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Impaired cerebral microcirculation in isolated REM sleep behaviour disorder

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DOI

  • Simon F Eskildsen
  • Alex Iranzo, Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
  • ,
  • Morten G Stokholm
  • Kristian Stær
  • Karen Østergaard, Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Mónica Serradell, Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
  • ,
  • Marit Otto
  • Kristina B Svendsen
  • Alicia Garrido, Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
  • ,
  • Dolores Vilas, Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
  • ,
  • Per Borghammer
  • Joan Santamaria, Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
  • ,
  • Arne Møller, Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark., Orthopaedic Research Unit, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus N, Denmark.
  • ,
  • Carles Gaig, Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
  • ,
  • David J Brooks
  • Eduardo Tolosa, Department of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
  • ,
  • Leif Østergaard
  • Nicola Pavese

During the prodromal period of Parkinson's disease and other α-synucleinopathy-related parkinsonisms, neurodegeneration is thought to progressively affect deep brain nuclei, such as the locus coeruleus, caudal raphe nucleus, substantia nigra, and the forebrain nucleus basalis of Meynert. Besides their involvement in the regulation of mood, sleep, behaviour, and memory functions, these nuclei also innervate parenchymal arterioles and capillaries throughout the cortex, possibly to ensure that oxygen supplies are adjusted according to the needs of neural activity. The aim of this study was to examine whether patients with isolated REM sleep behaviour disorder, a parasomnia considered to be a prodromal phenotype of α-synucleinopathies, reveal microvascular flow disturbances consistent with disrupted central blood flow control. We applied dynamic susceptibility contrast MRI to characterize the microscopic distribution of cerebral blood flow in the cortex of 20 polysomnographic-confirmed patients with isolated REM sleep behaviour disorder (17 males, age range: 54-77 years) and 25 healthy matched controls (25 males, age range: 58-76 years). Patients and controls were cognitively tested by Montreal Cognitive Assessment and Mini Mental State Examination. Results revealed profound hypoperfusion and microvascular flow disturbances throughout the cortex in patients compared to controls. In patients, the microvascular flow disturbances were seen in cortical areas associated with language comprehension, visual processing and recognition and were associated with impaired cognitive performance. We conclude that cortical blood flow abnormalities, possibly related to impaired neurogenic control, are present in patients with isolated REM sleep behaviour disorder and associated with cognitive dysfunction. We hypothesize that pharmacological restoration of perivascular neurotransmitter levels could help maintain cognitive function in patients with this prodromal phenotype of parkinsonism.

Original languageEnglish
JournalBrain : a journal of neurology
ISSN0006-8950
DOIs
Publication statusE-pub ahead of print - 20 Apr 2021

Bibliographical note

© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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