Genetic factors moderate everyday physical activity effects on executive functions in aging: Evidence from the Victoria Longitudinal Study

Objective: Everyday physical activity (EPA) is an important modifiable contributor to age-related variability in executive functioning (EF). However, its role may be moderated by nonmodifiable genetic factors. We tested independent and interactive effects of brain-derived neurotrophic factor (BDNF rs6265) and insulin degrading enzyme (IDE rs6583817) on EF and EPA-EF relationships. Method: The sample consisted of genotyped older adults (N = 577; M age = 70.47 years) over 3 waves (~9 years) of the Victoria Longitudinal Study. Analyses included (a) confirmatory factor analysis establishing a single latent EF factor from 4 standard EF tasks, (b) latent growth modeling over a 40-year band of aging (ages 53 to 95), and (c) structural regression to investigate the independent and interactive effects of BDNF, IDE, and EPA. Results: First, higher levels of EPA were associated with better EF performance at the centering age (75 years) and less EF decline. Second, IDE G+ (protective) carriers exhibited better EF performance at Age 75 than their G-(nonprotective) peers. Third, within the IDE G+ carrier group, those with higher EPA exhibited better EF performance and slower decline over time than those with lower EPA. Fourth, for the BDNF homozygote Val group, higher EPA was associated with better EF performance and more gradual EF change; however, this beneficial effect was not seen for Met carriers. Conclusion: The effect of modifiable physical health factors on EF is moderated by biological mechanisms associated with risk-protection genetic polymorphisms.