# Pretraining Transformer-Based Models on Diffusion-Generated Synthetic Graphs for Alzheimer's Disease Prediction

arXiv: https://arxiv.org/abs/2511.20704 · HTML: https://mlsanity.com/paper/2511.20704/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 18 of its 32 references that are in the map.
- First posted on arXiv 24 Nov 2025.

## Placed in

- Diffusion models / [Medical imaging and segmentation](https://mlsanity.com/diffusion/medical-imaging-and-segmentation/)

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

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Elucidating the Design Space of Diffusion-Based Generative Models](https://mlsanity.com/paper/2206.00364/) (2022)
- [Graph Contrastive Learning with Augmentations](https://mlsanity.com/paper/2010.13902/) (2020)
- [A Generalization of Transformer Networks to Graphs](https://mlsanity.com/paper/2012.09699/) (2020)
- [Masked Label Prediction: Unified Message Passing Model for Semi-Supervised Classification](https://mlsanity.com/paper/2009.03509/) (2020)
- [Rethinking Graph Transformers with Spectral Attention](https://mlsanity.com/paper/2106.03893/) (2021)
- [GPT-GNN: Generative Pre-Training of Graph Neural Networks](https://mlsanity.com/paper/2006.15437/) (2020)
- [Brain Imaging Generation with Latent Diffusion Models](https://mlsanity.com/paper/2209.07162/) (2022)
- [GAN-based Synthetic Medical Image Augmentation for increased CNN Performance in Liver Lesion Classification](https://mlsanity.com/paper/1803.01229/) (2018)
- [Generating Multi-label Discrete Patient Records using Generative Adversarial Networks](https://mlsanity.com/paper/1703.06490/) (2017)
- [Pure Transformers are Powerful Graph Learners](https://mlsanity.com/paper/2207.02505/) (2022)
- [Graph-Bert: Only Attention is Needed for Learning Graph Representations](https://mlsanity.com/paper/2001.05140/) (2020)
- [What Improves the Generalization of Graph Transformers? A Theoretical Dive into the Self-attention and Positional Encoding](https://mlsanity.com/paper/2406.01977/) (2024)
- [The Devil is in the Conflict: Disentangled Information Graph Neural Networks for Fraud Detection](https://mlsanity.com/paper/2210.12384/) (2022)

## Abstract (arXiv)

Early and accurate detection of Alzheimer's disease (AD) is crucial for enabling timely intervention and improving outcomes. However, developing reliable machine learning (ML) models for AD diagnosis is challenging due to limited labeled data, multi-site heterogeneity, and class imbalance. We propose a Transformer-based diagnostic framework that combines diffusion-based synthetic data generation with graph representation learning and transfer learning. A class-conditional denoising diffusion probabilistic model (DDPM) is trained on the real-world NACC dataset to generate a large synthetic cohort that mirrors multimodal clinical and neuroimaging feature distributions while balancing diagnostic classes. Modality-specific Graph Transformer encoders are first pretrained on this synthetic data to learn robust, class-discriminative representations and are then frozen while a neural classifier is trained on embeddings from the original NACC data. We quantify distributional alignment between real and synthetic cohorts using metrics such as Maximum Mean Discrepancy (MMD), Frechet distance, and energy distance, and complement discrimination metrics with calibration and fixed-specificity sensitivity analyses. Empirically, our framework outperforms standard baselines, including early and late fusion deep neural networks and the multimodal graph-based model MaGNet, yielding higher AUC, accuracy, sensitivity, and specificity under subject-wise cross-validation on NACC. These results show that diffusion-based synthetic pretraining with Graph Transformers can improve generalization in low-sample, imbalanced clinical prediction settings.