analysis of blood-based biomarkers, especially when investigating differences between APOE ε4 carriers and non-carriers. Our results also indicate that longer follow-up periods may be required to observe exercise-induced change in blood-based biomarkers.

Physical activity and brain amyloid beta: A longitudinal analysis of cognitively unimpaired older adults.

INTRODUCTION: The current study evaluated the relationship between habitual physical activity (PA) levels and brain amyloid beta (Aß) over 15 years in a cohort of cognitively unimpaired older adults. METHODS: PA and Aß measures were collected over multiple timepoints from 731 cognitively unimpaired older adults participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging. Regression modeling examined cross-sectional and longitudinal relationships between PA and brain Aß. Moderation analyses examined apolipoprotein E (APOE) ε4 carriage impact on the PA-Aß relationship. RESULTS: PA was not associated with brain Aß at baseline (ß = -0.001, p = 0.72) or over time (ß = -0.26, p = 0.24). APOE ε4 status did not moderate the PA-Aß relationship over time (ß = 0.12, p = 0.73). Brain Aß levels did not predict PA trajectory (ß = -54.26, p = 0.59). DISCUSSION: Our study did not identify a relationship between habitual PA and brain Aß levels. HIGHLIGHTS: Physical activity levels did not predict brain amyloid beta (Aß) levels over time in cognitively unimpaired older adults (≥60 years of age). Apolipoprotein E (APOE) ε4 carrier status did not moderate the physical activity-brain Aß relationship over time. Physical activity trajectories were not impacted by brain Aß levels.

The effect of acute exercise on objectively measured sleep and cognition in older adults.

Background: Exercise can improve cognition in aging, however it is unclear how exercise influences cognition, and sleep may partially explain this association. The current study aimed to investigate whether objectively measured sleep mediates the effect of an acute exercise intervention on cognition in older adults. Methods: Participants were 30 cognitively unimpaired, physically active older adults (69.2 ± 4.3 years) with poor sleep (determined via self-report). After a triple baseline cognitive assessment to account for any natural fluctuation in cognitive performance, participants completed either a single bout of 20-minutes of high intensity exercise on a cycle ergometer, or a control condition, in a cross-over trial design. Cognition was measured immediately post-intervention and the following day, and sleep (total sleep time, sleep onset latency, sleep efficiency, % of rapid eye movement sleep, light sleep and deep sleep) was characterized using WatchPAT™ at baseline (5 nights) and measured for one night after both exercise and control conditions. Results: Results showed no effect of the exercise intervention on cognition immediately post-intervention, nor an effect of acute exercise on any sleep variable. There was no mediating effect of sleep on associations between exercise and cognition. However, a change from baseline to post-intervention in light sleep and deep sleep did predict change in episodic memory at the ~24 h post-intervention cognitive assessment, regardless of intervention condition. Discussion: There was no effect of acute high intensity exercise on sleep or cognition in the current study. However, results suggest that associations between sleep and cognition may exist independently of exercise in our sample. Further research is required, and such studies may aid in informing the most effective lifestyle interventions for cognitive health.

The influence of baseline sleep on exercise-induced cognitive change in cognitively unimpaired older adults: A randomised clinical trial.

OBJECTIVES: Observational studies consistently demonstrate that physical activity is associated with elevated cognitive function, however, there remains significant heterogeneity in cognitive outcomes from randomized exercise interventions. Individual variation in sleep behaviours may be a source of variability in the effectiveness of exercise-induced cognitive change, however this has not yet been investigated. The current study aimed to (1) investigate the influence of a 6-month exercise intervention on sleep, assessed pre- and post-intervention and, (2) investigate whether baseline sleep measures moderate exercise-induced cognitive changes. METHODS: We utilised data from the Intense Physical Activity and Cognition (IPAC) study (n = 89), a 6-month moderate intensity and high intensity exercise intervention, in cognitively unimpaired community-dwelling older adults aged 60-80 (68.76 ± 5.32). Exercise was supervised and completed on a stationary exercise bicycle, and cognitive function was measured using a comprehensive neuropsychological battery administered pre- and post-intervention. Sleep was measured using the Pittsburgh sleep quality index. There was no effect of the exercise intervention on any sleep outcomes from pre- to post-intervention. RESULTS: There was a significant moderating effect of baseline sleep efficiency on both episodic memory and global cognition within the moderate intensity exercise group, such that those with poorer sleep efficiency at baseline showed greater exercise-induced improvements in episodic memory. CONCLUSIONS: These results suggest that those with poorer sleep may have the greatest exercise-induced cognitive benefits and that baseline sleep behaviours may be an important source of heterogeneity in previous exercise interventions targeting cognitive outcomes.

How does apolipoprotein E genotype influence the relationship between physical activity and Alzheimer's disease risk? A novel integrative model.

BACKGROUND: 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 (Aß) 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. CONCLUSIONS: 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.

The relationship between objective physical activity and change in cognitive function.

INTRODUCTION: The current study investigated the association between objectively measured physical activity and cognition in older adults over approximately 8 years. METHODS: We utilized data from 199 cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, aged ≥60. Actigraphy was used to measure physical activity (intensity, total activity, and energy expenditure) at baseline. Cognition was assessed using a comprehensive cognitive battery every 18-months. RESULTS: Higher baseline energy expenditure predicted better episodic recall memory and global cognition over the follow-up period (p = 0.031; p = 0.047, respectively). Those with higher physical activity intensity and greater total activity also had better global cognition over time (both p = 0.005). Finally, higher total physical activity predicted improved episodic recall memory over time (p = 0.022). DISCUSSION: These results suggest that physical activity can preserve cognition and that activity intensity may play an important role in this association. HIGHLIGHTS: Greater total physical activity predicts preserved episodic memory and global cognition. Moderate intensity physical activity (>3.7 metabolic equivalents of task [MET]) predicts preserved global cognition. Expending > 373 kilocalories per day may benefit episodic memory and global cognition.

The interaction between physical activity and sleep on cognitive function and brain beta-amyloid in older adults.

BACKGROUND: 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 (Aß) burden. OBJECTIVE: 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 Aß. METHODS: 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 Aß burden (measured by positron emission tomography) as the outcome. RESULT: Physical activity moderated the relationship between sleep duration and episodic memory (ß = -0.10, SE =0.03, p = .005), and sleep efficiency and episodic memory (ß = -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 Aß (ß = -0.13, SE =0.06, p = .031), and overall sleep quality and brain Aß (ß = 0.13, SE =0.06, p = .027). CONCLUSION: Our findings suggest that physical activity may play an important role in the relationship between sleep and cognitive function, and brain Aß.

Investigating the Link between Later-Life Brain Volume and Cardiorespiratory Fitness after Mild Traumatic Brain Injury Exposure.

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.

Non-Modifiable Factors as Moderators of the Relationship Between Physical Activity and Brain Volume: A Cross-Sectional UK Biobank Study.

BACKGROUND: Previous research suggests physical activity attenuates grey and white matter loss; however, there appears to be individual variability in this effect. Understanding factors that can influence the relationship between physical activity and brain volume may enable prediction of individual response. OBJECTIVE: 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, brain-derived neurotrophic factor (BDNF) Val66Met, or apolipoprotein (APOE) ɛ4 allele carriage. METHODS: Data from 10,083 men and women (50 years and over) of the UK Biobank were used to examine the study objectives. All participants underwent a magnetic resonance imaging scan to quantify grey and white matter volumes, physical activity monitoring via actigraphy, and genotyping. RESULTS: Physical activity was associated with total grey matter volume, total white matter volume, and right hippocampal volume. Only males had an association between higher physical activity levels and greater cortical grey matter volume, total grey matter volume, and right hippocampal volume. Age moderated the relationship between physical activity and white matter volume. CONCLUSION: Our results indicate that in males, but not females, an association exists between objectively-measured physical activity and grey matter volume. Age may also play a role in impacting the relationship between physical activity and brain volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of age and sex-effects on the physical activity and brain volume relationship.

Cognitive Aging and the Promise of Physical Activity.

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.

The Effect of Self-Paced Exercise Intensity and Cardiorespiratory Fitness on Frontal Grey Matter Volume in Cognitively Normal Older Adults: A Randomised Controlled Trial.

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 = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (ß = 0.29, p = 0.036, r = 0.27), right supplementary motor area (ß = 0.30, p = 0.031, r = 0.29), and both right (ß = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (ß = 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.

Relationships between physical activity, sleep and cognitive function: A narrative review.

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.

Fifteen Years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and Observations from 2,359 Older Adults Spanning the Spectrum from Cognitive Normality to 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 Aß-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.

The impact of exercise, sleep, and diet on neurocognitive recovery from mild traumatic brain injury in older adults: A narrative review.

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.

High-intensity exercise and cognitive function in cognitively normal older adults: a pilot randomised clinical trial.

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. METHODS: 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. 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. CONCLUSIONS: 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 individual variability in response to intervention. TRIAL REGISTRATION: This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000643370). Registered on 3 May 2017-retrospectively registered. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372780.

A Randomized Controlled Trial of High-Intensity Exercise and Executive Functioning in Cognitively Normal Older Adults.

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 (ß = 0.37, p = 0.01, r = 0.34) and Verbal Generativity (ß = 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.

Does APOE genotype moderate the relationship between physical activity, brain health and dementia risk? A systematic review.

INTRODUCTION: For decades, researchers have tried to understand the moderating effect of APOE ε4 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 ε4 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 ε4 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 ε4 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 ε4 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.

Age and APOE genotype affect the relationship between objectively measured physical activity and power in the alpha band, a marker of brain disease.

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.