A comparison of mixed-models for the analysis of non-linear longitudinal data: application to late-life cognitive trajectories

Several mixed-effects models for longitudinal data have been proposed to accommodate the non-linearity of late-life cognitive trajectories and assess the putative influence of covariates on it. No prior research provides a side-by-side examination of these models to offer guidance on their proper application and interpretation. In this work, we examined five statistical approaches previously used to answer research questions related to non-linear changes in cognitive aging: the linear mixed model (LMM) with a quadratic term, LMM with splines, the functional mixed model, the piecewise linear mixed model, and the sigmoidal mixed model. We first theoretically describe the models. Next, using data from two prospective cohorts with annual cognitive testing, we compared the interpretation of the models by investigating associations of education on cognitive change before death. Lastly, we performed a simulation study to empirically evaluate the models and provide practical recommendations. Except for the LMM-quadratic, the fit of all models was generally adequate to capture non-linearity of cognitive change and models were relatively robust. Although spline-based models have no interpretable nonlinearity parameters, their convergence was easier to achieve, and they allow graphical interpretation. In contrast, piecewise and sigmoidal models, with interpretable non-linear parameters, may require more data to achieve convergence.