| Objective:This article will systematically review the efficacy of non-steroidal anti-inf-lammatory drugs in the treatment of Alzheimer’s disease,to provide evidence-based medicine for clinical treatment.Mythods:We searched a total of seven databases,including China National Knowledge Infastructure,Wanfang Data Knowledge Service Platform,Chongqing Wipu-Chinese Science and Technology Journal Full-text Database,Chinese Biomedical Literature Service System,PubMed,Cochane Library and Embase database.The search terms include target disease,interventions.The word“OR”connnects the same search term,and The“AND”connects the different search terms.The search time was from the establishment of the database to December 31,2017.The language types were limited to Chinese and English.All officially published randomized controlled trials on non-steroidal anti-inflammatory drugs for Alzheimer’s disease were searched,and relevant references were further searched to ensure that all references are available.According to the established inclusion and exclusion criteria,all studies that meet the standards are screened out,and the quality of the included studies is evaluated and data are extracted.The meta-analysis of the eligible study results was performed using Review Manager 5.3 software and STATA 12.1 software.The Q-test and I~2 statistics of Rev Man 5.3 software were used to evaluate the heterogeneity among the studies.and subgroud analysis was performed based on heterogeneity.the fixed effect model or the random effect models was selected to combine the data.Use the Review Manager5.3 software to draw the funnel plot and the STATA12.1 software to perform the Egger’s test together to assess the publication bias.Results:A total of 7 articles were included in the study,all of which were foreign studies.The treatment used in the treatment group in these studies was non-steroidal anti-inflammatory drugs;The control group was treated with placebo.The outcomes reported by each study were not exactly the same,and the main outcomes were Alzheimer’s disease Assessment Scale-cognitive subscale(ADAS-cog).Secondary outcomes included The Clinical Dementia Rating Scale sum-of-boxes(CDR-SOB),Mini-Mental State Examination(MMSE),and Neuropsychiatric Inventory(NPI).Seven of them reported ADAS-cog scores,five reported CDR-SOB scores,and four reported MMSE scores and NPI scores.Finally,the meta-analysis showed that non-steroidal anti-inflammatory drugs were comparable to placebo in the Alzheimer’s disease assessment scales:ADAS-cog,CDR-SOB,MMSE,and NPI scores,with no statistically significant difference.The following are the results of the combined effects:[ADAS-cog(rofecoxib):MD=-0.18,95%CI(-0.92,0.56),P=0.63],[ADAS-cog(naproxen):MD=0.05,95%CI(-0.69,0.79),P=0.89],[CDR-SOB(rofecoxib):MD=0.02,95%CI(-0.48,0.52),P=0.94],[CDR-SOB(naproxen):MD=-0.00,95%CI(-0.51,0.50),P=0.99],[MMSE:MD=-0.26,95%CI(-0.77,0.24),P=0.31],[NPI(rofecoxib):MD=0.34,95%CI(-0.76,1.45),P=0.54],[NPI(naproxen):MD=0.37,95%CI(-0.75,1.49),P=0.52].Subgroup analysis showed that non-selective COX-2 inhibitors and selective COX-2inhibitors had no significant difference in efficacy of CDR-SOB scores from placebo:[Non-selective COX-2 inhibitors:MD=-0.18,95%CI(-1.08,0.72),P=0.70],[Selective COX-2 inhibitor:MD=0.17,95%CI(-0.32,0.66),P=0.45],the difference was not statistically significant.Conclusion:Non-steroidal anti-inflammatory drugs failed to show protective effect in improving cognitive function,severity of illness,and mental behavior of Alzheimer’s disease.Therefore,the results of this meta-analysis currently do not support non-steroidal anti-inflammatory drugs used in clinical treatment of alzheimer’s disease.However sample size that the randomized controlled trials included,is relatively small.the above conclusions still need more high quality,large sample,multi-center randomized double-blind controlled trials to confirm. |
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