The Effect of Donepezil on Gait and Balance in Parkinson's Disease
The Effect of Donepezil on Gait and Balance in Parkinson's Disease
This study involves Parkinson's disease (PD). Symptoms include slow movement, tremor, and
 muscle rigidity. Current medications for the treatment of PD do not improve gait and balance
 difficulties in individuals with PD. Donepezil (study drug) has been found to reduce falls in
 individuals with PD. The mechanism in which this reduction of falls occurs is unclear. The
 investigators study will look at what aspects of gait and balance are improved by the study
 drug. The study drug is not approved to treat PD in the United States or other countries
 because we do not know enough about it.
Parkinson's disease (PD) is a common neuro-degenerative disease affecting about 2% of the
 adult population in the United States over the age of 65. Some of the most disabling symptoms
 of Parkinson's disease are balance and gait dysfunction, leading to falls. These symptoms do
 not respond to current dopamine directed therapies. Evidence from both pathologic studies and
 advanced imaging has demonstrated that a cholinergic deficiency in the thalamus and basal
 ganglia is found in individuals with PD who fall compared to non-fallers. The central acting
 acetylcholine esterase inhibitor, donepezil, has been demonstrated to decrease falls in
 individuals with PD. The mechanism by which falls decreased is unknown. Our open label pilot
 data indicates that donepezil can improve quantitative measures of balance in individuals
 with PD. Suggesting that improvements in balance in the mechanism by which donepezil reduces
 falls. Our goal is to determine whether donepezil will:

 -  Improve quantitative measures of balance in subjects with Parkinson's disease compared
 to placebo.

 -  Improve quantitative measures of gait in subjects with Parkinson's disease compared to
 placebo.

 -  Improve cognitive measures in non-demented subjects with Parkinson's disease.
Inclusion Criteria:

 -  Idiopathic Parkinson's disease, defined by the UK Brain Bank criteria, with a Hoehn
 and Yahr score of 2 to 4

 -  Treated with levodopa for at least a year and on a stable antiparkinsonian regimen for
 at least one month

 -  Abnormal computerized dynamic posturography (CDP) on screening defined as a composite
 score below 65 (range 1-100)

 Exclusion Criteria:

 -  Dementia defined by MMSE less than 27

 -  Other medical conditions other than PD affecting balance or gait as determined by the
 investigators

 -  Unable to stand unassisted for 30 minutes

 -  Current use of an acetylcholinesterase inhibitors or drugs with known anticholinergic
 properties

 -  Medical or psychiatric co-morbidities that may interfere with compliance or might
 place subject in danger as determined by the investigators