Objective: In this follow-up study, we aimed to explore the temporal changes in brain acetylcholinesterase activity and cognitive function of iRBD patients.

Background: Isolated REM sleep behavior disorder (iRBD) is widely considered a prodromal phenotype of parkinsonism. Using ¹¹C-Donepezil PET, a marker of cholinergic function, we have previously reported the presence of reduced acetylcholinesterase activity in the cortex but not in the basal ganglia of iRBD patients with no cognitive deficits.

Method: Eleven polysomnography-confirmed iRBD patients with no clinical evidence of parkinsonism or cognitive deficits were scanned with ¹¹C-Donepezil PET twice over a 3-year period.
The Logan Reference Tissue model in the PXmod module of PMOD software 3.6 (PMOD technologies Ltd. Switzerland) was used to generate binding potential (BP_ND) images from the PET scans. The follow-up images were compared to the baseline images at a voxel level using Statistical Parametric Mapping (SPM12) (FIL Methods Group). Cognitive function was rated using Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Visual spatial ability was measured with a combined index of the visual spatial items from the MMSE and MoCA.

Results: SPM showed significant reductions (p < 0.04, FWE corrected) in acetylcholinesterase activity from baseline to follow-up across the study subjects in several cortical regions (the frontal, parietal and occipital lobes, and the left temporal lobe), but also in both thalami as well as striatal areas of both hemispheres.
No group decline was found of MMSE and MoCA scores on follow up. However, four patients individually showed a decline in MMSE scores, two in MoCA scores, and four in visual spatial scores. SPM showed that patients with MMSE decline had more widespread cortical cholinergic changes over time compared to patients with no MMSE decline (p < 0.05, FWE corrected). Additionally, patients with worsening in visual scores at follow-up had significant reduction of acetylcholinesterase activity in the left visual associative cortex (p < 0.05, FWE corrected).

Conclusion: Our results suggest that the severity and extent of cholinergic dysfunction in the brains of iRBD patients increase significantly over a 3-year period, and are more severe in patients who present a decline in MMSE score and visual skill scores.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/brain-cholinergic-dysfunction-in-patients-with-isolated-rem-sleep-behavior-disorder-a-clinical-and-11c-donepezil-pet-follow-up-study/