Default Mode Network Connectivity Moderates the Relationship Between the APOE Genotype and Cognition and Individualizes Identification Across the Alzheimer’s Disease Spectrum
Affiliations: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
Correspondence:
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Correspondence to: Qingguo Ren and Chunming Xie, Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China. Tel.: 0086 25 83262241; E-mails: 101011769@seu.edu.cn (Chunming Xie); 101011331@seu.edu.cn (Qingguo Ren).
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abstract: Although previous studies have investigated the effects of the apolipoprotein E (APOE) ɛ4 genotype on the default mode network (DMN) in the Alzheimer’s disease (AD) spectrum, it is still unclear how the APOE genotype regulates the DMN and subsequently affects cognitive decline in the AD spectrum. One hundred sixty-nine subjects with resting-state functional magnetic resonance imaging data and neuropsychological test scores were selected from the Alzheimer’s Disease Neuroimaging Initiative. The main effects and interaction of the APOE genotype and disease status on the DMN were explored. A moderation analysis was performed to investigate the relationship among the APOE genotype, DMN connectivity, and cognition. Additionally, the pair-wised DMN connectivity was used to classify AD spectrum, and the classification accuracy was validated. Compared to APOE ɛ4 non-carriers, APOE ɛ4 carriers showed the opposite trajectory of DMN connectivity across the AD spectrum. Specifically, the strengths in the posterior cingulate cortex (PCC) connecting with the right precuneus, insular, and fusiform area (FFA) were positively correlated with Mini-Mental State Examination (MMSE) scores in APOE ɛ4 non-carriers but not in APOE ɛ4 carriers. Furthermore, PCC-right FFA connectivity could moderate the effects of the APOE genotype on MMSE scores across the disease groups. More importantly, using a receiver operating characteristic analysis, these altered connectivities yielded strong classification powers in a pathological stage-dependent manner in the AD spectrum. These findings first identified the intrinsic DMN connectivity moderating the effect of the APOE genotype on cognition and provided a pathological stage-dependent neuroimaging biomarker for early differentiation of the AD spectrum.
Keywords: Alzheimer’s disease, apolipoprotein E, classification, moderation analysis, resting-state functional magnetic resonance imaging
