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


CONCLUSIONS
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.
Leroi
Iracema
I
Department of Psychiatry, North Manchester General Hospital, Manchester, UK. wendy.heap@mail.manhhc-tr.nwest.nhs.uk
Brandt
Jason
J
Reich
Stephen G
SG
Lyketsos
Constantine G
CG
Grill
Stephen
S
Thompson
Richard
R
Marsh
Laura
L
D000368:Aged; D000369:Aged, 80 and over; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003704:Dementia / Q000188:drug therapy* / Q000209:etiology; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use; D010300:Parkinson Disease / Q000523:psychology*; D010865:Pilot Projects; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil