Multivariate functional mixed model with MRI data: An application to Alzheimer's disease.

Alzheimer's Disease (AD) is the leading cause of dementia and impairment in various domains. Recent AD studies, (ie, Alzheimer's Disease Neuroimaging Initiative (ADNI) study), collect multimodal data, including longitudinal neurological assessments and magnetic resonance imaging (MRI) data, to better study the disease progression. Adopting early interventions is essential to slow AD progression for subjects with mild cognitive impairment (MCI). It is of particular interest to develop an AD predictive model that leverages multimodal data and provides accurate personalized predictions. In this article, we propose a multivariate functional mixed model with MRI data (MFMM-MRI) that simultaneously models longitudinal neurological assessments, baseline MRI data, and the survival outcome (ie, dementia onset) for subjects with MCI at baseline. Two functional forms (the random-effects model and instantaneous model) linking the longitudinal and survival process are investigated. We use Markov Chain Monte Carlo (MCMC) method based on No-U-Turn Sampling (NUTS) algorithm to obtain posterior samples. We develop a dynamic prediction framework that provides accurate personalized predictions of longitudinal trajectories and survival probability. We apply MFMM-MRI to the ADNI study and identify significant associations among longitudinal outcomes, MRI data, and the risk of dementia onset. The instantaneous model with voxels from the whole brain has the best prediction performance among all candidate models. The simulation study supports the validity of the estimation and dynamic prediction method.