Serum clinical laboratory tests and risk of incident dementia: a prospective cohort study of 407,190 individuals

He, Xiao‐Yu; Kuo, Kevin H.M.; Liu, Yang; Zhang, Yaru; Wu, Bang‐Sheng; Chen, Shi-Dong; Cheng, Wei; Feng, Jianfeng; Yu, Jin‐Tai

doi:10.1038/s41398-022-02082-x

Cited by 10 publications

(13 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results are inconsistent with some prior studies showing a significant harmful effect of elevated LDL-C 6,11,12,19,36,46 or no effect of HDL-C 10,11,19,20 on dementia risk. Many prior studies of HDL-C were likely too small to detect the effects of a magnitude we reported.…”

Section: Discussioncontrasting

confidence: 99%

“…Several studies have investigated the relationship between LDL-C, HDL-C, and ADRD risk. 6,9,12,17,20,36-38 Our finding of a U-shaped association between HDL-C and dementia is consistent with a recent study reporting an association between genetically determined high HDL-C and risk of AD using Mendelian randomization (OR per 1 SD increase = 1.10, 95% CI 1.05–1.16). 39 Together, our results additionally support recent literature suggesting complex effects of HDL-C on many diseases and mortality.…”

Section: Discussionsupporting

confidence: 92%

“…10,11 For example, the 3C study, with 7,470 participants, reported a 95% CI for HDL-C HR ranging from 0.91 to 1.09. 11 Even a large recent UK Biobank study, 12 which reported no association with HDL-C (HR = 1.04, 95% CI 0.92–1.17), had substantial uncertainty due to the relatively small number of accrued cases with dementia in its relatively young cohort with an average age of 57 years (5,334 cases compared with 25,214 in our sample). The UK Biobank study reported LDL-C as protective against dementia (HR 0.92, 95% CI 0.872–0.965) and did not find evidence for nonlinearity in the effect of HDL-C.…”

Section: Discussionmentioning

confidence: 72%

“…Because prior studies of the association between cholesterol and dementia additionally adjusted for BMI, 6,12 we included a supplementary analysis for the association between quintiles of cholesterol and risk of ADRD additionally adjusted for BMI. Due to concerns about measurement error of the self-reported measure, 31 we did not include BMI in the primary covariate set.…”

Section: Methodsmentioning

confidence: 99%

“…6,9,10 Strong links between lipoprotein cholesterol levels and social, behavioral, and clinical risk factors of dementia (eFigure 1, links.lww.com/WNL/D135) require careful control for confounders, but many prior studies used administrative data without detailed confounder assessments. 11,12 Finally, only a few studies have investigated nonlinear relationships between cholesterol measures and dementia, despite evidence of nonlinearities in effects of HDL-C 13,14 and LDL-C 15 on cardiovascular outcomes. A combination of these limiting factors has likely contributed to discrepancies in the literature on cholesterol and dementia risk.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan

Ferguson,

Zimmerman,

Jiang

et al. 2023

Neurology

View full text Add to dashboard Cite

Background and Objectives:The associations of high- and low-density lipoprotein cholesterol (HDL-C and LDL-C) with dementia risk in later life may be complex, and few studies have sufficient data to model non-linearities 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 prior to the survey, and had laboratory measurements of cholesterol within two years after survey completion were followed through December 2020 for incident dementia (Alzheimer’s Disease Related Dementia [ADRD]; Alzheimer’s, vascular, and/or non-specific dementia) based on ICD9 or ICD10 codes in EHRs. We used Cox models for incident dementia with follow-up time beginning 2 years post-survey (after cholesterol measurement) and censoring at end of membership, death, or end of study period. We evaluated non-linearities using b-splines, adjusted for demographic, clinical, and survey confounders, and tested for effect modification by baseline age or prior statin use.Results:184,367 participants [mean age at survey of 69.5 years, mean HDL-C=53.7 mg/dL (SD = 15.0), LDL-C=108 mg/dL (SD = 30.6)] were included. Higher and lower HDL-C values were associated with elevated ADRD risk compared to 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 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 lower risk for non-users (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.

show abstract