Predicting amyloid-beta pathology in the general population

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.