Abstract
BACKGROUND: Alzheimer's disease is a progressive neurodegenerative disease characterized by structural changes in the brain, including hippocampal atrophy, cortical thinning, amyloid plaques, and tau tangles. Due to the aging of the global population, the burden of Alzheimer's disease is expected to increase, making the exploration of non-pharmacological interventions, such as physical exercise, an urgent priority. RESULTS: There is emerging evidence that regular physical exercise may mitigate the structural and functional declines associated with Alzheimer's disease. The underlying mechanisms, however, remain poorly understood. Gut-brain axis research is a promising area for further investigation. This system involves bidirectional communication between the gut microbiome and the brain. According to recent studies, the gut microbiome may influence brain health through modulating neuroinflammation, producing neuroactive compounds, and altering metabolic processes. Exercise has been shown to alter the composition of the gut microbiome, potentially impacting brain structure and function. In this review, we aim to synthesize current research on the relationship between physical exercise, structural brain changes in Alzheimer's disease, and the gut-brain axis. CONCLUSIONS: In this study, we will investigate whether changes in the gut microbiome induced by physical exercise can mediate its neuroprotective effects, offering new insights into the prevention and treatment of Alzheimer's disease. By integrating findings from neuroimaging studies, clinical trials, and microbiome research, this review will highlight potential mechanisms. It will also identify key gaps in the literature. This will pave the way for future research directions.