Protection against Brain Atrophy by Anti-Dementia Medication in Mild Cognitive Impairment and AD: Meta-Analysis of Longitudinal Randomized Placebo- Controlled Trials

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.