BrainVAE: Exploring the role of white matter BOLD in preclinical Alzheimer's disease classification.

INTRODUCTION

Like gray matter (GM), white matter (WM) BOLD functional signals change in preclinical AD. However, the potential of WM BOLD for identifying preclinical AD remains underexplored.

METHODS

We developed BrainVAE, a transformer-based variational autoencoder with interpretability, to classify preclinical AD and normal controls using resting-state fMRI data. We benchmarked BrainVAE against nine alternative models under three input configurations: WM-only, GM-only, and combined WM+GM. Interpretability analysis was also performed to investigate each brain region's contribution to the classification task.

RESULTS

BrainVAE outperformed other models and performed well (accuracy = 83.42%, F1-score = 91.62%, AUC = 64.50%) using the combined input compared to WM-only and GM-only. Specific WM bundles--including corpus callosum, fornix, and corticospinal tract-were among the most influential features contributing to the classification.

DISCUSSION

Incorporating WM BOLD signals improves the distinction of preclinical AD from controls, underscoring the potential role of WM BOLD features for detecting early-stage AD.