Becoming active in midlife can increase the brain's resistance to Alzheimer's

Becoming active in midlife can increase the brain's resistance to Alzheimer's

Staying active during your 40s and 50s can help your brain withstand the changes in early Alzheimer's, especially if you follow activity recommendations, this study finds.

In a recent article published in the JournalAlzheimer's & DementiaResearchers examined how changes in physical activity in midlife may affect brain changes associated with Alzheimer's disease (AD) in people at higher risk of developing the disease.

Their results suggest that World Health Organization (WHO) physical activity was associated with reduced amyloid burden in the brain and both becoming and remaining active at less than recommended levels was associated with greater cortical thickness in areas compared to remaining seed. Conversely, residual sedentary sedentary behavior was implicated in reduced cortical thickness in areas vulnerable to AD.

background

Alzheimer's disease (AD) begins with a long preclinical phase characterized by early brain changes such as neurodegeneration and amyloid-β (Aβ) buildup, which can be detected by biomarkers years before symptoms begin.

Researchers believe that up to a third of cases are linked to modifiable lifestyle factors, and there is increasing interest in AD prevention through behavior modification, particularly physical activity.

Sedentary behavior is a known risk factor for dementia, while physical activity in midlife has been shown to reduce the risk of AD and cognitive decline. This could be through avenues such as improved mental and cardiovascular health.

Midlife is a crucial time because age-related brain changes and AD pathologies often begin then, especially in people at genetic or familial risk. While previous studies have demonstrated cross-sectional associations between physical activity and reduced AD biomarkers, few have examined how changes in activity levels—particularly adherence to WHO recommendations—affect the progression of AD-related changes in at-risk individuals.

About the study

In this study, researchers assessed a critical research gap by examining whether increasing physical activity, including adherence to WHO guidelines, is associated with risk of AD in middle-aged, cognitively unimpaired adults with lower Aβ burden and better brain structure.

They analyzed data from 337 cognitively unimpaired participants in Catalonia from a larger study of preclinical Alzheimer's disease (AD). Participants, aged between 45 and 65 years and primarily with a family history of AD, had physical activity data collected at baseline (2013–2014) and follow-up (approximately 4 years later). Only those with MRI and/or amyloid PET data at follow-up were included.

Physical activity was assessed using a questionnaire that recorded weekly minutes of moderate or vigorous activity. Participants were grouped based on adherence to WHO guidelines at both time points: maintained, maintained, non-adherent, adherent, non-adherent and adherent. A continuous measure of activity change was also calculated.

Brain amyloid burden was assessed by positron emission tomography (PET) imaging, and cortical thickness in AD-sensitive regions was measured using structural magnetic resonance imaging (MRI). The AD signature region was defined using a composite of medial temporal lobe areas susceptible to early AD atrophy.

Statistical models examined how physical activity groups and changes in activity predicted amyloid burden and cortical thickness at follow-up, adjusting for age, sex, education, apolipoprotein E (APOE)-ε4 status, and time between assessments.

Sensitivity analyzes also controlled for cardiovascular and mental health factors such as symptoms of depression and anxiety.

It is worth noting that the brain imaging results were only measured at follow-up, so causality cannot be firmly established. Additionally, 99.4% of participants were Caucasian, limiting the generalizability of the results to other populations.

Results

Participants were divided into five groups based on adherence to WHO physical activity guidelines. Nearly 30% remained sedentary while 15.7% adhered to their treatment. Those who became adherent showed the greatest increase in minutes of physical activity. There were no significant group differences for age, education, gender or ApoE-ε4 status.

Participants who maintained sedentary behavior had significantly lower cortical thickness of Alzheimer's disease (AD)-sensitive brain regions than those who were adherent or even those who were non-adherent but not sedentary. Additionally, those who became adherent had significantly lower amyloid-β (Aβ) burden than those who did not become adherent, a finding that remained statistically significant even after correction for multiple comparisons. The difference in amyloid burden between those who became adherent and those who remained sedentary was also present but less robust.

A dose-response association was found, with increased physical activity correlating with lower Aβ burden; However, this dose-dependent effect was not observed for cortical thickness. These results remained largely robust after adjusting for cardiovascular risk and mental health outcomes, although some associations with cortical thickness were attenuated after these adjustments.

Conclusions

The study shows that increased or sustained physical activity in midlife is associated with lower Aβ burden and greater cortical thickness in AD-prone brain regions, highlighting the potential neuroprotective effects.

Even partial adherence to activity guidelines (i.e., non-adherent but non-sedentary) appeared to be beneficial. A dose-dependent relationship between increased activity and decreased Aβ supports this association.

Strengths of this analysis include longitudinal design, biomarker data, and adjustment for confounders. However, the study is limited by the observational nature of the survey design, limited ethnic diversity, use of self-reported physical activity, and inability to rule out reverse causation due to brain outcomes measured only at follow-up. Potential unmeasured mediators such as sleep or neurogenesis were also not assessed.

Overall, the results suggest that adopting WHO-recommended physical activity during midlife can improve resilience to early AD pathology even in at-risk individuals.

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