Ires Ghielen

90 Chapter 5 medication and its adverse effects renders the relationship between FoG and anxiety insignificant. FoG is easily exacerbated by multiple factors such as disease progression [42], cognitive dysfunctions such as attention [52], long-term use of medication, fluctuations and adverse effects [8]. Our results confirm that FoG should probably not be addressed with only drug treatment [53], since its adverse effects also play an important role. When adjusting the multivariate model for disease characteristics, the contribution of FoF to FoG diminishes (although remains significant). A low acitivity level has been described as a possible confounder in FoF and FoG [51]. FoF studies unrelated to PD show conflicting results, regarding the relationship between FoF and physical deterioration [65,66]. These studies in elderly without PD reported that FoF is related to physical inactivity and an increased risk of falling. In our PD cohort, low activity levels were also found (dynamic activity (% time) median = 10, IQR = 11). With regard to the effect of medication and adverse effects on the reported associations between FoG, FoF, and anxiety, literature on response fluctuations is relevant. With disease progression and chronic exposure to levodopa, many patients develop a range of levodopa-induced motor and non-motor response fluctuations, including wearing-off. Patients with wearing-off symptoms report higher depression and anxiety scores in the ‘off’ state, as compared to the ‘on’ state [54]. In addition, panic attacks, which represent a high level of anxiety, are more frequent in the ‘off’ than in the ‘on’ state [55, 56]. Non-motor symptoms, such as anxiety, can fluctuate with pulsatile dopaminergic treatment. Also, non-motor fluctuations can vary unpredictably during the day [57]. The here reported effect of medication and its adverse effects in our FoG – anxiety association may be explained by the fact that higher anxiety and depression scores are related to complications of medication [51]. Medication and its adverse effects seem to influence both FoG and anxiety symptoms [58] and their association. Psychological approaches, such as cognitive behavioral therapy, explicitly focus on anxiety symptoms, which are typically seen separate from the motor symptoms. However, due to the mutual interactions between FoG, FoF, and anxiety, and the impact of medication and its adverse effects, this artificial separation between psychological and somatic health care seems unnatural and may prevent optimal diagnostics and treatment. An integrated treatment with psychological and physiotherapeutic elements is necessary in order to address the interactions between motor and non-motor symptoms. For example, the body awareness (BEWARE) training [5] is designed to specifically address these PD related problems.