AUTHOR=Zhou Zhike , Liang Yifan , Zhang Xiaoqian , Xu Junjie , Lin Jueying , Zhang Rongwei , Kang Kexin , Liu Chang , Zhao Chuansheng , Zhao Mei 

TITLE=Low-Density Lipoprotein Cholesterol and Alzheimer's Disease: A Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=12

YEAR=2020

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.00005

DOI=10.3389/fnagi.2020.00005

ISSN=1663-4365

ABSTRACT=<p><bold>Objective:</bold> To assess the association between low-density lipoprotein cholesterol (LDL-c) and risk of Alzheimer's disease (AD).</p><p><bold>Methods:</bold> Embase, Pubmed, and Web of Science were searched until June 2019. Standard mean difference (SMD) with 95% confidence intervals (CI) was estimated using random-effects models.</p><p><bold>Results:</bold> Our meta-analysis of 26 studies revealed higher levels of LDL-c in AD than that of non-dementia controls (SMD = 0.35, 95% CI 0.12–0.58, <italic>p</italic> &lt; 0.01). The meta-regression analysis on confounders showed that age (<italic>p</italic> &lt; 0.01, Adj <italic>R</italic>-squared = 92.41%) and cardiovascular disease (<italic>p</italic> = 0.01, Adj <italic>R</italic>-squared = 85.21%), but not the body mass index, education, smoking, hypertension and diabetes mellitus, exerted an impact on the relationship between LDL-c and risk of ICH. Further subgroup analysis of age showed LDL-c levels in AD patients aged 60–70 were higher than that of non-dementia (60 ≤ age &lt; 70: SMD = 0.80, 95% CI 0.23–1.37, <italic>p</italic> &lt; 0.01); but no association between the SMD of AD in LDL-c and age over 70 was noted across the studies (70 ≤ age &lt; 77: SMD = −0.02, 95% CI −0.39~0.34, <italic>p</italic> = 9.0; 77 ≤ age &lt; 80: SMD = 0.15, 95% CI −0.17~0.47, <italic>p</italic> = 0.35; ≥80: SMD = 0.53, 95% CI −0.04~1.11, <italic>p</italic> = 0.07). The concentrations of LDL-c during the quintile interval of 3~4 were positively associated with AD (121 ≤ concentration &lt; 137: SMD = 0.98, 95% CI 0.13~1.82, <italic>p</italic> = 0.02; ≥137: SMD = 0.62, 95% CI 0.18~1.06, <italic>p</italic> &lt; 0.01); whereas there was no correlation between AD and LDL-c within the quintile interval of 1~2 (103.9 ≤ concentration &lt; 112: SMD = 0.08, 95% CI −0.20~0.35, <italic>p</italic> = 0.59; 112 ≤ concentration &lt; 121: SMD = −0.26, 95% CI −0.58~0.06, <italic>p</italic> = 0.11).</p><p><bold>Conclusions:</bold> Elevated concentration of LDL-c (&gt;121 mg/dl) may be a potential risk factor for AD. This association is strong in patients aged 60–70 years, but vanishes with advancing age.</p>