Investigating factors associated with impulse control behaviours in Parkinson’s disease

Hall, Alison (2023). Investigating factors associated with impulse control behaviours in Parkinson’s disease. University of Birmingham. Ph.D.

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Abstract

Destructive behaviours resulting from impaired impulse control can manifest in patients with Parkinson’s disease (PD), more commonly in those who take dopamine agonist (DA) medication. 14-40% of those who take such medication develop these behaviours, known as impulse control behaviours (ICBs). There are risk factors associated with the presence or development of ICBs, including higher agonist dosage, longer duration of treatment, greater severity of motor symptoms, apathy and autonomic and cognitive functions. However, there is currently no clear, reliable procedure or test to predict who is most likely to develop these ICBs. This thesis investigated novel factors which may be associated with the incidence, frequency and change over time of ICBs, with the intention to provide the first steps towards future prediction and prevention of ICB development.

The most important results from this project highlight the potential predictive power of a dopamine genetic risk score (DGRS) for PD patients on DA medication who suffer from ICBs. The DGRS theoretically quantifies central dopamine neurotransmission within MCL regions which are implicated in impulse control. Some of the results in this thesis mirrored the inverted-U relationship between impulse control and dopamine previously reported, where PD patients with lower dopamine neurotransmission displayed worse impulse control and PD patients with higher dopamine neurotransmission displayed worsening impulse control over time. Moreover, lab-based behavioural impulsivity task performance was also associated with ICBs in PD patients on DA medication. We first confirmed that impulsive behaviour measured by the anticipatory response inhibition task was a valid measure of non-selective inhibition network activity. We then found that greater impulsive behaviour on the Balloon Analogue Risk Task (BART), was associated with higher ICB frequency. We also found preliminary evidence that greater impulsive behaviour determined by the BART and Gambling task, measuring cognitive and limbic impulsivity, was associated with the DGRS in a young healthy sample. Finally, a possible relationship was observed between high concentrations of the metabolite of dopamine, homovanillic acid (HVA), and a high DGRS, in a young healthy cohort. It is possible that HVA could be important in confirming the DGRS theoretical quantification of central dopamine neurotransmission.

The results in this thesis replicate some important outcomes already reported in the literature and this work also presents several exciting novel findings. Collectively, this body of work highlights that a cumulative genetic score (DGRS) and behavioural impulsivity task measures are associated with ICBs in PD. The results presented provide insight for future investigations to perhaps predict which PD patients who take DA medication are most likely to develop ICBs.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):