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From the Department of Clinical Neurosciences (Dr. Salloway), Brown University, Providence, RI; Silberstein Institute for Aging and Dementia (Drs. Ferris and Kluger), New York University School of Medicine, New York; Department of Psychology (Dr. Kluger), Lehman College, CUNY, Bronx, NY; Pfizer Inc. (Drs. Goldman and Griesing), New York, NY; and Eisai Inc. (D. Kumar and Dr. Richardson), Teaneck, NJ.
Address correspondence and reprint requests to Dr. Stephen Salloway, Director of Neurology and The Memory Disorders Program, Butler Hospital, Associate Professor of Clinical Neurosciences, Brown Medical School, 345 Blackstone Boulevard, Providence, RI 02906; e-mail: SSalloway{at}Butler.org
Objective: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI).
Methods: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician’s Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations.
Results: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient.
Conclusion: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.
Received October 13, 2003. Accepted in final form May 5, 2004.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the August 24 issue to find the title link for this article.
*Members of the Donepezil "401" Study Group are listed in the Appendix on page 656.
Dr. Salloway is a consultant and receives research support from Eisai Inc. and Pfizer Inc. Dr. Ferris and Dr. Kluger are consultants and received support from Eisai Inc. and Pfizer Inc. Dr. Goldman and Dr. Griesing are employees of Pfizer Inc. Dr. Richardson and D. Kumar are employees of Eisai Inc.
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