Hussain Sultana Monira, Robb Catherine, Tonkin Andrew M, Lacaze Paul, Chong Trevor T-J, Beilin Lawrence J, Yu Chenglong, Watts Gerald F, Ryan Joanne, Ernst Michael E, Zhou Zhen, Neumann Johannes T, McNeil John J
School of Public Health and Preventive Medicine, Monash University, Victoria, 3004, Australia.
Department of Medical Education, Melbourne Medical School, The University of Melbourne, Victoria, 3010, Australia.
Lancet Reg Health West Pac. 2023 Nov 29;43:100963. doi: 10.1016/j.lanwpc.2023.100963. eCollection 2024 Feb.
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.
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.
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 genotype.
In a population of initially-healthy older adults aged ≥75 years, high HDL-C levels were associated with increased risk of all-cause dementia.
National Institutes of Health, USA; National Health and Medical Research Council Australia; Monash University (Melbourne, VIC, Australia); and the Victorian Cancer Agency (Australia).
近期研究报告了血浆高密度脂蛋白胆固醇（HDL-C）水平升高与全因死亡率、年龄相关性黄斑变性、败血症和骨折风险之间的关联，但与痴呆症风险的关联仍不明确。为了确定血浆HDL-C水平升高是否与初始健康的老年人患痴呆症风险增加有关。
我们对阿司匹林降低老年人事件风险（ASPREE）试验进行了事后分析；这是一项针对健康老年人的每日低剂量阿司匹林双盲、随机、安慰剂对照试验。ASPREE在2010年至2014年期间招募了16703名年龄≥70岁（来自澳大利亚）和2411名年龄≥65岁（来自美国）的参与者。参与者在入组时没有诊断出心血管疾病、痴呆症、身体残疾或危及生命的疾病，并且认知健康（3MS评分≥78）。全因痴呆症是主要试验终点，并根据DSM-IV标准确定。使用Cox回归来检查HDL-C类别<40mg/dL、40-60mg/dL（参考类别）、60-80mg/dL和>80mg/dL与痴呆症之间的风险比。使用受限立方样条曲线来确定非线性关联。数据分析于2022年10月至2023年1月进行。
在18668名参与者中，在6.3（标准差1.8）年期间记录了850例（4.6%）新发痴呆症病例。HDL-C水平高（>80mg/dL）的参与者患痴呆症的风险高27%（风险比1.27，95%置信区间1.03，1.58）。年龄分层分析表明，与<75岁的参与者相比，≥75岁的参与者患新发痴呆症的风险更高（风险比1.42，95%置信区间1.10，1.83对风险比1.02，95%置信区间0.68，1.51）。在调整了包括年龄、性别、入组国家、日常锻炼、教育、饮酒、随时间的体重变化、非HDL-C、HDL-C遗传风险评分和基因型等协变量后，关联仍然显著。
在初始健康的≥75岁老年人群中，HDL-C水平升高与全因痴呆症风险增加有关。
美国国立卫生研究院；澳大利亚国家卫生与医学研究委员会；莫纳什大学（澳大利亚维多利亚州墨尔本）；以及维多利亚癌症局（澳大利亚）。
