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Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial
S Salloway1, S Ferris, A Kluger
1Department of Clinical Neurosciences, Brown University, Providence, RI, USA. SSalloway@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.
Insights
Donepezil did not significantly improve primary outcomes in mild cognitive impairment (MCI) patients. However, secondary measures showed benefits in cognition, attention, and global impression, suggesting potential for further research.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Trials
Background:
- Mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease.
- Acetylcholinesterase inhibitors, like donepezil, are used to treat Alzheimer's disease symptoms.
- The efficacy of donepezil in MCI requires further investigation.
Purpose of the Study:
- To assess the efficacy and safety of donepezil in patients with mild cognitive impairment (MCI).
- To compare donepezil's effects against a placebo in a controlled trial setting.
Main Methods:
- A 24-week, multicenter, randomized, double-blind, placebo-controlled study.
- 270 MCI patients received either donepezil (escalating dose from 5 to 10 mg/day) or placebo.
- Primary outcomes included NYU Paragraph Delayed Recall and ADCS CGIC-MCI; secondary outcomes included ADAS-cog, PGA, and neuropsychological tests.
Main Results:
- No significant differences were observed in primary efficacy measures (NYU Paragraph Recall, ADCS CGIC-MCI) between donepezil and placebo groups.
- Donepezil showed improvements in secondary measures like ADAS-cog, attention, psychomotor speed, and Patient Global Assessment.
- Adverse events were more frequent in the donepezil group but were generally mild to moderate and transient.
Conclusions:
- While primary endpoints were not met, secondary outcomes suggest potential benefits of donepezil in specific cognitive domains for MCI patients.
- Further research is warranted to explore donepezil's role in managing mild cognitive impairment.
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