Cholinergic imaging in GBA1 Parkinson's disease
Parkinson’s disease is a common brain disorder that causes not only movement problems, but also a range of non-motor symptoms. Approximately 15% of people with Parkinson’s disease in the Netherlands carry a variant in the GBA1-gene. On average, these patients have a faster and more severe disease course and a higher risk of cognitive decline, including difficulties with thinking and memory.
This thesis of Sofie Slingerland investigates the role of the cholinergic system, a network of nerve cells in the brain that contributes to cognitive functioning. Using a specialised PET scan with the tracer ¹⁸F-FEOBV, cholinergic innervation in the brain was studied in people with Parkinson’s disease with and without a GBA1 variant. Cognitive performance, the dopaminergic system and the activity of the enzyme glucocerebrosidase (GCase) were also investigated. GCase is an enzyme that plays an important role in lysosomes, the ‘recycling systems’ of cells. In people with a GBA1 variant, the activity of this enzyme is often reduced.
The results show that people with GBA1-associated Parkinson’s disease have more pronounced cholinergic abnormalities early in the course of the disease than people without a GBA1 variant. These abnormalities were found in several brain regions involved in cognitive functioning. Patients carrying a GBA1 variant also performed less well on measures of attention and executive functioning.
These findings suggest that the cholinergic system plays an important role in the characteristic clinical course of GBA1-associated Parkinson’s disease. The results provide a basis for future research into treatments that may help prevent or slow cognitive decline.