Predicting time to dementia using a quantitative template of disease progression

INTRODUCTION: Characterization of longitudinal trajectories of biomarkers implicated in sporadic Alzheimer's disease (AD) in decades before clinical diagnosis is important for disease prevention and monitoring. METHODS: We used a multivariate Bayesian model to temporally align 1369 Alzheimer's disease Neuroimaging Initiative participants based on the similarity of their longitudinal biomarker measures and estimated a quantitative template of the temporal evolution of cerebrospinal fluid A [Formula: see text] , p- [Formula: see text] , and t-tau and hippocampal volume, brain glucose metabolism, and cognitive measurements. We computed biomarker trajectories as a function of time to AD dementia and predicted AD dementia onset age in a disjoint sample. RESULTS: Quantitative template showed early changes in verbal memory, cerebrospinal fluid Aβ(1–42) and p-tau(181p), and hippocampal volume. Mean error in predicted AD dementia onset age was [Formula: see text] years. DISCUSSION: Our method provides a quantitative approach for characterizing the natural history of AD starting at preclinical stages despite the lack of individual-level longitudinal data spanning the entire disease timeline.