Wickens_2026_Parkinsonism.Relat.Disord_144_108226

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of alpha-synucleinopathy such as Parkinson's disease (PD). Brain cholinergic alterations have been reported in these diseases, but direct comparisons of terminal density between iRBD and clinically manifest PD have not yet been performed. OBJECTIVES: To assess brain cholinergic terminal density in iRBD using positron emission tomography (PET) with [(18)F]-fluoroethoxybenzovesamicol (FEOBV), and to compare findings with both healthy controls and patients with PD. METHODS: Forty-six participants (16 with polysomnography-confirmed iRBD, 12 with PD, and 18 controls) underwent high-resolution PET neuroimaging with FEOBV. Voxel-wise analyses and effect size mapping were conducted to compare the groups, using standardized uptake value ratios (SUVRs). Correlations were performed between whole-cortex SUVR and clinical measures. RESULTS: Compared to controls, both the iRBD and PD groups exhibited significant cortical cholinergic denervation of similar magnitudes (11-12 %). Effect size mapping revealed very large losses (Cohen's ds < -1.5) in the posterior cortex in both patient groups, predominantly occipital-parietal in iRBD and occipital-temporal in PD. In iRBD, lower cortical uptake was associated with poorer performance on executive and visuospatial tests. Moreover, in iRBD but not in PD, there was a trend toward higher FEOBV uptake in subcortical areas, including brainstem regions. CONCLUSIONS: Cholinergic denervation in iRBD is comparable in extent to that in PD, with subtle topographic distinctions, and correlates with cognitive deficits.