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BackgroundPhysical activity (PA) is a promising strategy for the promotion of brain health, although substantial variation exists in the effects of PA at the individual level. Given the greater prevalence and faster progression of Alzheimer's disease in women compared to men, and known sex differences in brain architecture, analysis of sex differences in the relationship between PA, cognition, and brain region volumes is warranted.MethodsTo address this, we conducted secondary analyses of data from the Health, Aging, and Body Composition study. To determine whether longitudinal changes in PA over 10 years predicted declines in global cognitive functioning and executive functions and processing speed differently in males and females, latent growth curve modeling was utilized. Magnetic resonance imaging was performed at year 10, and the hippocampus and dorsolateral prefrontal cortex were identified as regions of interest.ResultsMaintaining PA over 10 years predicted less declines in executive functions and processing speed in females but not males. Maintaining PA over 10 years was significantly associated with greater volume of the left dorsolateral prefrontal cortex, a brain region involved in executive functions, in year 10 in females only. Maintaining physical activity was associated with better global cognitive function in both males and females, and also predicted volume of the left hippocampus, albeit in different directions with females showing a negative relationship and males showing a positive relationship.ConclusionsThese findings suggest that the relationship of PA with cognition and its neurobiological correlates differ by sex, with females apparently benefiting from PA to a greater extent than males. Development of personalized, tailored exercise recommendations to promote healthy brain aging should account for sex differences.

The number of older people worldwide living with cognitive impairment and neurodegenerative diseases is growing at an unprecedented rate. Despite accumulating evidence that engaging in physical activity is a promising primary behavioral strategy to delay or avert the deleterious effects of aging on brain health, a large degree of variation exists in study findings. Thus, before physical activity and exercise can be prescribed as "medicine" for promoting brain health, it is imperative to understand how different biological factors can attenuate or amplify the effects of physical activity on cognition at the individual level. In this review article, we briefly discuss the current state of the literature, examining the relationship between physical activity and brain health in older adults and we present the argument that biological sex is a potent moderator of this relationship. Additionally, we highlight some of the potential neurobiological mechanisms underlying this sex difference for this relatively new and rapidly expanding line of research. [ABSTRACT FROM AUTHOR]