Barbosa, Pedro Melo; (2019) Impulsive compulsive behaviours in Parkinson's disease: an observational, eye movement and neuropathological study. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis focuses on impulsive compulsive behaviours (ICBs) in Parkinson’s disease (PD), behavioural complications that can arise in association with dopaminergic treatment. Initially, the long-term outcome of ICBs was assessed, revealing that 58% of the patients remained symptomatic after 8 years of follow up. Reduction of dopaminergic treatment was effective in decreasing symptoms but did not guarantee long-term remission. The presence of ICBs was associated with depression and worse quality of life but it did not increase the risk of cognitive impairment. Compulsive sexual behaviour in PD was found to be more frequent in males and associated with multiple ICBs and higher doses of levodopa when compared to other ICBs. The outcome of patients with dopamine dysregulation syndrome (DDS) until death was investigated in a brain bank cohort showing that half of the patients remained symptomatic and that remission was associated with lower levodopa dose at death. Punding in PD was associated with higher impulsivity and worse frontal function compared to other ICBs. Apomorphine infusion was found to be less likely to trigger or worsen ICBs in PD patients than other dopamine agonists in a retrospective analysis. Automatic and voluntary saccadic eye movements of PD patients with ICBs (PD+ICB) were compared to PD patients without ICBs and healthy controls. PD+ICB had hypometric voluntary saccades and made a significantly higher number of direction errors in the anti-saccades task. Considering that ICBs are under-reported, this finding, if confirmed, could lead to the development of a novel way of identifying these abnormal behaviours. Lastly, brain tissue from 24 PD patients with DDS were assessed for alpha-synuclein, tyrosine hydroxylase, and dopamine D2 and D3 receptors protein levels. Lower levels of alpha-synuclein were found in the nucleus accumbens of patients with ICBs suggesting a central role for this structure in the pathophysiology of ICBs.

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