Protection against brain atrophy by anti-dementia medication in mild cognitive impairment and Alzheimer's disease: Meta-analysis of longitudinal randomized placebo-controlled trials

Taro Kishi, Shinji Matsunaga, Kazuto Oya, Toshikazu Ikuta, Nakao Iwata

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalInternational Journal of Neuropsychopharmacology
Volume18
Issue number12
DOIs
Publication statusPublished - 01-01-2015

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Atrophy
Dementia
Meta-Analysis
Alzheimer Disease
Randomized Controlled Trials
Placebos
Rivastigmine
Confidence Intervals
Brain
Pharmaceutical Preparations
Placebo Effect
Cognitive Dysfunction
PubMed
Libraries
Magnetic Resonance Imaging
Databases

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

@article{3912d937795d483b8e9963958bcfca71,
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.",
author = "Taro Kishi and Shinji Matsunaga and Kazuto Oya and Toshikazu Ikuta and Nakao Iwata",
year = "2015",
month = "1",
day = "1",
doi = "10.1093/ijnp/pyv070",
language = "English",
volume = "18",
pages = "1--7",
journal = "International Journal of Neuropsychopharmacology",
issn = "1461-1457",
publisher = "Cambridge University Press",
number = "12",

}

TY - JOUR

T1 - Protection against brain atrophy by anti-dementia medication in mild cognitive impairment and Alzheimer's disease

T2 - Meta-analysis of longitudinal randomized placebo-controlled trials

AU - Kishi, Taro

AU - Matsunaga, Shinji

AU - Oya, Kazuto

AU - Ikuta, Toshikazu

AU - Iwata, Nakao

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

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U2 - 10.1093/ijnp/pyv070

DO - 10.1093/ijnp/pyv070

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JF - International Journal of Neuropsychopharmacology

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