In vivo assessment of brain neurotransmitter

In vivo assessment of brain neurotransmitter dysfunction and microglial activation in patients with REM sleep behavior disorder as early markers of Parkinsonian disorders

Project title
In vivo assessment of brain neurotransmitter dysfunction and microglial activation in patients with REM sleep behavior disorder as early markers of Parkinsonian disorders

Grant holder
Associate Professor Nicola Pavese, Dept. of Nuclear Medicine & PET Centre, Aarhus University

Project description
Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by abnormal or disruptive behaviors emerging during normally atonic rapid eye movement sleep. There is growing evidence indicating that RBD is highly associated with alpha-synucleinopathies such as Parkinson’s disease (PD) and Multiple System Atrophy (MSA) and it has been suggested that it may represent the first feature of neurodegeneration and, therefore, an early marker of these disorders.  In fact, several studies have shown that more than 50% of the subjects diagnosed with RBD will develop PD or another neurodegenerative disease within a time span of 5 -12 years.  Serial SPECT scans have shown progressive nigrostriatal dysfunction before the onset of parkinsonism in RBD patients.

In this international project, which involves Aarhus University, Barcelona University and Imperial College London, we will use PET imaging to explore functional changes in RBD patients that could represent the earliest pathological events of PD. In particular, we will use 11C-PK11195 PET to detect early inflammation in RBD patients and its temporal relationship to striatal and extrastriatal dysfunction. A better understanding of the extent of microglia activation in RBD and its role in driving synucleinopathies is crucial as microglia modulating agents begin to be available. We will also use 18F-dopa PET, a marker of monoaminergic function and 11C-donepezil PET, a marker of acetylcholine esterase activity to shed light on temporal relationship between dopaminergic and non-dopaminergic degeneration in PD.

Project design
Twenty polysomnography-confirmed RBD patients with no clinical evidence of parkinsonism (age 45−85 years; M/F) will be recruited in this cross-sectional study. In order to make meaningful interpretation of the data obtained from RBD patients, a group of 10 PD patients and control group of 10 age-matched normal subjects for each PET tracer will also be investigated.

PET will be performed at the Nuclear Medicine Department & PET Centre at Aarhus University Hospital. The study consists of 3 visits that will be performed on 3 separate days.


Project Status
Recruitment of PhD student
Submittal of ethical application
Planning of logistics with Spanish collaborators

Project staff
Chief Investigator: Associate Professor Nicola Pavese, Aarhus University
Co-investigators: Professor  Karen Østergaard, Dr Kristina Bacher Svendsen, Dr  Marit Otto, Professor David J Brooks, Dr Arne Møller , Dr Per Borghammer.
International Co-investigators: Dr Alex Iranzo, Prof Edoardo Tolosa, Barcelona
PhD student: To be recruited
Administrator: Anne Sofie Møller Andersen

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