Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2014 Dec 28;18(5):pyu115.
doi: 10.1093/ijnp/pyu115.

Combination therapy with cholinesterase inhibitors and memantine for Alzheimer's disease: a systematic review and meta-analysis

Shinji Matsunaga  1 , Taro Kishi  2 , Nakao Iwata  2
Affiliations
Meta-Analysis

Combination therapy with cholinesterase inhibitors and memantine for Alzheimer's disease: a systematic review and meta-analysis

Shinji Matsunaga et al. Int J Neuropsychopharmacol. .

Abstract

Background: We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease.

Methods: We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects.

Results: Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects.

Conclusions: Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated.

Keywords: Alzheimer’s disease; cholinesterase inhibitors; memantine; meta-analysis; systematic review.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Forest plot of cognitive function, neuropsychiatric inventory (NPI), activity of daily living, and global assessment. (a) Cognitive function (prior to Alzheimer’s Disease Assessment Scale cognitive subscale [ADAS-cog], 6 studies, n=2027). (b) NPI (6 studies, n=1994). (c) Activity of daily living (6 studies, n=2033). (d) Global assessment (4 studies, n=1640). CI, confidence interval.
Figure 2.
Figure 2.
Forest plot of discontinuation rate. (a) Discontinuation due to all causes (5 studies, n=1832). (b) Discontinuation due to inefficacy (5 studies, n=1832). (c) Discontinuation due to adverse events (6 studies, n=1832). CI, confidence interval; M-H, Mantel-Haenszel.
Figure 3.
Figure 3.
Forest plot of sensitivity and subgroup analysis (when dividing for cases where Alzheimer’s disease (AD) staging was mild to moderate or moderate to severe). (a) Cognitive function (prior to Alzheimer’s Disease Assessment Scale cognitive subscale [ADAS-cog], 6 studies, n=2027). (b) Neuropsychiatric inventory (NPI) (6 studies, n=1994). (c) Activity of daily living (6 studies, n=2033). (d) Global assessment (4 studies, n=1640). CI, confidence interval.
See this image and copyright information in PMC

References

    1. Ametamey SM, Bruehlmeier M, Kneifel S, Kokic M, Honer M, Arigoni M, Buck A, Burger C, Samnick S, Quack G, Schubiger PA. (2002). PET studies of 18F-memantine in healthy volunteers. Nucl Med Biol 29:227–231. - PubMed
    1. Asada T. (2012). [Prevalence of dementia in Japan: past, present and future]. Rinsho shinkeigaku 52:962–964. - PubMed
    1. Berman K, Brodaty H, Withall A, Seeher K. (2012). Pharmacologic treatment of apathy in dementia. Am J Geriatr Psychiatry 20:104–122. - PubMed
    1. Boada M, Arranz FJ (2013). Transdermal is better than oral: observational research of the satisfaction of caregivers of patients with Alzheimer’s disease treated with rivastigmine. Dement Geriatr Cogn Disord 35:23–33. - PubMed
    1. Bucks RS, Ashworth DL, Wilcock GK, Siegfried K (1996). Assessment of activities of daily living in dementia: development of the Bristol Activities of Daily Living Scale. Age Ageing 25:113–120. - PubMed

MeSH terms