Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 18 (5)

Combination Therapy With Cholinesterase Inhibitors and Memantine for Alzheimer's Disease: A Systematic Review and Meta-Analysis

Affiliations
Review

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.

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.

Similar articles

See all similar articles

Cited by 19 articles

See all "Cited by" articles

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

Feedback