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Authors: Okuya, Makoto | Matsunaga, Shinji | Ikuta, Toshikazu | Kishi, Taro | Iwata, Nakao

Article Type: Short Communication

Abstract: A systematic review and meta-analysis of the efficacy/safety of intravenous immunoglobulin (IVIG) administration in mild-to-moderate Alzheimer’s disease (AD) patients was performed. Six randomized double-blind, placebo-controlled trials (n  = 801) were included in this study. No significant difference in cognitive function was observed between the groups. Moreover, IVIG was inferior to placebo in behavioral disturbances (mean difference = 2.19). Further, IVIG administration was associated with a higher incidence of rash than placebo. Our results do not support IVIG administration for mild-to-moderate AD, suggesting that IVIG is not effective to treat mild-to-moderate AD and that it deteriorates behavioral and psychological symptoms of dementia in mild-to-moderate …AD. Show more

Keywords: Efficacy, intravenous immunoglobulin, meta-analysis, mild-to-moderate Alzheimer’s disease, safety, systematic review

DOI: 10.3233/JAD-180888

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1379-1387, 2018

Authors: Kishi, Taro | Matsunaga, Shinji | Oya, Kazuto | Nomura, Ikuo | Ikuta, Toshikazu | Iwata, Nakao

Article Type: Research Article

Abstract: Background: The clinical benefit of memantine for Alzheimer’s disease (AD) remains inconclusive. Objective: We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. Methods: We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses. Results: Thirty studies (n  = 7,567; memantine versus placebo: N = 11, n  = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N = 17, n  = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = –0.24, …95% confidence intervals (95% CIs) = –0.34, –0.15, p  < 0.00001, I2  = 35% ] and BD (SMD = –0.16, 95% CIs = –0.29, –0.04, p  = 0.01, I2  = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate–severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = –0.20, 95% CIs = –0.34, –0.07, p  = 0.003, I2  = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = –0.20, 95% CIs = –0.36, –0.03, p  = 0.02, I2  = 77%) and a trend of CF improvement (SMD = –0.11, 95% CIs = –0.22, 0.01, p  = 0.06, I2  = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction in BD compared with ChEIs without considerable heterogeneity (SMD = –0.11, 95% CIs = –0.21, –0.01, p  = 0.04, I2  = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = –0.18, 95% CIs = –0.31, –0.05, p  = 0.006, I2  = 49%). No differences were detected in all-cause discontinuation between the groups. Conclusions: The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs. Show more

Keywords: Alzheimer’s disease, behavioral disturbances, cognitive function, memantine, meta-analysis, systematic review

DOI: 10.3233/JAD-170424

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 401-425, 2017