Predicting amyloid-beta pathology in the general population.

Abstract

Reliable models to predict amyloid beta (Aβ) positivity in the general aging population are lacking but could become cost-efficient tools to identify individuals at risk of developing Alzheimer's disease. We developed Aβ prediction models in the clinical Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study (n=4,119) including a broad range of easily ascertainable predictors (demographics, cognition and daily functioning, health and lifestyle factors). Importantly, we determined the generalizability of our models in the population-based Rotterdam Study (n=500). The best performing model in the A4 Study (area under the curve [AUC]=0.73 [0.69-0.76]), including age, apolipoprotein E (APOE) ε4 genotype, family history of dementia, and subjective and objective measures of cognition, walking duration and sleep behavior, was validated in the independent Rotterdam Study with higher accuracy (AUC=0.85 [0.81-0.89]). Yet, the improvement relative to a model including only age and APOE ε4 was marginal. Aβ prediction models including inexpensive and non-invasive measures were successfully applied to a general population-derived sample more representative of typical older non-demented adults.