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

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.