BackgroundLate-life depression (LLD) is linked to various medical conditions and influenced by aging-related processes. Sleep disturbances and insomnia symptoms may be early indicators or risk factors for depression. Neuroimaging studies have attempted to understand the neural mechanisms underlying LLD, focusing on different brain networks. This study aims to further delineate discriminative brain structural profiles for LLD with insomnia using MRI. MethodsWe analyzed 24 cases in the LLD with insomnia group, 26 cases in the LLD group, and 26 in the healthy control (HC) group. Patients were evaluated using the Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Mini-Mental State Examination (MMSE), and Pittsburgh Sleep Quality Index (PSQI). Structural MRI data were gathered and analyzed using voxel-based morphometry (VBM) to identify differences in gray matter volume (GMV) among the groups. Correlation analyses were conducted to explore the relationships between GMV and clinical characteristics. ResultsSignificant difference in sex distribution was observed across the groups (p = 0.029). However, no significant differences were detected in age and MMSE scores among the groups. LLD with insomnia group exhibited significantly higher HAMA (p = 0.041) and PSQI scores (p < 0.05) compared to the LLD group. ANOVA identified significant difference in GMV of anterior lobe of cerebellum (peak MNI coordinate: x = 52, y = -40, z = -30) among HC, LLD, and LLD with insomnia. Post-hoc two-sample t-tests revealed that the significant difference in GMV was only found between the LLD group and the HC group (p < 0.05). The mean GMV in the cerebellum was positively correlated with HAMA scale in LLD patients (r = 0.47, p < 0.05). ConclusionThere is significant difference in GMV in the LLD group, the association between late-life depression and insomnia may be linked to anxiety. This study provides insights into the discriminative brain structural profiles of LLD and LLD with insomnia, advancing the understanding of the underlying neural mechanisms and potential targets for intervention.