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, 8,35963.3% female, mean SD age 71.08.4).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.
Stark et al. (Fri,) studied this question.