Assessing Stages of Objective Memory Impairment and neuroimaging as risk factors of incident cognitive impairment

Abstract

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.