The Donepezil-DLB Study Investigators are listed in the Appendix on page xxx.
Version of Record online: 23 JUL 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 72, Issue 1, pages 41–52, July 2012
How to Cite
Mori, E., Ikeda, M., Kosaka, K. and on behalf of the Donepezil-DLB Study Investigators (2012), Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial. Ann Neurol., 72: 41–52. doi: 10.1002/ana.23557
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- Issue online: 23 JUL 2012
- Version of Record online: 23 JUL 2012
- Accepted manuscript online: 8 FEB 2012 12:46AM EST
- Manuscript Revised: 1 FEB 2012
- Manuscript Accepted: 1 FEB 2012
- Manuscript Received: 19 OCT 2011
- Unknown funding agency
Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double-blind, placebo-controlled exploratory phase 2 trial.
One-hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini-Mental State Examination (MMSE) and several domain-specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician's Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus). Safety measures included the Unified Parkinson's Disease Rating Scale part III.
Donepezil at 5 and 10mg/day was significantly superior to placebo on both the MMSE (5mg: mean difference, 3.8; 95% confidence interval [CI], 2.3–5.3; p < 0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9–3.9; p = 0.001) and CIBIC-plus (p < 0.001 for each); 3mg/day was significantly superior to placebo on CIBIC-plus (p < 0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p < 0.001) at 5 and 10mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups.
Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated. ANN NEUROL 2012;72:41–52