# 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

arXiv: https://arxiv.org/abs/2603.25322 · HTML: https://mlsanity.com/paper/2603.25322/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 16 of its 65 references that are in the map.
- First posted on arXiv 26 Mar 2026.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 16 of 16)

- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [GPT-4o System Card](https://mlsanity.com/paper/2410.21276/) (2024)
- [Gemini 2.5: Pushing the Frontier with Advanced Reasoning, Multimodality, Long Context, and Next Generation Agentic Capabilities](https://mlsanity.com/paper/2507.06261/) (2025)
- [Large Language Models Encode Clinical Knowledge](https://mlsanity.com/paper/2212.13138/) (2022)
- [Plan-and-Solve Prompting: Improving Zero-Shot Chain-of-Thought Reasoning by Large Language Models](https://mlsanity.com/paper/2305.04091/) (2023)
- [SynthStrip: Skull-Stripping for Any Brain Image](https://mlsanity.com/paper/2203.09974/) (2022)
- [A Survey of LLM-based Agents in Medicine: How far are we from Baymax?](https://mlsanity.com/paper/2502.11211/) (2025)
- [Flex-MoE: Modeling Arbitrary Modality Combination via the Flexible Mixture-of-Experts](https://mlsanity.com/paper/2410.08245/) (2024)
- [AD-AutoGPT: An Autonomous GPT for Alzheimer's Disease Infodemiology](https://mlsanity.com/paper/2306.10095/) (2023)
- [Cascaded Multi-Modal Mixing Transformers for Alzheimer's Disease Classification with Incomplete Data](https://mlsanity.com/paper/2210.00255/) (2022)
- [Cross-Cohort Generalizability of Deep and Conventional Machine Learning for MRI-based Diagnosis and Prediction of Alzheimer's Disease](https://mlsanity.com/paper/2012.08769/) (2020)
- [ADAgent: LLM Agent for Alzheimer's Disease Analysis with Collaborative Coordinator](https://mlsanity.com/paper/2506.11150/) (2025)
- [Linguistic Features Extracted by GPT-4 Improve Alzheimer's Disease Detection based on Spontaneous Speech](https://mlsanity.com/paper/2412.15772/) (2024)
- [Ada-FCN: Adaptive Frequency-Coupled Network for fMRI-Based Brain Disorder Classification](https://mlsanity.com/paper/2511.04718/) (2025)
- [MemoryCompanion: A Smart Healthcare Solution to Empower Efficient Alzheimer's Care Via Unleashing Generative AI](https://mlsanity.com/paper/2311.14730/) (2023)
- [AD-GPT: Large Language Models in Alzheimer's Disease](https://mlsanity.com/paper/2504.03071/) (2025)

## Built on by (most cited first, 2 of 2)

- [NeuroAgent: LLM Agents for Multimodal Neuroimaging Analysis and Research](https://mlsanity.com/paper/2605.06584/) (2026)
- [The Path to Self-Evolving Clinical Systems: Scaling Medical Agents from Assistance to Autonomy](https://mlsanity.com/paper/2607.11175/) (2026)

## Abstract (arXiv)

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.