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Impaired cerebral microcirculation in isolated rapid eye movement sleep behaviour disorder

Lookup NU author(s): Professor David BrooksORCiD, Professor Nicola PaveseORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


During the prodromal period of Parkinson’s disease and other alpha-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 rapid eye movement sleep behaviour disorder, a parasomnia that is considered to be a prodromal phenotype of alpha-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 rapid eye movement 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 rapid eye movement sleep behaviour disorder and associated with cognitive dysfunction. We hypothesise that pharmacological restoration of perivascular neurotransmitter levels could help maintain cognitive function in patients with this prodromal phenotype of parkinsonism.

Publication metadata

Author(s): Eskildsen SF, Iranzo A, Stokholm MG, Stær K, Østergaard K, Serradell M, Otto M, Svendsen KB, Garrido A, Vilas D, Borghammer P, Santamaria J, Møller A, Gaig C, Brooks DJ, Tolosa E, Østergaard L, Pavese N

Publication type: Article

Publication status: Published

Journal: Brain

Year: 2021

Volume: 144

Issue: 5

Pages: 1498-1508

Print publication date: 01/05/2021

Online publication date: 20/04/2021

Acceptance date: 09/12/2020

Date deposited: 09/12/2020

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

Publisher: Oxford University Press


DOI: 10.1093/brain/awab054


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Funder referenceFunder name
Independent Research Fund Denmark and Instituto de Salud Carlos III (Spain)