Public Health & Health Science Division, ULAB

Parkinson's disease (PD) is commonly treated with dopaminergic therapies that effectivelyaddress motor symptoms; however, their effects on the non-motor aspects of one’s life remain underexplored. By systematically synthesizing data across mood, sleep, and cognition, this study intends to evaluate how levodopa, dopamine agonists, and monoamine oxidase B (MAO-B) inhibitors influence non-motor symptoms and overall quality of life in patients with PD. Data were collected from nine studies published between 1999 and 2025, spanning longitudinal observational, cross-sectional, within-subject ON/OFF, randomized crossover, systematic review, and case series designs to ensure that both the breadth and depth of current research are considered. Dopamine agonists are associated with reduced motivational and apathy symptoms, while MAO-B inhibitors are associated with reduced depressive symptoms; anxiety scores were higher in the ON medication state. Moreover, higher dopaminergic exposure was associated with impulse control behaviors. Each type of therapy was associated with variable cognitive effects. Ultimately, Levodopa was associated with benefits in attention, processing speed, working memory, executive function, and episodic memory but with worsened cognitive inhibition. At the same time, rasagiline showed benefits in working memory and verbal fluency, and pramipexole and selegiline were linked to worse episodic memory, impulse control, globalcognition, and concept formation. Treatment universally worsened sleep outcomes; totaldopaminergic dose was a stronger predictor of excessive daytime sleepiness than agonists.Although these findings are substantiated, there remains a lack of comparative evidence in current PD literature, so we have a limited understanding of the long-term trade-offs between therapy type and quality of life. This study therefore calls for more patient-centered treatment strategies in the future to address both the motor and non-motor manifestations of PD.