ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Analyzing heterogeneity in Alzheimer disease using multimodal normative modeling on imaging-based ATN biomarkers.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Longitudinal trajectories of divergent cortical tau patterns in preclinical Alzheimer's disease.Brain : a journal of neurology · 2026Article
- Real-World Multimodal Machine Learning for Risk Enrichment Across the Alzheimer's Disease Spectrum.Journal of clinical medicine · 2026Article
- Analyzing heterogeneity in Alzheimer disease using multimodal normative modeling on imaging-based ATN biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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Abstract
introductionPrevious 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.
methodsWe selected cross-sectional discovery (n = 665) and replication cohorts (n = 430) with available T1-weighted magnetic resonance imaging (MRI), amyloid, and tau positron emission tomography (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.
resultsGreater 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. HIGHLIGHTS: Normative modeling examined AD heterogeneity across multimodal imaging biomarkers. Heterogeneity in spatial patterns of gray matter atrophy, amyloid, and tau burden. Higher within-group heterogeneity for AD patients at advanced dementia stages. Patient-specific metric summarized extent of neurodegeneration and neuropathology. Metric is a marker of poor brain health and can monitor risk of disease progression.
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