| Objective:Clarify the relationship between the use of statins and the risk of dementia,and further guide the clinical application of statins.Methods:With Hydroxymethylglutaryl-CoA Reductase Inhibitors,Dementia,Alzheimer Disease Dementia,Vascular,hydroxymethylglutaryl-CoA reductase inhibitors,dementia,Alzheimer’s disease,vascular dementia as the subject terms,combined with free words,a comprehensive search of Chinese and foreign databases Pubmed,Medline,Cochrane,Embase,Web of Science,Weipu,CBM,Wanfang,CNKI,etc.The literature on all observational studies on "The relationship between statins and the risk of dementia" from the establishment of the database to December 2020,and manually search for unpublished studies in the clinical registry,developed strict inclusion and exclusion criteria,and two researchers respectively carry out the literature screening,quality evaluation,and data extraction,Revman5.1 software and Stata15.0 software were used for meta-analysis.Take the fully adjusted risk ratio(HR)as the effect indicator,There are two special cases:1.When the included study does not provide an adjusted HR,use the unadjusted HR;2.When the report is stratified by gender,age or type of statin and does not provide summary statistics,estimate summary HR.Use I ~2 and P values to judge whether the included studies are heterogeneous,when I~2<50% or P≥0.1,it indicates that there is no heterogeneity among the included studies,choose the Fixed Effect Model(FE)to calculate the combined effect index,when I~2≥50% or Q-test P value <0.1,it indicates that there is heterogeneity among the included studies,choose Random Effect Model(RE)to calculate the combined effect index,and further through subgroup analysis and sensitivity analysis to find out the reasons for heterogeneity,the final combined statistical value is expressed in HR(95% confidence interval,95% CI),HR=1.0indicates that there is no significant correlation between the use of statins and the risk of dementia,HR<1.0 indicates that the use of statins can significantly reduce the risk of dementia,HR>1.0 indicates that the use of statins can increase the risk of dementia,when P<0.05,the result is statistically significant,and use funnel plot and Egger regression test to evaluate whether the included studies have publication bias.Results:A total of 34 observational studies were included in this study,the total sample size is 9286685 cases,of which 92614 cases of dementia,there were 1992799 cases in the statin group and 2,953,533 cases in the control group,the results showed that the risk of dementia in the statin group was 84% of that in the control group,and it was statistically significant [HR=0.84,95%CI(0.81-0.87),P<0.00001];when subgroup analysis was performed according to the type of study(case-control study/cohort study),the results of the case-control study showed that the risk of dementia in the statin group was 76% of that in the control group,and it was statistically significant [HR=0.76,95 %CI(0.64-0.89),P=0.0009];the results of the cohort study showed that the risk of dementia in the statin group was 84% of that in the control group,and it was statistically significant [HR=0.84,95%CI(0.81,0.88),P<0.00001];when subgroup analysis is stratified according to gender,whether to carry the apolipoprotein E-4(Apo Eε4)allele and duration of use,the results showed that: for male patients,the risk of dementia in the statin group was 87% of the control group [HR=0.87,95%CI(0.79-0.97),P=0.011];for female patients,the risk of dementia in the statin group was 88% of the control group [HR=0.88,95%CI(0.79-0.98),P=0.017];the results show that statins have no obvious gender differences in reducing the risk of dementia.Compared with subjects with negative Apo Eε4 alleles [HR=0.66,95%CI(0.48-0.91),P=0.011],the use of statins has a more significant effect on reducing the risk of dementia in subjects carrying the Apo Eε4 allele [HR=0.49,95%CI(0.35-0.70),P<0.0001].Short-term continuous use(<1 year)of statins [HR = 1.03,95% CI(0.90-1.19),P = 0.666] has no significant correlation with the risk of dementia,medium and long-term continuous use(1-3years)of statins [HR: 0.80,95%CI(0.66-0.98),p=0.031] and long-term continuous use(>3 years)of statins [HR: 0.35,95% CI(0.26-0.46),P <0.0001] can significantly reduce the risk of dementia.Conclusion:1.The use of statins can reduce the risk of dementia,no gender difference;2.Continuous use of statins for ≥ 1 year can significantly reduce the risk of dementia;3.Compared with subjects with negative Apo Eε4 alleles,the use of statins has a more significant effect on reducing the risk of dementia in subjects carrying Apo Eε4 alleles. |
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