# Spatio-Temporal Graph Deep Learning with Stochastic Differential Equations for Uncovering Alzheimer's Disease Progression

arXiv: https://arxiv.org/abs/2509.21735 · HTML: https://mlsanity.com/paper/2509.21735/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 12 of its 56 references that are in the map.
- First posted on arXiv 26 Sep 2025.

## Builds on (most cited first, 12 of 12)

- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Fundamentals of Recurrent Neural Network (RNN) and Long Short-Term Memory (LSTM) Network](https://mlsanity.com/paper/1808.03314/) (2018)
- [A Note on Over-Smoothing for Graph Neural Networks](https://mlsanity.com/paper/2006.13318/) (2020)
- [Disease Prediction using Graph Convolutional Networks: Application to Autism Spectrum Disorder and Alzheimer's Disease](https://mlsanity.com/paper/1806.01738/) (2018)
- [Learning Continuous System Dynamics from Irregularly-Sampled Partial Observations](https://mlsanity.com/paper/2011.03880/) (2020)
- [Generalizing Graph ODE for Learning Complex System Dynamics across Environments](https://mlsanity.com/paper/2307.04287/) (2023)
- [BrainIB: Interpretable Brain Network-based Psychiatric Diagnosis with Graph Information Bottleneck](https://mlsanity.com/paper/2205.03612/) (2022)
- [BrainNNExplainer: An Interpretable Graph Neural Network Framework for Brain Network based Disease Analysis](https://mlsanity.com/paper/2107.05097/) (2021)
- [BrainODE: Dynamic Brain Signal Analysis via Graph-Aided Neural Ordinary Differential Equations](https://mlsanity.com/paper/2405.00077/) (2024)
- [Interpretable Graph Convolutional Network of Multi-Modality Brain Imaging for Alzheimer's Disease Diagnosis](https://mlsanity.com/paper/2204.13188/) (2022)
- [Beyond the Snapshot: Brain Tokenized Graph Transformer for Longitudinal Brain Functional Connectome Embedding](https://mlsanity.com/paper/2307.00858/) (2023)
- [A Discriminative Event Based Model for Alzheimer's Disease Progression Modeling](https://mlsanity.com/paper/1702.06408/) (2017)

## Built on by (most cited first, 1 of 1)

- [SDE-Driven Spatio-Temporal Hypergraph Neural Networks for Irregular Longitudinal fMRI Connectome Modeling in Alzheimer's Disease](https://mlsanity.com/paper/2603.20452/) (2026)

## Abstract (arXiv)

Identifying objective neuroimaging biomarkers to forecast Alzheimer's disease (AD) progression is crucial for timely intervention. However, this task remains challenging due to the complex dysfunctions in the spatio-temporal characteristics of underlying brain networks, which are often overlooked by existing methods. To address these limitations, we develop an interpretable spatio-temporal graph neural network framework to predict future AD progression, leveraging dual Stochastic Differential Equations (SDEs) to model the irregularly-sampled longitudinal functional magnetic resonance imaging (fMRI) data. We validate our approach on two independent cohorts, including the Open Access Series of Imaging Studies (OASIS-3) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our framework effectively learns sparse regional and connective importance probabilities, enabling the identification of key brain circuit abnormalities associated with disease progression. Notably, we detect the parahippocampal cortex, prefrontal cortex, and parietal lobule as salient regions, with significant disruptions in the ventral attention, dorsal attention, and default mode networks. These abnormalities correlate strongly with longitudinal AD-related clinical symptoms. Moreover, our interpretability strategy reveals both established and novel neural systems-level and sex-specific biomarkers, offering new insights into the neurobiological mechanisms underlying AD progression. Our findings highlight the potential of spatio-temporal graph-based learning for early, individualized prediction of AD progression, even in the context of irregularly-sampled longitudinal imaging data.