Summary: A large new study led by Monash University found that unusually high levels of HDL-C (high-density lipoprotein cholesterol), commonly called “good cholesterol,” were linked to an increased risk of dementia in older adults.
This analysis of participants in the ASPREE study included 18,668 initially healthy older adults and found that those with very high HDL-C levels (>80 mg/dL or >2.07 mmol/L) experienced a significantly greater risk of developing dementia over an average follow-up of 6.3 years. Overall, very high HDL-C was associated with a 27% higher dementia risk, with the effect notably stronger in people aged 75 and older, who showed a 42% increased risk.
Key Facts:
- Very high HDL-C (>80 mg/dL) was associated with a 27% higher risk of developing dementia in the study population.
- Among participants aged 75 and older, very high HDL-C was linked to a 42% higher dementia risk compared with optimal HDL-C levels.
- Very high HDL-C levels in this cohort were uncommon and appeared more likely related to underlying metabolic differences than to diet.
Source: Monash University
Elevated HDL-C levels—often considered protective for the heart—may have a different relationship with brain health in older adults, according to this Monash University-led investigation.
The researchers emphasize that very high HDL-C was rare among participants and, based on available data, seemed unlikely to be caused by diet alone. Instead, such levels could reflect metabolic or genetic differences that merit further study. Identifying older adults with these unusually high HDL-C values may help clinicians flag individuals who could be at higher risk of dementia.
Published in The Lancet Regional Health – Western Pacific, this is among the largest cohort analyses to examine the association between elevated HDL-C and dementia in an initially healthy older population. Most participants were over age 70 when recruited to the Aspirin in Reducing Events in the Elderly (ASPREE) trial.
Over a mean follow-up of 6.3 years, people who entered the study with very high HDL-C (>80 mg/dL) had a 27% higher risk of being diagnosed with all-cause dementia compared to those whose HDL-C fell within the study’s optimal range. The optimal HDL-C range used in the analysis was 40–60 mg/dL for men and 50–60 mg/dL for women, levels generally regarded as heart-healthy.
In total, 18,668 participants were included in the analysis and 2,709 of them had very high HDL-C at baseline. Within this group there were 38 incident dementia cases among participants younger than 75 and 101 cases among those aged 75 or older.
Dr Monira Hussain, senior research fellow at the Monash University School of Public Health and Preventive Medicine and lead author on the paper, said additional research is needed to clarify why very high HDL-C is linked to dementia risk. The current findings point to a need for deeper investigation into the biological pathways that might connect extremely high HDL-C with cognitive decline.
“While HDL cholesterol is typically viewed as beneficial for cardiovascular health, our results indicate that very high HDL levels may have complex associations with brain health in older age,” Dr Hussain said. “Future studies should examine mechanisms behind this relationship and consider whether very high HDL-C could be incorporated into dementia risk prediction tools.”
Note on ASPREE: The Aspirin in Reducing Events in the Elderly (ASPREE) trial is a double-blind, randomized, placebo-controlled study assessing daily low-dose aspirin in healthy older adults. ASPREE enrolled 16,703 participants aged 70 and older in Australia and 2,411 participants aged 65 and older in the United States between 2010 and 2014. Enrollees were free of diagnosed cardiovascular disease, dementia, physical disability, or life-threatening illness at baseline. The cohort remains under observational follow-up in the ASPREE-XT extension.
About this dementia research news
Author: Cheryl Critchley
Source: Monash University
Contact: Cheryl Critchley – Monash University
Image credit: 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., published in 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
Previous research has linked high plasma HDL-C to diverse outcomes such as mortality, age-related macular degeneration, sepsis and fractures, but its relationship with dementia risk has been uncertain. This study aimed to assess whether elevated plasma HDL-C is associated with incident dementia in an initially healthy older population.
Methods
The analysis used post-hoc data from the ASPREE trial, which randomized healthy older adults to daily low-dose aspirin or placebo. Participants were cognitively healthy at baseline. Researchers categorized HDL-C into four groups: <40 mg/dL, 40–60 mg/dL (reference), 60–80 mg/dL, and >80 mg/dL, and used Cox regression models and restricted cubic spline analyses to examine associations between HDL-C categories and incident all-cause dementia. Analyses adjusted for multiple covariates and genomic risk factors.
Findings
Among 18,668 participants followed for a mean of 6.3 years, there were 850 incident dementia cases (4.6%). Participants with HDL-C >80 mg/dL had a 27% higher risk of dementia (hazard ratio 1.27, 95% CI 1.03–1.58) compared with the reference group. The association was stronger in those aged 75 and older (HR 1.42, 95% CI 1.10–1.83) and persisted after adjustment for demographic, lifestyle, lipid, polygenic, and APOE factors.
Interpretation
In this large cohort of initially healthy older adults, very high HDL-C was associated with greater risk of all-cause dementia, particularly among participants aged 75 years and older. The findings suggest a need for mechanistic studies and consideration of very high HDL-C in dementia risk assessment.
Funding
This research was supported by the National Institutes of Health (USA), the National Health and Medical Research Council (Australia), Monash University (Melbourne), and the Victorian Cancer Agency (Australia).