The causal association between hyperlipidemia and Alzheimer disease: A combined NHANES and Mendelian randomization study

This study examines the causal association between hyperlipidemia and Alzheimer disease (AD) by utilizing a mix of data from the National Health and Nutrition Examination Survey (NHANES) and 2 sample Mendelian randomization (MR) analysis. The NHANES cross-sectional data (2011-2012 and 2013-2014) was used to investigate the correlation between hyperlipidemia and cognitive impairment in individuals with AD, as measured by the consortium to establish a registry for AD word learning (CERAD-WL). This was accomplished by employing multivariable logistic regression models to compute odds ratios (ORs). The MR analysis leveraged summary-level genetic data to assess the causal effects of various cholesterol traits, consisting of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol, medium HDL cholesterol, and cholesteryl ester levels in small very LDL, on AD risk. There were several MR approaches that were utilized, including the inverse-variance weighted, weighted median, MR-Egger, and weighted mode. The NHANES data showed that participants with low cognition (lowest quartile of CERAD-Total score) had significantly greater incidences of hyperlipidemia in comparison to individuals who possessed normal cognitive abilities. The multivariable-adjusted OR was 2.159 (95% CI: 1.161-4.451, P <.001) for the lowest versus highest CERAD-Total score quartile. The MR analysis provided evidence for causal links between cholesterol traits and AD risk. Higher levels of total cholesterol (OR: 0.867, 95% CI: 0.776-0.968, P = .011), triglycerides (OR:0.870, 95% CI: 0.767-0.985, P = .028) were connected to increased AD risk. Higher HDL cholesterol was protective (OR: 1.045, 95% CI: 1.000-1.092, P = .049). Not a very strong causative effect was found for LDL cholesterol, medium HDL cholesterol or cholesteryl ester in small very LDL and AD. This combined NHANES and MR analysis provides robust evidence that hyperlipidemia, specifically elevated total cholesterol, and triglycerides, is causally associated with increased risk of AD, while higher HDL cholesterol is protective. These data indicate that addressing irregularities in cholesterol levels could be a potential strategy for controlling and preventing AD.