Ires Ghielen

167 General discussion patients experience motor fluctuations within 5 years of dopamine replacement therapy [9]. With these motor fluctuations, another 75% of PD patients experience mood and anxiety fluctuations in parallel [10]. Motor and anxiety symptoms might interact over time, so longitudinal data may represent the interplay between these symptoms better than cross-sectional data. In chapter 5 we showed that motor and anxiety symptoms influence one another over time, in which fear of falling and potentially anxiety precede freezing of gait. In addition, medication and its adverse effects (including fluctuations) seem to influence both freezing of gait and anxiety symptoms as well as their association, which is in line with previous research [11]. Motor and anxiety symptoms can co-occur simultaneously, as is shown in chapters 2,3, and 4 . These symptoms might originate in a subsequent manner over time, possibly creating a vicious cycle, which is indicated by our longitudinal analysis in chapter 5 . This is also what is seen in clinical practice, and is evidenced by previous research [12, 13]. This vicious cycle can be a process that takes place within minutes [14] and we only investigated the symptom interactions over a time-period of a few weeks. Our results indicate that anxiety can have an impact on motor symptoms and vice versa, which is important to take into account in the treatment of both anxiety and motor symptoms in PD patients. Besides PD, other progressive neurological disorders such as MS and Huntington’s disease are also accompanied by both motor and psychiatric symptoms [15, 16]. Resulting from our meta-analyses in chapter 6 , psychological treatments show small to moderate effects in reducing psychiatric symptoms in patients with PD and MS, which indicates that treatments can be optimized. Optimizing psychological treatments could include taking the interactions with motor symptoms into account. Since the nature of neurodegenerative diseases involves progressive decline and inevitability of occurring symptoms, especially motor symptoms, the effects on symptom reduction can be expected to be unsatisfactory. The effect on psychiatric symptoms, however, can result in reduction of psychiatric symptoms. The interaction with inevitable motor symptoms, thereafter, makes the treatment of psychiatric symptoms in PD patients challenging. Especially regarding wearing-off, it is important to discuss treatment options to improve motor symptom fluctuations. First line treatment in improving motor as well as non-motor fluctuations is dopamine replacement therapy [17]. When motor symptom fluctuations diminish, non-motor symptoms (including anxiety) might also diminish [18]. However, available pharmacological treatments are considered insufficient to alleviate the complications (e.g. response fluctuations) of PD [19]. Also, a small percentage of patients can develop a dopamine dysregulation syndrome 9