Impact Of Lowering Low-Density Lipoprotein Cholesterol With Contemporary Lipid-Lowering Medicine On Cognitive Function

Objective:To evaluate the potential association between lowing low-density lipoprotein cholesterol with contemporary lipid-lowering medicine and cognitive function.Methods:Two reviewers independently collected randomized controlled trials(RCTs)in public databases including Pubmed,Embase,Web of Science,Cochrane library database and ClinicalTrials.gov and tracked references of included studies from inception to January 1,2020.Two reviewers independently finished the tasks of selecting the literature,extracting data and evaluating the quality.The meta-analysis was conducted using Stata.Results:A total of 2910 studies were obtained from Pubmed,Embase,Web of Science,Cochrane library database,ClinicalTrials.gov and other sources.33 studies were selected by screening,there were 11 studies of Alirocumab,9 studies of Evolocumab and 11 studies on Statins and 2 studies on Ezetimibe(select deadline as January 1,2020).In our study,a total of 128691 patients with no cognitive impairment were randomized into intervention group(66330 patients)and control group(62361 patients).The data used a random effect model or a fixed effect model for meta-analysis.The contemporary lipid-lowering medicines significantly reduced LDL-C both in percentage(WMD:-45.06%,95%CI-50.12%to-40.00%,P＜0.001)and absolute value(WMD:-64.01 mg/dl,95%CI-72.25 to-55.78,P＜0.001).Compared with control group,treatment with contemporary lipid-lowering medicines in intervention group showed no statistically significant difference in the rate of neurocognitive disorder(RR:1.02,95%CI 0.90 to 1.16,12=0.0%,p=0.696).The subgroup analysis was performed according to the intervention and achieved LDL-C stratification.This result of subgroup analysis was consisted with the main findings.As for global cognitive performance,no difference in major cognitions was found in a pooled data(SMD:0.02,95%CI-0.01 to 0.04,P=0.002)except psychomotor speed(SMD:0.09,95%CI 0.02 to 0.16,P=0.0024)Conclusions:Contemporary lipid-lowering medicines were not associated with cognitive impairment in RCTs.The low level of LDL-C did not influence the incident of cognitive disorder and global cognitive performance.