HealthDay News — Cognitive co-activation is associated with a significantly smaller levodopa effect on resting tremor in Parkinson’s disease (PD), according to a study published in CNS Neuroscience & Therapeutics.

Heidemarie Zach, MD, from the Radboud University Medical Center in Nijmegen, Netherlands, and colleagues examined whether cognitive stress modulates the levodopa effect on resting tremor in 69 tremulous PD patients. The authors measured the effect of treatment on tremor intensity and tremor variability in 2 treatment conditions (OFF versus ON levodopa) and in 2 behavioral contexts (rest versus cognitive co-activation).

The researchers found that levodopa significantly reduced tremor intensity across behavioral contexts, while tremor intensity was increased by cognitive co-activation across treatment conditions. Compared with during rest, during cognitive co-activation, the levodopa effect was significantly smaller. There was an increase in resting tremor variability after levodopa, while a decrease was seen during cognitive co-activation.

“Cognitive stress reduces the levodopa effect on Parkinson’s tremor,” the authors write. “This effect may be explained by a stress-related depletion of dopamine in the basal ganglia motor circuit, by stress-related involvement of nondopaminergic mechanisms in tremor (e.g., noradrenaline), or both. Targeting these mechanisms may open new windows for treatment.”


Zach H, Dirkx MF, Pasman JW, Bloem BR, Helmich RC. Cognitive Stress Reduces the Effect of Levodopa on Parkinson’s Resting Tremor [published online January 10, 2017. CNS Neurosci Ther. doi: 10.1111/cns.12670