• Dieter Kunz, Sophia Stotz, Jan de Zeeuw, Alexandra Papakonstantinou, Susanne Dümchen, Martin Haberecht, Michail Plotkin, and Frederik Bes.
• Sleep Research & Clinical Chronobiology, Institute of Physiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany dieter.kunz@charite.de.
• J. Neurol. Neurosurg. Psychiatr. 2023 Jul 1; 94 (7): 532540532-540.

BackgroundIsolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a prodromal state of clinical α-synucleinopathies such as Parkinson's disease and Lewy body dementia. The lead-time until conversion is unknown. The most reliable marker of progression is reduced striatal dopamine transporter (DAT) binding, but low availability of imaging facilities limits general use. Our prospective observational study aimed to relate metrics of REM sleep without atonia (RWA)-a hallmark of RBD-to DAT-binding ratios in a large, homogeneous sample of patients with RBD to explore the utility of RWA as a marker of progression in prodromal α-synucleinopathies.MethodsDAT single-photon emission CT (SPECT) and video polysomnography (vPSG) were performed in 221 consecutive patients with clinically suspected RBD.ResultsvPSG confirmed RBD in 176 patients (162 iRBD, 14 phenoconverted, 45 non-synucleinopathies). Specific DAT-binding ratios differed significantly between groups, but showed considerable overlap. Most RWA metrics correlated significantly with DAT-SPECT ratios (eg, Montreal tonic vs most-affected-region: r=-0.525; p<0.001). In patients taking serotonergic/noradrenergic antidepressants or dopaminergic substances or with recent alcohol abuse, correlations were weaker, suggesting a confounding influence, unlike other possible confounders such as beta-blocker use or comorbid sleep apnoea.ConclusionsIn this large single-centre prospective observational study, we found evidence that DAT-binding ratios in patients with iRBD can be used to describe a continuum in the neurodegenerative process. Overlap with non-synucleinopathies and clinical α-synucleinopathies, however, precludes the use of DAT-binding ratios as a precise diagnostic marker. The parallel course of RWA metrics and DAT-binding ratios suggests in addition to existing data that RWA, part of the routine diagnostic workup in these patients, may represent a marker of progression. Based on our findings, we suggest ranges of RWA values to estimate whether patients are in an early, medium or advanced state within the prodromal phase of α-synucleinopathies, providing them with important information about time until possible conversion.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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