Summary: A new study found that abnormally high levels of HDL-C (high-density lipoprotein cholesterol), often referred to as ‘good cholesterol’, may increase the risk of dementia in older adults.
This large-scale study, part of the ASPREE project, observed over 18,668 participants, noting that those with very high HDL-C levels had a 27% higher risk of dementia. The findings were particularly pronounced in individuals aged 75 and older, who showed a 42% increased risk.
This research highlights the need for further investigation into the role of HDL-C in brain health and could aid in developing prediction algorithms for dementia risk.
Key Facts:
- Very high levels of HDL-C (>80 mg/dL) are associated with a 27% increased risk of dementia.
- Individuals aged 75 and older with these high HDL-C levels face a 42% higher dementia risk.
- The study suggests a need for further research to understand the role of HDL-C in brain health and its potential impact on dementia risk assessment.
Source: Monash University
Abnormally high levels of HDL-C, colloquially known as ‘good cholesterol’, are associated with an increased risk of dementia in older adults, a Monash University-led study has found.
Researchers said very high levels of HDL-C linked to dementia risk in this study were uncommon and not diet related, but more likely to reflect a metabolic disorder.
The findings may help doctors to recognise a group of older patients potentially at risk of dementia, particularly in those aged 75 and older.
Published in The Lancet Regional Health – Western Pacific, this is one of the largest studies of elevated HDL-C levels and dementia in initially healthy older people aged mostly over 70, enrolled in the ASPREE* study.
Over an average 6.3 years, participants with very high HDL-C (>80 mg/dL or >2.07 mmol/L) at study entry were observed to have a 27 per cent higher risk of dementia compared to participants with optimal HDL-C levels, while those aged 75 years and older also showed a 42 per cent increased risk compared to those with optimal levels.
Very high HDL-C levels were categorised as 80 mg/dL (>2.07 mmol/L) or above. The optimal level of HDL-C of 40 to 60 mg/dL (1.03–1.55 mmol/L) for men and 50 to 60 mg/dL (1.55–2.07 mmol/L) for women was generally beneficial for heart health.
Among 18,668 participants included in this analysis, 2709 had very high HDL-C at study entry, with 38 incidents of dementia in those aged less than 75 years with very high levels, and 101 in those aged 75 and more with very high levels.
First author and Monash University School of Public Health and Preventive Medicine senior research fellow Dr Monira Hussain said that further research was needed to explain why a very high HDL cholesterol level appeared to affect the risk of dementia.
Dr Hussain said these study findings could help improve our understanding of the mechanisms behind dementia, but more research was required.
“While we know HDL cholesterol is important for cardiovascular health, this study suggests that we need further research to understand the role of very high HDL cholesterol in the context of brain health,” she said.
“It may be beneficial to consider very high HDL cholesterol levels in prediction algorithms for dementia risk.”
*The Aspirin in Reducing Events in the Elderly (ASPREE) trial is a double-blind, randomised, placebo-controlled trial of daily aspirin in healthy older people. ASPREE recruited 16,703 participants aged ≥70 years (from Australia) and 2,411 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. The study continues in the observational follow-up phase, ASPREE-XT (Extension).
About this dementia research news
Author: Cheryl Critchley
Source: Monash University
Contact: Cheryl Critchley – Monash University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults” by Monira Hussain et al. The Lancet Regional Health – Western Pacific
Abstract
Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults
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).
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