Depression symptoms moderate the relationship between gray matter volumes and cognitive function in patients with mild cognitive impairment

Previous studies have demonstrated that decreased gray matter volume (GMV) correlates with cognitive function in elderly patients with mild cognitive impairment (MCI). However, it is unclear whether those correlations are present in MCI patients with depressive symptoms (MCID). This study investigated the association among depressive symptoms, GMV and cognitive function. We included 210 participants, namely, 70 elderly MCID patients, 70 MCI patients without depressive symptoms (MCIND) and 70 healthy controls (HCs). Voxel-based morphometry (VBM) was used to investigate the structural disruptions among the patients in the three groups, and correlation analysis was performed between the GMV of regions showing group differences and cognitive function. Moderation analyses were conducted to verify the conditional effect of depressive symptoms on the relationship between structural changes and cognitive function. We found decreased GMV in the bilateral fusiform gyrus, inferior temporal gyrus, parahippocampal gyrus, and hippocampus in the MCIND group compared to the HC group. Moreover, we identified decreased GMV in the bilateral fusiform gyrus in the elderly MCID patients compared with the elderly MCIND patients, which provides further insights into the neural mechanisms of depressive symptoms in patients with MCID. Most importantly, the severity of depressive symptoms moderated the positive correlation between the GMV of abnormal brain regions and cognitive function. Furthermore, this study is the first report of the moderating effect of depressive symptoms on the GMV of abnormal brain areas and cognitive function in patients with MCID, indicating the significance of clinical intervention in elderly MCI patients with depressive symptoms.