{"doi":"10.1101/2024.07.07.24310055","title":"Identifying Sex-Specific Sub-phenotypes of Alzheimer’s Disease Progression Using Longitudinal Electronic Health Records","abstract":"Alzheimer's Disease (AD) is a complex neurodegenerative disorder strongly influenced by sex differences, with women comprising nearly two-thirds of cases. However, sex-specific progression patterns remain underexplored due to unclear clinical and molecular mechanisms. To address this gap, we developed a temporal autoencoder framework to identify sex-specific AD sub-phenotypes using longitudinal electronic health record (EHR) data from the OneFlorida+ Clinical Research Consortium. Sequential EHRs were encoded into latent representations and clustered to derive disease states, which were assembled into progression pathways. This approach uncovered five primary sex-stratified sub-phenotypes with distinct trajectories and phenotypic characteristics. Survival and cumulative prevalence analyses further revealed heterogeneous temporal dynamics of AD onset and comorbidity accumulation between female- and male-dominant groups. By integrating deep learning with large-scale real-world data, our framework advances understanding of sex-based heterogeneity in AD progression and provides a scalable tool for early risk stratification, personalized intervention, and improved clinical trial design.","journal":"medRxiv","year":2024,"id":486242,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9505,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":476827,"name":"Qiang Yang","orcid":"0000-0001-8367-1755","position":1,"is_corresponding":false},{"id":394673,"name":"Jie Xu","orcid":"0000-0001-5291-5198","position":2,"is_corresponding":false},{"id":6697,"name":"Yu Huang","orcid":"0000-0003-4535-4331","position":3,"is_corresponding":false},{"id":257822,"name":"Cankun Wang","orcid":"0000-0002-0225-9855","position":4,"is_corresponding":false},{"id":1329658,"name":"Qianqian Song","orcid":"0000-0001-6106-3505","position":5,"is_corresponding":false},{"id":436332,"name":"Lixin Song","orcid":"0000-0001-8286-319X","position":6,"is_corresponding":false},{"id":23318,"name":"Jiang Bian","orcid":"0000-0002-2238-5429","position":7,"is_corresponding":false},{"id":95255,"name":"Qin Ma","orcid":"0000-0001-5325-7596","position":8,"is_corresponding":false},{"id":235824,"name":"Anjun Ma","orcid":"0000-0001-6269-398X","position":9,"is_corresponding":false},{"id":1039990,"name":"Rui Yin","orcid":"0000-0002-1403-0396","position":10,"is_corresponding":false},{"id":1328497,"name":"Weimin Meng","orcid":"0009-0009-3075-9396","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T02:07:57.049469Z","pmid":"39040206","pmcid":null,"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":[]}