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

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Main Authors: Das, Ayantika, Ram, Keerthi, Sivaprakasam, Mohanasankar
Format: Preprint
Published: 2026
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author Das, Ayantika
Ram, Keerthi
Sivaprakasam, Mohanasankar
author_facet Das, Ayantika
Ram, Keerthi
Sivaprakasam, Mohanasankar
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2603_01552
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Align-cDAE: Alzheimer's Disease Progression Modeling with Attention-Aligned Conditional Diffusion Auto-Encoder
Das, Ayantika
Ram, Keerthi
Sivaprakasam, Mohanasankar
Computer Vision and Pattern Recognition
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.
title Align-cDAE: Alzheimer's Disease Progression Modeling with Attention-Aligned Conditional Diffusion Auto-Encoder
topic Computer Vision and Pattern Recognition
url https://arxiv.org/abs/2603.01552