Alzheimer's disease prevention: Apolipoprotein e4 moderates the effect of physical activity on brain beta-amyloid deposition in healthy older adults

Objectives: To investigate if higher baseline physical activity levels are associated with less beta-amyloid burden and whether the ApoE4 genotype moderates this association cross-sectionally and longitudinally. Design: Prospective cohort study. Methods: 204 cognitively normal older adults (74.5 +/- 6.6 years; 26 % ApoE4-carrier) were analyzed. Baseline physical activity was measured using the Minnesota Physical Activity Questionnaire. Brain beta-amyloid burden was measured with positron emission tomography using 11C-labeled Pittsburgh compound. A subsample of 128 participants underwent longitudinal positron emission tomography (2.0 +/- 0.9 scans over 5 +/- 3 years). Statistical analysis was run according to physical activity (high/low group) and the ApoE4 genotype (carrier/noncarrier). Results: The ApoE4 genotype moderated the relationship between physical activity and beta-amyloid, such that low physical activity had a greater impact on beta-amyloid deposition in ApoE4-carriers than noncarriers. This ApoE4 x physical activity effect on brain beta-amyloid deposition was also observed when all available beta-amyloid scan timepoints were included in the model. beta-amyloid deposition increased over time (p < 0.001), and ApoE4-carriers had disproportionately greater beta-amyloid accumulation than ApoE4-noncarriers. The lower physical activity group had marginally greater beta-amyloid accumulation than the higher physical activity group (p = 0.099), but there was no significant ApoE4 effect on beta-amyloid accumulation. Conclusions: Low physical activity in combination with the ApoE4-carrier genotype is associated with increased beta-amyloid burden, suggesting that ApoE4 moderates the effect of physical activity on beta-amyloid load. However, this effect was insufficient for baseline physical activity to modulate the change in beta-amyloid accumulation over time. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of Sports Medicine Australia. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).