Exercise and the Aging Brain: Considerations for Sex Differences

Engaging in targeted exercise interventions is a promising, non-pharmacological strategy to mitigate the deleterious effects of aging and disease on brain health. However, despite its therapeutic potential, a large amount of variation exists in exercise efficacy in older adults aged 55 and older. In this review, we present the argument that biological sex may be an important moderator of the relationship between physical activity and cognition. Sex differences exist in dementia as well as in several associated risk factors, including genetics, cardiovascular factors, inflammation, hormones and social and psychological factors. Different exercise interventions, such as aerobic training and resistance training, influence cognition and brain health in older adults and these effects may be sex-dependent. The biological mechanisms underlying the beneficial effects of exercise on the brain may be different in males and females. Specifically, we examine sex differences in neuroplasticity, neurotrophic factors and physiological effects of exercise to highlight the possible mediators of sex differences in exercise efficacy on cognition. Future studies should address the potential sex difference in exercise efficacy if we are to develop effective, evidence-based exercise interventions to promote healthy brain aging for all individuals.