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Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion
Miriam H Terkelsen1,2, Alex Iranzo3,4,5, Mónica Serradell3,5
1Department of Nuclear Medicine and PET, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Patients with isolated rapid eye movement sleep behaviour disorder (iRBD) who show reduced parietal cortex 11C-donepezil uptake are at higher risk for phenoconversion to synucleinopathies. Dopaminergic dysfunction also predicts progression.
Area of Science:
- Neuroscience
- Neurology
- Sleep Medicine
Background:
- Most patients with isolated rapid eye movement sleep behaviour disorder (iRBD) eventually develop parkinsonian alpha-synucleinopathies.
- The rate of phenoconversion varies significantly among iRBD patients.
Purpose of the Study:
- To determine if cholinergic and dopaminergic dysfunction in iRBD patients predict phenoconversion.
- Investigate the association between neurochemical deficits and the progression to synucleinopathies.
Main Methods:
- Utilized positron emission tomography (PET) with 11C-donepezil (cholinergic) and 18F-DOPA (dopaminergic) in 21 iRBD patients.
- Monitored patients for up to 8 years for phenoconversion to Parkinson's disease or dementia with Lewy bodies.
- Analyzed PET data using linear and Cox regression, comparing low and high tracer uptake groups.
Main Results:
- Eight of 17 followed patients progressed to synucleinopathy.
- Phenoconverters showed significantly lower 11C-donepezil uptake in cortical regions (parietal, frontal) and thalamus compared to non-converters.
- Lower 18F-DOPA uptake in the putamen was observed in all phenoconverters.
- Low parietal 11C-donepezil uptake increased phenoconversion rate 13.46-fold (p=0.023).
Conclusions:
- Cortical cholinergic dysfunction, especially in the parietal cortex, may serve as a biomarker for predicting short-term phenoconversion in iRBD.
- Findings support previous research linking dopaminergic dysfunction to impending phenoconversion in iRBD.
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