Possible Contribution of Altered Cholinergic Activity in the Visual Cortex in Visual Hallucinations in Parkinson’s Disease

Introduction
Up to 1/3 of patients with Parkinson’s disease (PD) experience visual hallucinations (VH). Lewy bodies are sparse in the visual cortices and seem unlikely to explain the hallucinations. Some neuroimaging studies have found that perfusion is reduced in the occipital lobe in those with VH. Recent work suggested that decreased cholinergic input may directly lead to the decreased perfusion.
We hypothesised that individuals with Parkinson’s disease and visual hallucinations would have biochemical evidence of reduced microvascular perfusion and reduced cholinergic activity in areas of the brain which process visual images.
Methods
We obtained Brodmann area (BA) 18 and BA19 tissue from a well characterised cohort matched for age, gender and post-mortem interval: 11 individuals with PD but not VH (PD-VH), 26 with PD+VH and 32 controls. Von Willebrand factor, vascular endothelial growth factor-A (VEGF), myelin-associated glycoprotein:proteolipid protein-1 (MAG:PLP1) ratio–a measure of tissue oxygenation relative to metabolic demand, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), choline acetyltransferase (ChAT) and α-synuclein were quantified by ELISA. MAG:PLP1 was the primary outcome.
Results
There was no biochemical evidence of chronic hypoperfusion in PD, although microvessel density was decreased in ventral BA18 & BA19. There was no between-group difference in BChE in either dorsal BA18 or BA19. AChE concentration was reduced in PD relative to controls, in dorsal and ventral BA18 and dorsal BA19, and increased in ventral BA19. These changes were most marked in PD+VH.
Conclusion
Our results suggest that changes in cholinergic activity rather than chronic hypoperfusion may underlie visual hallucinations in PD.