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

Objectives To investigate if higher baseline leisure time physical activity level (LTA) is associated with less brain Aβ burden and whether 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. Energy expenditure (METs٠min/week) in LTA was measured at baseline using the Minnesota Physical Activity Questionnaire. Positron emission tomography (PET) data with 11C-PiB-PET imaging was carried out to assess brain Aβ burden and quantified using global cortical distribution volume ratios (DVRs). A subsample of 128 participants underwent longitudinal PiB-PET (2.0 ± 0.9 scans over 5 ± 3 years). Statistical analysis was run according to LTA (high/low group) and ApoE4 genotype (carrier/noncarrier). Results ApoE4 genotype moderated the relationship between LTA and Aβ, such that low LTA had a greater impact on PiB-DVR in ApoE4-carriers than noncarriers. This ApoE4 x LTA effect on PiB was also observed when all available PiB timepoints were included in the model. Brain Aβ deposition increased over time (p < 0.001), and ApoE4-carriers had disproportionately greater Aβ accumulation than ApoE4-noncarriers. The lower LTA group had marginally greater Aβ accumulation than the higher LTA group (p = 0.099), but there was no significant ApoE4 effect on Aβ accumulation. Conclusions Low LTA in combination with ApoE4-carrier genotype is associated with increased Aβ burden, suggesting that ApoE4 moderates the effect of LTA on Aβ load. However, this effect was insufficient for baseline PA to modulate the change in Aβ accumulation over time.