Visual hallucinations are a significant issue for many patients with Parkinson’s disease. A recent study published in the journal Brain reveals that these hallucinations are associated with a marked deficiency of cholinergic activity in specific regions of the brain, particularly the left ventral visual stream and the left superior temporal lobe. This research highlights the importance of cholinergic denervation in visual hallucinations, offering new insights into the underlying mechanisms and potential treatment options.
Parkinson’s disease is commonly associated with motor symptoms, but non-motor symptoms like visual hallucinations are also prevalent and can severely impact the quality of life. Approximately 25% of Parkinson’s patients experience visual hallucinations, which can become more common in the later stages of the disease. These hallucinations often involve seeing people or animals that are not present, adding to the disease’s complexity and burden.
Traditional views linked visual hallucinations to the side effects of dopaminergic treatments. However, recent studies suggest that dopaminergic stimulation alone does not fully explain these symptoms. Instead, researchers have proposed that deficiencies in the cholinergic system, which involves the neurotransmitter acetylcholine, may play a critical role. This study aimed to investigate the in vivo cholinergic activity in Parkinson’s patients, specifically comparing those with and without visual hallucinations, to better understand the neurochemical underpinnings of these symptoms.
“Visual hallucinations are an often under recognized problem in Parkinson’s disease. Very often they are considered be part of complications of long-term dopaminergic treatment, not resulting from underlying pathology. With this study, we wanted to assess whether presence of visual hallucinations in Parkinson’s disease is associated with cholinergic denervation and if so, which specific brain areas are involved,” explained study author Emile d’Angremont, a postdoctoral researcher at the Amsterdam University Medical Center
The research team studied 38 patients with Parkinson’s disease and 10 healthy controls. All participants underwent positron emission tomography (PET) scans using a tracer called [18F]FEOBV, which binds to the vesicular acetylcholine transporter, allowing visualization of cholinergic activity in the brain. Additionally, participants received a T1-weighted MRI scan and standardized assessments of psychotic symptoms and cognition.
Participants were divided into three groups: 13 patients who experienced visual hallucinations in the past month (VH+ group), 20 patients who never experienced visual hallucinations (VH- group), and five patients who had experienced hallucinations but not in the past month (excluded from the primary analysis).
The study revealed significant differences in cholinergic activity between Parkinson’s patients and healthy controls, as well as between patients with and without visual hallucinations.
Parkinson’s patients showed a widespread reduction in cholinergic activity compared to healthy controls. This reduction was most pronounced in the occipital lobe but extended to the parietal, temporal, and frontal lobes.
Patients experiencing visual hallucinations had significantly lower cholinergic activity in the left precuneus, left lingual gyrus, left fusiform gyrus, left inferior temporal gyrus, left middle and superior temporal gyri, and the left supramarginal gyrus compared to those without hallucinations.
These findings support the Perception and Attention Deficit (PAD) model, which suggests that visual hallucinations in Parkinson’s disease result from poor visual perception and impaired object attention, exacerbated by cholinergic hypoactivity. The results remained significant even after adjusting for cognitive scores, indicating that the observed cholinergic deficiencies were specifically related to the presence of visual hallucinations rather than general cognitive decline.
“It is likely that visual hallucinations in Parkinson’s disease are at least partly caused by cholinergic denervation, specifically in the ventral visual pathway and some brain areas related to attention,” d’Angremont told PsyPost. “These findings provides the neurochemical basis for treatment of visual hallucinations with cholinesterase inhibitors.”
Interestingly, the differences were predominantly observed in the left hemisphere of the brain. Previous studies have shown mixed results regarding hemispheric involvement in psychotic symptoms, with some suggesting left hemisphere dominance and others right hemisphere or bilateral involvement.
“We found that the differences in cholinergic tracer uptake between patients with and without hallucinations were particularly prominent in the left hemisphere,” d’Angremont said. “This was not expected and we are also unsure how to interpret this finding.”
This study, while insightful, has some limitations, including a small sample size that may limit the generalizability of the findings and potential confounding due to the more advanced disease stage in the hallucinating group. Future research could validate these findings in larger, more diverse populations, consider the role of visual acuity, and explore treatments targeting cholinergic deficiencies, such as cholinesterase inhibitors, to manage visual hallucinations in Parkinson’s disease.
“My long-term goal for this line of research to personalize Parkinson care,” d’Angremont explained. “In the future, we hope to be able to use a cholinergic biomarker, such as the PET tracer applied in this study, to identify patients who will benefit from treatment with cholinesterase inhibitors.”
The study, “Cholinergic deficiency in Parkinson’s disease patients with visual hallucinations,” was authored by Emile d’Angremont, Sygrid van der Zee, Sofie Slingerland, Anne C. Slomp, Erik F. J. de Vries, Teus van Laar, and Iris E. Sommer.
