IC‐P‐200: Effects of depression and mild cognitive impairment on the hippocampal functional connectivity network in the elderly (2013)

Late-life depression (LLD) and amnestic mild cognitive impairment (MCI) are highly prevalent in the elderly, and is associated with increased risk for the incident Alzheimer's disease when they occur alone or in combination (Steffens et al., 2006). However, the neural mechanistic similarities and differences associated with these disorders when they occur alone or coexist are unclear. The purpose of this study is to characterize the hippocampal functional connectivity (HFC) abnormalities implicated in LLD and/or MCI with resting-state fMRI (R-fMRI) approach. Eighteen LLD, 17 MCI, 12 MCI with LLD, and 25 age-matched cognitively normal (CN) participants that were recruited completed neuropsychiatric assessments and MRI scan. The intrinsic connectivity of bilateral hippocampus (seed regions) was measured by the R-fMRI approach at a 3.0 T GE scanner. The correlation coefficient maps of individual participant were generated by cross-correlating each voxel timecourse with the average time course of seed regions. Fisher's Z-transformation was then performed in the resulting datasets, and data normalized to a standard Talairach space. Voxelwise 2 × 2 ANCOVA analysis was used to examine the main effects and interactive effects of LLD and MCI on the HFC networks in the four groups, after controlling for age, gender, education and gray matter volumes. The main effects of depression on the bilateral HFC was seen in the regions previously implicated in mood regulation, including bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), thalamus, and dorsal striatum; main effects of MCI on the bilateral HFCs were seen in the default mode, executive control and salience network-related regions (Fig 1a representing right HFC); The interactive effects of depression and MCI on the right HFC network were identified in the bilateral ventromedial PFC, dorsal anterior cingulate cortex, right DLPFC and middle occipital gyrus (Fig 1b). Divergent hippocampal network abnormalities were associated with LLD and MCI, whereas shared and interactive effects of these disorders were also identified. The presence of specific medial temporal lobe-based network dysfunction may increase the vulnerability of individuals with LLD and/or MCI to progress to AD. Main effects of depression and mild cognitive impairment on the right hippocampal functional connectivity (RHFC) networks across all subjects (p < 0.05, AlphaSim correction). Bright color indicates increased connectivity and blue color indicates decreased connectivity. Abbreviation: Dep: depression; CI: mild cognitive impairment. R1: left dorsolateral prefrontal cortex; R2: left middle occipital gyrus; R3: left hippocampus; R4: left thalamus; R5: left putamen; R6: left caudate; R7: right lentiform nucleus; R8: right thalamus; R9: right middle occipital gyrus; R10: left ventrolateral prefrontal cortex; R11: left anterior temporal pole; R12: left inferior parietal cortex; R13: left posterior middle temporal gyrus; R14: right supramarginal gyrus/inferior parietal cortex; R15: right anterior temporal pole; R16: left parahippocampal gyrus; R17: right inferior temporal cortex. Fig. 1b. Interactive effects of late-life depression and amnestic mild cognitive impairment on the right hippocampal functional connectivity (RHFC) networks (p < 0.05, AlphaSim correction). Top: Brain regions with significant interactive effects between late-life depression and mild cognitive impairment on the RHFC network. Bottom: Numerical representation of significant interactive effects of depression and cognitive impairment on the RHFC network. *: p < 0.05; **: p < 0.01. Abbreviation: LMOC, left middle occipital gyrus; LdACC, left dorsal cingulate cortex; vmPFC, ventromedial prefrontal cortex; RdACC, right dorsal anterior cingulate cortex; RMOG, right middle occipital gyrus; RDLPFC, right dorsolateral prefrontal cortex; CN, cognitively normal; aMCI, amnestic mild cognitive impairment; Dep, Late-life depression; dMCI, comorbid late-life depression and amnestic mild cognitive impairment.