title: Protection against Brain Atrophy by Anti-dementia Medication in Mild Cognitive Impairment and Alzheimer's Disease: Meta-Analysis of Longitudinal Randomized Placebo-Controlled Trials.
abstract: BACKGROUND
  There has not been conclusive evidence for prevention of brain atrophy by anti-dementia drugs in mild cognitive impairment and Alzheimer's Disease.
  
  
  METHODS
  Relevant studies were identified through searches of PubMed, databases of the Cochrane Library, and PsycINFO citations up to 16 May, 2015. Only double-blind, randomized, placebo-controlled clinical trials of anti-dementia drugs in patients with mild cognitive impairment or Alzheimer's Disease were included. Primary outcomes were annualized percent change of total brain volume (%TBV/y), annualized percent change of hippocampal volume (%HV/y), and annualized percent change of ventricular volume (%VV/y) measured by magnetic resonance imaging. Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated for relevant outcomes.
  
  
  RESULTS
  Seven randomized, placebo-controlled clinical trials (n=1708) were found to meet the inclusion criteria, including 4 mild cognitive impairment studies (n=1327) and 3 Alzheimer's Disease studies (n=381) [3 donepezil studies (2 mild cognitive impairment studies and 1 Alzheimer's Disease study), 1 galantaime study for mild cognitive impairment, 2 mementine studies for Alzheimer's Disease, and 1 rivastigmine study for mild cognitive impairment]. Pooled anti-dementia drugs showed superior protective outcomes compared with placebo regarding %TBV/y (SMD=-0.21, 95%CI=-0.37 to -0.04, P=.01, N=4, n=624) and %VV/y (SMD=-0.79, 95%CI=-1.40 to -0.19, P=.01, N=3, n=851). However, %HV/y failed to show difference between both groups. Among anti-dementia drugs, donepezil showed significantly greater protective effects than placebo regarding %TBV/y (SMD=-0.43, 95%CI=-0.74 to -0.12, P=.007, N=1, n=164) and %VV/y (SMD=-0.51, 95%CI=-0.73 to -0.29, P<.00001, N=2, n=338). Rivastigmine was also superior to placebo regarding %VV/y (SMD=-1.33, 95%CI=-1.52 to -1.14, P<.00001).
  
  
  CONCLUSIONS
  The results favored the hypothesis that anti-dementia drugs may prevent brain atrophy in patients with mild cognitive impairment and Alzheimer's Disease.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Drs Kishi, Matsunaga, Oya, and Iwata); Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University, Mississippi (Dr Ikuta). tarok@fujita-hu.ac.jp tikuta@olemiss.edu.
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Drs Kishi, Matsunaga, Oya, and Iwata); Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University, Mississippi (Dr Ikuta).
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Drs Kishi, Matsunaga, Oya, and Iwata); Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University, Mississippi (Dr Ikuta).
authors.forename: Kazuto
authors.initials: K
authors.lastname: Oya
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Drs Kishi, Matsunaga, Oya, and Iwata); Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University, Mississippi (Dr Ikuta).
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ikuta
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Drs Kishi, Matsunaga, Oya, and Iwata); Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University, Mississippi (Dr Ikuta).
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D001284:Atrophy / Q000188:drug therapy; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D018696:Neuroprotective Agents; D018697:Nootropic Agents
keywords: anti-dementia drugs; brain atrophy; magnetic resonance imaging; meta-analysis; mild cognitive impairment/Alzheimer’s Disease