Microsleep disturbances are associated with noradrenergic dysfunction in Parkinson’s disease
Open Access
- 20 February 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Sleep
- Vol. 44 (8)
- https://doi.org/10.1093/sleep/zsab040
Abstract
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. We analyzed 27 PD patients and 13 healthy control (HC) subjects who underwent overnight 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. 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. Sleep microstructure is more severely altered than sleep macrostructure in PD patients and is associated with widespread dysfunction of the noradrenergic arousal system.Keywords
Funding Information
- Lundbeck Foundation (6970)
- Danish Council for Independent Research, medical sciences (0602-02700)
- Aarhus University Research Foundation
- Danish Association of Parkinson’s Disease
- Swiss National Science Foundation (P2SKP3_161812)
- Hildegard Henssler-Stiftung
- University of Cologne (453/2018)
- University of Cologne
- Deutsche Forschungsgemeinschaft (FI 773/15-1)
- Else Kröner-Fresenius-Stiftung (2019_EKES.02)
This publication has 42 references indexed in Scilit:
- The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson’s diseaseBrain, 2013
- Challenges in the differentiation of midbrain raphe nuclei in neuroimaging researchProceedings of the National Academy of Sciences of the United States of America, 2012
- Cyclic alternating pattern (CAP): The marker of sleep instabilitySleep Medicine Reviews, 2012
- Systematic review of levodopa dose equivalency reporting in Parkinson's diseaseMovement Disorders, 2010
- Tuning arousal with optogenetic modulation of locus coeruleus neuronsNature Neuroscience, 2010
- Development of a Large-Scale Functional Brain Network during Human Non-Rapid Eye Movement SleepJournal of Neuroscience, 2010
- Sleep disorders and extrapyramidal diseases: an historical reviewSleep Medicine, 2004
- Atlas, rules, and recording techniques for the scoring of cyclic alternating pattern (CAP) in human sleepSleep Medicine, 2001
- Origin and Significance of the Cyclic Alternating Pattern (CAP): REVIEW ARTICLESleep Medicine Reviews, 2000
- The Nighttime Problems of Parkinsonʼs DiseaseClinical Neuropharmacology, 1988