# Align-cDAE: Alzheimer's Disease Progression Modeling with Attention-Aligned Conditional Diffusion Auto-Encoder

arXiv: https://arxiv.org/abs/2603.01552 · HTML: https://mlsanity.com/paper/2603.01552/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 18 of its 28 references that are in the map.
- First posted on arXiv 2 Mar 2026.

## Builds on (most cited first, 18 of 18)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (2020)
- [Adding Conditional Control to Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.05543/) (2023)
- [Aggregated Residual Transformations for Deep Neural Networks](https://mlsanity.com/paper/1611.05431/) (2016)
- [Diffusion Autoencoders: Toward a Meaningful and Decodable Representation](https://mlsanity.com/paper/2111.15640/) (2021)
- [SynthSeg: Segmentation of brain MRI scans of any contrast and resolution without retraining](https://mlsanity.com/paper/2107.09559/) (2021)
- [Towards Understanding Cross and Self-Attention in Stable Diffusion for Text-Guided Image Editing](https://mlsanity.com/paper/2403.03431/) (2024)
- [Automated brain extraction of multi-sequence MRI using artificial neural networks](https://mlsanity.com/paper/1901.11341/) (2019)
- [MAISI: Medical AI for Synthetic Imaging](https://mlsanity.com/paper/2409.11169/) (2024)
- [SODA: Bottleneck Diffusion Models for Representation Learning](https://mlsanity.com/paper/2311.17901/) (2023)
- [Rethinking the Spatial Inconsistency in Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2404.05384/) (2024)
- [SADM: Sequence-Aware Diffusion Model for Longitudinal Medical Image Generation](https://mlsanity.com/paper/2212.08228/) (2022)
- [Learning to synthesise the ageing brain without longitudinal data](https://mlsanity.com/paper/1912.02620/) (2019)
- [Degenerative Adversarial NeuroImage Nets for Brain Scan Simulations: Application in Ageing and Dementia](https://mlsanity.com/paper/1912.01526/) (2019)
- [TADM: Temporally-Aware Diffusion Model for Neurodegenerative Progression on Brain MRI](https://mlsanity.com/paper/2406.12411/) (2024)
- [Novel View Synthesis with Pixel-Space Diffusion Models](https://mlsanity.com/paper/2411.07765/) (2024)
- [Individualized multi-horizon MRI trajectory prediction for Alzheimer's Disease](https://mlsanity.com/paper/2408.02018/) (2024)
- [Anatomy-Grounded Weakly Supervised Prompt Tuning for Chest X-ray Latent Diffusion Models](https://mlsanity.com/paper/2506.10633/) (2025)

## Abstract (arXiv)

Generative AI framework-based modeling and prediction of longitudinal human brain images offer an efficient mechanism to track neurodegenerative progression, essential for the assessment of diseases like Alzheimer's. Among the existing generative approaches, recent diffusion-based models have emerged as an effective alternative to generate disease progression images. Incorporating multi-modal and non-imaging attributes as conditional information into diffusion frameworks has been shown to improve controllability during such generations. However, existing methods do not explicitly ensure that information from non-imaging conditioning modalities is meaningfully aligned with image features to introduce desirable changes in the generated images, such as modulation of progression-specific regions. Further, more precise control over the generation process can be achieved by introducing progression-relevant structure into the internal representations of the model, lacking in the existing approaches. To address these limitations, we propose a diffusion autoencoder-based framework for disease progression modeling that explicitly enforces alignment between different modalities. The alignment is enforced by introducing an explicit objective function that enables the model to focus on the regions exhibiting progression-related changes. Further, we devise a mechanism to better structure the latent representational space of the diffusion auto-encoding framework. Specifically, we assign separate latent subspaces for integrating progression-related conditions and retaining subject-specific identity information, allowing better-controlled image generation. These results demonstrate that enforcing alignment and better structuring of the latent representational space of diffusion auto-encoding framework leads to more anatomically precise modeling of Alzheimer's disease progression.