R-GenIMA: Integrating Neuroimaging and Genetics with Interpretable Multimodal AI for Alzheimer's Disease Progression

TL;DR

R-GenIMA is an interpretable multimodal AI model that integrates neuroimaging and genetic data to improve Alzheimer's disease diagnosis and understand its underlying mechanisms.

Contribution

The paper introduces R-GenIMA, a novel large language model combining vision transformers and genetic prompts for joint analysis of MRI and SNP data in AD.

Findings

Achieved state-of-the-art classification accuracy across four cognitive stages.

Identified biologically meaningful brain regions and gene signatures linked to AD.

Revealed gene associations consistent with established GWAS risk loci.

Abstract

Early detection of Alzheimer's disease (AD) requires models capable of integrating macro-scale neuroanatomical alterations with micro-scale genetic susceptibility, yet existing multimodal approaches struggle to align these heterogeneous signals. We introduce R-GenIMA, an interpretable multimodal large language model that couples a novel ROI-wise vision transformer with genetic prompting to jointly model structural MRI and single nucleotide polymorphisms (SNPs) variations. By representing each anatomically parcellated brain region as a visual token and encoding SNP profiles as structured text, the framework enables cross-modal attention that links regional atrophy patterns to underlying genetic factors. Applied to the ADNI cohort, R-GenIMA achieves state-of-the-art performance in four-way classification across normal cognition (NC), subjective memory concerns (SMC), mild cognitive impairment (MCI), and AD. Beyond predictive accuracy, the model yields biologically meaningful explanations by identifying stage-specific brain regions and gene signatures, as well as coherent ROI-Gene association patterns across the disease continuum. Attention-based attribution revealed genes consistently enriched for established GWAS-supported AD risk loci, including APOE, BIN1, CLU, and RBFOX1. Stage-resolved neuroanatomical signatures identified shared vulnerability hubs across disease stages alongside stage-specific patterns: striatal involvement in subjective decline, frontotemporal engagement during prodromal impairment, and consolidated multimodal network disruption in AD. These results demonstrate that interpretable multimodal AI can synthesize imaging and genetics to reveal mechanistic insights, providing a foundation for clinically deployable tools that enable earlier risk stratification and inform precision therapeutic strategies in Alzheimer's disease.