# PRA-PoE: Robust Multimodal Alzheimer's Diagnosis with Arbitrary Missing Modalities

arXiv: https://arxiv.org/abs/2605.13081 · HTML: https://mlsanity.com/paper/2605.13081/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 9 of its 34 references that are in the map.
- First posted on arXiv 13 May 2026.

## Builds on (most cited first, 9 of 9)

- [Variational Mixture-of-Experts Autoencoders for Multi-Modal Deep Generative Models](https://mlsanity.com/paper/1911.03393/) (2019)
- [Multi-modal Learning with Missing Modality via Shared-Specific Feature Modelling](https://mlsanity.com/paper/2307.14126/) (2023)
- [mmFormer: Multimodal Medical Transformer for Incomplete Multimodal Learning of Brain Tumor Segmentation](https://mlsanity.com/paper/2206.02425/) (2022)
- [M3Care: Learning with Missing Modalities in Multimodal Healthcare Data](https://mlsanity.com/paper/2210.17292/) (2022)
- [Flex-MoE: Modeling Arbitrary Modality Combination via the Flexible Mixture-of-Experts](https://mlsanity.com/paper/2410.08245/) (2024)
- [FuseMoE: Mixture-of-Experts Transformers for Fleximodal Fusion](https://mlsanity.com/paper/2402.03226/) (2024)
- [Towards Balanced Active Learning for Multimodal Classification](https://mlsanity.com/paper/2306.08306/) (2023)
- [ADAgent: LLM Agent for Alzheimer's Disease Analysis with Collaborative Coordinator](https://mlsanity.com/paper/2506.11150/) (2025)
- [MCE: Towards a General Framework for Handling Missing Modalities under Imbalanced Missing Rates](https://mlsanity.com/paper/2510.10534/) (2025)

## Abstract (arXiv)

Missing modalities are prevalent in real-world Alzheimer's disease (AD) assessment and pose a significant challenge to multimodal learning, particularly when the distribution of observed modality subsets differs between training and deployment. Such missingness pattern mismatch induces a conditional representation shift across modality subsets. Existing approaches that rely on implicit imputation or modality synthesis often fail to explicitly model modality availability and uncertainty, leading to overconfident dependence on synthesized features, reduced robustness, and miscalibrated uncertainty estimates. To address these limitations, we propose PRA-PoE, an incomplete multimodal learning framework that is equipped with Prototype-anchored Representation Alignment (PRA) and an Uncertainty-aware Product of Experts (UA-PoE) fusion mechanism. First, PRA uses learnable global prototypes and availability-conditioned tokens to encode modality availability, distinguish observed from missing modalities, re-synthesize features for missing modalities, and adaptively refine observed representations to align latent spaces across modality subsets, with the goal of reducing representation shift under varying missingness patterns. Second, UA-PoE models each modality as a Gaussian expert and performs closed-form Product of Experts fusion, where experts with higher uncertainty are automatically down-weighted via lower precision, improving uncertainty reliability. We evaluate PRA-PoE under a clinically realistic protocol by training with naturally missing data and testing on all non-empty modality combinations. PRA-PoE consistently outperforms the state-of-the-art across datasets, achieving a 5.4% relative improvement in average accuracy on ADNI and a 10.9% relative gain in average F1 on OASIS-3 over the strongest baseline across all non-empty modality subsets.