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Effects of donepezil 23 mg on Severe Impairment Battery domains in patients with moderate to severe Alzheimer's disease: evaluating the impact of baseline severity

Steven Ferris1, Jeffrey Cummings2*, Daniel Christensen3, Rachelle Doody4, Martin Farlow5, Marwan Sabbagh6, Liang Liu7, Joan Mackell8 and Randi Fain7

Author Affiliations

1 Alzheimer Disease Center, New York University Langone Medical Center, 145 E 32nd St, Room 506, New York, NY 10016, USA

2 Cleveland Clinic Lou Ruvo Center for Brain Health, 888 W. Bonneville, Las Vegas, NV 89106, USA

3 Neuropsychiatric Institute, University of Utah, 501 Chipeta Way, Salt Lake City, UT 84108, USA

4 Department of Neurology, Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX 07730, USA

5 Department of Neurology, Indiana University School of Medicine, 541 Clinical Drive, CL299, Indianapolis, IN, 46202, USA

6 The Cleo Roberts Center for Clinical Research, Banner-Sun Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA

7 Eisai Inc., 100 Tice Boulevard, Woodcliff Lake, NJ 07677, USA

8 Pfizer Inc, 235 East 42nd Street, New York, NY 10017, USA

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Alzheimer's Research & Therapy 2013, 5:12  doi:10.1186/alzrt166

Published: 21 February 2013



The US Food and Drug Administration approved a 23 mg daily dose of donepezil for treatment of moderate to severe Alzheimer's disease (AD) based on outcomes from a large trial comparing the 23 mg/day dose with the standard 10 mg/day dose. Results from this study indicated that after 24 weeks, donepezil 23 mg/day provided significant cognitive benefits over donepezil 10 mg/day, measured using the Severe Impairment Battery (SIB). In the analyses reported herein, we further characterize the range of cognitive domains impacted by treatment with donepezil 23 mg/day.


A post hoc analysis was conducted using data from a 24-week, randomized, double-blind trial comparing donepezil 23 mg/day versus 10 mg/day in 1,467 patients with moderate to severe AD (baseline Mini-Mental State Examination (MMSE) score 0 to 20). Changes from baseline to week 24 in the nine SIB domain scores were analyzed in the intent-to-treat (ITT) population (baseline MMSE 0 to 20), in patients with more severe baseline AD (MMSE 0 to 16), and in severity strata based on baseline MMSE scores (0 to 5, 6 to 10, 11 to 15, 16 to 20).


In the ITT population, changes in six of the nine SIB domains favored donepezil 23 mg/day over donepezil 10 mg/day. LS mean treatment differences were significant for the language, visuospatial ability, and construction domains. In the more advanced cohort of patients (MMSE 0 to 16 at baseline), LS mean treatment differences were statistically significant favoring donepezil 23 mg/day in five of the nine domains: language, memory, visuospatial ability, attention, and construction. Descriptive analysis of LS mean changes in SIB domain scores in the four baseline severity strata showed variable patterns of response; overall, cognitive benefits of donepezil 23 mg/day were greatest in patients with MMSE scores of 0 to 15.


These results suggest that donepezil 23 mg/day provides benefits over 10 mg/day across a range of cognitive domains. The magnitude of benefit and domains impacted varied depending on the stage of AD; significant benefits with higher dose donepezil were most apparent at more advanced stages of AD and were most prominent in the language domain.