{"doi":"10.1002/alz.70737","title":"Clonal hematopoiesis of indeterminate potential and the risk of cognitive impairment in the Women's Health Initiative Memory Study","abstract":"INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) confers an increased risk of several chronic aging-related diseases. Paradoxically, CHIP was associated with lower risk of dementia in recent studies. METHODS: We examined associations between baseline CHIP and incident mild cognitive impairment (MCI) and/or probable dementia in the Women's Health Initiative Memory Study. CHIP was detected using blood-based targeted sequencing. Cox proportional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors. RESULTS: Using a conventional variant allele fraction (VAF) threshold of 2%, CHIP was not associated with incident cognitive impairment. The presence of larger CHIP clone (VAF ≥ 8%) was associated with a lower incidence of adjudicated probable dementia (hazard ratio = 0.62 [95% confidence interval = 0.41 to 0.94], p = 0.025), while the association with the composite outcome MCI/probable dementia was weaker and overlapped 1.0. DISCUSSION: The association of CHIP with lower risk of cognitive impairment in postmenopausal women may be dependent on VAF and impairment severity. HIGHLIGHTS: The WHIMS comprises ∼5000 postmenopausal women, followed for up to 25 years. CHIP was associated with reduced risk of adjudicated probable dementia in WHIMS. Large CHIP clones (> 8% VAF), but not small clones (<8% VAF), showed an association. CHIP was not associated with MCI in the WHIMS cohort.","journal":"Alzheimer s & Dementia","year":2025,"id":515249,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":825093,"name":"Aaron P. Smith","orcid":"0000-0002-5417-014X","position":1,"is_corresponding":false},{"id":890548,"name":"Xiaoyan Leng","orcid":"0000-0002-7610-7977","position":2,"is_corresponding":false},{"id":596094,"name":"Megan E. Hall","orcid":"0000-0001-8163-5988","position":3,"is_corresponding":false},{"id":1368329,"name":"Daniel Ezzat","orcid":"0009-0002-6850-4275","position":4,"is_corresponding":false},{"id":641922,"name":"Yash Pershad","orcid":"0000-0002-2282-1403","position":5,"is_corresponding":false},{"id":594952,"name":"Jason M. Collins","orcid":"0000-0002-2903-797X","position":6,"is_corresponding":false},{"id":561964,"name":"Md Mesbah Uddin","orcid":"0000-0003-1846-0411","position":7,"is_corresponding":false},{"id":244999,"name":"David W. Fardo","orcid":"0000-0002-7207-4696","position":8,"is_corresponding":false},{"id":24665,"name":"Pradeep Natarajan","orcid":"0000-0001-8402-7435","position":9,"is_corresponding":false},{"id":27378,"name":"Alexander G. Bick","orcid":"0000-0001-5824-9595","position":10,"is_corresponding":false},{"id":40413,"name":"Jacob O. Kitzman","orcid":"0000-0002-6145-882X","position":11,"is_corresponding":false},{"id":373536,"name":"Michael C. Honigberg","orcid":"0000-0001-8630-5021","position":12,"is_corresponding":false},{"id":258460,"name":"Kathleen M. Hayden","orcid":"0000-0002-7745-3513","position":13,"is_corresponding":false},{"id":128467,"name":"JOANN E. MANSON","orcid":null,"position":14,"is_corresponding":false},{"id":621763,"name":"Siddhartha Jaiswal","orcid":"0000-0002-9597-0477","position":15,"is_corresponding":false},{"id":218550,"name":"Eric A. Whitsel","orcid":"0000-0003-4843-3641","position":16,"is_corresponding":false},{"id":14704,"name":"Alexander P. Reiner","orcid":null,"position":17,"is_corresponding":false},{"id":501258,"name":"Yasminka A. Jakubek","orcid":"0000-0003-1427-1015","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T02:48:39.436300Z","pmid":"41025350","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":[]}