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Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial†‡

  1. Etsuro Mori MD, PhD1,*,
  2. Manabu Ikeda MD, PhD2,
  3. Kenji Kosaka MD, PhD3,
  4. on behalf of the Donepezil-DLB Study Investigators3

Article first published online: 23 JUL 2012

DOI: 10.1002/ana.23557

Issue

Annals of Neurology

Annals of Neurology

Volume 72, Issue 1, pages 41–52, July 2012

Additional Information

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

Author Information

  1. 1

    Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai

  2. 2

    Department of Psychiatry and Neuropathobiology, Faculty of Life Sciences, Kumamoto University, Kumamoto

  3. 3

    Department of Psychiatry, Yokohama City University School of Medicine, Yokohama, Japan

*Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

  1. †

    The Donepezil-DLB Study Investigators are listed in the Appendix on page xxx.

  2. ‡

    Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

Publication History

  1. Issue published online: 23 JUL 2012
  2. Article first published online: 23 JUL 2012
  3. Accepted manuscript online: 8 FEB 2012 12:46AM EST
  4. Manuscript Revised: 1 FEB 2012
  5. Manuscript Accepted: 1 FEB 2012
  6. Manuscript Received: 19 OCT 2011

Funded by

  • Unknown funding agency

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Abstract

Objective:

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.

Methods:

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.

Results:

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.

Interpretation:

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

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