Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease

Int J Geriatr Psychiatry. 2004 Jan;19(1):1-8. doi: 10.1002/gps.993.


Objective: To evaluate the efficacy and safety of donepezil, an acetylcholinesterase inhibitor, as a treatment for cognitive impairment and dementia in patients with Parkinson' s disease (PD).

Methods: Using a randomized, double-blind, placebo-controlled design, nine patients received placebo and seven patients received donepezil (2.5-10 mg/day) for a mean (SD) duration of 15.2 (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory, attention, psychomotor speed, and visuospatial and executive functions. Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings. Primary safety measures were motor signs and assessments of adverse effects.

Results: Patients on donepezil showed selective and significant (p<0.05) improvement on the memory subscale of the Dementia Rating Scale. There was also a trend toward improvement on a measure of psychomotor speed and attention. There were no group differences in psychiatric status, motor function, or activities of daily living as measured at baseline or end-point. Adverse effects resulted in premature withdrawal of four patients on donepezil, two for peripheral cholinergic effects and one for increased parkinsonism. Side effects were associated with dosage increases.

Conclusion: Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment. However, variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD, especially with dosage increases.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / therapeutic use*
  • Dementia / drug therapy*
  • Dementia / etiology
  • Donepezil
  • Double-Blind Method
  • Female
  • Humans
  • Indans / adverse effects
  • Indans / therapeutic use*
  • Male
  • Memory Disorders / drug therapy
  • Memory Disorders / etiology
  • Middle Aged
  • Neuropsychological Tests
  • Nootropic Agents / adverse effects
  • Nootropic Agents / therapeutic use
  • Parkinson Disease / psychology*
  • Pilot Projects
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Treatment Outcome


  • Cholinesterase Inhibitors
  • Indans
  • Nootropic Agents
  • Piperidines
  • Donepezil