Changes in brain structure are a hallmark of aging. However, the rate of deterioration appears to be modulated by lifestyle factors. Evidence suggests that greater physical activity levels are associated with better brain health outcomes in both healthy and pathologic aging.1,2 Increasing physical activity has long been proposed as a neuroprotective lifestyle strategy to protect the aging brain. However, although the positive association between physical activity and brain structure has been studied, questions remain about the specificity of the impact of different intensities of physical activity, the areas of the brain that may be most affected, and the molecular pathways that may underlie this association. Answers to these questions have implications for our ability to harness physical activity as a neuroprotective preventive strategy and to provide evidence-based clinical recommendations.