Comparison of amyloid chronicity and EYO in autosomal dominant Alzheimer's disease

Abstract

INTRODUCTION: Preclinical Alzheimer's disease (AD) can be described relative to biomarker positivity onset time. METHODS: We estimated time from amyloid positivity (A+) using sampled iterative local approximation (SILA) in a longitudinal autosomal dominant AD (ADAD) sample (N = 379) with amyloid positron emission tomography. We compared (1) predicted age at A+ to imputed age, (2) estimated age at A+ to estimated age at symptom onset, and (3) variance in cognitive performance explained. RESULTS: Mean error between imputed and SILA-estimated age at A+ (N = 26) was 1.15 years. Age at A+ explained 39% of estimated years to symptom onset (EYO) variance. Time from A+ explained 19% of cognitive composite variance and 14% of Clinical Dementia Rating Sum of Boxes CDR-SB variance; EYO explained 43% and 57%, respectively. DISCUSSION: SILA estimates A+ age in ADAD with reasonably good accuracy. SILA-estimated time from A+ describes the start of pathology, but the time from A+ onset to symptoms is variable in ADAD and better described by EYO. Highlights: Amyloid chronicity predicts a 14-year preclinical AD phase in ADAD. SILA accurately estimates age at A+ (MAE < 2 years). EYO outperforms chronicity in predicting symptom onset. APP mutation carriers show atypical amyloid accumulation. Chronicity models help reveal AD heterogeneity in preclinical stages.