Exercise as a Potential Therapeutic Strategy to Target the Clinical Link Between Depression and Alzheimer's Disease: A Narrative Review

Alzheimer's disease (AD) and major depressive disorder (MDD) affect millions worldwide and both cause significant morbidity and mortality. While clinically distinctive, patients with MDD can present with memory dysfunction and patients with AD commonly report symptoms of depression. Additionally, brain pathology in MDD and AD both demonstrate decreased hippocampal volumes, and severe disease is associated with smaller hippocampal volumes in both disorders. Hippocampal neurogenesis occurs daily in healthy individuals, an impaired process in AD and MDD. MDD is thus suggested to be a risk factor for developing AD later in life; moreover, depression onset alongside AD indicates a worse prognosis. Treatment options that target hippocampal neurogenesis are being evaluated for both diseases, and aerobic exercise has shown promising results. We searched PubMed for relevant review articles published since 2000 encompassing the topics of hippocampal neurogenesis and exercise in relation to depression and AD, including novel clinical trials if they contributed information not in the chosen reviews. While much data indicates that exercise increases hippocampal neurogenesis in both MDD and AD, mood improvement in MDD, mild quality of life and cognitive improvement in AD, and reduced risk of those with MDD developing AD in response to various exercise regimens, this result was not universal. Some data indicated no difference between exercise groups and controls. Further randomized control trials into exercise as an intervention in treating MDD and preventing AD is required. However, exercise is a low-risk, affordable treatment option and is a feasible additive therapy in patients with AD and MDD.