Non-motor symptons in Parkinson's disease including the dopamine dysregulation syndrome and impulse control

This thesis focuses on the non-motor symptoms (NMS) of Parkinson's disease (PD), with particular emphasis on impulsive-compulsive spectrum behaviours (ICBs). The relevance of NMS is investigated as presenting complaints amongst 21% of 433 patients with pathologically-proven PD. These patients had delayed diagnosis of PD, and often underwent unnecessary and potentially harmful interventions. Motor and NMS of LRRK2- associated PD are compared with idiopathic PD, and NMS of LRRK2-associated PD are more benign than in idiopathic PD. Increased Lewy body burden was shown to correlate with NMS in a subgroup of idiopathic PD patients at post-mortem. A metanalysis investigates pathological gambling and the dopamine dysregulation syndrome in PD, highlighting the importance of dopamine agonists in pathological gambling. A new ICB in PD, named "reckless generosity", occurring in association with dopamine agonist use is described. Dopamine agonists are also implicated in the development of ICBs in patients with pathologically-confirmed progressive supranuclear palsy. An increased prevalence of excessive hoarding as a NMS of PD is shown, particularly in patients with other ICBs. Hoarding is shown to relate more to impulsivity measures than obsessive-compulsive symptoms. The overlap between sleep disturbance, dreams, mood and ICBs in PD is demonstrated. Sleep disturbance is independent of dopaminergic medication use, and instead relates to anxiety, depression, and the presence of ICBs. Reward learning in PD patients with and without ICBs, and healthy controls is tested on a reaction time game, the Salience Attribution Test. PD patients with ICBs show increased impulsivity on temporal discounting tasks, but do not show increased aberrant salience to rewards. Positron emission tomography (PET) scanning is used to investigate the dopaminergic pathways involved in ICBs by comparing PD patients with ICBs to those without ICBs after a L-dopa challenge and visual reward-related cue exposure. The results differ from studies on PD patients with addictive dopamine dysregulation, or other non-PD drug addicted individuals. The role of deep brain stimulation surgery for PD, patients with ICBs is investigated in a case series of 21 operated PD patients exhibiting ICBs at some stage during the course of their disease. The mixed results suggest the need for careful selection of patients for this procedure