Study Rationale:
Impairments of gait and balance are common and life-altering in patients with Parkinson’s disease (PD). These impairments are incompletely controlled with medications acting on the dopaminergic system or with deep brain stimulation.
Indirect evidence implicates a second neurotransmitter, acetylcholine, as a contributor to falls and gait impairments. This proposal will be the most direct test of the role of cholinergic systems in gait and balance.
Hypothesis:
We hypothesize that cholinergic systems contribute to mobility such that measures of gait, balance and/or attention will improve in response to cholinergic augmentation.
Study Design:
This randomized, double-blind, crossover study will test a drug that increases levels of acetylcholine (cholinesterase inhibitor named donepezil) and a placebo in 54 people with PD. The outcome measures will include standing stability, walking stability, effects of dual-tasking on balance and gait stability, and attention.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Our ultimate goal is to determine the potential utility of cholinergic drugs as a strategy for preventing or treating balance and gait dysfunction in PD.
Next Steps for Development:
If donepezil improves measures of balance and gait that are associated with falls, a multisite study would test whether donepezil reduced falls in daily life.
Trial Phase: II-A