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Donepezil for dementia in Parkinson’s disease: a randomised, double blind, placebo controlled, crossover study
  1. B Ravina1,
  2. M Putt2,
  3. A Siderowf3,
  4. J T Farrar2,
  5. M Gillespie1,
  6. A Crawley1,
  7. H H Fernandez4,
  8. M M Trieschmann5,
  9. S Reichwein3,
  10. T Simuni6
  1. 1National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
  2. 2University of Pennsylvania, Center for Clinical Epidemiology and Biostatistics, Philadelphia, PA, USA
  3. 3University of Pennsylvania, Department of Neurology, Philadelphia, PA, USA
  4. 4University of Florida at Gainesville, Department of Neurology, Gainesville, FL, USA
  5. 5Brown University, Department of Neurology, Providence, RI, USA
  6. 6Northwestern University, Department of Neurology, Chicago, IL, USA
  1. Correspondence to:
 Dr B Ravina
 Program Director, Clinical Trials, NINDS, Neuroscience Center Rm 2225, 6001 Executive Blvd, Rockville, MD 20892-9257, USA;


Objective: To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson’s disease (PD).

Methods: This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5–10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAScog).

Results: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson’s Disease Rating Scale.

There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant.

Conclusions: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study.

  • AD, Alzheimer’s disease
  • ADAScog, Alzheimer’s Disease Assessment Scale Cognitive Subscale
  • BPRS, Brief Psychiatric Rating Scale
  • CGI, Clinical Global Impression of Change
  • CIBIC, Clinicians’ Interview Based Impression of Change
  • DLB, dementia with Lewy bodies
  • DSM IV, Diagnostic and statistical manual of mental disorders, 4th ed
  • MDRS, Mattis Dementia Rating Scale
  • MMSE, Mini Mental Status Examination
  • PD, Parkinson’s disease
  • UPDRS, Unified Parkinson’s Disease Rating Scale
  • Parkinson’s disease
  • dementia
  • donepezil

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  • See Editorial Commentary, p 903

  • Competing interests: none declared

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