Rethinking “Good” Cholesterol: Study Links High HDL-C Levels to Increased Dementia Risk

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A Monash University-led study discovered a link between high levels of HDL-C (‘good cholesterol’) and increased dementia risk in older adults, particularly those over 75. This significant finding calls for further research to explore the impact of high HDL-C on brain health.

Research from Monash University indicates that high levels of ‘good cholesterol’ (HDL-C) are associated with an increased risk of dementia in the elderly, highlighting a need for more in-depth study in this area.

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 recognize a group of older patients potentially at risk of dementia, particularly in those aged 75 and older.

Findings in Elderly Populations

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 percent higher risk of dementia compared to participants with optimal HDL-C levels, while those aged 75 years and older also showed a 42 percent increased risk compared to those with optimal levels.

Very high HDL-C levels were categorized 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.

Participant Data

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.

Further Research Required

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.”

Reference: “Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults” by Sultana Monira Hussain, Catherine Robb, Andrew M. Tonkin, Paul Lacaze, Trevor T.-J. Chong, Lawrence J. Beilin, Chenglong Yu, Gerald F. Watts, Joanne Ryan, Michael E. Ernst, Zhen Zhou, Johannes T. Neumann and John J. McNeil, 29 November 2023, The Lancet Regional Health – Western Pacific.
DOI: 10.1016/j.lanwpc.2023.100963

*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).

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