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

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.

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.

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.

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.