Ensemble-Based Estimation of Alzheimer’s Disease Incidence from Dynamic Population Reconstructions

We present a two-stage methodology for reconstructing Alzheimer's disease (AD) incidence overtime using ensemble Kalman inversion (EKI) applied to mortality data. In the first stage, we use EKI to infer temporal trends in all-cause and Alzheimer's-specific mortality by fitting an age-structured demographic model to observed death counts. This yields posterior estimates of evolving population structure and age-specific AD mortality rates. In the second stage, we apply a back-calculation procedure that uses these estimates, along with the hazard of AD-related death following disease onset, to infer time- and age-specific incidence rates. This reverse-inference framework enables the reconstruction of latent disease dynamics in the absence of direct incidence surveillance. By integrating demographic structure, disease-specific hazards, and observed mortality into a coherent inferential pipeline, our approach offers a principled and flexible tool for monitoring chronic disease trends and estimating historical disease burden.