Role of sex and ethnicity in the relationships among physical activity, cognition, and AD biomarkers in the HABS-HD cohort.

INTRODUCTION: Dementia prevalence is rising with population aging, disproportionately affecting females and ethnically diverse groups. Physical activity (PA) may mitigate age-related cognitive and brain decline; sex- and ethnicity-specific associations remain poorly understood. METHODS: Data from the Health and Aging Brain Study-Health Disparities were analyzed from 3585 participants (63% female). PA was categorized using the Rapid Assessment of Physical Activity (RAPA) questionnaire as no/little (< 4) or moderate/high (≥ 4). Outcomes included cognitive composites, plasma biomarkers, and magnetic resonance imaging-derived hippocampal subregions and dorsolateral prefrontal cortex volumes. RESULTS: Higher PA was associated with higher global cognition and executive functions in all females and in Hispanic males (ps < 0.05), higher episodic memory and larger hippocampal volumes across participants (ps < 0.05), and lower amyloid beta 40, total tau, and larger hippocampal subregion volumes in females (ps < 0.05). CONCLUSIONS: Findings support PA as a modifiable factor associated with healthy brain aging, emphasizing the importance of incorporating sex and ethnicity into future research.