Effects of Cholinergic Augmentation on Measures of Balance and Gait

This study will compare the effects of placebo and donepezil, a drug that helps conserve
concentrations of the neurotransmitter, acetylcholine on measures of balance and gait in
subjects with Parkinson's disease (PD). This study is a double-blind, placebo controlled,
cross-over randomized clinical trial. Short-latency afferent inhibition (SAI), a
physiological index of cholinergic function will be measured to determine if the deficits in
balance and gait correlate with abnormalities of the SAI and if SAI is altered by donepezil
as a measure of drug efficacy. Cognitive tests like the attention network test will be
administered to determine if changes in gait and balance are mediated by changes in
attention.

The results of this study will be the most direct test of the hypothesized role of
cholinergic neurons and the neurotransmitter, acetylcholine in terms of gait and balance.
The study is exploratory because it is not known whether donepezil will affect gait, balance
or attention, nor which measures of gait, balance or attention will be sensitive to drug
manipulation. The study's immediate goal is to determine the potential utility of
cholinergic manipulation as a strategy for preventing or treating balance and gait
dysfunction in PD. The findings of this trial are intended to lead to more sharply focused
questions about the role of cholinergic neurons in balance and gait and eventually to Phase
II B trials to determine clinical utility of cholinergic manipulation to prevent falls and
improve mobility.