EMAD: Evidence-Centric Grounded Multimodal Diagnosis for Alzheimer's Disease

Alzheimer's disease (AD) diagnosis requires integrating neuroimaging with heterogeneous clinical evidence and reasoning under established criteria, yet most multimodal models remain opaque and weakly guideline-aligned. We present AD-Reasoning, a multimodal framework that couples structural MRI with six clinical modalities and a rule-based verifier to generate structured, NIA-AA-consistent diagnoses. AD-Reasoning combines modality-specific encoders, bidirectional cross-attention fusion, and reinforcement fine-tuning with verifiable rewards that enforce output format, guideline evidence coverage, and reasoning--decision consistency. We also release AD-MultiSense, a 10,378-visit multimodal QA dataset with guideline-validated rationales built from ADNI/AIBL. On AD-MultiSense, AD-Reasoning achieves state-of-the-art diagnostic accuracy and produces structured rationales that improve transparency over recent baselines, while providing transparent rationales.

Alzheimer's disease (AD) is a growing global health challenge as populations age, and timely, accurate diagnosis is essential to reduce individual and societal burden. However, real-world AD assessment is hampered by incomplete, heterogeneous multimodal data and variability across sites and patient demographics. Although large language models (LLMs) have shown promise in biomedicine, their use in AD has largely been confined to answering narrow, disease-specific questions rather than generating comprehensive diagnostic reports that support clinical decision-making. Here we expand LLM capabilities for clinical decision support by introducing AD-CARE, a modality-agnostic agent that performs guideline-grounded diagnostic assessment from incomplete, heterogeneous inputs without imputing missing modalities. By dynamically orchestrating specialized diagnostic tools and embedding clinical guidelines into LLM-driven reasoning, AD-CARE generates transparent, report-style outputs aligned with real-world clinical workflows. Across six cohorts comprising 10,303 cases, AD-CARE achieved 84.9% diagnostic accuracy, delivering 4.2%-13.7% relative improvements over baseline methods. Despite cohort-level differences, dataset-specific accuracies remain robust (80.4%-98.8%), and the agent consistently outperforms all baselines. AD-CARE reduced performance disparities across racial and age subgroups, decreasing the average dispersion of four metrics by 21%-68% and 28%-51%, respectively. In a controlled reader study, the agent improved neurologist and radiologist accuracy by 6%-11% and more than halved decision time. The framework yielded 2.29%-10.66% absolute gains over eight backbone LLMs and converges their performance. These results show that AD-CARE is a scalable, practically deployable framework that can be integrated into routine clinical workflows for multimodal decision support in AD.

Medical multimodal large language models (MLLMs) can perform well on existing medical visual question answering (MedVQA) benchmarks, but their training data often does not match clinical diagnosis. Most supervision is organized around isolated images or short QA pairs, leaving two structures weakly specified: how evidence leads to a decision, and how views, series, modalities, and patient context from the same case are linked. We introduce MultiViewDx, a partly physician-validated multimodal instruction dataset for evidence-linked multi-view medical imaging diagnosis. MultiViewDx uses the clinical case as the supervision unit. It links imaging studies with patient context, normalizes heterogeneous reports into an evidence-linked workflow (evidence -> findings -> differential discussion -> diagnosis), and uses a unified image-text retriever to constrain instruction synthesis to source-supported evidence. It covers X-ray, CT, MRI, ultrasound, histopathology, and other clinical visual sources. We fine-tune MultiViewDx-8B-AN and evaluate it on both existing MedVQA benchmarks and real-world case-based diagnostic reasoning. Across four MedVQA benchmarks, it achieves the best average accuracy among compared systems (79.0%), outperforming HuatuoGPT-Vision-34B (66.7%) and Claude3-Opus (55.7%). Beyond MedVQA, on JAMA Clinical Challenge cases, it receives the strongest overall rating under a physician-designed rubric for key clinical points, diagnostic inference, and evidence grounding. Controlled ablations and clinician evaluation show that both case-level multi-view organization and evidence-linked reasoning targets contribute to the gain.