Physical activity and APOE neuropathology score modify the association of age and -PiB-PET amyloid burden in a cohort enriched with risk for Alzheimer's disease

BackgroundPhysical activity (PA) is a protective factor against amyloid-{beta} (A{beta}) accumulation in adults at risk for Alzheimers disease (AD). This association, however, may differ by apolipoprotein E (APOE) genotype. This work examines interactions between age, PA, and neuropathology-based genetic risk for AD (APOEnp) on A{beta} burden in cortical regions sensitive to its accumulation. Materials and MethodsIncluded were 388 cognitively unimpaired, older (mean age {+/-} SD = 68.10 {+/-} 7.09; 66% female) participants from the Wisconsin Registry for Alzheimers Prevention (WRAP) study. The cohort was enriched with both family history of AD at enrollment and a higher overall prevalence of APOE {varepsilon}4 allele carriage than typically observed in the general population. PA was assessed using a self-reported questionnaire. A{beta} burden was measured using Pittsburg Compound B (11C-PiB) PET imaging, which allowed us to derive volume corrected distribution volume ratio (DVR) maps from nine bilateral regions of interest (ROIs) and a global cortical composite score. Linear regression models examined the interactions between age, PA, and APOEnp on A{beta} burden. Finally, APOEnp scores were aggregated according to estimated risk to illustrate the differential effects between active (weekly moderate PA > 150 minutes) and inactive individuals. ResultsThree-way interactions (Age x PA x APOEnp) were significant (all Ps [≤] 0.05) for the global cortical composite and six of the examined ROIs (the PPC, ACC, mOFC, SMG, MTG, and STG). Models stratified by APOEnp and PA showed greater levels of age-related A{beta} accumulation in each of these ROIs, with the greatest effects in inactive participants with high APOEnp scores. ConclusionIndividuals with high APOEnp scores who concomitantly engage in suboptimal weekly moderate-intensity PA have greater A{beta} burden. These findings underscore how both PA and APOEnp haplotype play intersect in modifying age-related A{beta} burden in brain regions susceptible to its deposition in cognitively unimpaired, older adults at risk for AD.