A curvilinear bivariate random changepoint model to assess temporal order of markers.

In biomedical research, various longitudinal markers measuring different quantities are often collected over time. For example, repeated measures of psychometric scores are very informative about the degradation process toward dementia. These trajectories are generally nonlinear with an acceleration of the decline a few years before the diagnosis and a large heterogeneity between psychometric tests depending on the underlying cognitive function to be evaluated and the metrological properties of the test. Comparing the times of acceleration of the decline before diagnosis between cognitive tests is useful to better understand the natural history of the disease. Our objective is to propose a bivariate random changepoint model that allows for the comparison of the mean time of change between two markers. A frequentist approach is proposed that gives validated statistical tests to assess the temporal order of the changepoints. Using a spline transformation function, the model is designed to handle non-Gaussian data, that are common for cognitive scores which frequently exhibit a strong ceiling effect. The procedure is assessed through a simulation study and applied to a French cohort of elderly to identify the order of the decline of several cognitive scores. The whole methodology has been implemented in a R package freely available.