# A Multimodal Explainable Deep Learning Framework for Alzheimer's Disease Diagnosis using 3D Magnetic Resonance Imaging and Clinical Data

arXiv: https://arxiv.org/abs/2609.12410 · HTML: https://mlsanity.com/paper/2609.12410/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 17 of its 33 references that are in the map.
- First posted on arXiv 11 Sep 2026.

## Builds on (most cited first, 17 of 17)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Grad-CAM: Visual Explanations from Deep Networks via Gradient-based Localization](https://mlsanity.com/paper/1610.02391/) (2016)
- [Densely Connected Convolutional Networks](https://mlsanity.com/paper/1608.06993/) (2016)
- [A Unified Approach to Interpreting Model Predictions](https://mlsanity.com/paper/1705.07874/) (2017)
- [Axiomatic Attribution for Deep Networks](https://mlsanity.com/paper/1703.01365/) (2017)
- [Class-Balanced Loss Based on Effective Number of Samples](https://mlsanity.com/paper/1901.05555/) (2019)
- [Multimodal Machine Learning: A Survey and Taxonomy](https://mlsanity.com/paper/1705.09406/) (2017)
- [Grad-CAM++: Improved Visual Explanations for Deep Convolutional Networks](https://mlsanity.com/paper/1710.11063/) (2017)
- [Score-CAM: Score-Weighted Visual Explanations for Convolutional Neural Networks](https://mlsanity.com/paper/1910.01279/) (2019)
- [MONAI: An open-source framework for deep learning in healthcare](https://mlsanity.com/paper/2211.02701/) (2022)
- [Layer-wise Relevance Propagation for Neural Networks with Local Renormalization Layers](https://mlsanity.com/paper/1604.00825/) (2016)
- [XRAI: Better Attributions Through Regions](https://mlsanity.com/paper/1906.02825/) (2019)
- [Convolutional Neural Networks for Classification of Alzheimer's Disease: Overview and Reproducible Evaluation](https://mlsanity.com/paper/1904.07773/) (2019)
- [Guided Integrated Gradients: An Adaptive Path Method for Removing Noise](https://mlsanity.com/paper/2106.09788/) (2021)
- [Multimodal Attention-based Deep Learning for Alzheimer's Disease Diagnosis](https://mlsanity.com/paper/2206.08826/) (2022)
- [Finer-CAM: Spotting the Difference Reveals Finer Details for Visual Explanation](https://mlsanity.com/paper/2501.11309/) (2025)
- [Not Only Grey Matter: OmniBrain for Robust Multimodal Classification of Alzheimer's Disease](https://mlsanity.com/paper/2507.20872/) (2025)

## Abstract (arXiv)

Dementia is a major and growing global health burden, with Alzheimer's disease (AD) accounting for most cases. Timely and accurate diagnosis is central to managing this burden and increasingly depends on integrating complementary clinical and imaging information. Multimodal deep learning can combine these modalities for AD diagnosis, but how its explanations behave across modalities, fusion strategies, and cohorts remains unclear. We developed an explainable multimodal framework pairing a 3D CNN encoder for T1-weighted MRI with a feedforward network for harmonized clinical and demographic data, comparing varied model setups on three-way and pairwise diagnostic tasks using 6,479 internal records from the ADNI and 1,703 independent records from the OASIS-3. On ADNI, the tabular-only model achieved the highest three-class AUC-ROC of 0.879 and best discriminated cognitively normal (CN) versus mild cognitive impairment (MCI; 0.903), while cross-attention performed best for MCI versus AD (0.861); CN versus AD was highly discriminative overall. On OASIS-3, the vision-only model performed best (three-class AUC-ROC 0.910); CN versus MCI remained difficult, and no fusion strategy consistently outperformed single modalities across tasks and cohorts. SHAP and Integrated Gradients identified the MMSE as the dominant tabular feature in both cohorts, with global feature rankings agreeing strongly in ADNI (ρ=0.94) and OASIS-3 (ρ=0.96); CAM-based explanations, however, changed with model configuration and cohort. These findings show that multimodal performance and explanations are task, modality, fusion, and cohort-dependent: a dominant cognitive signal persisted across cohorts, but feature contributions and CAM explanations did not, underscoring the need to evaluate explainability under cohort shift rather than as a stable, intrinsic property.