The impact of exercise on cognitive function and brain health across the lifespan: A systematic review

Abstract Exercise has profound positive effects on cognitive function and brain health throughout different life stages. This systematic review aims to evaluate the multifaceted impacts of exercise on cognitive function, neuroplasticity, neurotransmitter expression, cerebrovascular function, and age‐related cognitive decline across the lifespan. Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 guidelines, we systematically searched PubMed, Web of Science, and Scopus databases for studies examining exercise interventions and cognitive function. Eligibility criteria included studies involving human participants across all age groups and animal models focusing on molecular mechanisms. The review employed qualitative synthesis to examine exercise modalities and age‐specific effects. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists. A total of 37 studies were included in the final synthesis (young adults: 2, middle‐aged adults: 7, older adults/neurodegenerative diseases: 13, molecular mechanisms: 15). Regular physical activity, including aerobic, resistance, and combined training, significantly enhances cognitive abilities, promotes neuroplasticity, and mitigates age‐related cognitive decline. Key molecular mechanisms include upregulation of brain‐derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), and modulation of dopaminergic and serotonergic systems. Exercise serves as a potent non‐pharmacological intervention for maintaining cognitive vitality and mental health. Limitations include heterogeneity in exercise protocols and outcome measures across studies. Future research should focus on multi‐omics approaches to further elucidate cell‐type‐specific effects.