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 six cohorts from the MCR consortium (N = 1987). A weakly-supervised clustering algorithm called HYDRA (Heterogeneity through Discriminative Analysis) was applied to volumetric magnetic resonance imaging (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, and 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. Highlights: Different patterns of brain atrophy were observed among the people with moderate and slow gait speedsSlower gait speeds were associated with substantial cortical atrophy, higher rates of Motoric Cognitive Risk Syndrome (MCR), and worse cognitive performanceThis approach can aid patient stratification at early asymptomatic stages and have implications for precision health.