Cholinergic deficits and hallucinations in Parkinson disease

People with Parkinson disease frequently develop hallucinations. However, the underlying neurobiology remains poorly understood. This study investigated the relationship between cholinergic denervation and the presence, overall severity, and development of hallucinations in Parkinson disease. Parkinson disease participants ( N = 95) completed baseline vesicular acetylcholine transporter ([ 18 F]VAT) PET scans to measure cholinergic pathways and longitudinal clinical interviews to assess hallucinations. After controlling for age, sex, and duration since motor symptom onset, Parkinson disease participants with visual hallucinations ( N = 22) had less [ 18 F]VAT binding than those without visual hallucinations ( N = 40) in the thalamus, lateral occipital, precuneus, middle temporal, caudal middle frontal ( p < 0.05, 5% FDR) and pons, ventral diencephalon, fusiform, insular, and precentral cortices ( p < 0.05, 10% FDR). More severe hallucinations were associated with lower [ 18 F]VAT binding in subcortical, occipitoparietal, and middle frontotemporal regions. Finally, comparing those who did ( N = 17) and did not ( N = 20) develop visual hallucinations at follow-up, lower [ 18 F]VAT binding in the middle frontal ( p < 0.05, 5% FDR) and ventral diencephalon, thalamus, fusiform, insular, temporal, and precentral cortices ( p < 0.05, 10% FDR) predicted subsequent development of visual hallucinations. These findings implicate multifocal cortical and subcortical cholinergic deficits in the presence, severity, and development of hallucinations in Parkinson disease.