Structural and functional brain alterations in depression with Alzheimer’s disease and mild cognitive impairment: a multimodal coordinate-based meta-analysis

Background Depression is a common neuropsychiatric symptom in Alzheimer’s Disease (AD) and mild cognitive impairment (MCI). Inconsistent results for comparison between AD with depression (ADD), MCI with depression (MCID), and those without depression were obtained from previous neuroimaging studies. Therefore, a multimodal coordinate-based meta-analysis was conducted in this study. Methods We searched PubMed, Embase, PsycINFO and the Cochrane Library for neuroimaging studies on ADD and MCID patients from December 1995 to December 2025. Activation likelihood estimate (ALE) coordinate-based meta-analyses were performed to explore brain regions showing abnormalities in ADD and MCID compared to AD without depression (ADND) and MCI without depression (MCIND). Moreover, we performed modality and subgroup analysis of the difference in structural and neural activity. Results A total of 30 studies, comprising 1973 participants (520 ADD patients, 297 MCID patients, 748 ADND patients, and 408 MCIND patients), were included in this meta-analysis. ADD and MCID showed significantly decreased gray matter volume (GMV) in the right hippocampus and neural activity in the right superior frontal gyrus (SFG) and left inferior temporal gyrus (ITG) compared to ADND and MCID. Subgroup analysis revealed decreased neural activity in the left SFG in the ADD group compared to the ADND group, and decreased neural activity in the right SFG and left ITG in the MCID group compared to the MCIND group. Conclusion Our findings that decreased GMV of the hippocampus and abnormal neural activities of SFG and ITG in ADD and MCID expand novel insights into the neural mechanisms of depression in AD and MCI, representing potential neural correlates for depression in ADD and MCID.