title: Oral Chinese herbal medicine for kidney nourishment in Alzheimer's disease: a systematic review of the effect on MMSE index measures and safety.
abstract: OBJECTIVE
  To evaluate the effectiveness and safety of the Chinese herbal medicine for kidney nourishment (CHMK) assessed with the Mini-Mental Status Examination (MMSE) index objective outcome measures in individuals with Alzheimer's disease.
  
  
  METHODS
  Searches were conducted in 7 medical databases from their inceptions until July 19, 2014 for randomized controlled trials (RCTs) that compared the oral administration of CHMK plus conventional pharmacotherapy with the same conventional pharmacotherapy alone with MMSE index measures as outcomes. Relevant resources were also manually retrieved. Two reviewers screened the citations of the reports, assessed the risk of bias and extracted data independently. Data analysis was carried out with Cochrane Collaboration's RevMan5.2.6 software and evidence quality grading evaluation of the systematic review was conducted with Grades of Recommendations Assessment Development and Evaluation (GRADE) profiler software.
  
  
  RESULTS
  A total of 20 studies involving 1682 participants were included in the meta-analysis. There were 15 trials that compared CHMK with conventional pharmacotherapy and 5 trials that compared CHMK plus conventional pharmacotherapy with conventional pharmacotherapy alone. The main meta-analysis results showed relative benefits in effective rates in five studies (odds ratio [OR] 2.74, 95% confidence interval [CI] 1.55-4.85) and cure rate/clinical-control rates in five studies (OR 1.91, 95% CI 1.27-2.88) in favor of the CHMK plus conventional pharmacotherapy group. As for CHMK compared with conventional pharmacotherapy, no significant differences were noted in the effective rate (OR 1.09, 95% CI 0.82-1.46; cure rate (OR 1.06, 95% CI 0.81-1.38) and detailed sub-group of MMSE scores from the onset time to 4 weeks (weighted mean difference [WMD] 0.31, 95% confidence interval [CI] -0.81 to 1.42, 8 weeks WMD 1.12, 95% CI -0.54 to 2.78, 12 weeks (WMD 0.43, 95% CI -1.62 to 2.48, or 24 weeks WMD 1.92, 95% CI -1.60 to 5.44) follow-up and the overall effect (WMD 0.79, 95% CI -0.11 to 1.69). Moreover, weaknesses in methodological quality were identified in most studies according to Cochrane Risk of Bias tool assessment, while the quality level of GRADE classification indicated "very low". The incidence of adverse events with CHMK (0.87%) was lower than in the conventional pharmacotherapy group (4.08%), which revealed use of CHMK was relatively safer than conventional pharmacotherapy alone.
  
  
  CONCLUSIONS
  The effectiveness and safety of oral administration of CHMK cannot be currently determined because of publication bias and the low quality level of the included trials. Further studies on a larger scale and with more rigorous designs are required to define the role of CHMK in the treatment of AD.
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; The 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
authors.forename: Ling-feng
authors.initials: LF
authors.lastname: Zeng
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: nswang@gzucm.edu.cn.
authors.forename: Ning-sheng
authors.initials: NS
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; The 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China. Electronic address: wqdme01@163.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Yuan-ping
authors.initials: YP
authors.lastname: Zou
authors.affiliation: School of Information Technology, York University, Toronto, Canada.
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Liang
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Ling-shuo
authors.initials: LS
authors.lastname: Kong
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Nan-ying
authors.initials: NY
authors.lastname: Liao
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: Xiao-wen
authors.initials: XW
authors.lastname: Liang
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
authors.forename: You-sheng
authors.initials: YS
authors.lastname: Mo
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy*; D015982:Bias; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans
chemical_list: D004365:Drugs, Chinese Herbal
keywords: Alzheimer's disease (AD); Chinese herbal medicine (CHM); Kidney-nourishing; Meta-analysis; Pharmacotherapy; Randomized controlled trial (RCT); Senile dementia; Systematic review