Identifying Progression-Specific Alzheimer's Subtypes Using Multimodal Transformer.

ABSTRACT

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet its current treatments are limited to stopping disease progression. Moreover, the effectiveness of these treatments remains uncertain due to the heterogeneity of the disease. Therefore, it is essential to identify disease subtypes at a very early stage. Current data-driven approaches can be used to classify subtypes during later stages of AD or related disorders, but making predictions in the asymptomatic or prodromal stage is challenging. Furthermore, the classifications of most existing models lack explainability, and these models rely solely on a single modality for assessment, limiting the scope of their analysis. Thus, we propose a multimodal framework that utilizes early-stage indicators, including imaging, genetics, and clinical assessments, to classify AD patients into progression-specific subtypes at an early stage. In our framework, we introduce a tri-modal co-attention mechanism (Tri-COAT) to explicitly capture cross-modal feature associations. Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (slow progressing = 177, intermediate = 302, and fast = 15) were used to train and evaluate Tri-COAT using a 10-fold stratified cross-testing approach. Our proposed model outperforms baseline models and sheds light on essential associations across multimodal features supported by known biological mechanisms. The multimodal design behind Tri-COAT allows it to achieve the highest classification area under the receiver operating characteristic curve while simultaneously providing interpretability to the model predictions through the co-attention mechanism.