Information-Theoretic Clustering of Neuroimaging Metrics Related to Cognitive Decline in the Elderly
As Alzheimer’s disease progresses, there are changes in metrics of brain atrophy and network breakdown derived from anatomical or diffusion MRI. Neuroimaging biomarkers of cognitive decline are crucial to identify, but few studies have investigated how sets of biomarkers cluster in terms of the information they provide. Here, we evaluated more than 700 frequently studied diffusion and anatomical measures in 247 elderly participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). We used a novel unsupervised machine learning technique - CorEx - to identify groups of measures with high multivariate mutual information; we computed latent factors to explain correlations among them. We visualized groups of measures discovered by CorEx in a hierarchical structure and determined how well they predict cognitive decline. Clusters of variables significantly predicted cognitive decline, including measures of cortical gray matter, and correlated measures of brain networks derived from graph theory and spectral graph theory.
KeywordsMachine learning Diffusion weighted imaging Brain connectivity Spectral graph theory Gray matter
Algorithm development and image analysis for this study was funded, in part, by grants to PT from the NIBIB (R01 EB008281, R01 EB008432) and by the NIA, NIBIB, NIMH, the National Library of Medicine, and the National Center for Research Resources (AG016570, AG040060, EB01651, MH097268, LM05639, RR019771 to PT). Data collection and sharing for this project was funded by ADNI (NIH Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from the following: Abbott; Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; Novartis Pharmaceuticals Corporation; Pfizer Inc.; 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. 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. This research was also supported by NIH grants P30 AG010129 and K01 AG030514 from the National Institute of General Medical Sciences; and by a Consortium grant (U54 EB020403) from the NIH Institutes contributing to the Big Data to Knowledge (BD2 K) Initiative, including the NIBIB and NCI.
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