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Donepezil for cognitive impairment in Parkinson's disease: a randomised controlled study
  1. D Aarsland1,
  2. K Laake2,
  3. J P Larsen3,
  4. C Janvin1
  1. 1Section of Geriatric Psychiatry, Psychiatric Hospital of Rogaland, Stavanger, Norway
  2. 2Department of Geriatric Medicine, Ullevål Hospital, Oslo, Norway
  3. 3Department of Neurology, Central Hospital of Stavanger, Norway
  1. Correspondence to:
 Dr D Aarsland, Section of Geriatric Psychiatry, Psychiatric Hospital of Rogaland, Arm. Hansen v 20, 4095 Stavanger, Norway;


Objective: To study the safety and efficacy of the cholinesterase inhibitor donepezil in patients with Parkinson's disease (PD) and cognitive impairment.

Methods: This was a double blind, randomised and placebo controlled, crossover study in which 14 patients with PD and cognitive impairment received donepezil (5 or 10 mg per day) or matching placebo during two sequential periods lasting 10 weeks each. The primary outcome measures were the mini mental state examination (MMSE) score, the clinician's interview based impression of change plus caregiver input (CIBIC+) score, and the motor subscale of the unified Parkinson's disease rating scale (UPDRS).

Results: Two patients on donepezil (14%) dropped out after one and four weeks of the first treatment period because of peripheral cholinergic side effects, otherwise the adverse effects were few and not severe. Carryover or residual effects were not observed. Parkinsonism did not increase during donepezil treatment. After 10 weeks of treatment, the mean MMSE score was increased by 2.1(SD 2.7) points on donepezil and 0.3 (SD 3.2) points on placebo, and the CIBIC+ score was 3.3 (SD 0.9) on donepezil and 4.1 (SD 0.8) on placebo. Statistical analysis of the repeated measurements and crossover study design showed significant effects of donepezil compared with placebo for MMSE (p=0.013) and CIBIC+ (p=0.034). Five (42%) patients on donepezil and two (17%) on placebo were rated as improved on the basis of the CIBIC+ score.

Conclusions: Donepezil improves cognition, and seems to be well tolerated and not to worsen parkinsonism in patients with cognitive impairment.

  • Parkinson's disease
  • cognitive impairment
  • donepezil
  • PD, Parkinson's disease
  • MMSE, mini mental state examination
  • UPDRS, unified Parkinson's disease rating scale
  • NPI, neuropsychiatric inventory
  • DLB, dementia with Lewy bodies

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Supplementary materials

  • Aarsland D et al. Donepezil for cognitive impairment in Parkinson�s disease: a randomised controlled study. J Neurol Neurosurg Psychiatry 2002;72:708-712

    An error occurred in the production process in which the codes of the two lines were erroneously interchanged.

    Figure 2 Change in mini mental state examination (MMSE) score from baseline over the two treatment sequences. Values are mean (SE).


  • Competing interests: DA, JPL, and KL have been reimbursed by Pfizer Inc, the manufacturer of donepezil, for attending several conferences, and have received fees for speaking, consulting, and organising education. The present study was partially funded by a grant from Pfizer Inc. None of the authors have been employed by, or hold any stocks or shares in, Pfizer.

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