摘要：
Objective To assess the absolute efficacy and safety of cerebrolysin for patients with Alzheimer''s disease(AD).Methods CENTRAL, MEDLINE、EMBASE, PsycINFO, CBMDisc(up to September 30,2015) were searched for the randomized, placebo-controlled, parallel-group clinical trials evaluating cerebrolysin as monotherapy for patients with AD dementia or mild cognitive impairment due to AD.The methodological quality of the original studies were evaluated by using the Cochrane collaboration''s tool.The influences of study limitations, inconsistency of results, imprecision of effect estimates, indirectness of evidence and publication bias on the quality of the body of evidence were assessed by using GRADEpro software (version 3.2).Results Six studies were included, involving 950 patients with AD dementia.Subgroup analyses indicated cerebrolysin at a dose of 30 ml improved cognitive function in patients with mild-to-moderate AD dementia at one month or six months of follow-up [standard mean difference (SMD)=-0.360,95%CI:-0.600——0.130,P=0.003;SMD =-0.350,95%CI:-0.590——0.100,P=0.005)].There was improvement in behavioural and psychiatric symptoms at six months of follow-up(SMD=-0.290,95%CI:-0.540——0.050,P=0.020).Cerebrolysin did not improve activities of daily living at one month or six months of follow-up (SMD=-0.160,95%CI:-0.350-0.040,P=0.120;SMD=-0.210,95%CI:-0.450-0.030,P=0.080).The incidence of adverse events (AEs) at one month or six month of follow-up was not different between the cerebrolysin group and the placebo group.No serious AEs occurred in both groups.All studies had methodological limitations, mainly on an unclear risk of detection bias.The pharmaceutical company funded or participated in the clinical trials, therefore,the potential risk of bias was high.Furthermore, the total sample size for most outcomes was insufficient, and the 95%CI of most results was wide.All these factors contributed to a decreased quality level of the evidence.Conclusions There is low/very low-quality evidence to show that cerebrolysin has slight effects in improving cognitive function and behavioural and psychiatric symptoms in patients with mild-to-moderate AD dementia.It has no effects in improving activities of daily living.%目的 评价脑活素治疗Alzheimer''s病(AD)的绝对有效性和安全性.方法 检索CENTRAL、MEDLINE、EMBASE、PsycINFO、CBMdisc(检索截至2015年9月30日)关于脑活素单药治疗AD痴呆或AD源性轻度认知障碍的随机、安慰剂平行对照临床试验.采用Cochrane协作网的偏倚风险评价工具评价原始研究方法学质量,GRADEpro 3.2软件评价原始研究的局限性、结果的不一致性和不精确性、证据的间接性、发表偏倚对主体证据质量的影响.结果 共纳入6项研究,共950例AD痴呆患者.亚组分析结果显示脑活素30 ml可改善轻中度AD痴呆患者随访1月时或随访6个月时认知功能[标准均数差(SMD)=-0.360,95%CI:-0.600 ~-0.130,P=0.003;SMD=-0.350,95%CI:-0.590~-0.100,P=0.005)].随访6个月时精神行为症状改善(SMD=-0.290,95%CI:-0.540~-0.050,P=0.020).脑活素不能改善随访1个月时或随访6个月时日常能力(SMD=-0.160,95%CI:-0.350~0.040,P=0.120;SMD=-0.210,95%CI:-0.450~0.030,P=0.080).随访1个月和6个月时脑活素组和安慰剂组不良事件的发生率无差异,无严重不良事件发生.所有研究均存在方法学局限性,主要缺陷为测量偏倚风险不清楚,且制药企业资助或参与研究,潜在偏倚风险较高.绝大多数结局指标的总样本量不足,并且部分结果的95%CI过宽,导致证据质量下降.结论 低/极低级别证据表明,脑活素对轻中度AD痴呆患者的认知功能和精神行为症状有轻微的改善作用,但不能改善患者的日常能力.
