Ires Ghielen

180 Appendix English summary Parkinson’s disease (PD) is a neurodegenerative disorder with a prevalence of 100 to 200 per 100,000 people and an annual incidence of 15 per 100,000 people. Due to ageing and other factors such as genetic mutations and environmental risk factors (e.g. pesticides), the occurrence of PD is increasing. Recently, PD has even been described as a pandemic. PD is characterized by its main motor symptoms bradykinesia, rigidity and tremor, and additional motor and non-motor symptoms. Non-motor characteristics may include cognitive dysfunction, autonomic failure, and neuropsychiatric symptoms and disorders such as anxiety, depression, psychosis, impulse control disorders, sleep disorders, and apathy. As compared to the motor symptoms, neuropsychiatric symptoms are often reported to have a higher impact on quality of life of both patients and their caregivers. Amongst neuropsychiatric symptoms, anxiety and depression are considered major predictors of reduced quality of life, followed by cognitive dysfunction. Currently, up to 45% of PD patients experience either clinically relevant anxiety symptoms or fulfill the criteria for an anxiety disorder, including generalized anxiety disorder, panic attacks, and social phobia. Anxiety in PD can also occur in the context of response fluctuations in PD symptoms, especially related to wearing-off, i.e., the re-emergence of PD symptoms while transitioning from an ‘on’ state to an ‘off’ state, typically occurring prior to the next scheduled dose of dopaminergic medication taking effect. About 75% of patients with motor fluctuations experience fluctuations in mood and/or anxiety in parallel. Therefore, diagnosing and treating anxiety in PD is complicated, due to overlapping motor and autonomic symptoms, comorbid psychiatric symptoms, and the interplay between anxiety and motor symptoms over time. This thesis mainly focuses on understanding (part 1) and treating (part 2) anxiety symptoms in the context of motor symptoms. Chapter 1 provides a general introduction on anxiety in PD including the multiple factors that complicate diagnosis and treatment. The first part of this thesis ( chapters 2 through 5 ) focuses on understanding the complex associations and interactions between anxiety, motor and other non-motor