Donepezil for dementia with Lewy bodies: A randomized, placebo‐controlled trial

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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Cited by papers we hold 3

• Impact of Behavioral and Psychological Symptoms on Caregiver Burden in Patients With Dementia With Lewy Bodies · 2021
  Not checked
• Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials · 2020
  Not checked
• Differences of Behavioral and Psychological Symptoms of Dementia in Disease Severity in Four Major Dementias. · 2016
  Not checked

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