Differential Associations of Lipid Profiles with Dementia and Cardiovascular Disease: Findings from the UK Biobank Cohort

Abstract

Purpose: Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for cardiovascular disease (CVD) prevention, but its impact on cognitive function-and the potential differences by dementia subtype and cholesterol-lowering medication use-remain unclear. This study aimed to examine the associations between lipid levels and dementia and CVD risks, considering dementia subtypes and cholesterol-lowering medication use. Materials and Methods: A prospective cohort study was conducted using UK Biobank data. Serum lipid levels, including LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol, and remnant cholesterol, were categorized into clinically relevant ranges. Accounting for cholesterol-lowering medication use, the primary outcomes were incident all-cause dementia, Alzheimer&apos;s dementia (AD), vascular dementia (VD), and CVD. Results: High LDL-C (>= 160 mg/dL) increased AD risk across all groups {hazard ratio (HR): 1.23 [95% confidence interval (CI): 1.10-1.38], p<0.001; HR: 1.45 (95% CI: 1.08-1.93), p=0.013; HR: 1.25 (95% CI: 1.10-1.42), p<0.001, respectively}, whereas low LDLC (<70 mg/dL) showed higher VD risk in those not taking cholesterol-lowering medication [HR: 3.02 (95% CI: 1.73-5.27), p<0.001]. Low HDL-C (<= 40 mg/dL) was associated with increased AD and VD risk in non-users. High LDL-C (>= 160 mg/dL) was associated with increased CVD risk in those taking cholesterol-lowering medication. Conclusion: This study underscores the differential associations of lipid levels with dementia and CVD risk, depending on dementia subtype and cholesterol-lowering medication use. High LDL-C was linked to increased AD risk, whereas low LDL-C was linked to increased VD risk in those not taking cholesterol-lowering medication.