Representing Alzheimer's Disease Progression via Deep Prototype Tree

For decades, a variety of predictive approaches have been proposed and evaluated in terms of their predicting capability for Alzheimer's Disease (AD) and its precursor - mild cognitive impairment (MCI). Most of them focused on prediction or identification of statistical differences among different clinical groups or phases (e.g., longitudinal studies). The continuous nature of AD development and transition states between successive AD related stages have been overlooked, especially in binary or multi-class classification. Though a few progression models of AD have been studied recently, they mainly designed to determine and compare the order of specific biomarkers. How to effectively predict the individual patient's status within a wide spectrum of AD progression has been understudied. In this work, we developed a novel structure learning method to computationally model the continuum of AD progression as a tree structure. By conducting a novel prototype learning with a deep manner, we are able to capture intrinsic relations among different clinical groups as prototypes and represent them in a continuous process for AD development. We named this method as Deep Prototype Learning and the learned tree structure as Deep Prototype Tree - DPTree. DPTree represents different clinical stages as a trajectory reflecting AD progression and predict clinical status by projecting individuals onto this continuous trajectory. Through this way, DPTree can not only perform efficient prediction for patients at any stages of AD development (77.8% accuracy for five groups), but also provide more information by examining the projecting locations within the entire AD progression process.