Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers

• URL: http://arxiv.org/abs/2404.05748v2
• Date: Mon, 1 Jul 2024 19:13:36 GMT
• Title: Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers
• Authors: Sayantan Kumar, Tom Earnest, Braden Yang, Deydeep Kothapalli, Andrew J. Aschenbrenner, Jason Hassenstab, Chengie Xiong, Beau Ances, John Morris, Tammie L. S. Benzinger, Brian A. Gordon, Philip Payne, Aristeidis Sotiras,
• Abstract summary: We employed a deep learning-based normative framework to analyze individual-level variation across amyloid-tau-degeneration (ATN) imaging biomarkers. An individual-level disease severity index (DSI) was calculated using both the spatial extent and magnitude of abnormal deviations across ATN.
• Score: 0.0
• License: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Abstract: INTRODUCTION: Previous studies have applied normative modeling on a single neuroimaging modality to investigate Alzheimer Disease (AD) heterogeneity. We employed a deep learning-based multimodal normative framework to analyze individual-level variation across ATN (amyloid-tau-neurodegeneration) imaging biomarkers. METHODS: We selected cross-sectional discovery (n = 665) and replication cohorts (n = 430) with available T1-weighted MRI, amyloid and tau PET. Normative modeling estimated individual-level abnormal deviations in amyloid-positive individuals compared to amyloid-negative controls. Regional abnormality patterns were mapped at different clinical group levels to assess intra-group heterogeneity. An individual-level disease severity index (DSI) was calculated using both the spatial extent and magnitude of abnormal deviations across ATN. RESULTS: Greater intra-group heterogeneity in ATN abnormality patterns was observed in more severe clinical stages of AD. Higher DSI was associated with worse cognitive function and increased risk of disease progression. DISCUSSION: Subject-specific abnormality maps across ATN reveal the heterogeneous impact of AD on the brain.

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