A graph theoretic approach to neurodegeneration: five data-driven neuropsychological subtypes in mild cognitive impairment

ABSTRACT

Mild cognitive Impairment (MCI) is notoriously heterogenous in terms of clinical presentation, neuroimaging correlates, and subsequent progression. Predicting who will progress to dementia, which type of dementia, and over what timeframe is challenging. Previous work has attempted to identify MCI subtypes using neuropsychological measures in an effort to address this challenge; however, there is no consensus on approach, which may account for some of the variability. Using a hierarchical community detection approach, we examined cognitive subtypes within an MCI sample (from the Alzheimer’s Disease Neuroimaging Initiative [ADNI] study). We then examined whether these subtypes were related to biomarkers (e.g., cortical volumes, fluorodeoxyglucose (FDG)-positron emission tomography (PET) hypometabolism) or clinical progression. We identified five communities (i.e., cognitive subtypes) within the MCI sample: 1) predominantly memory impairment, 2) predominantly language impairment, 3) cognitively normal, 4) multidomain, with notable executive dysfunction, 5) multidomain, with notable processing speed impairment. Community membership was significantly associated with 1) cortical volume in the hippocampus, entorhinal cortex, and fusiform cortex; 2) FDG PET hypometabolism in the posterior cingulate, angular gyrus, and inferior/middle temporal gyrus; and 3) conversion to dementia at follow up. Overall, community detection as an approach appears a viable method for identifying unique cognitive subtypes in a neurodegenerative sample that were linked to several meaningful biomarkers and modestly with progression at one year follow up.

KEYWORDS:

• Mild cognitive impairment
• graph theory
• cognitive subtype
• Alzheimer’s disease
• heterogeneity

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: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; 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.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. 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 Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. D. Edler, A. Eriksson and M. Rosvall, The MapEquation software package, is available at the mapequation.org.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13825585.2022.2163973