Discovering Subtypes with Imaging Signatures in the Motoric Cognitive Risk Syndrome Consortium using Weakly-Supervised Clustering.

Introduction: Understanding the heterogeneity of brain structure in individuals with the Motoric Cognitive Risk Syndrome (MCR) may improve the current risk assessments of dementia.
Methods: We used data from 6 cohorts from the MCR consortium (N=1987). A weakly-supervised clustering algorithm called HYDRA was applied to volumetric MRI measures to identify distinct subgroups in the population with gait speeds lower than one standard deviation (1SD) above mean.
Results: Three subgroups (Groups A, B & C) were identified through MRI-based clustering with significant differences in regional brain volumes, gait speeds, and performance on Trail Making (Part-B) and Free and Cued Selective Reminding Tests.
Discussion: Based on structural MRI, our results reflect heterogeneity in the population with moderate and slow gait, including those with MCR. Such a data-driven approach could help pave new pathways toward dementia at-risk stratification and have implications for precision health for patients.
Competing Interests: HMB serves as a consultant for Neural+. RBL is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He also receives support from the Migraine Research Foundation and the National Headache Foundation and research grants from TEVA, Satsuma and Amgen. He serves on the editorial board of Neurology, senior advisor to Headache, and associate editor to Cephalalgia. He has reviewed for the NIA and NINDS, holds stock and stock options in Axon, Biohaven Holdings, CoolTech and Manistee; serves as consultant, advisory board member, or has received honoraria from: Abbvie (Allergan), American Academy of Neurology, American Headache Society, Amgen, Avanir, Axon, Axsome, Biohaven, Biovision, Boston Scientific, Dr. Reddy’s (Promius), Electrocore, Eli Lilly, eNeura Therapeutics, Equinox, GlaxoSmithKline, Grifols, Lundbeck (Alder), Manistee, Merck, Pernix, Pfizer, Satsuma, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff’s Headache 7th and 8th Edition, Oxford Press University, 2009, Wiley and Informa. JV serves as an Advisory Committee Member for MedRhythms, and a holds a uncompensated voluntary position at CatchU. Authors BTN, AE, KKP, EA, VGPK, SV, RB, OB, TD, HS, SM, and SA do not have any conflicts of interest to disclose.