Narrative review synthesizing evidence on motor and non-motor drivers of health-related quality of life in advanced Parkinson's disease, the impact on caregivers, the use of patient-reported outcome measures, and how advanced therapies affect HRQoL outcomes.

Useful for guiding patient-centered outcome selection and trial/endpoints design and for informing clinical care priorities, but offers limited mechanistic or therapeutic-discovery insights for novel drug development.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a wide range of motor and non-motor symptoms that lead to substantial disability over time, particularly in advanced stages, with a significant impact on patients' quality of life (QoL). Given the chronic and currently incurable nature of the disease, symptom management and the preservation of health-related QoL (HRQoL) are central therapeutic priorities from a patient-centered perspective. In this context, there has been a growing emphasis on the use of patient-reported outcome measures (PROMs) to capture the subjective burden of disease and to better reflect the real-world benefits of therapeutic interventions beyond traditional clinical endpoints. In parallel, increasing attention has been paid to the consequences of PD on caregivers, whose HRQoL is often substantially affected, especially as the disease progresses and care demands intensify in advanced PD. This narrative review synthesizes current evidence on HRQoL in advanced PD, with particular focus on the contribution of motor symptoms, non-motor symptoms, and other disease-related factors to HRQoL impairment in patients and caregivers. Additionally, the available data on the impact of advanced therapies on HRQoL outcomes in patients are critically discussed, highlighting their role in comprehensive, patient-centered care.