A Mixed-Effects Model with Time Reparametrization for Longitudinal Univariate Manifold-Valued Data

Mixed-effects models provide a rich theoretical framework for the analysis of longitudinal data. However, when used to analyze or predict the progression of a neurodegenerative disease such as Alzheimer’s disease, these models usually do not take into account the fact that subjects may be at different stages of disease progression and the interpretation of the model may depend on some implicit reference time. In this paper, we propose a generative statistical model for longitudinal data, described in a univariate Riemannian manifold setting, which estimates an average disease progression model, subject-specific time shifts and acceleration factors. The time shifts account for variability in age at disease-onset time. The acceleration factors account for variability in speed of disease progression. For a given individual, the estimated time shift and acceleration factor define an affine reparametrization of the average disease progression model. This statistical model has been used to analyze neuropsychological assessments scores and cortical thickness measurements from the Alzheimer’s Disease Neuroimaging Initiative database. The numerical results showed that we can distinguish between slow versus fast progressing and early versus late-onset individuals.