journal articles
STAGES OF OBJECTIVE MEMORY IMPAIRMENT (SOMI) AS A PREDICTOR OF CLINICAL PROGRESSION IN THE A4 STUDY
Priyanka Kumari, Richard B. Lipton, Andrew J. Aschenbrenner, Reisa Sperling, Michael C. Donohue, Ellen Grober
BACKGROUND: About one third of amyloid positive, cognitively normal individuals develop mild cognitive impairment or clinical Alzheimer dementia (AD) over 5 years of follow-up. Sensitive cognitive measures, in addition to biomarkers of amyloid pathology, add to the efficiency of secondary prevention trials by identifying cognitively normal individuals at greatest risk of clinical progression. The Stages of Objective Memory Impairment (SOMI) system, based on the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR), predicted clinical progression in two observational studies.
OBJECTIVE: Our objective was to extend SOMI’s findings to clinical trials using participants from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s(A4) study.
METHODS: Eligible participants were cognitively normal, had a Clinical Dementia Rating (CDR) =0, an elevated amyloid level, the pFCSRT+IR, pTau217, and longitudinal data on the CDR. Cox proportional hazards model was used to assess the association of baseline SOMI stage for clinical progression defined by time to the first of 2 consecutive CDRs > 0 or CDR>0 at last assessment. The sample was censored at 4.5 years of follow-up.
RESULTS: Of the 911 eligible participants, mean age was 72 years, 59% were female, 62% were APOE ε4 carriers, and 37% progressed over 4.5 years. Hazard ratios (HR) for progression were estimated with follow-up time as the timescale and the SOMI 0 group as the reference. The HRs for progression across SOMI stage increased from 1.48(1.15–1.92 p=.003) for SOMI-1, to 1.83 (1.32–2.54, p ≤ 0.001) for SOMI-2, and to 3.04 (1.97–4.68, p ≤ 0.001) for SOMI 3/4. SOMI remained an independent and significant predictor when pTau217 was added to the model.
CONCLUSION: SOMI’s risk profile in A4 was similar to prior findings in observational cohorts. SOMI provides a low-cost, non-invasive enrichment tool for identifying individuals at risk for early cognitive decline in secondary prevention trials.
CITATION:
Priyanka Kumari ; Richard B. Lipton ; Andrew J. Aschenbrenner ; Reisa Sperling ; Michael C. Donohue ; Ellen Grober (2026): Stages of objective memory impairment (SOMI) as a predictor of clinical progression in the A4 study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100641