Longitudinal Effects of Physical Activity Change on Hippocampal Volumes over Up to 12 Years in Middle and Older Age Community-Dwelling Individuals

The objectives of this study were to investigate the long-term associations between changes in physical activity levels and hippocampal volumes over time, while considering the influence of age, sex, and APOE-ε4 genotype. We investigated the effects of change in physical activity on hippocampal volumes in 411 middle age (mean age = 47.2 years) and 375 older age (mean age = 63.1 years) adults followed up to 12 years. An annual volume decrease was observed in the left (middle age: 0.46%; older age: 0.51%) but not in the right hippocampus. Each additional 10 metabolic equivalents (METs, ~2 h of moderate exercise) increase in weekly physical activity was associated with 0.33% larger hippocampal volume in middle age (equivalent to ~1 year of typical aging). In older age, each additional MET was associated with 0.05% larger hippocampal volume; however, the effects declined with time by 0.005% per year. For older age APOE-ε4 carriers, each additional MET was associated with a 0.10% increase in hippocampal volume. No sex effects of physical activity change were found. Increasing physical activity has long-term positive effects on hippocampal volumes and appears especially beneficial for older APOE-ε4 carriers. To optimize healthy brain aging, physical activity programs should focus on creating long-term exercise habits.