Physical Activity and Mobility Differentially Predict Nondemented Executive Function Trajectories: Do Sex and APOE Moderate These Associations?

BACKGROUND: In nondemented aging, higher levels of everyday physical activity (EPA) and mobility performance are associated with better executive function (EF) trajectories. However, these associations may be moderated by both sex and Alzheimer's disease (AD) genetic risk.

OBJECTIVES: In a longitudinal study, we investigate sex differences in (a) EPA and mobility effects on EF performance (level) and change (slope) and (b) AD genetic risk moderation of these associations.

METHODS: The longitudinal design included nondemented adults (n = 532, mean age = 70.4 years, range 53-95) from the Victoria Longitudinal Study. Using structural equation analyses on an EF latent variable, we tested (a) sex moderation and (b) interactive effects of sex and APOE on observed EPA-EF and mobility-EF performance and change relationships.

RESULTS: First, we observed independent sex effects for the EPA-EF and mobility-EF predictions. Whereas EPA had a significant effect on EF performance and change only for females, mobility had a significant effect for both sexes. Notably, males with lower mobility levels experienced steeper EF decline than females with lower mobility levels. Second, we observed significant sex × APOE interaction effects. The combination of lower genetic risk and higher EPA benefitted females but not males. In contrast, lower genetic risk and higher mobility benefited both sexes, although male APOE no-risk carriers with lower mobility levels had EF decline patterns that were similar to APOE risk carriers.

CONCLUSIONS: Longitudinal analyses across a broad band of aging show that sex moderates the effects of both EPA and mobility on EF performance and change. Notably, this moderation occurs differentially across the AD genetic risk status. These results point to a precision health approach to observational and interventional research in which effects of physical activity and mobility on EF trajectories and dementia are examined in the personalized and interactive context of sex and AD risk.