Dynamic classification of latent disease progression with auxiliary surrogate labels

Abstract

Disease progression prediction based on patients' evolving health information is challenging when true disease states are unknown due to diagnostic capabilities or high costs. For example, the absence of gold-standard neurological diagnoses hinders distinguishing Alzheimer's disease (AD) from related conditions such as AD-related dementias (ADRDs), including Lewy body dementia (LBD). Combining temporally dependent surrogate labels and health markers may improve disease prediction. However, existing literature models informative surrogate labels and observed variables that reflect the underlying states using purely generative approaches, often posing unrealistic assumptions on the outcomes and suffering from misspecification thereof. We propose integrating the conventional hidden Markov model as a generative model with a time-varying discriminative classification model to simultaneously handle potentially misspecified surrogate labels and incorporate important markers of disease progression. We develop an adaptive forward-backward algorithm with subjective labels for estimation, and utilize the modified posterior and Viterbi algorithms to predict the progression of future states or new patients based on objective markers only. Importantly, the adaptation eliminates the need to model the marginal distribution of longitudinal markers, a requirement in traditional algorithms. Asymptotic properties are established, and significant improvements in finite samples are demonstrated via simulation studies. Analysis of the neuropathological dataset of the National Alzheimer's Coordinating Center (NACC) shows much improved accuracy in distinguishing LBD from AD.