Integrative Multi-Omics and Multivariate Longitudinal Data Analysis for Dynamic Risk Estimation in Alzheimer's Disease.

Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder, characterized by diverse cognitive and functional impairments that manifest heterogeneously across individuals, domains, and time. The accurate assessment of AD's severity and progression requires integrating a variety of data modalities, including multivariate longitudinal neuropsychological tests and multi-omics datasets such as metabolomics and lipidomics. These data sources provide valuable insights into risk factors associated with dementia onset. However, effectively utilizing omics data in dynamic risk estimation for AD progression is challenging due to issues including high dimensionality, heterogeneity, and complex intercorrelations. To address these challenges, we develop a novel joint-modeling framework that effectively combines multi-omics factor analysis (MOFA) for dimension reduction and feature extraction with a multivariate functional mixed model (MFMM) for modeling longitudinal outcomes. This integrative joint modeling approach enables dynamic evaluation of dementia risk by leveraging both omics and longitudinal data. We validate the efficacy of our integrative model through extensive simulation studies and its practical application to the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset.