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. 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.

Hippocampal‐DMN disconnectivity in MS is related to WM lesions and depression

“…In this context, the intrinsic activity of the default-mode network (DMN), a medial cortical network involving several fronto-parietal brain regions and the hippocampus, which is active at rest, and deactivated during performance of goal-oriented tasks, is of particular interest . An abnormal RS functional connectivity (FC) of the hippocampus with frontal, temporal, and parietal regions has also been demonstrated in these patients [Cao et al, 2012;Shu et al, 2014;Zeng et al, 2012]. An abnormal RS functional connectivity (FC) of the hippocampus with frontal, temporal, and parietal regions has also been demonstrated in these patients [Cao et al, 2012;Shu et al, 2014;Zeng et al, 2012].…”

“…In patients with major depressive disorders, DMN abnormalities have been shown [Bluhm et al, 2009;Chen et al, 2015;Zeng et al, 2012;Zhu et al, 2012] and have been linked to aberrant psychological processes occurring in this condition, such as alterations of self-referential schemes, cognitive biases, ruminations, and processing mode (over-general vs. concrete) [Belzung et al, 2015]. An abnormal RS functional connectivity (FC) of the hippocampus with frontal, temporal, and parietal regions has also been demonstrated in these patients [Cao et al, 2012;Shu et al, 2014;Zeng et al, 2012]. Interestingly, abnormalities of the DMN and hippocampal/parahippocampal regions had the highest discriminative power in classifying major depressive individuals vs. healthy controls .…”

Current Versus Lifetime Depression, APOE Variation, and Their Interaction on Cognitive Performance in Younger and Older Adults

“…Hippocampal atrophy is also a feature of depression in the older people; depressed individuals (≥60 years old) showed larger atrophy in the left hippocampus, accompanied by greater cognitive decline, than did the nondepressed elders (19). In an elderly Chinese population, the presence of depression and the APOE e4 allele was related to greater disruption of the hippocampal functional connectivity network projecting to the bilateral dorsal anterior cingulate cortex, and the amount of disruption was associated with poorer cognitive functioning (20). The potential of synergistic effects of depression and APOE has also been reported in terms of cognitive decline.…”

Neuroimaging genomic studies in major depressive disorder: A systematic review

“…In studies using rs‐fMRI, genetic polymorphisms (LHPP, BDNF, APOE ε4, DAOA, and ACE I/D genes) were associated with particular patterns of brain activity in MDD patients. Alterations in hippocampal functional connectivity networks were associated with genetic variants in BDNF and APOE ε4 genes . Associations between APOE ε4 and ACE genes and functional connectivity of a default‐mode network have also been reported .…”

“…Alterations in hippocampal functional connectivity networks were associated with genetic variants in BDNF and APOE ε4 genes. 57,58 Associations between APOE ε4 and ACE genes and functional connectivity of a default-mode network have also been reported. 59,60 An association between the DAOA gene and activity was found in left uvula of cerebellum and left middle temporal gyrus among people with MDD, 61 and significant LHPP genotype-diagnosis effects existed in the bilateral dorsal lateral frontal cortex and left medial prefrontal gyrus in another study.…”