Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

Miglis, Mitchell G.; Adler, Charles H.; Antelmi, Elena; Arnaldi, Dario; Baldelli, Luca; Boeve, Bradley F.; Cesari, Matteo; Dall'Antonia, Irene; Diederich, Nico J.; Doppler, Kathrin; Dušek, Petr; Ferri, Raffaele; Gagnon, Jean François; Gan‐Or, Ziv; Hermann, W.; Högl, Birgit; Hu, Michele T.M.; Iranzo, Álex; Janzen, Annette; Kuzkina, Anastasia; Lee, Jee Young; Leenders, Klaus L.; Lewis, Simon J.G.; Liguori, Claudio; Liu, Jun; Lo, Christine; Martens, Kaylena A. Ehgoetz; Nepožitek, Jiří; Plazzi, Giuseppe; Provini, Federica; Puligheddu, Monica; Rolinski, Michal; Rusz, Ján; Stefani, Ambra; Summers, Rebekah L.S.; Yoo, Dallah; Zitser, Jennifer; Oertel, Wolfgang H.

doi:10.1016/s1474-4422(21)00176-9

Cited by 126 publications

(108 citation statements)

References 110 publications

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“…According to a latest review by Galbiati, the average conversion rate from isolated/idiopathic RBD to an overt neurodegenerative syndrome was 33.5% at 5 years follow-up, 82.4% at 10.5 years and 96.6% at 14 years [ 31 ]. Besides, many biomarkers of neurodegeneration have been reported to be associated with isolated RBD, ranging from neurophysiology, cognitive decline, neuroimaging findings, motor dysfunction to autonomic impairment [ 32 ]. For instance, a wearable-based, real-world gait monitoring study has detected reduced gait velocity, variability, and rhythm in RBD patients compared with their age-matched controls [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…The presence of more axial symptoms, freezing gait, and akinetic-rigid subtype in PD patients with RBD also verified this kind of speculation [ 37 – 39 ]. On the other hand, autonomic symptoms encompassing orthostatic hypotension (OH) is also common in RBD patients [ 32 ] while OH has been well-recognized to pose high risk of falls among older adults [ 40 ]. According to Pilotto’s systematic review, numerous studies suggested a closely linked diad of OH and RBD among PD patients while the OH-RBD cluster generally induced increased postural sway in standing and more severe impairment of static balance [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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The influence of probable rapid eye movement sleep behavior disorder and sleep insufficiency on fall risk in a community-dwelling elderly population

Han

Chan

2021

BMC Geriatr

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Background The objective was to investigate the individual effect and potential interactions of probable rapid eye movement sleep behavior disorder (pRBD) and sleep insufficiency on fall risk among a Chinese elderly population. Methods Community-dwelling population aged 55 years or above were recruited from the Beijing Longitudinal Study on Aging II cohort from 2010 to 2011. Odds ratio (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression models. Multiplicative and additive interactions between pRBD and sleep insufficiency were examined using likelihood ratio tests and relative excess risk due to interaction (RERI), respectively. Results Among 6891 included participants, 479 experienced at least once fall. pRBD and sleep insufficiency were both independently associated with elevated fall risk. Compared to the elderly without pRBD or sleep insufficiency, pRBD and sleep insufficiency was each associated with a 2.57-fold (OR = 2.57, 95%CI: 1.46–4.31) and 1.45-fold (OR = 1.45, 95%CI: 1.11–1.88) risk of falls individually, while their coexistence was associated with a less-than-additive 17% (OR = 1.17, 95%CI: 0.43–2.63) increased risk of falls. The combination of these two factors demonstrated evidence of a negative interaction on both multiplicative (ratio of ORs = 0.31, 95%CI: 0.10, 0.86) and additive (RERI = − 1.85, 95%CI: − 3.61, − 0.09) scale. Conclusions Our study has provided robust evidence for the adverse effect of pRBD and sleep insufficiency, as well as their negative interaction on increasing fall risk in a Chinese elderly population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The influence of probable rapid eye movement sleep behavior disorder and sleep insufficiency on fall risk in a community-dwelling elderly population

Han

Chan

2021

BMC Geriatr

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“…Aside from the neurophysiological characteristics of RBD described above, several other features are now being evaluated for consideration as markers of the disease and possibly its evolution to neurodegeneration. However, not all markers seem to have a prognostic value (although some have a role in the diagnosis of RBD) in the monitoring of its progression in severity and response to therapy or in a combination of these roles [ 8 ].…”

Section: Role Of Neurophysiological Assessment In the Study Of Rbdmentioning

confidence: 99%

“…The polysomnographic (PSG) hallmark of RBD is decreased muscle atonia during REM sleep, also called REM sleep without atonia (RSWA), because of increased electromyographic (EMG) activity during this stage, and this is a feature essential for the diagnosis of this condition, which is thus based on both clinical and laboratory findings [ 1 ]. The search for reliable biomarkers of RBD and its evolution into an overt synucleinopathy is a very lively field of interest, with many studies being published [ 8 ]. However, RSWA remains the most important neurophysiological aspect, being necessary for the diagnosis of RBD [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Neurophysiological Aspects of REM Sleep Behavior Disorder (RBD): A Narrative Review

et al. 2021

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REM sleep without atonia (RSWA) is the polysomnographic (PSG) hallmark of rapid eye movement (REM) sleep behavior disorder (RBD), a feature essential for the diagnosis of this condition. Several additional neurophysiological aspects of this complex disorder have also recently been investigated in depth, which constitute the focus of this narrative review, together with RSWA. First, we describe the complex neural network underlying REM sleep and its muscle atonia, focusing on the disordered mechanisms leading to RSWA. RSWA is then described in terms of its polysomnographic features, and the methods (visual and automatic) currently available for its scoring and quantification are exposed and discussed. Subsequently, more recent and advanced neurophysiological features of RBD are described, such as electroencephalography during wakefulness and sleep, transcranial magnetic stimulation, and vestibular evoked myogenic potentials. The role of the assessment of neurophysiological features in the study of RBD is then carefully discussed, highlighting their usefulness and sensitivity in detecting neurodegeneration in the early or prodromal stages of RBD, as well as their relationship with other proposed biomarkers for the diagnosis, prognosis, and monitoring of this condition. Finally, a future research agenda is proposed to help clarify the many still unclear aspects of RBD.

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“…Aus diesem Grund ist die Entwicklung reliabler Biomarker zur frühzeitigen Detektion der Synukleinopathien im sehr frühen (präklinischen) bis frühen nonmotorischen (prodromalen) Erkrankungsstadien ein wachsendes Forschungsfeld. Unter den letzteren ist hier insbesondere die REM-Schlaf-Verhaltensstörung (RBD) als Kandidat für zukünftige neuroprotektive Therapiestudien zu nennen [ 11 , 15 , 22 ].…”

Section: Natürlicher Erkrankungsverlauf Und üBerlegungen Zur Therapieentwicklungunclassified

Neuroprotektive Therapien bei idiopathischen, genetischen und atypischen Parkinson-Syndromen mit α-Synuklein – Pathologie

et al. 2021

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ZusammenfassungKernpunkt der Klassifikation neurodegenerativer Erkrankungen ist der histopathologische Nachweis von Ablagerungen bestimmter Proteine im Gehirn. Hierbei unterscheiden sich die verschiedenen Krankheitsentitäten sowohl hinsichtlich der Art der nachweisbaren Proteine als auch hinsichtlich der Konfiguration und Lokalisation der entsprechenden Proteinaggregate. Gemeinsames Kernmerkmal der als Synukleinopathien zusammengefassten Erkrankungen sind Ablagerungen des Proteins α‑Synuklein (ASYN). Die bekanntesten Erkrankungen dieses Spektrums sind die Parkinson-Krankheit (PK) mit neuronalem Nachweis von Lewy-Körperchen, die Demenz vom Lewy-Körper-Typ (DLK) mit zusätzlichem Nachweis von β‑Amyloid-Ablagerungen sowie die seltene Multisystematrophie (MSA) mit glialem Nachweis sog. Papp-Lantos-Körperchen. Da neben der diagnostischen mittlerweile auch die zentrale pathophysiologische Bedeutung des ASYN erwiesen ist, fokussiert sich die Entwicklung neuer Therapien aktuell auf die Beeinflussung der toxischen Wirkung dieses Proteins. Die verschiedenen Therapiekonzepte lassen sich grob in sechs Gruppen zusammenfassen: 1. die Verringerung der ASYN-Expression (Antisense-Therapie), 2. die Verhinderung der Bildung toxischer ASYN-Aggregate (Antiaggregativa, Chelatoren), 3. das Auflösen bzw. die Beseitigung intra- oder extrazellulärer toxischer ASYN-Aggregate (aktive und passive Immuntherapie, Antiaggregativa), 4. die Verstärkung zellulärer Abräummechanismen (Autophagie, lysosomale Mikrophagie) zur Beseitigung toxischer Formen von α‑Synuklein, 5. die Modulation neuroinflammatorischer Prozesse sowie 6. neuroprotektive Strategien. In diesem Artikel fassen wir die aktuellen Therapieentwicklungen zusammen und geben einen Ausblick auf vielversprechende zukünftige Therapieansätze.

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Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

Cited by 126 publications

References 110 publications

The influence of probable rapid eye movement sleep behavior disorder and sleep insufficiency on fall risk in a community-dwelling elderly population

The influence of probable rapid eye movement sleep behavior disorder and sleep insufficiency on fall risk in a community-dwelling elderly population

Neurophysiological Aspects of REM Sleep Behavior Disorder (RBD): A Narrative Review

Neuroprotektive Therapien bei idiopathischen, genetischen und atypischen Parkinson-Syndromen mit α-Synuklein – Pathologie

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