Effects of augmenting cholinergic neurotransmission on balance in Parkinson's disease

Martina Mancini, Katherine Chung, Alexander Zajack, Douglas N. Martini, Katrina Ramsey, Jodi Lapidus, Fay B. Horak, John G. Nutt

Research output: Contribution to journalArticle

Abstract

Introduction: Degeneration of cholinergic systems may contribute to impairments of balance and gait in Parkinson's disease (PD) and phase 2 clinical trials have suggested that centrally acting cholinesterase inhibitors reduce falls. Here, we examined the effects of augmenting cholinergic neurotransmission on static and dynamic balance, indices of fall risk. Methods: A single-site, randomized, double-blind, crossover trial examined the effect of donepezil in patients with PD. Forty-nine participants with idiopathic PD were randomized and 45 completed the trial. Each treatment period was 6 weeks with a 6-week washout between treatments. Donepezil in 2.5 mg capsules, or identical appearing placebo capsules, was increased from two per day (5 mg) to four capsules (10 mg) after 3 weeks. The primary outcome measures were the range of the medio-lateral sway when standing (static balance) and the variability of the stride duration when walking (dynamic balance). A linear mixed model was used to investigate whether the change in outcomes between weeks 0 and 6 differed between phases. Results: There were no significant differences in treatment effects between placebo and donepezil for medio-lateral sway range during quiet standing (p = 0.28), nor in gait variability (p = 0.31). None of the secondary outcome measures or exploratory analyses were significant although one secondary measure of static balance was increased by donepezil. Conclusions: Contrary to our hypothesis, cholinergic augmentation with donepezil at 10 mg/day for 6 weeks did not affect measures of static or dynamic balance in people with PD. These results are compared with other phase 2 trials of cholinesterase inhibitors and considerations for future trials are discussed.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalParkinsonism and Related Disorders
Volume69
DOIs
StatePublished - Dec 2019

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Synaptic Transmission
Cholinergic Agents
Parkinson Disease
Capsules
Cholinesterase Inhibitors
Gait
Outcome Assessment (Health Care)
Placebo Effect
Cross-Over Studies
Walking
Linear Models
Therapeutics
Placebos
donepezil
Clinical Trials

Keywords

  • Cholinergic augmentation
  • Gait and balance
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Effects of augmenting cholinergic neurotransmission on balance in Parkinson's disease. / Mancini, Martina; Chung, Katherine; Zajack, Alexander; Martini, Douglas N.; Ramsey, Katrina; Lapidus, Jodi; Horak, Fay B.; Nutt, John G.

In: Parkinsonism and Related Disorders, Vol. 69, 12.2019, p. 40-47.

Research output: Contribution to journalArticle

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