Ires Ghielen

10 Chapter 1 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 [1]. Due to ageing and accompanying factors such as genetic mutations and environmental risk factors (e.g. pesticides), the occurrence of PD is increasing [1, 2]. Recently, PD has even been described as a pandemic [3]. PD was first described by James Parkinson in 1817 [4] as a neurological syndrome characterized by involuntary tremors and muscular weakness. He also stated ‘ the senses and intellects being uninjured ’ [4]. However, Jean-Martin Charcot described PD as not only showing tremors, but also bradykinesia, autonomic dysfunction, and pain [5]. Furthermore, together with one of his students in 1892, he described depression and hallucinations in PD patients with dementia, as reported by Walusinski [6]. Nowadays, 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 [7, 8]. According to Braak and colleagues [9], PD is caused by a neuropathological process, affecting serotonergic, noradrenergic, cholinergic, and dopaminergic systems. This neuropathological process is defined by the accumulation of the protein alpha- synuclein into so-called Lewy bodies, that spread out through the brain in a caudal (brainstem) to rostral (neocortex) gradient [9, 10]. This neurodegenerative process also affects the neurotransmitter systems. When over 60% of dopaminergic neurons of the basal ganglia have degenerated, the motor symptoms on which the clinical diagnosis of PD is based, appear [11]. Together with the affected dopaminergic system, the affected serotonergic, noradrenergic, and cholinergic systems are postulated to cause other motor and autonomic and neuropsychiatric symptoms. 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 [12-15]. Amongst neuropsychiatric symptoms, anxiety and depression are considered major predictors of quality of life, followed by cognitive dysfunction [13, 14]. The lifetime prevalence of an anxiety disorder in PD patients is 49% [16], depression occurs in up to 50% of PD patients at some point in the course of the disease [8], and up to 80% of PD patients develop PD dementia [17, 18].