Multi-Modal Fusion with Supervised Contrastive Learning Model for Early Alzheimer's Disease Diagnosis and Multi-Modal Biomarker Identification.

Early and accurate diagnosis of mild cognitive impairment (MCI), a prodromal stage of Alzheimer's disease (AD), is critical for timely intervention and management. Nevertheless, effectively integrating heterogeneous multi-modal data for AD diagnosis remains worthy of further investigation. Therefore, we propose a supervised contrastive learning framework that integrates single nucleotide polymorphisms (SNPs), plasma proteomics, and T1-weighted structural magnetic resonance imaging (sMRI) from a biologically informed perspective, with SNPs influencing protein structure or gene expression levels, ultimately altering brain structure. Through a supervised contrastive learning mechanism, we construct a cross-modal feature space and introduce a similarity-based symmetrical attention mechanism to capture intermodal interactions and mitigate modality heterogeneity. We validate the proposed method on the Alzheimer's Disease Neuroimaging Initiative dataset, and experimental results demonstrate accuracy of 96.1%, 86.2%, and 86.1% for the AD-NC task, MCI-NC task, and AD-MCI task. In addition, the application of explainable methods to our model identified multi-modal biomarkers related to AD diagnosis. The experimental results validate the effectiveness of our model in the diagnosis of AD and MCI.