Association between brain volume and depression in Alzheimer's disease: Neuroimaging insights

INTRODUCTION Alzheimer's disease (AD) often co‐occurs with depression, affecting cognitive function and quality of life. Understanding the neurobiological links between brain abnormalities and depressive symptoms is essential for effective treatment. METHODS We analyzed 2,722 participants from the National Alzheimer's Coordinating Center, including 886 AD patients and 1,836 cognitively normal controls. Neuroimaging assessed brain volumes, while depressive symptoms were measured using the Geriatric Depression Scale. Multiple linear regression and mediation analyses evaluated associations between brain structure, cognitive function, and depression. RESULTS AD patients had significantly higher rates of depressive symptoms (35.3% vs. 14.7%; p < 0.001) and cognitive impairments (mean Mini‐Mental State Examination [MMSE]: 23.1 vs. 28.9; p < 0.001). Hippocampal atrophy mediated the relationship between depression and AD (indirect effect = −0.107; p < 0.001). CONCLUSION Hippocampal atrophy significantly mediates the relationship between depression and AD, suggesting targeted interventions may enhance patient outcomes.