{"doi":"10.1101/2023.08.15.553412","title":"Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":391938,"datarank":0.34157181039152645,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.04968528803322939,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.04968528803322939,"corpus_percentile":48.773884118511646,"corpus_rank":6623,"citation_count":6,"citer_count":5,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.631,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":560797,"name":"Tom Earnest","orcid":"0000-0001-8671-8424","position":1,"is_corresponding":false},{"id":1074032,"name":"Braden Yang","orcid":"0000-0002-2558-4132","position":2,"is_corresponding":false},{"id":633743,"name":"Deydeep Kothapalli","orcid":null,"position":3,"is_corresponding":false},{"id":479431,"name":"Andrew J. Aschenbrenner","orcid":"0000-0002-4317-7282","position":4,"is_corresponding":false},{"id":226993,"name":"Jason Hassenstab","orcid":"0000-0002-7802-3371","position":5,"is_corresponding":false},{"id":1165112,"name":"Chengie Xiong","orcid":"0009-0001-0289-148X","position":6,"is_corresponding":false},{"id":226074,"name":"Beau M. Ances","orcid":"0000-0003-3862-7397","position":7,"is_corresponding":false},{"id":27593,"name":"John C. Morris","orcid":"0000-0001-9820-5618","position":8,"is_corresponding":false},{"id":301875,"name":"Tammie L.S. Benzinger","orcid":"0000-0002-8114-0552","position":9,"is_corresponding":false},{"id":255192,"name":"Brian A. Gordon","orcid":"0000-0003-2109-2955","position":10,"is_corresponding":false},{"id":225274,"name":"Philip Payne","orcid":"0000-0002-9532-2998","position":11,"is_corresponding":false},{"id":236740,"name":"Aristeidis Sotiras","orcid":"0000-0003-0795-8820","position":12,"is_corresponding":false},{"id":265450,"name":"the Alzheimer’s Disease Neuroimaging Initiative","orcid":null,"position":13,"is_corresponding":false},{"id":985442,"name":"Sayantan Kumar","orcid":"0000-0001-7213-0734","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:18:52.232318Z","pmid":"37662280","pmcid":"PMC10473626","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}