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

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 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.
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.



Doppler 2021

Figure. 11C-MeNER binding and its correlation with CAP metrics. Coronal section of averaged 11C-MeNER distribution volume ratio (DVR) of 13 healthy controls (HC, red border) and 27 Parkinson’s disease patients (PD, blue border) at the level of the dorsal brainstem as indicated on anatomical T1 image - images are levelled from 0.8 (dark blue) to 1.8 (red).


 
Publication:

Doppler, C. E. J., Smit, J. A. M., Hommelsen, M., Seger, A., Horsager, J, Kinnerup, M. B., Hansen, A. K., Fedorova, T. D., Knudsen, K., Otto, M., Nahimi, A., Borghammer, P., Sommerauer, M. (2021). Microsleep disturbances are associated with noradrenergic dysfunction in Parkinson's disease. Sleep, zsab040.


Correspondence to:

Dr. Christopher Doppler