Prefrontal cortex activity and gait in Parkinson's disease with cholinergic and dopaminergic therapy

Stuart, Sam, Morris, Rosie, Giritharan, Andrew, Quinn, Joseph, Nutt, John and Mancini, Martina (2020) Prefrontal cortex activity and gait in Parkinson's disease with cholinergic and dopaminergic therapy. Movement Disorders, 35 (11). pp. 2019-2027. ISSN 0885-3185

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Abstract

Objectives: Degradation of striatal dopamine in Parkinson’s disease (PD) may initially be supplemented by increased cognitive control mediated by cholinergic mechanisms. Shift to cognitive control of walking can be quantified by prefrontal cortex (PFC) activation. Levodopa improves certain aspects of gait and worsens others, and cholinergic augmentation influence on gait and PFC activity remains unclear. This study examined dopaminergic and cholinergic influence on gait and PFC activity while walking in PD.
Methods: A single-site, randomized, double-blind, cross-over trial examined effects of levodopa and donepezil in PD. 20 PD participants were randomized and 19 completed the trial. Participants were randomized to either levodopa+donepezil (5mg) or levodopa+placebo treatments, with two-weeks with treatment and a two-week washout. The primary outcome was change in PFC activity while walking, and secondary outcomes were change in gait, dual-task performance and attention.
Results: Levodopa decreased PFC activity compared to Off medication (effect size: -0.51), whereas the addition of donepezil reversed this decrease. Gait speed and stride length, under single and dual-task conditions, improved with combined donepezil and levodopa compared to Off medication (effect size: 1 for gait speed and 0.75 for stride length). Dual-task reaction time was quicker with levodopa compared to Off medication (effect size: -0.87), and accuracy improved with combined donepezil and levodopa (effect size: 0.47).
Conclusions: Cholinergic therapy, specifically donepezil 5mg/day for two-weeks, can alter PFC activity when walking, and improve secondary cognitive task accuracy and gait in PD. Further studies will investigate whether higher PFC activity while walking is associated with gait changes.

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