Physical Activity And Longitudinal Trajectory In Brain Beta-amyloid Accumulation

The effects of PA on longitudinal change on beta-amyloid (Aβ) burden have not been thoroughly investigated. PURPOSE: To examine if subjects with higher baseline leisure time physical activity level (LTA) exhibit less Aβ accumulation longitudinally, and whether ApoE4 genotype moderates the effect of LTA on Aβ over time. METHODS: 128 cognitively normal older adults (74.6 ± 5.4 yrs; 29% ApoE4 carrier) with available longitudinal Aβ positron emission tomography (PET) data (2 ± 1 scans over 5 ± 3 yrs) from the Berkeley Aging Cohort Study (BACS) were analyzed. Energy expenditure (METs min/week) in LTA was measured at baseline using the Minnesota Physical Activity Questionnaire. 11C-PiB PET imaging was carried out to assess brain Aβ burden, and quantified using global cortical PiB distribution volume ratios (DVRs). Linear mixed effects models were used to examine baseline and longitudinal relationships between LTA (high/low group), ApoE4 genotype (carrier/noncarrier) and PiB PET measures over time, controlling for covariates. RESULTS: ApoE4 noncarriers had lower baseline Aβ burden than ApoE4 carriers (p = .012), and subjects in the low LTA group had higher Aβ burden than high LTA subjects (p < .01). There was a significant ApoE4 genotype x LTA interaction such that LTA-related elevations in Aβ burden were greater for ApoE4 carriers than noncarriers. Levels of brain Aβ increased over time (p < .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 = .099), but there was no significant ApoE4 effect on Aβ accumulation (Figure 1). CONCLUSION: Low LTA in combination with an ApoE4 carrier genotype is associated with increased Aβ deposition suggesting that LTA may play a protective role in individuals who are genetically predisposed to accumulate Aβ.Supported by NIH Grant R01AG062542.