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| Main Authors: | , , , , , , , , |
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| Format: | Preprint |
| Published: |
2026
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| Subjects: | |
| Online Access: | https://arxiv.org/abs/2601.16467 |
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Table of Contents:
- Discovery of sensitive and biologically grounded biomarkers is essential for early detection and monitoring of Alzheimer's disease (AD). Structural MRI is widely available but typically relies on hand-crafted features such as cortical thickness or volume. We ask whether self-supervised learning (SSL) can uncover more powerful biomarkers from the same data. Existing SSL methods underperform FreeSurfer-derived features in disease classification, conversion prediction, and amyloid status prediction. We introduce Residual Noise Contrastive Estimation (R-NCE), a new SSL framework that integrates auxiliary FreeSurfer features while maximizing additional augmentation-invariant information. R-NCE outperforms traditional features and existing SSL methods across multiple benchmarks, including AD conversion prediction. To assess biological relevance, we derive Brain Age Gap (BAG) measures and perform genome-wide association studies. R-NCE-BAG shows high heritability and associations with MAPT and IRAG1, with enrichment in astrocytes and oligodendrocytes, indicating sensitivity to neurodegenerative and cerebrovascular processes.