Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study

Blood lipid profiles have been ambiguously reported as biomarkers of AD in recent years. This study was conducted to evaluate the correlation between blood lipid levels and AD in later-life and to explore the effectiveness and reliability of blood lipid profiles as biomarkers of AD. Database searching was conducted using PubMed, the Cochrane Library, EMBASE, and Medline. This study was designed following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria. Review Manager 5.3 (RevMan 5.3) software was adopted to perform meta-analysis evaluating the standard mean difference (SMD) with its 95% confidence intervals (CI). A total of 5,286 participants were enrolled from 27 case-control studies in this meta-analysis. The pooled results demonstrated that total cholesterol (TC) level was significantly associated with AD in late-life (SMD = 0.17, 95% CI: [0.01, 0.32], = 0.03), especially in the subgroup under 70 years old (SMD: 0.45, 95% CI: [0.11, 0.79], = 0.01) and the subgroup of Western population (SMD: 0.29, 95% CI: [0.04, 0.53], = 0.02). In the subgroup under 70 years old, the high-density lipoprotein cholesterol (HDL-C) level (SMD = -0.50, 95% CI: [-0.76, -0.25], = 0.0001) and the low-density lipoprotein cholesterol (LDL-C) level (SMD = 0.59, 95% CI: [0.02, 1.16], = 0.04) in the AD group were significantly lower and higher than in the control group, respectively. In the subgroup with a sample size larger than 100 subjects, the LDL-C level was significantly higher in AD patients than in the control elderly group (SMD = 0.31, 95% CI: [0.05, 0.56], = 0.02). There was no significant association between triglyceride (TG) levels and AD in later-life (SMD = -0.00, 95% CI: [-0.12, 0.12], = 1.00). TC can be a new predictive biomarker of AD or cognitive decline in later-life. Increased TC levels are found to be associated with an elevated risk of AD. Decreased HDL-C levels and increased LDL-C levels may relate to an elevated risk of AD in subjects aged 60-70. Further comprehensive researches will be necessary in the future.