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

 

Ask your doctor to suggest and deliver the right ratio of good cholesterol to bad cholesterol, assuming you don't want to get dementia or a heart attack or a stroke.

I looked at my chart and it doesn't even have these levels described

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.”

Recent research found that older adults with higher levels of high-density lipoprotein cholesterol have a higher risk of dementia. Image: Adobe Stock

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.

Sources/Disclosures

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Source:

Hussain SM, et al. Lancet Reg. Health. 2023;doi:10.1016/j.lanwpc.2023.100963.

Disclosures: Hussain reports receiving support from the National Health and Medical Research Council Early Career Fellowship. Please see the study for all other authors’ relevant financial disclosures. The research was funded by the NIH, the National Health and Medical Research Council Australia, Monash University and the Victorian Cancer Agency.

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

Ask your doctor to suggest and deliver the right ratio of good cholesterol to bad cholesterol, assuming you don't want to get dementia or a heart attack or a stroke.

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
• et al.
• Show all authors

Open AccessPublished:November 29, 2023DOI:https://doi.org/10.1016/j.lanwpc.2023.100963

Summary

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.(What is high?)

Funding

National Institutes of Health, USA; National Health and Medical Research Council Australia; Monash University (Melbourne, VIC, Australia); and the Victorian Cancer Agency (Australia).

Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan

I have no clue what my levels were or currently are and I don't ever plan on worrying about them.

Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan

View ORCID ProfileErin L Ferguson, View ORCID ProfileScott C Zimmerman, View ORCID ProfileChen Jiang, View ORCID ProfileMinhyuk Choi, Kaitlin Swinnerton, Vidhu Choudhary, Travis J Meyers, View ORCID ProfileThomas J Hoffmann, View ORCID ProfilePaola Gilsanz, View ORCID ProfileAkinyemi Oni-Orisan, Rachel A Whitmer, View ORCID ProfileNeil Risch, View ORCID ProfileRonald Krauss, Catherine A Schaefer, M. Maria Glymour

First published October 4, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207876

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• Article
• Info & Disclosures

Abstract

Background and Objectives: The associations of high- and low-density lipoprotein cholesterol (HDL-C and LDL-C) with dementia risk in later life may be complex, and few studies have sufficient data to model non-linearities or adequately adjust for statin use. We evaluated the observational associations of HDL-C and LDL-C with incident dementia in a large and well-characterized cohort with linked survey and electronic health record (EHR) data.

Methods: Kaiser Permanente Northern California health plan members aged 55 years and older who completed a health behavior survey between 2002 and 2007, had no history of dementia prior to the survey, and had laboratory measurements of cholesterol within two years after survey completion were followed through December 2020 for incident dementia (Alzheimer’s Disease Related Dementia [ADRD]; Alzheimer’s, vascular, and/or non-specific dementia) based on ICD9 or ICD10 codes in EHRs. We used Cox models for incident dementia with follow-up time beginning 2 years post-survey (after cholesterol measurement) and censoring at end of membership, death, or end of study period. We evaluated non-linearities using b-splines, adjusted for demographic, clinical, and survey confounders, and tested for effect modification by baseline age or prior statin use.

Results: 184,367 participants [mean age at survey of 69.5 years, mean HDL-C=53.7 mg/dL (SD = 15.0), LDL-C=108 mg/dL (SD = 30.6)] were included. Higher and lower HDL-C values were associated with elevated ADRD risk compared to the middle quantile: HDL-C in the lowest quintile was associated with an HR of 1.07 (95% CI: 1.03-1.11) and HDL-C in the highest quintile was associated with an HR of 1.15 (95% CI: 1.11-1.20). LDL-C was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL-C was associated with slightly greater risk of ADRD for statin users (53% of the sample, HR per 10 mg/dL increase=1.01, 95% CI: 1.01-1.02) and lower risk for non-users (HR per 10 mg/dL increase=0.98; 95% CI: 0.97-0.99). There was evidence for effect modification by age with linear HDL-C (p=0.003) but not LDL-C (p=0.59).

Discussion: Both low and high levels of HDL-C were associated with elevated dementia risk. The association between LDL-C and dementia risk was modest.

• Received March 30, 2023.
• Accepted in final form August 24, 2023.

• © 2023 American Academy of Neurology