Serum lipid traits and the risk of dementia: A cohort study of 254,575 women and 214,891 men in the UK Biobank

Abstract

Background: Serum lipid traits are associated with cardiovascular disease, but uncertainty remains regarding their associations with dementia.

Methods: From 2006 to 2010, 254,575 women and 214,891 men were included from the UK Biobank. Cox regression estimated overall and sex-specific hazard ratios (HRs) for apolipoprotein A (ApoA), apolipoprotein B (ApoB), HDL, LDL, total cholesterol, triglycerides, lipoprotein A, and various lipid ratios, by quarters and standard deviation (SD) higher, associated with all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD). Subgroup analyses by age and social deprivation were conducted.

Findings: Over 11·8 years (median), 3734 all-cause dementia (1,716 women), 1231 AD and 929 VaD were recorded. Compared to respective lowest quarters, highest quarter of ApoA was associated with lower dementia risk (HR, [95% confidence interval (95% CI)]: 0·77 [0·69, 0·86]) while the highest quarter of ApoB was associated with greater risk (HR, 1·12 [1·01, 1·24]). Higher HDL/ApoA and ApoB/ApoA, were associated with greater risk of dementia (HR, 1·12 [1·00, 1·25], per standard deviation (SD), 1.23 [1·11, 1·37], per SD, respectively), LDL/ApoB was inversely associated (HR, 0·85 [0·76, 0·94], per SD. Higher triglycerides was associated with higher dementia risk in <60 years, but the inverse was observed for ≥60 years. Similar associations were observed for VaD and AD.

Interpretation: Apolipoproteins, and their ratios, were associated with the risk of dementia. It may be prudent to consider apolipoproteins, along with circulating cholesterol, when assessing dementia risk.

Funding: University of New South Wales, UK Medical Research Council, and the Australian National Health and Medical Research Council.

Keywords: Apolipoprotein; Dementia; Lipids; UK Biobank.

Figure 1

Multiple-adjusted incident all-cause dementia hazard ratios for lipid traits by quarters and per standard deviation. ApoA, apolipoprotein A; ApoB, Apolipoprotein B; HDL, high density lipoprotein; LDL, low density lipoprotein; SD, standard deviation; HR, hazard ratio. Adjusted for sex, age, ethnicity, Townsend Deprivation Index, body mass index, systolic blood pressure, smoking status, diabetes, lipids lowering drugs, blood pressure lowering drugs.

Figure 2

Forest plot for multiple-adjusted incident all-cause dementia hazard ratios for lipid traits per standard deviation, by sex, and women-to-men ratio of hazard ratios. ApoA, apolipoprotein A; ApoB, Apolipoprotein B; HDL, high density lipoprotein; LDL, low density lipoprotein; HR, hazard ratio; CI, confidence interval; RHR, ratio of hazard ratios; SD, standard deviation. Adjusted for age, ethnicity, Townsend Deprivation Index, body mass index, systolic blood pressure, smoking status, diabetes, lipids lowering drugs, blood pressure lowering drugs.

Figure 3

Multiple-adjusted sex-specific restricted cubic splines (with kernel density plots) showing hazard ratios for the risk of incident all-cause dementia associated with lipid traits, by sex. ApoA, apolipoprotein A; ApoB, Apolipoprotein B; HDL, high density lipoprotein; LDL, low density lipoprotein. Splines were adjusted for baseline age, ethnicity, smoking status, systolic blood pressure, body mass index, diabetes, Townsend index, lipids lowering drugs, blood pressure lowering drugs. Pink dotted line represents the hazard ratio for women, and the pink shaded area is the 95% confidence intervals for women; the solid blue line represents the hazard ratio for men, and the blue shaded area is the 95% confidence intervals for men. Extreme values in the upper and lower 5% of the lipid trait distribution were excluded. Reference values are the median value in women: Apolipoprotein A=1·42 g/L, Apolipoprotein B=1·02 g/L, HDL cholesterol=1·27 mmol/L, LDL cholesterol=3·49 mmol/L, Triglycerides=1·64 mmol/L, Total cholesterol=5·52 mmol/L, HDL/ApoA=0·34, LDL/ApoB=1·32, ApoB/ApoA=0·71, Lp(a)=19·91 nmmol/L.

Figure 4

Multiple-adjusted hazard ratios for lipid traits by quarters and per standard deviation, in associations with the risk of incident vascular dementia and Alzheimer's disease. ApoA, apolipoprotein A; ApoB, Apolipoprotein B; HDL, high density lipoprotein; LDL, low density lipoprotein; SD, standard deviation; HR, hazard ratio. Adjusted for sex, age, ethnicity, Townsend Deprivation Index, body mass index, systolic blood pressure, smoking status, diabetes, lipids lowering drugs, blood pressure lowering drugs. Red represents vascular dementia, navy represents Alzheimer's disease.