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Microsleep disturbances are associated with noradrenergic dysfunction in Parkinson's disease

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DOI

  • Christopher E J Doppler, Department of Cardiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Heart Center Cologne, Cologne, Germany.
  • ,
  • Julia A M Smit, Department of Cardiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Heart Center Cologne, Cologne, Germany.
  • ,
  • Maximilian Hommelsen, Forschungszentrum Jülich
  • ,
  • Aline Seger, Department of Cardiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Heart Center Cologne, Cologne, Germany.
  • ,
  • Jacob Horsager
  • Martin B Kinnerup
  • Allan K Hansen, Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark; and., 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.
  • ,
  • Tatyana D Fedorova
  • Karoline Knudsen
  • Marit Otto
  • Adjmal Nahimi
  • Per Borghammer
  • Michael Sommerauer, University Hospital of Cologne, Cologne, Germany., Department of Cardiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Heart Center Cologne, Cologne, Germany., Rheinisches Institut für Umweltforschung an der Universität zu Köln, Aachener Strasse 209, 50931, Köln, Germany, Forschungszentrum Jülich, Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark; and., 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.

STUDY OBJECTIVES: Parkinson's disease (PD) commonly involves degeneration of sleep-wake regulating brainstem nuclei; likewise, sleep-wake disturbances are highly prevalent in PD patients. As polysomnography macroparameters typically show only minor changes in PD, we investigated sleep microstructure, particularly cyclic alternating pattern (CAP), and its relation to alterations of the noradrenergic system in these patients.

METHODS: We analysed 27 PD patients and 13 healthy control (HC) subjects who underwent over-night polysomnography and 11C-MeNER positron emission tomography for evaluation of noradrenaline transporter density. Sleep macroparameters as well as CAP metrics were evaluated according to the consensus statement from 2001. Statistical analysis comprised group comparisons and correlation analysis of CAP metrics with clinical characteristics of PD patients as well as noradrenaline transporter density.

RESULTS: PD patients and HC subjects were comparable in demographic characteristics (age, sex, body mass index) and polysomnography macroparameters. CAP rate as well as A index differed significantly between groups, with PD patients having a lower CAP rate (46.7 ± 6.6% versus 38.0 ± 11.6%, p = 0.015) and lower A index (49.0 ± 8.7/hour versus 40.1 ± 15.4/hour, p = 0.042). In PD patients, both CAP metrics correlated significantly with diminished noradrenaline transporter density in arousal prompting brainstem nuclei (locus coeruleus, raphe nuclei) as well as arousal propagating brain structures like thalamus and bitemporal cortex.

CONCLUSIONS: Sleep microstructure is more severely altered than sleep macrostructure in PD patients and is associated with widespread dysfunction of the noradrenergic arousal system.

Original languageEnglish
JournalSleep
ISSN0161-8105
DOIs
Publication statusE-pub ahead of print - 20 Feb 2021

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