Minor neuropsychological deficits and stage 2 of Alzheimer’s disease

AI Summary

Subjective cognitive decline and minor neuropsychological deficits markedly increase risk of MCI and dementia, including among amyloid-positive cognitively normal individuals.
Participants with both SCD and MNPD triple amyloid testing's positive predictive value for five-year MCI and reduce trial sample size to one quarter.
Incorporating SCD and MNPD into preclinical AD assessment improves risk stratification, informing trial design, counselling, and early treatment identification.

Alzheimers Dement. 2026 May;22(5):e71458. doi: 10.1002/alz.71458.

ABSTRACT

INTRODUCTION: Subtle symptoms, like subjective cognitive decline (SCD) and minor neuropsychological deficits (MNPD), can improve the risk stratification in preclinical Alzheimer´s disease (AD) but their importance is insufficiently elaborated.

METHODS: We pooled data from cognitively normal individuals participating in three longitudinal cohort studies (N = 13,192, 8,359[63.3%] female, mean [SD] age 71.0[8.4]).

RESULTS: Compared to participants without SCD and MNPD (SCD-/MNPD-), SCD-/MNPD+, SCD+/MNPD-, and SCD+/MNPD+ participants had an increased risk for mild cognitive impairment (MCI) and dementia, including in amyloid-positive individuals. Focusing on SCD+/MNPD+ participants triples the positive predictive value of amyloid biomarker testing for the 5-year prediction of MCI and reduces the required samples size for trials in preclinical AD to one fourth, compared to considering all cognitively normal participants regardless of subtle symptoms.

DISCUSSION: SCD and MNPD offer a powerful approach for risk stratification in preclinical AD, which can improve clinical trial designs, risk counseling, and future case identifications for early treatment.

PMID:42129577 | DOI:10.1002/alz.71458

Document this CPD