Older adults with greatest HDL-C levels have higher risk of dementia

Key takeaways:

• The study included more than 18,000 individuals from the U.S and Australia.
• Risk of incident dementia was higher for those aged 75 years and older compared with those aged younger than 75 years.

In a cohort of older adults, those with the highest percentage of high-density lipoprotein cholesterol had a 27% higher risk of incident dementia, with the risk higher for those aged 75 years and older, according to a study.

“A series of recent reports has highlighted a relationship between high [high-density lipoprotein cholesterol] and a range of adverse health conditions,” Sultana Monira Hussain, MBBS, MPH, PhD, a senior research fellow at the School of Public Health and Preventive Medicine at Monash University in Australia, and colleagues wrote in The Lancet Regional Health Western Pacific. “These include a recent report from two large community-based cohorts from Denmark which found an association between very high HDL-C levels and an increased future risk of all-cause dementia and Alzheimer’s disease.”

Hussain and colleagues sought to determine whether high plasma HDL-C levels are associated with increased incident dementia risk in initially healthy older adults.

They conducted a post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, a double-blind, randomized, placebo-controlled study of daily low-dose aspirin in healthy individuals. The study recruited 16,703 participants from Australia aged 70 years and older, and 2,411 participants from the United States aged 65 years and older, all between 2010 and 2014. Those included in the analysis had no diagnosed cardiovascular disease, dementia, physical disability or life-threatening illness at time of enrollment, and were cognitively healthy (score 78 on the Modified Mini Mental State test). Participants, whose cognitive abilities were assessed with 3MS at baseline, year 1 and biennially thereafter, were randomized to receive 100 mg aspirin daily or placebo.

The primary analysis endpoint was all-cause dementia determined by DSM-IV criteria. Researchers performed Cox regression to examine hazard ratios between four separate HDL-C categories (<40 mg/dL, 40 mg/dL to 60 mg/dL [reference category], 60 mg/dL to 80 mg/dL, and >80 mg/dL) and dementia.

The final analysis included 18,668 individuals. A total of 850 cases of incident dementia were recorded over 6.3 years.

Those with the highest HDL-C (>80 mg/dL) showed a 27% higher risk of dementia (HR = 1.27; 95% CI: 1.03-1.58), while risk of incident dementia was higher in participants aged 75 years or older compared with those aged younger than 75 years (HR = 1.42; 95% CI: 1.1-1.83 vs. HR = 1.02; 95% CI: 0.68-1.51). Data further showed significant associations after adjusting for covariates including age, sex, country of enrollment, daily exercise, education, alcohol consumption, weight change over time, non-HDL-C and HDL-C-PRS.

“These findings are timely and may suggest that identifying individuals with very high HDL-C could act as a new strategy for the early identification of high-risk individuals,” Hussain and colleagues wrote.