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Main Authors: Reynolds, Maxwell, Srinivasan, Chaitanya, Cherupally, Vijay, Leone, Michael, Yu, Ke, Sun, Li, Chaudhary, Tigmanshu, Pfenning, Andreas, Batmanghelich, Kayhan
Format: Preprint
Published: 2026
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Online Access:https://arxiv.org/abs/2601.16467
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author Reynolds, Maxwell
Srinivasan, Chaitanya
Cherupally, Vijay
Leone, Michael
Yu, Ke
Sun, Li
Chaudhary, Tigmanshu
Pfenning, Andreas
Batmanghelich, Kayhan
author_facet Reynolds, Maxwell
Srinivasan, Chaitanya
Cherupally, Vijay
Leone, Michael
Yu, Ke
Sun, Li
Chaudhary, Tigmanshu
Pfenning, Andreas
Batmanghelich, Kayhan
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.
format Preprint
id arxiv_https___arxiv_org_abs_2601_16467
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle A Cautionary Tale of Self-Supervised Learning for Imaging Biomarkers: Alzheimer's Disease Case Study
Reynolds, Maxwell
Srinivasan, Chaitanya
Cherupally, Vijay
Leone, Michael
Yu, Ke
Sun, Li
Chaudhary, Tigmanshu
Pfenning, Andreas
Batmanghelich, Kayhan
Machine Learning
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.
title A Cautionary Tale of Self-Supervised Learning for Imaging Biomarkers: Alzheimer's Disease Case Study
topic Machine Learning
url https://arxiv.org/abs/2601.16467