{"doi":"10.1002/alz.14575","title":"Independent associations of high‐density lipoprotein cholesterol and triglyceride levels with Alzheimer's disease and related dementias","abstract":"INTRODUCTION: We evaluated the independent associations between high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels with Alzheimer's disease and related dementias (ADRD). METHODS: Among 177,680 members of Kaiser Permanente Northern California who completed a survey on health risks, we residualized TGs and HDL-C conditional on age, sex, and body mass index. We included these residuals individually and concurrently in Cox models predicting ADRD incidence. RESULTS: Low (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02-1.10) and high quintiles (HR 1.07, 95% CI 1.03-1.12) of HDL-C residuals were associated with an increased risk of ADRD compared to the middle quintile. Additional adjustment for TGs attenuated the association with high HDL-C (HR 1.03, 95% CI 0.99-1.08). Low TG residuals were associated with an increased ADRD risk (HR 1.10, 95% CI 1.06-1.15); high TG residuals were protective (HR 0.92, 95% CI 0.88-0.96). These estimates were unaffected by HDL-C adjustment. DISCUSSION: Low HDL-C and TG levels are independently associated with increased ADRD risk. The correlation with low TG level explains the association of high HDL-C with ADRD. HIGHLIGHTS: Strong correlations between lipid levels are important considerations when investigating lipids as late-life risk factors for Alzheimer's disease and related dementias (ADRD). Low levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) were independently associated with an increased risk of ADRD. We found no evidence for an association between high HDL-C and increased ADRD risk after adjustment for TGs. High levels of TGs were consistently associated with a decreased risk of ADRD. There may be interaction between TG and HDL-C levels, where both low HDL-C and TG levels increase the risk of ADRD compared to average levels of both.","journal":"Alzheimer s & Dementia","year":2025,"id":517123,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9186,"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":486557,"name":"Scott C. Zimmerman","orcid":"0000-0002-4431-6520","position":1,"is_corresponding":false},{"id":1031102,"name":"Chen Jiang","orcid":"0000-0002-0336-4518","position":2,"is_corresponding":false},{"id":1031103,"name":"Minhyuk Choi","orcid":"0009-0000-6658-5054","position":3,"is_corresponding":false},{"id":233925,"name":"Travis J. Meyers","orcid":"0000-0001-9186-9745","position":4,"is_corresponding":false},{"id":1219657,"name":"Thomas J. Hoffmann","orcid":"0000-0003-4129-9478","position":5,"is_corresponding":false},{"id":366568,"name":"Paola Gilsanz","orcid":"0000-0002-7635-381X","position":6,"is_corresponding":false},{"id":471243,"name":"Akinyemi Oni‐Orisan","orcid":"0000-0002-5897-5543","position":7,"is_corresponding":false},{"id":845828,"name":"Jingxuan Wang","orcid":"0000-0003-0380-6352","position":8,"is_corresponding":false},{"id":226637,"name":"Rachel A. Whitmer","orcid":"0009-0006-9511-6138","position":9,"is_corresponding":false},{"id":108774,"name":"Neil Risch","orcid":"0000-0002-4126-2061","position":10,"is_corresponding":false},{"id":364930,"name":"Ronald M. Krauss","orcid":"0000-0002-1238-3489","position":11,"is_corresponding":false},{"id":5354,"name":"Catherine Schaefer","orcid":"0000-0003-2644-055X","position":12,"is_corresponding":false},{"id":106142,"name":"M. Maria Glymour","orcid":"0000-0001-9644-3081","position":13,"is_corresponding":false},{"id":1031101,"name":"Erin L. Ferguson","orcid":"0000-0003-3136-0001","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"40008914","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":[]}