Objective: The Stages of Objective Memory Impairment (SOMI) system, based on the Free and Cued Selective Reminding Test (FCSRT), is a potential marker of subtle cognitive impairment in cognitively normal persons defined by a Clinical Dementia Rating (CDR) = 0. We investigated SOMI’s ability to predict incident cognitive impairment (CDR >0) in combination with demographic features and neuroimaging biomarkers. Methods: Cognitively unimpaired participants (CDR = 0) from the Harvard Aging Brain Study had baseline FCSRT scores, MRI, FDG-PET, and PiB-PET as well as follow-up CDRs for 5 years. Cox proportional hazards models with correction for multiple testing assessed the predictive validity of SOMI and neuroimaging biomarkers for progression (CDR >0). Comprehensive sensitivity analyses examined alternative outcomes and stricter screening criteria. Results: Participants (N = 231) were 73.7 years (SD = 6.0), 60.2% were female, 29.0% were APOE4 positive, and 54 (23.4%) progressed to CDR >0. At baseline, 67% were SOMI-0, 22% were SOMI-1, 4% were SOMI-2, and 7% were SOMI-3/4. After multiple testing correction, hazard ratios (HRs) using SOMI-0 as reference were: SOMI-1 = 2.06 (CI: 1.09 – 3.88), SOMI-2 = 2.85 (CI: 1.08 – 7.54), and SOMI-3/4 = 3.73 (CI: 1.58 – 8.79, p = 0.016). SOMI-3/4 remained significant across most biomarker models. Entorhinal thickness emerged as the most robust biomarker predictor (HR = 0.57 – 0.65, p ≤ 0.015). Sensitivity analyses confirmed robustness across alternative outcomes and stricter screening criteria. Conclusions: SOMI stages predict progression to incident cognitive impairment with SOMI-3/4 maintaining significance after rigorous multiple testing correction. Entorhinal thickness provides the strongest biomarker enhancement to prediction models. SOMI demonstrates substantial incremental predictive value beyond standard demographic and biomarker predictors.

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 speeds
- Slower gait speeds were associated with substantial cortical atrophy, higher rates of Motoric Cognitive Risk Syndrome (MCR), and worse cognitive performance
- This approach can aid patient stratification at early asymptomatic stages and have implications for precision health.