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Comparison of ApoE-related brain connectivity differences in early MCI and normal aging populations: an fMRI study

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Abstract

In this study, we used resting-state functional magnetic resonance imaging (rs-fMRI) scans from subjects with early mild cognitive impairment (EMCI) and control subjects to study functional network connectivity. The scans were acquired by the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We used genetic data from the ADNI database to further subdivide the EMCI and control groups into genotype groups with or without the Apolipoprotein E allele e4 (APOE e4). Region of interest (ROI)-to-ROI resting-state functional connectivity was measured using Freesurfer and the Functional Connectivity Toolbox for Matlab (CONN). In our analysis, we compared whole-brain ROI connectivity strength and ROI-to-ROI functional network connectivity strength between EMCI, control and genotype subject groups. We found that the ROI network properties were disrupted in EMCI and APOE e4 carrier groups. Notably, we show that (1) EMCI disrupts functional connectivity strength in many important functionally-linked areas; (2) APOE e4 disrupts functional connectivity strength in similar areas to EMCI; and (3) the differences in functional connectivity between groups shows a multifactor contribution to functional network dysfunction along the trajectory leading to dementia.

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Acknowledgments

Data collection and sharing for this project was funded by the Alzheimer’s disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare;; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

Conflict of interest

Faye McKenna, Bang-Bon Koo and Ronald Killiany declare that they have no conflict of interest.

Ethical standard

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

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Correspondence to Faye McKenna.

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Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (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

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McKenna, F., Koo, BB., Killiany, R. et al. Comparison of ApoE-related brain connectivity differences in early MCI and normal aging populations: an fMRI study. Brain Imaging and Behavior 10, 970–983 (2016). https://doi.org/10.1007/s11682-015-9451-z

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