Learning disorders and Parkinson’s disease: tremor predicts effects of medication

The effect of dopaminergic medication on the learning abilities of patients with Parkinson’s disease turns out to be linked to the presence of tremor symptoms. In patients who do not experience tremor, dopaminergic medication improves the ability to learn from rewards (reinforcement learning). Remarkably, the medication brings no benefit in reward learning to patients who do exhibit tremor. These were the results from a new study by brain researchers at Radboudumc and the Donders Institute of Radboud University, published on 6 November in the scientific journal Brain.

“It is somewhat surprising that until now, studies of cognition in Parkinson’s disease never assessed the distinction between patients who exhibit tremor and those who do not”, says Hanneke den Ouden, brain researcher at Radboud University. “Our study shows that there is a link between problems with motor skills and problems with cognition in patients with Parkinson’s disease.”

Learning abilities and Parkinson’s disease

Most patients with Parkinson’s disease experience tremor –shaking in an arm or leg. Only one in four patients does not experience these symptoms. In addition, many patients experience mental issues. Due to a decrease in dopamine, a chemical messenger molecule that occurs in the brain, patients with Parkinson’s disease become less sensitive to learning through rewards.

A large number of prior studies have shown that this learning disorder can be remedied by administering dopaminergic medication. It remained a mystery, however, why medication had no effect in many patients. The study of the Radboud researchers reveals that this improvement through medication only occurs in patients who experience tremor.

Presence and absence of tremor

“The fact that we only observe results from earlier studies in patients without tremor suggests that prior studies only included with these patients. This would make sense, as it is easier for patients without tremor to participate in an experiment. However, it is important to realise that three out of four patients actually do experience tremor, and our study shows that the medication has a different effect on these patients. We see this as a major warning: Always be aware of the diversity of patients in your study, as you might otherwise draw the wrong conclusions.”

Predictive value

According to the researchers, it is crucial to improve our understanding of such patient diversity. “This study tells us that the dopamine systems of Parkinson’s disease patients with and without tremor are affected in different ways, and that this goes beyond the level of just motor problems, affecting cognition as well”, according to co-author Rick Helmich, neurologist at Radboudumc. “Whether someone experiences tremor or not might therefore potentially have a significant predictive value regarding the effectiveness of medication in the cognitive domain. However, more and larger studies are needed before this can be confirmed.”

Publication

Annelies J. van Nuland, Rick C. Helmich, Michiel F. Dirkx, Heidemarie Zach, Ivan Toni, Roshan Cools and Hanneke E. M. den Ouden, Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype (Brain, 2020)