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Alzheimer's disease is a firmly incurable and progressive disease. The pathology of Alzheimer's disease usually evolves from cognitive normal, to mild cognitive impairment, to Alzheimer's disease. The aim of this paper is to develop a Bayesian hidden Markov model to characterize disease pathology, identify hidden states corresponding to the diagnosed stages of cognitive decline, and examine the dynamic changes of potential risk factors associated with the cognitive normal-mild cognitive impairment-Alzheimer's disease transition. The hidden Markov model framework consists of two major components. The first one is a state-dependent semiparametric regression for delineating the complex associations between clinical outcomes of interest and a set of prognostic biomarkers across neurodegenerative states. The second one is a parametric transition model, while accounting for potential covariate effects on the cross-state transition. The inter-individual and inter-process differences are taken into account via correlated random effects in both components. Based on the Alzheimer's Disease Neuroimaging Initiative data set, we are able to identify four states of Alzheimer's disease pathology, corresponding to common diagnosed cognitive decline stages, including cognitive normal, early mild cognitive impairment, late mild cognitive impairment, and Alzheimer's disease and examine the effects of hippocampus, age, gender, and APOE- ε4 on degeneration of cognitive function across the four cognitive states. [ABSTRACT FROM AUTHOR]

In psychological, social, behavioral, and medical studies, hidden Markov models (HMMs) have been extensively applied to the simultaneous modeling of heterogeneous observation and hidden transition in the analysis of longitudinal data. However, the majority of the existing HMMs are developed in a parametric framework without latent variables. This study considers a novel semiparametric HMM, which comprises a semiparametric latent variable model to investigate the complex interrelationships among latent variables and a nonparametric transition model to examine the linear and nonlinear effects of potential predictors on hidden transition. The Bayesian P-splines approach and Markov chain Monte Carlo methods are developed to estimate the unknown, a Bayesian model comparison statistic, is employed to conduct model comparison. The empirical performance of the proposed methodology is evaluated through simulation studies. An application to a data set derived from the National Longitudinal Survey of Youth is presented. [ABSTRACT FROM PUBLISHER]