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Open Access Research article

Evaluating the cognitive effects of donepezil 23 mg/d in moderate and severe Alzheimer’s disease: analysis of effects of baseline features on treatment response

Marwan Sabbagh1*, Jeffrey Cummings2, Daniel Christensen3, Rachelle Doody4, Martin Farlow5, Liang Liu6, Joan Mackell7 and Randi Fain6

Author Affiliations

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

2 Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA

3 University of Utah, Salt Lake City, UT, USA

4 Baylor College of Medicine, Houston, TX, USA

5 Department of Neurology, IU Alzheimer’s Disease and Related Disorders, Indianapolis, IN, USA

6 Eisai Inc., Woodcliff Lake, NJ, USA

7 Pfizer Inc., New York, NY, USA

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BMC Geriatrics 2013, 13:56  doi:10.1186/1471-2318-13-56

Published: 6 June 2013

Abstract

Background

Treatment of Alzheimer’s disease with acetylcholinesterase inhibitors can result in symptomatic benefits, but patients often show variable responses. The objective of this post hoc analysis was to investigate relationships between easily identifiable baseline characteristics/demographics and cognitive response in patients treated with either donepezil 23 mg/d or 10 mg/d and to identify factors potentially influencing response.

Methods

A post hoc analysis was conducted using data from a large, 24-week, randomized, double-blind, international study enrolling patients with moderate to severe Alzheimer’s disease (baseline Mini-Mental State Examination [MMSE], 0-20) (NCT 00478205). Cognitive changes in subgroups of patients based on selected baseline and demographic characteristics were compared using the least squares mean changes in Severe Impairment Battery scores at Week 24. Univariate and multivariate analyses were also performed.

Results

Donepezil 23 mg/d provided statistically significant incremental cognitive benefits over donepezil 10 mg/d irrespective of baseline functional severity, measured by scores on the Alzheimer’s Disease Cooperative Study-Activities of Daily Living-severe version (P < 0.05). When patients were categorized by baseline cognitive severity (MMSE score), significant benefits of donepezil 23 mg/d over 10 mg/d were seen in both subgroups when based on MMSE scores of 0-9 versus 10-20 (P < 0.02 and P < 0.01, respectively), and in the more severe subgroup when based on MMSE scores of 0-16 versus 17-20 (P < 0.0001 and P > 0.05). Statistically significant incremental cognitive benefits of donepezil 23 mg/d over 10 mg/d were also observed regardless of age, gender, weight, or prestudy donepezil 10 mg/d treatment duration (P < 0.05). In the multivariate analysis, the only significant interaction was between treatment and baseline MMSE score.

Conclusions

The cognitive benefits of donepezil 23 mg/d over 10 mg/d were achieved regardless of the patient’s age, gender, weight, duration of prior donepezil 10 mg/d, and functional severity. The influence of baseline cognitive severity on response seemed to be dependent on the level of impairment, with cognitive benefits of donepezil 23 mg/d over 10 mg/d most apparent in those patients at a more advanced stage of disease. These data may be useful in helping practicing physicians make informed decisions for their patients with advanced Alzheimer’s disease.

Keywords:
Alzheimer’s disease; Cognitive dysfunction; Donepezil; Severe impairment battery (SIB)