Physical Activity and BrainAGE: Exploring the Impact on Brain Health and Plasticity in Older Adults

With an aging global population, cognitive decline in older adults presents significant healthcare challenges. Emerging evidence suggests that physical activity can support cognitive health by promoting plasticity, functional reorganization, and structural adaptation of the brain. In the FIT4BRAIN study, we examined the effects of multi-component physical activity on cognitive and brain health. Here, we report the results on one of the secondary outcomes, namely changes in brain age (BrainAGE), which estimates the difference between chronological and predicted brain age based on structural MRI data, and changes in brain structure, assessed through voxel-based morphometry (VBM). Ninety-two healthy older adults were randomized into a multi-component physical activity group, performing aerobic, coordination, and balance exercises, or an active control group engaging in non-aerobic relaxation exercises and educational content (physical activity group (PAG): 36 participants; active control group (CON): 33 participants). Of these, 69 participants underwent MRI assessment and were included in the present analyses. BrainAGE analyses revealed a greater decrease in the physical activity group compared to the control group, indicating a beneficial effect of physical activity on brain aging. Subgroup analyses based on baseline cardiorespiratory fitness (CRF) further revealed that participants with lower CRF showed greater benefits, consistent with VBM findings of structural changes in the same subgroup. These results underscore BrainAGE as a sensitive biomarker for intervention outcomes and suggest that stratification by baseline fitness level may help identify differences in the benefits of physical activity on brain health.