{"doi":"10.1016/j.lanwpc.2023.100963","title":"Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults","abstract":"Background Recent studies have reported associations between high plasma high-density lipoprotein cholesterol (HDL-C) levels and risk of all-cause mortality, age-related macular degeneration, sepsis and fractures, but associations with dementia risk remain unclear. To determine whether high plasma HDL-C levels are associated with increased incident dementia risk in initially-healthy older people. Methods We conducted a post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial; a double-blind, randomized, placebo-controlled trial of daily low-dose aspirin in healthy older people. ASPREE recruited 16,703 participants aged ≥70 years (from Australia) and 2411 participants aged ≥65 years (from the US) between 2010 and 2014. Participants had no diagnosed cardiovascular disease, dementia, physical disability, or life-threatening illness at enrolment and were cognitively healthy (3MS score ≥78). All-cause dementia was a primary trial endpoint, and determined by DSM-IV criteria. Cox regression was used to examine hazard ratios between HDL-C categories <40 mg/dL, 40–60 mg/dL (reference category), 60–80 mg/dL, and >80 mg/dL and dementia. Restricted cubic spline curves were used to determine nonlinear associations. Data analysis was performed from October 2022 to January 2023. Findings Of the 18,668 participants, 850 (4.6%) cases of incident dementia were recorded over 6.3 (SD 1.8) years. Participants with high HDL-C (>80 mg/dL) had a 27% higher risk of dementia (HR 1.27, 95% CI 1.03, 1.58). Age stratified analyses demonstrated that the risk of incident dementia was higher in participants ≥75 years compared to participants <75 years (HR 1.42, 95% CI 1.10, 1.83 vs HR 1.02, 95% CI 0.68, 1.51). Associations remained significant after adjusting for covariates including age, sex, country of enrolment, daily exercise, education, alcohol consumption, weight change over time, non-HDL-C, HDL-C-PRS, and APOE genotype. Interpretation In a population of initially-healthy older adults aged ≥75 years, high HDL-C levels were associated with increased risk of all-cause dementia. Funding National Institutes of Health, USA; National Health and Medical Research Council Australia; Monash University (Melbourne, VIC, Australia); and the Victorian Cancer Agency (Australia).","journal":"The Lancet Regional Health - Western Pacific","year":2023,"id":320491,"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":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"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":1031171,"name":"Catherine Robb","orcid":"0000-0001-7586-5533","position":1,"is_corresponding":false},{"id":284811,"name":"Andrew Tonkin","orcid":"0000-0001-5291-0610","position":2,"is_corresponding":false},{"id":301792,"name":"Paul Lacaze","orcid":"0000-0002-0902-6798","position":3,"is_corresponding":false},{"id":792045,"name":"Trevor T.‐J. Chong","orcid":"0000-0001-7764-3811","position":4,"is_corresponding":false},{"id":241477,"name":"Lawrence J. Beilin","orcid":"0000-0003-4853-7360","position":5,"is_corresponding":false},{"id":436268,"name":"Chenglong Yu","orcid":"0000-0002-0546-2779","position":6,"is_corresponding":false},{"id":226211,"name":"Gerald F. Watts","orcid":"0000-0003-2276-1524","position":7,"is_corresponding":false},{"id":332013,"name":"Joanne Ryan","orcid":"0000-0002-7039-6325","position":8,"is_corresponding":false},{"id":104597,"name":"Michael E. Ernst","orcid":"0000-0003-0267-4888","position":9,"is_corresponding":false},{"id":636786,"name":"Zhen Zhou","orcid":"0000-0002-0835-8686","position":10,"is_corresponding":false},{"id":732597,"name":"Franz–Josef Neumann","orcid":"0000-0002-9478-2757","position":11,"is_corresponding":false},{"id":264297,"name":"John J. McNeil","orcid":"0000-0002-1049-5129","position":12,"is_corresponding":false},{"id":933961,"name":"Sultana Monira Hussain","orcid":"0000-0001-7894-2485","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T01:07:22.377587Z","pmid":"38456089","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":[]}