Abstract
BACKGROUND: Apolipoprotein E (APOE) ε4 allele and a history of geriatric depression are confirmed risk factors of Alzheimer׳s disease (AD). Coexistence of both factors could notably enhance the risk of cognitive impairment in nondemented elderly. However, neural basis of the association remains unclear. METHODS: Thirty-one remitted geriatric depression (RGD) patients and 29 cognitively normal subjects were recruited and underwent resting-state functional MRI scans. They were further divided into four groups according to their APOE genotypes. Hippocampal seed-based network analysis and two-way factorial analysis of covariance were employed to detect the main effects and interactive effects of RGD and APOE ε4 allele on the hippocampal functional connectivity (HFC) networks. Partial correlation analysis was applied to examine the cognitive significance of these altered HFC networks. RESULTS: The HFC networks of RGD patients were decreased in the dorsal frontal and increased in the right temporal-occipital regions. For APOE ε4 carriers, the HFC networks were reduced primarily in medial prefrontal regions and enhanced in the bilateral insula. Additionally, when both factors coexisted, the left HFC network was significantly disrupted in the dorsal anterior cingulate cortex and increased in somatomotor and occipital regions. Importantly, the extent of network alterations was linked to inferior cognitive performances in RGD patients and APOE ε4 carriers. LIMITATIONS: The small sample size may limit the generalizability of our findings. CONCLUSIONS: RGD and APOE ε4 allele, and their interaction, are associated with the imbalanced HFC network, which may contribute to cognitive deterioration for subjects with a high risk of AD.