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

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.