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. 2025 Feb;21(2):e14575.
doi: 10.1002/alz.14575.

Independent associations of high-density lipoprotein cholesterol and triglyceride levels with Alzheimer's disease and related dementias

Erin L Ferguson  1 , Scott C Zimmerman  1 , Chen Jiang  2 , Minhyuk Choi  1 , Travis J Meyers  2 , Thomas J Hoffmann  1   3 , Paola Gilsanz  2 , Akinyemi Oni-Orisan  3   4 , Jingxuan Wang  1 , Rachel A Whitmer  5 , Neil Risch  1   2   3 , Ronald M Krauss  6 , Catherine A Schaefer  2 , M Maria Glymour  7
Affiliations

Independent associations of high-density lipoprotein cholesterol and triglyceride levels with Alzheimer's disease and related dementias

Erin L Ferguson et al. Alzheimers Dement. 2025 Feb.

Abstract

Introduction: We evaluated the independent associations between high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels with Alzheimer's disease and related dementias (ADRD).

Methods: Among 177,680 members of Kaiser Permanente Northern California who completed a survey on health risks, we residualized TGs and HDL-C conditional on age, sex, and body mass index. We included these residuals individually and concurrently in Cox models predicting ADRD incidence.

Results: Low (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02-1.10) and high quintiles (HR 1.07, 95% CI 1.03-1.12) of HDL-C residuals were associated with an increased risk of ADRD compared to the middle quintile. Additional adjustment for TGs attenuated the association with high HDL-C (HR 1.03, 95% CI 0.99-1.08). Low TG residuals were associated with an increased ADRD risk (HR 1.10, 95% CI 1.06-1.15); high TG residuals were protective (HR 0.92, 95% CI 0.88-0.96). These estimates were unaffected by HDL-C adjustment.

Discussion: Low HDL-C and TG levels are independently associated with increased ADRD risk. The correlation with low TG level explains the association of high HDL-C with ADRD.

Highlights: Strong correlations between lipid levels are important considerations when investigating lipids as late-life risk factors for Alzheimer's disease and related dementias (ADRD). Low levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) were independently associated with an increased risk of ADRD. We found no evidence for an association between high HDL-C and increased ADRD risk after adjustment for TGs. High levels of TGs were consistently associated with a decreased risk of ADRD. There may be interaction between TG and HDL-C levels, where both low HDL-C and TG levels increase the risk of ADRD compared to average levels of both.

Keywords: Alzheimer's disease; cardiovascular risk factors; dementia; high‐density lipoprotein cholesterol; lipids; modifiable risk factors; triglycerides; vascular risk factors.

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Conflict of interest statement

The authors report no relevant conflicts of interest or disclosures. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Hazard ratios for ADRD with b‐splines for HDL‐C residuals. Knots at the 25th, 50th, and 75th percentiles of residuals of square root–transformed HDL‐C, without (A) and with (B) adjustment for residuals of TGs. ADRD, Alzheimer's disease and related dementias; HDL‐C, high‐density lipoprotein cholesterol; TGs, triglycerides.
FIGURE 2
FIGURE 2
Hazard ratios for ADRD with b‐splines for TG residuals. Knots at the 25th, 50th, and 75th percentiles of residuals of log‐transformed TGs, without (A) and with (B) adjustment for residuals of HDL‐C. ADRD, Alzheimer's disease and related dementias; HDL‐C, high‐density lipoprotein cholesterol; TGs, triglycerides.
See this image and copyright information in PMC

References

    1. Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020;396(10248):413‐446. doi:10.1016/S0140-6736(20)30367-6 - DOI - PMC - PubMed
    1. Liu C, Dhindsa D, Almuwaqqat Z, Sun YV, Quyyumi AA. Very high high‐density lipoprotein cholesterol levels and cardiovascular mortality. Am J Cardiol. 2022;167:43‐53. doi:10.1016/j.amjcard.2021.11.041 - DOI - PubMed
    1. Nordestgaard LT, Christoffersen M, Afzal S, Nordestgaard BG, Tybjærg‐Hansen A, Frikke‐Schmidt R. Triglycerides as a shared risk factor between dementia and atherosclerotic cardiovascular disease: a study of 125 727 individuals. Clin Chem. 2021;67(1):245‐255. doi:10.1093/clinchem/hvaa269 - DOI - PubMed
    1. Dayimu A, Wang C, Li J, et al. Trajectories of lipids profile and incident cardiovascular disease risk: a longitudinal cohort study. J Am Heart Assoc. 2019;8(21):e013479. doi:10.1161/JAHA.119.013479 - DOI - PMC - PubMed
    1. Tóth PP, Potter D, Ming EE. Prevalence of lipid abnormalities in the United States: the National Health and Nutrition Examination Survey 2003‐2006. J Clin Lipidol. 2012;6(4):325‐330. doi:10.1016/j.jacl.2012.05.002 - DOI - PubMed