In initially-healthy older adults, high plasma HDL-C levels (>80 mg/dL) were associated with an increased risk of incident all-cause dementia (HR 1.27; 95% CI 1.03-1.58).
Cohort (n=18,668)
Yes
Are high plasma HDL-C levels associated with an increased risk of incident dementia in initially-healthy older adults?
In initially-healthy older adults, very high HDL-C levels (>80 mg/dL) are associated with an increased risk of incident all-cause dementia, particularly in those aged ≥75 years.
Hazard Ratio: 1.27 (95% CI 1.03–1.58)
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 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).
Hussain et al. (2023) conducted a cohort in Healthy older adults (n=18,668). High plasma HDL-C (>80 mg/dL) vs. HDL-C 40-60 mg/dL was evaluated on All-cause dementia (HR 1.27, 95% CI 1.03-1.58). In initially-healthy older adults, high plasma HDL-C levels (>80 mg/dL) were associated with an increased risk of incident all-cause dementia (HR 1.27; 95% CI 1.03-1.58).