Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan
Abstract
Background and Objectives
The associations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with dementia risk in later life may be complex, and few studies have sufficient data to model nonlinearities or adequately adjust for statin use. We evaluated the observational associations of HDL-C and LDL-C with incident dementia in a large and well-characterized cohort with linked survey and electronic health record (EHR) data.
Methods
Kaiser Permanente Northern California health plan members aged 55 years and older who completed a health behavior survey between 2002 and 2007, had no history of dementia before the survey, and had laboratory measurements of cholesterol within 2 years after survey completion were followed up through December 2020 for incident dementia (Alzheimer disease–related dementia [ADRD]; Alzheimer disease, vascular dementia, and/or nonspecific dementia) based on ICD-9 or ICD-10 codes in EHRs. We used Cox models for incident dementia with follow-up time beginning 2 years postsurvey (after cholesterol measurement) and censoring at end of membership, death, or end of study period. We evaluated nonlinearities using B-splines, adjusted for demographic, clinical, and survey confounders, and tested for effect modification by baseline age or prior statin use.
Results
A total of 184,367 participants [mean age at survey = 69.5 years, mean HDL-C = 53.7 mg/dL (SD = 15.0), mean LDL-C = 108 mg/dL (SD = 30.6)] were included. Higher and lower HDL-C values were associated with elevated ADRD risk compared with the middle quantile: HDL-C in the lowest quintile was associated with an HR of 1.07 (95% CI 1.03–1.11), and HDL-C in the highest quintile was associated with an HR of 1.15 (95% CI 1.11–1.20). LDL-C was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL-C was associated with a slightly greater risk of ADRD for statin users (53% of the sample, HR per 10 mg/dL increase = 1.01, 95% CI 1.01–1.02) and a lower risk for nonusers (HR per 10 mg/dL increase = 0.98; 95% CI 0.97–0.99). There was evidence for effect modification by age with linear HDL-C (p = 0.003) but not LDL-C (p = 0.59).
Discussion
Both low and high levels of HDL-C were associated with elevated dementia risk. The association between LDL-C and dementia risk was modest.
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© 2023 American Academy of Neurology.
Publication History
Received: March 30, 2023
Accepted: August 24, 2023
Published online: October 4, 2023
Published in issue: November 21, 2023
Disclosure
The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.
Study Funding
This work was supported by the NIH/National Institute on Aging grants RF1AGO69259 and T32AG049663-06A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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