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Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults
Journal article   Open access   Peer reviewed

Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults

Sultana Monira Hussain, Catherine Robb, Andrew M. Tonkin, Paul Lacaze, Trevor T.-J. Chong, Lawrence J. Beilin, Chenglong Yu, Gerald F. Watts, Joanne Ryan, Michael E. Ernst, …
The Lancet regional health. Western Pacific, Vol.43, 100963
02/2024
DOI: 10.1016/j.lanwpc.2023.100963
PMCID: PMC10920036
PMID: 38456089
url
https://doi.org/10.1016/j.lanwpc.2023.100963View
Published (Version of record) Open Access

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.

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