Donepezil and Memantine for moderate-to-severe Alzheimer's disease
. (2012) Donepezil and Memantine for moderate-to-severe Alzheimer's disease. New England Journal of Medicine, Vol.366 (No.10). pp. 893-903. ISSN 0028-4793
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Official URL: http://dx.doi.org/10.1056/NEJMoa1106668
Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer’s disease. It is not known whether treatment benefits
continue after the progression to moderate-to-severe disease.
We assigned 295 community-dwelling patients who had been treated with donepezil
for at least 3 months and who had moderate or severe Alzheimer’s disease (a score
of 5 to 13 on the Standardized Mini–Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and
on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically
important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS.
Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points
(95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points
higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not
differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone.
In patients with moderate or severe Alzheimer’s disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months.
|Item Type:||Journal Article|
|Subjects:||R Medicine > RC Internal medicine|
|Divisions:||Faculty of Medicine > Warwick Medical School > Health Sciences
Faculty of Medicine > Warwick Medical School
|Library of Congress Subject Headings (LCSH):||Alzheimer's disease -- Treatment, Cholinesterase inhibitors|
|Journal or Publication Title:||New England Journal of Medicine|
|Official Date:||March 2012|
|Page Range:||pp. 893-903|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Medical Research Council (Great Britain) (MRC), Alzheimer’s Society (AS)|
1. Kaduszkiewicz H, Zimmerman T,
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