Dementia-R1: Reinforced Pretraining and Reasoning from Unstructured Clinical Notes for Real-World Dementia Prognosis

Dementia diagnosis requires integrating multi-modal clinical assessments from diverse informants and clinicians under incomplete and heterogeneous data conditions. Yet most AI-driven approaches remain Alzheimer's disease (AD)-centric, framing the problem as binary AD detection or three-stage AD progression modeling within well-curated research settings. This pathology-driven paradigm overlooks the broader, syndrome-level nature of dementia, which spans multiple stages, phenotypes, and etiologies. In this paper, we propose Dementia-Agents, a clinically aligned multi-agent framework for real-world dementia staging and phenotyping. The framework follows a three-step workflow: (1) a data agent translates structured clinical records into semantically faithful textual representations that preserve missing-data signals and routes them to domain-aligned experts; (2) five fine-tuned expert agents generate domain-level predictions; and (3) a coordinator agent performs probabilistic aggregation to produce final staging and phenotyping decisions. We develop and evaluate Dementia-Agents on a real-world clinical cohort of 1,066 patients from two cognitive neurology services. Compared with monolithic multi-modal large language models (MLLMs) and prior medical multi-agent systems, our approach achieves consistent improvements in diagnostic performance for real-world syndrome-level dementia staging and phenotyping, while preserving domain-level interpretability.

Modern clinical practice increasingly depends on reasoning over heterogeneous, evolving, and incomplete patient data. Although recent advances in multimodal foundation models have improved performance on various clinical tasks, most existing models remain static, opaque, and poorly aligned with real-world clinical workflows. We present Cerebra, an interactive multi-agent AI team that coordinates specialized agents for EHR, clinical notes, and medical imaging analysis. These outputs are synthesized into a clinician-facing dashboard that combines visual analytics with a conversational interface, enabling clinicians to interrogate predictions and contextualize risk at the point of care. Cerebra supports privacy-preserving deployment by operating on structured representations and remains robust when modalities are incomplete. We evaluated Cerebra using a massive multi-institutional dataset spanning 3 million patients from four independent healthcare systems. Cerebra consistently outperformed both state-of-the-art single-modality models and large multimodal language model baselines. In dementia risk prediction, it achieved AUROCs up to 0.80, compared with 0.74 for the strongest single-modality model and 0.68 for language model baselines. For dementia diagnosis, it achieved an AUROC of 0.86, and for survival prediction, a C-index of 0.81. In a reader study with experienced physicians, Cerebra significantly improved expert performance, increasing accuracy by 17.5 percentage points in prospective dementia risk estimation. These results demonstrate Cerebra's potential for interpretable, robust decision support in clinical care.

Longitudinal clinical notes contain rich evidence of how patients evolve over time, but converting this signal into training supervision for clinical prediction remains challenging. We extend Foresight Learning to clinical prediction by converting time-ordered MIMIC-III notes into examples consisting of past patient context, a natural-language question about a possible future event, and a label resolved from later documentation. This process yields 6,900 prediction examples from 702 admissions across medications, procedures, organ support, microbiology, and mortality. A small LoRA adapter trained on these examples improves over the prompted base model, reducing expected calibration error from 0.1269 to 0.0398 and Brier score from 0.199 to 0.145, while slightly outperforming GPT-5 point estimates on held-out questions. The approach enables reusable clinical prediction supervision from longitudinal notes without hand-engineered structured features or endpoint-specific classifiers.