Diagnosing Alzheimer's disease (AD) involves a deliberate diagnostic process owing to its innate traits of irreversibility with subtle and gradual progression. These characteristics make AD biomarker identification from structural brain imaging (e.g., structural MRI) scans quite challenging. Furthermore, there is a high possibility of getting entangled with normal aging. We propose a novel deep-learning approach through eXplainable AD Likelihood Map Estimation (XADLiME) for AD progression modeling over 3D sMRIs using clinically-guided prototype learning. Specifically, we establish a set of topologically-aware prototypes onto the clusters of latent clinical features, uncovering an AD spectrum manifold. We then measure the similarities between latent clinical features and well-established prototypes, estimating a "pseudo" likelihood map. By considering this pseudo map as an enriched reference, we employ an estimating network to estimate the AD likelihood map over a 3D sMRI scan. Additionally, we promote the explainability of such a likelihood map by revealing a comprehensible overview from two perspectives: clinical and morphological. During the inference, this estimated likelihood map served as a substitute over unseen sMRI scans for effectively conducting the downstream task while providing thorough explainable states.
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