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The following is a summary of “Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion,” published in the October 2024 issue of Neurology by Terkelsen et al.
Most individuals with isolated rapid eye movement (REM) isolated rapid eye movement sleep behavior disorder (iRBD) develop parkinsonian alpha-synucleinopathies, such as Parkinson’s disease (PD) or dementia with Lewy bodies, though the time to phenoconversion varies widely.
Researchers conducted a retrospective study investigating if cholinergic and dopaminergic dysfunction were linked to phenoconversion in individuals with iRBD.
They studied 21 patients with polysomnography-confirmed iRBD using baseline positron emission tomography (PET) with 2 tracers, 11C-donepezil and 6-Fluoro-(18F)-l-3,4-dihydroxyphenylalanine (18F-DOPA). Patients were monitored for phenoconversion over 8 years. The PET images were analyzed based on diagnoses after 3 and 8 years using linear regression, and time-to-event analysis was conducted via Cox regression, comparing high and low tracer uptake groups.
The results showed follow-up of 17 patients, with 8 phenoconverting to either PD (n = 4) or dementia with Lewy bodies (n = 4) while 9 remained non-phenoconverters. After 8 years, phenoconverters had lower mean 11C-donepezil uptake in the parietal (P=0.032) and frontal cortex (P=0.042), while after 3 years, phenoconverters had lower uptake in the parietal cortex (P=0.005), frontal cortex (P=0.025), thalamus (P=0.043), and putamen (P=0.049). Both 3- and 8-year phenoconverters had significantly lower 18F-DOPA uptake in the putamen (P<0.001). Patients with low parietal 11C-donepezil uptake had a 13.46 times higher rate of phenoconversion (95% CI 1.42;127.21) than those with higher uptake (P=0.023). Those with low 18F-DOPA uptake in the most affected putamen were all phenoconverters (P=0.0002).
They concluded that cortical cholinergic dysfunction, especially in the parietal cortex, may serve as a biomarker for short-term phenoconversion in patients with iRBD, aligning with prior evidence linking dopaminergic dysfunction to phenoconversion.
Source: onlinelibrary.wiley.com/doi/full/10.1111/ene.16503
