Elevated levels of high-density lipoprotein cholesterol associated with new-onset dementia: Lancet

A new study published in The Lancet Regional Health found that among older adults aged 75 years or above who were initially healthy, elevated levels of high-density lipoprotein cholesterol (HDL-C) were linked to a higher likelihood of experiencing all-cause dementia.

A retrospective analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, a double-blind, placebo-controlled study involving daily low-dose aspirin in healthy older individuals, was conducted. ASPREE enrolled 16,703 participants aged 70 years and older from Australia and 2,411 participants aged 65 years and older from the US between 2010 and 2014. The participants had no diagnosed cardiovascular disease, physical disability, dementia, or life-threatening illness at enrollment, and they were cognitively healthy (3MS score ≥78).

The primary trial endpoint was all-cause dementia, determined by DSM-IV criteria. Cox regression was utilized to examine hazard ratios for dementia across HDL-C categories (<40 mg/dL, 40–60 mg/dL as the reference, 60–80 mg/dL, and >80 mg/dL), and nonlinear associations were assessed using restricted cubic spline curves. Data analysis spanned from October 2022 to January 2023.

Out of the 18,668 participants, 850 cases (4.6%) of new-onset dementia were documented over a span of 6.3 years (with a standard deviation of 1.8 years).

Individuals with elevated HDL-C levels (>80 mg/dL) faced a 27% increased risk of developing dementia. Analyses stratified by age revealed a higher risk of incident dementia in participants aged 75 years or older compared to those below 75 years.

These associations remained statistically significant even after adjusting for various covariates, including age, sex, country of enrollment, daily exercise, education, alcohol consumption, weight changes over time, non-HDL-C, HDL-C-PRS, and APOE genotype.

In summary, the heightened risk of dementia linked to elevated HDL-C levels seemed unrelated to conventional dementia risk factors such as physical activity, alcohol consumption, education, diabetes, or smoking.

Source:

Hussain, S. M., Robb, C., Tonkin, A. M., Lacaze, P., Chong, T. T.-J., Beilin, L. J., Yu, C., Watts, G. F., Ryan, J., Ernst, M. E., Zhou, Z., Neumann, J. T., & McNeil, J. J. (2023). Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults. The Lancet Regional Health. Western Pacific, 100963, 100963. https://doi.org/10.1016/j.lanwpc.2023.100963