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Purpose: This study aimed to determine how limited medication knowledge as one aspect of health literacy contributes to poorer health-related quality of life (HRQoL) in people with Parkinson's disease (PD). Methods: Demographical data, PD-specific data (MDS-Unified Parkinson's Disease-Rating Scale, Nonmotor symptom scale), and data about depressive symptoms (Beck's depression inventory), cognition (Montreal cognitive assessment), HRQoL (Short-Form Health Questionnaire-36, SF-36), and medication knowledge (names, time of taking, indication, dosage) were assessed in 193 patients with PD. Multivariate analysis of variance (MANOVA), multivariate analysis of covariance, and mediation analyses were used to study the relationship between medication knowledge and HRQoL in combination with different mediators and covariates. Results: Overall, 43.5% patients showed deficits in at least one of the 4 knowledge items, which was associated with higher age, number of medications per day and depression level, and poorer cognitive function, motor function, and lower education level. Using one-way MANOVA, we identified that medication knowledge significantly impacts physical functioning, social functioning, role limitations due to physical problems, and role limitations due to emotional problems. Mediation models using age, education level, and gender as covariates showed that the relationship between knowledge and SF-36 domains was fully mediated by Beck's Depression Inventory but not by Montreal Cognitive Assessment. Conclusions: Patients who expressed unawareness of their medication did not necessarily have cognitive deficits; however, depressive symptoms may instead be present. This concomitant depressive symptomatology is crucial in explaining the contribution of nonadherence and decreased medication knowledge to poor quality of life. [ABSTRACT FROM AUTHOR]