Subtype-Specific Biomarkers of Alzheimer’s Disease from Anatomical and Functional Connectomes via Graph Neural Networks

Heterogeneity is present in Alzheimer's disease (AD), making it challenging to study. To address this, we propose a graph neural network (GNN) approach to identify disease subtypes from magnetic resonance imaging (MRI) and functional MRI (fMRI) scans. Subtypes are identified by encoding the patients' scans in brain graphs (via cortical similarity networks) and clustering the representations learnt by the GNN. These subtyping information are used to construct population graphs for an ensemble of local networks, each producing intermediate predictions that are subsequently combined to produce the model's final decision. Using MRI and fMRI scans from two datasets on AD, we demonstrate that our proposed architecture outperforms existing methods. Three subtypes of AD were identified and left cuneus was found to be a consistent class-wide biomarker. Subtype-specific biomarkers produced by our method further revealed deeper insights, including a unique subtype with significant degeneration in the left isthmus cingulate cortex.