Changes in prefrontal cortical activity and turning in response to dopaminergic and cholinergic therapy in Parkinson's disease: A randomized cross-over trial

Parkinsonism Relat Disord. 2021 May:86:10-14. doi: 10.1016/j.parkreldis.2021.03.014. Epub 2021 Mar 27.

Abstract

Introduction: Cholinergic dysfunction contributes to mobility deficits in Parkinson's disease (PD). People with PD rely on limited prefrontal executive-attentional resources for the control of locomotion, including turning. Cortical and behavioral responses to cholinergic augmentation during turning remains unclear. We examined prefrontal cortex (PFC) activity while turning-in-place and spatiotemporal measures of turns in response to usual dopaminergic medication and adjunct cholinergic augmentation.

Methods: This study consisted of a single-site, randomized, double-blind crossover trial. Twenty PD participants were assessed in the levodopa-off state and then randomized to either levodopa + donepezil (5 mg) or levodopa + placebo treatments for two weeks followed by a 2-week washout before crossover. The primary outcome was change from off state in PFC activity while turning-in-place (assessed with functional near-infrared spectroscopy). Secondary outcomes were changes in spatiotemporal turning measures (assessed with body-worn inertial measurement units) and accuracy in the secondary task.

Results: Nineteen participants completed the trial. While levodopa + placebo had no effect on PFC activity when turning-in-place with a dual-task, levodopa + donepezil led to a large reduction in PFC activity (effect size, -0.82). Spatiotemporal measures of turning improved with both treatments, with slightly greater effect sizes observed for levodopa + donepezil. Additionally, the accuracy in the concurrent cognitive task improved only with levodopa + donepezil (effect size, 0.63).

Conclusion: The addition of cholinergic therapy with donepezil (5 mg/day for 2 weeks) to standard dopaminergic therapy reduced the burden on prefrontal executive-attentional resources while turning with a dual-task and improved secondary task accuracy and turning.

Keywords: Cognition; Locomotion; Parkinson's disease; Prefrontal cortex; fNIRS.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiparkinson Agents / therapeutic use
  • Cholinesterase Inhibitors / therapeutic use*
  • Cross-Over Studies
  • Donepezil / therapeutic use*
  • Dopamine Agents / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Levodopa / therapeutic use
  • Male
  • Middle Aged
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy*
  • Prefrontal Cortex / drug effects*
  • Psychomotor Performance / drug effects*

Substances

  • Antiparkinson Agents
  • Cholinesterase Inhibitors
  • Dopamine Agents
  • Levodopa
  • Donepezil