AD-CARE: A Guideline-grounded, Modality-agnostic LLM Agent for Real-world Alzheimer's Disease Diagnosis with Multi-cohort Assessment, Fairness Analysis, and Reader Study

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.

JMedEthicBench: A Multi-Turn Conversational Benchmark for Evaluating Medical Safety in Japanese Large Language Models

As Large Language Models (LLMs) are increasingly deployed in healthcare field, it becomes essential to carefully evaluate their medical safety before clinical use. However, existing safety benchmarks remain predominantly English-centric, and test with only single-turn prompts despite multi-turn clinical consultations. To address these gaps, we introduce JMedEthicBench, the first multi-turn conversational benchmark for evaluating medical safety of LLMs for Japanese healthcare. Our benchmark is based on 67 guidelines from the Japan Medical Association and contains over 50,000 adversarial conversations generated using seven automatically discovered jailbreak strategies. Using a dual-LLM scoring protocol, we evaluate 27 models and find that commercial models maintain robust safety while medical-specialized models exhibit increased vulnerability. Furthermore, safety scores decline significantly across conversation turns (median: 9.5 to 5.0, $p < 0.001$). Cross-lingual evaluation on both Japanese and English versions of our benchmark reveals that medical model vulnerabilities persist across languages, indicating inherent alignment limitations rather than language-specific factors. These findings suggest that domain-specific fine-tuning may accidentally weaken safety mechanisms and that multi-turn interactions represent a distinct threat surface requiring dedicated alignment strategies.

Ada-FCN: Adaptive Frequency-Coupled Network for fMRI-Based Brain Disorder Classification

Resting-state fMRI has become a valuable tool for classifying brain disorders and constructing brain functional connectivity networks by tracking BOLD signals across brain regions. However, existing mod els largely neglect the multi-frequency nature of neuronal oscillations, treating BOLD signals as monolithic time series. This overlooks the cru cial fact that neurological disorders often manifest as disruptions within specific frequency bands, limiting diagnostic sensitivity and specificity. While some methods have attempted to incorporate frequency informa tion, they often rely on predefined frequency bands, which may not be optimal for capturing individual variability or disease-specific alterations. To address this, we propose a novel framework featuring Adaptive Cas cade Decomposition to learn task-relevant frequency sub-bands for each brain region and Frequency-Coupled Connectivity Learning to capture both intra- and nuanced cross-band interactions in a unified functional network. This unified network informs a novel message-passing mecha nism within our Unified-GCN, generating refined node representations for diagnostic prediction. Experimental results on the ADNI and ABIDE datasets demonstrate superior performance over existing methods. The code is available at https://github.com/XXYY20221234/Ada-FCN.