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Modélisation dynamique des sphères anatomique, cognitive et fonctionnelle dans la maladie d’Alzheimer : une approche par processus latents

Abstract : In public health, the study of the progression of a chronic disease and its mechanisms may require the joint modeling of several longitudinal markers and their dependence structure. Modeling approaches exist in the literature to partially address these modeling objectives. But these approaches become rapidly numerically expensive and difficult to use in some complex diseases involving latent, dynamic and multidimensional aspects, such as in Alzheimer’s disease. The aim of this thesis was to propose an innovative methodology for modeling the dynamics of several latent processes and their temporal influences for the purpose of causal interpretations, from repeated observations of continuous Gaussian and non Gaussian markers. The proposed latent process approach defines a structural model in discrete time for the latent processes trajectories and an observation model to relate longitudinal markers to the process they measure. In the structural model, the initial level and the rate of change of individual-specific processes are modeled by mixedeffect linear models. The rate of change model has a first order auto-regressive component that can model the effect of a process on another process by explicitly accounting for time. The structural model as defined benefits from the same causal interpretations as the models with differential equations (ODE) of the mechanistic approach of the causality while avoiding major numerical problems. The observation model uses parameterized link functions to handle possibly non-Gaussian continuous markers. The consistency of the ML estimators and the accuracy of the inference of the influence structures between the latent processes have been validated by simulation studies. This approach, applied to Alzheimer’s disease, allowed to jointly describe the dynamics of hippocampus atrophy, the decline of episodic memory, the decline of verbal fluency, and loss of autonomy as well as the temporal influences between these dimensions in several stages of Alzheimer’s dementia from the data of the ADNI initiative.
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Oladédji Bachirou Tadde. Modélisation dynamique des sphères anatomique, cognitive et fonctionnelle dans la maladie d’Alzheimer : une approche par processus latents. Médecine humaine et pathologie. Université de Bordeaux, 2018. Français. ⟨NNT : 2018BORD0306⟩. ⟨tel-02080338⟩

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