Objective: To investigate the relationship between cholinergic system changes, as measured by vesicular acetylcholine transporters (VAChT) [¹⁸F] fluoroethoxybenzovesamicol ([¹⁸F] FEOBV) binding in PET, and cognitive performance, measured as visual choice reaction time (VCRT) in person with Parkinson’s disease (PD). We hypothesized that lower cholinergic availability in specific brain regions would correlate with slower and less accurate VCRT.

Background: Reduced cholinergic activity has been implicated in PD-related cognitive decline. [¹⁸F]FEOBV PET imaging allows for the quantification of VAChT availability, while VCRT serves as a measure of cognitive processing speed and decision-making.

Method: Brain imaging studies using [¹⁸F]-FEOBV PET and MRI were conducted on 23 patients with PD (6F/17M; age 68.56±5.60, disease duration 6.09±4.40, MDS-UPDRS-III scores 44.10±14.80, HY 2.35±0.44). Subsequently, participants performed a standardized VCRT task. Participants were asked to stand on a gaming mat with arrows on it and respond to visual stimuli presented on a television screen by pressing corresponding arrow on the mat with their foot. They were given a short practice round to familiarize themselves with the task and were directed to correct any errors, which were indicated by an incorrect tone, as quicky as they could. We measured the reaction time as the mean time required to complete each visual stimulus correctly. Voxel-wise regression analyses were performed using SPM12 to assess the relationship between VAChT binding and VCRT performance.

Results: We observed a lower VAChT binding in various cortical and subcortical regions, particularly in the anterior to mid cingulum, left more than right peri-central/SMA regions, and left insula (figure 1; p<0.001;FDR-corrected). No significant associations were found for visual cortical striata, and cerebellar regions and very limited for the thalamus.

Conclusion: The findings indicate that central cholinergic neurotransmission based on VAChT [¹⁸F]FEOBV PET imaging, is significantly linked to lower limb stepping VCRT performance, especially in sensorimotor and paralimbic structures. The anterior cingulum and insula play a role in attentional processing, whereas the mid cingulum plays a role in cognitive control, sensory processing, and movement execution.

Figure 1

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MDS Abstracts - https://www.mdsabstracts.org/abstract/decreased-cholinergic-activity-in-specific-brain-regions-associated-with-slower-lower-limb-visual-choice-reaction-time-in-parkinsons-disease-a-18f-feobv-pet-study/