On the role of dopamine replacement therapy in decision-making, working memory, and reward in Parkinson’s disease: does the therapy-dose matter?

Background: Dopaminergic therapy proved to ameliorate motor deficits in Parkinson’s disease but its effects on behavior and cognition vary according to factors that include, among others, the evolution of the disease and the nature of the task that is tested. This study addressed the question of whether, in moderate to advanced Parkinson’s disease (PD) with motor fluctuations, changes in decision-making and sensitivity to reward occur and to what extent dopaminergic therapy plays a role. Methods: Fifteen PD patients (On and Off medication) and thirteen healthy controls were compared on two different tasks which analyzed decision-making processes (the Cambridge Gamble Task, CGT) and working memory abilities with and without the prospect of reward (modified N-back task). Results: We found that the PD patients were unable to choose an optimal betting strategy and were impulsive in their choices relative to the control group. Further, a detrimental dose-dependent effect of dopaminergic therapy was detected, meaning that those patients who were taking higher doses of therapy were more impulsive in selecting bets and more impaired in making probabilistic choices. Such a dose-dependent effect was not found on the N-back task. However, the results of the PD group in this task supported indirect evidence of the amelioration of performance in rewarded conditions. Conclusion: Our results suggest that the detrimental effects of dopaminergic therapy may be dose-related and that the interaction between monetary reward and dopaminergic therapy can affect and improve some cognitive abilities, such as working memory.