title: Imbalanced hippocampal functional networks associated with remitted geriatric depression and apolipoprotein E ε4 allele in nondemented elderly: a preliminary study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China; Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Shu
authors.affiliation: Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Xie
authors.affiliation: Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Jiayong
authors.initials: J
authors.lastname: You
authors.affiliation: Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Lingjiang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Neurologic Department of Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, China. Electronic address: janemengzhang@vip.163.com.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology; D003863:Depression / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D009415:Nerve Net / Q000503:physiopathology
chemical_list: D053327:Apolipoprotein E4
keywords: Apolipoprotein E ε4 allele; Functional connectivity; Functional magnetic resonance imaging; Hippocampus; Remitted geriatric depression; Resting state