Physical Activity Is Associated With Age‐Related Differences in Hippocampal Macrostructure and Microstructure in Middle‐Aged and Older Adults

Abstract

Physical activity is found to promote healthy brain aging that is often indexed by hippocampal structure and function; however, evidence from cross‐sectional studies remains limited and inconsistent, particularly for hippocampal morphology. Discrepancies in the literature may be explained by a historical focus on volumetric analyses, which obscure nuanced changes in cortical geometry, particularly in heavily folded regions of the hippocampus. In this study, we conducted a cross‐sectional analysis to examine whether moderate‐to‐vigorous physical activity (MVPA) was associated with hippocampal macrostructure (thickness and surface area) and microstructure (T1w/T2w ratio) among 555 cognitively healthy adults (ages 36–90 years) from the Human Connectome Project–Aging cohort. Weekly MVPA was measured using the International Physical Activity Questionnaire, and participants were categorized as low‐active (≥ 0–< 150 min/week), moderately active (≥ 150–< 300 min/week), or highly active (≥ 300 min/week) according to the World Health Organization 2020 guidelines on physical activity. Hippocampal thickness, surface area, and T1w/T2w ratio were derived from unfolded hippocampal surfaces using HippUnfold. Multivariate general linear models tested linear and quadratic age effects and MVPA × age interactions separately for each hemisphere, controlling for demographic and health covariates. Among the low‐active group, age was associated with widespread multivariate differences in hippocampal macrostructure and microstructure, characterized by lower regionally specific thickness and surface area and by a higher T1w/T2w ratio. MVPA moderated age‐related changes in the left hippocampus, with significant effects observed in the moderate‐ and high‐MVPA groups. These effects were characterized by greater surface area and T1w/T2w ratio and were associated with lower thickness values. These results suggest that individuals who meet or exceed physical activity recommendations exhibit distinct age‐related differences in hippocampus macrostructure and microstructure compared with those who do not.