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Extrastriatal monoaminergic dysfunction and enhanced microglial activation in idiopathic rapid eye movement sleep behaviour disorder

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  • Morten Gersel Stokholm
  • Alex Iranzo, Department of Neurology, Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain; Multidisciplinary Sleep Unit, Hospital Clinic, Barcelona, Spain.
  • ,
  • Karen Østergaard
  • ,
  • Mónica Serradell, Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
  • ,
  • Marit Otto
  • Kristina Bacher Svendsen
  • Alicia Garrido, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain; Parkinson disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Catalonia, Spain.
  • ,
  • Dolores Vilas, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain; Parkinson disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Catalonia, Spain.
  • ,
  • Peter Parbo
  • Per Borghammer
  • Joan Santamaria, Department of Neurology, Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain; Multidisciplinary Sleep Unit, Hospital Clinic, Barcelona, Spain.
  • ,
  • Arne Møller
  • Carles Gaig, Department of Neurology, Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain; Multidisciplinary Sleep Unit, Hospital Clinic, Barcelona, Spain.
  • ,
  • David J Brooks
  • Eduardo Tolosa, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain; Parkinson disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Catalonia, Spain.
  • ,
  • Nicola Pavese

Background: The majority of patients diagnosed with idiopathic rapid eye movement sleep behaviour disorder (iRBD) progress over time to a Lewy-type α-synucleinopathy such as Parkinson's disease or dementia with Lewy bodies. This in vivo molecular imaging study aimed to investigate if extrastriatal monoaminergic systems are affected in iRBD patients and if this coincides with neuroinflammation. Methods: We studied twenty-one polysomnography-confirmed iRBD patients with 18F-DOPA and 11C-PK11195 positron emission tomography (PET) to investigate extrastriatal monoaminergic function and microglial activation. Twenty-nine healthy controls (n = 9 18F-DOPA and n = 20 11C-PK11195) were also investigated. Analyses were performed within predefined regions of interest and at voxel-level with Statistical Parametric Mapping. Results: Regions of interest analysis detected monoaminergic dysfunction in iRBD thalamus with a 15% mean reduction of 18F-DOPA Ki values compared to controls (mean difference = −0.00026, 95% confidence interval [−0.00050 to −0.00002], p-value = 0.03). No associated thalamic changes in 11C-PK11195 binding were observed. Other regions sampled showed no 18F-DOPA or 11C-PK11195 PET differences between groups. Voxel-level interrogation of 11C-PK11195 binding identified areas with significantly increased binding within the occipital lobe of iRBD patients. Conclusion: Thalamic monoaminergic dysfunction in iRBD patients may reflect terminal dysfunction of projecting neurons from the locus coeruleus and dorsal raphe nucleus, two structures that regulate REM sleep and are known to be involved in the early phase of PD. The observation of significantly raised microglial activation in the occipital lobe of these patients might suggest early local Lewy-type α-synuclein pathology and possibly an increased risk for later cognitive dysfunction.

Original languageEnglish
JournalNeurobiology of Disease
Volume115
Pages (from-to)9-16
Number of pages8
ISSN0969-9961
DOIs
Publication statusPublished - Jul 2018

    Research areas

  • C-PK11195, Dementia with Lewy bodies, F-DOPA, Idiopathic rapid-eye-movement sleep behaviour disorder, PD, Positron emission tomography

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