Men and women show partly distinct effects of physical activity on brain integrity

INTRODUCTION: Physical inactivity and female sex are independently associated with increased Alzheimer's disease (AD) lifetime risk. This study investigates the possible interactions between sex and physical activity on neuroimaging biomarkers. METHODS: In 134 cognitively unimpaired older adults (≥65 years, 82 women) from the Age‐Well randomized controlled trial (baseline data), we investigated the association between physical activity and multimodal neuroimaging (gray matter volume, glucose metabolism, perfusion, and amyloid burden), and how sex modulates these associations. RESULTS: The anterior cingulate cortex volume was independently associated with sex and physical activity. Sex and physical activity interacted on perfusion and amyloid deposition in medial parietal regions, such that physical activity was related to perfusion only in women, and to amyloid burden only in men. DISCUSSION: Physical activity has both sex‐dependent and sex‐independent associations with brain integrity. Our findings highlight partly distinct reserve mechanisms in men and women, which might in turn influence their risk of AD. HIGHLIGHTS: Sex and physical activity have been linked to Alzheimer's disease (AD) progression. The association of sex and physical activity with brain health is partly independent. Different reserve mechanisms exist in men and women.