Cholesterol and Alzheimer’s Disease Risk: A Meta-Meta-Analysis

Background: Alzheimer’s disease (AD) is the most common subtype of dementia. In the last ten years, the relationship between cholesterol and AD has been investigated. Evidence suggests that cholesterol is associated with AD and represents promising targets for intervention. However, the causality of these associations is unclear. Therefore, we sought to conduct a meta-meta-analysis to determine the effect of cholesterol on the development AD. Then, we assessed the effect of serum levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglycerides (TG), on AD risk. Methods: A systematic search of meta-analyses was conducted. Scopus, Web of Science, Science direct, PubMed and Google academic system databases were reviewed. Results: We found 100 primary studies and five meta-analyses to analyze the relationships between cholesterol and AD. The total effect of cholesterol on risk of AD was significant and heterogeneous. Subgroup analysis shows that LDL-C levels influence the development of AD. However, non-significant effects of HDL-C, TC and TG levels on AD were found. Conclusions: These results strengthen the evidence that LDL-C cholesterol levels increase risk for AD. More initiatives to investigate the relationship between cholesterol and AD are needed.