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Effects on Gait and Balance of Augmenting Cholinergic Function

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.

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


  • Fay B. Horak, PhD, PT

    Portland, OR United States

  • John G. Nutt, MD

    Portland, OR United States

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