The Hypocholinergic Parkinsonian Brain: the link to psychosis and the quest for a biomarker

Parkinson's disease is a highly complex and heterogeneous brain disorder. In addition to typical symptoms such as tremors and muscle stiffness, there are also many non-motor symptoms, including cognitive decline and even hallucinations and delusions. This thesis describes the relationship between the presence of visual hallucinations in Parkinson's disease and a deficiency of the neurotransmitter acetylcholine. We also discuss the beneficial effects of cholinesterase inhibitors (medications that increase acetylcholine levels) on the presence of hallucinations and delusions in both Parkinson's and Alzheimer's disease. In the second part of this thesis, we explore possible methods for detecting a potential acetylcholine deficiency in individual patients. A method using magnetic stimulation (short-latency afferent inhibition) appears suboptimal for this purpose. However, a specific type of PET scan, combined with the appropriate statistical methods, shows promising results. Using this, we were able to identify certain brain patterns associated with decline in various cognitive domains. Finally, we investigate the value of MRI in this research. Functional MRI, in particular, might be a good alternative to the expensive PET scan, although further research is needed.