Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder

Postuma, Ronald B.; Gagnon, Jean‐François; Vendette, Mélanie; Fantini, María Livia; Massicotte-Marquez, Jessica; Montplaisir, Jacques

doi:10.1212/01.wnl.0000340980.19702.6e

Cited by 667 publications

(278 citation statements)

References 20 publications

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“…Neurodegenerative diagnoses included PD, LBD, Alzheimer's disease, and MSA [523]. A retrospective case series study that focused on cases with RBD preceding PD, LBD, or MSA with more than 15 years reported a median interval between onset of RBD and neurodegenerative disease of 25 years [524].…”

Section: Rem Sleep Behavior Disordermentioning

confidence: 99%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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Section: Rem Sleep Behavior Disordermentioning

confidence: 99%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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“…For example, 40 -65% of patients develop Parkinson's disease within 12 years of the initial RBD diagnosis (Schenck et al, 2003;Iranzo et al, 2006;Postuma et al, 2009). Although Parkinson's is typically considered a dopamine system disease, it also involves degeneration of GABA and glycine function (Lloyd et al, 1977;Rinne et al, 1978;Nishino et al, 1988).…”

Section: Increasing Inhibitory Tone Improves Rbd Symptomsmentioning

confidence: 99%

Impaired GABA and Glycine Transmission Triggers Cardinal Features of Rapid Eye Movement Sleep Behavior Disorder in Mice

Brooks¹,

Peever²

2011

J. Neurosci.

111

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Rapid eye movement (REM) sleep behavior disorder (RBD) is a neurological disease characterized by loss of normal REM motor inhibition and subsequent dream enactment. RBD is clinically relevant because it predicts neurodegenerative disease onset (e.g., Parkinson's disease) and is clinically problematic because it disrupts sleep and results in patient injuries and hospitalization. Even though the cause of RBD is unknown, multiple lines of evidence indicate that abnormal inhibitory transmission underlies the disorder. Here, we show that transgenic mice with deficient glycine and GABA transmission have a behavioral, motor, and sleep phenotype that recapitulates the cardinal features of RBD. Specifically, we show that mice with impaired glycine and GABA A receptor function exhibit REM motor behaviors, non-REM muscle twitches, sleep disruption, and EEG slowing-the defining disease features. Importantly, the RBD phenotype is rescued by drugs (e.g., clonazepam and melatonin) that are routinely used to treat human disease symptoms. Our findings are the first to identify a potential mechanism for RBD-we show that deficits in glycine-and GABA A -mediated inhibition trigger the full spectrum of RBD symptoms. We propose that these mice are a useful resource for investigating in vivo disease mechanisms and developing potential therapeutics for RBD.

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“…Longitudinal studies have shown that >80% of individuals with idiopathic REM sleep behavior disorder (RBD) developed Parkinson's disease (PD) or dementia with Lewy bodies (DLB) on long‐term follow‐up 1, 2, 3, 4, 5. RBD subjects represent a suitable group to study the prodromal stage of these disorders and may be crucial for disease‐modification trials.…”

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confidence: 99%

FDG PET, dopamine transporter SPECT, and olfaction: Combining biomarkers in REM sleep behavior disorder

et al. 2017

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BackgroundIdiopathic REM sleep behavior disorder is a prodromal stage of Parkinson's disease and dementia with Lewy bodies. Hyposmia, reduced dopamine transporter binding, and expression of the brain metabolic PD‐related pattern were each associated with increased risk of conversion to PD. The objective of this study was to study the relationship between the PD‐related pattern, dopamine transporter binding, and olfaction in idiopathic REM sleep behavior disorder.MethodsIn this cross‐sectional study, 21 idiopathic REM sleep behavior disorder subjects underwent 18F‐fluorodeoxyglucose PET, dopamine transporter imaging, and olfactory testing. For reference, we included 18F‐fluorodeoxyglucose PET data of 19 controls, 20 PD patients, and 22 patients with dementia with Lewy bodies. PD‐related pattern expression z‐scores were computed from all PET scans.ResultsPD‐related pattern expression was higher in idiopathic REM sleep behavior disorder subjects compared with controls (P = 0.048), but lower compared with PD (P = 0.001) and dementia with Lewy bodies (P < 0.0001). PD‐related pattern expression was higher in idiopathic REM sleep behavior disorder subjects with hyposmia and in subjects with an abnormal dopamine transporter scan (P < 0.05, uncorrected).ConclusionPD‐related pattern expression, dopamine transporter binding, and olfaction may provide complementary information for predicting phenoconversion. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder

Abstract: Although we have found a slightly lower risk than other reports, the risk of developing neurodegenerative disease in idiopathic REM sleep behavior disorder is substantial, with the majority of patients developing Parkinson disease and Lewy body dementia.

Cited by 667 publications

References 20 publications

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Impaired GABA and Glycine Transmission Triggers Cardinal Features of Rapid Eye Movement Sleep Behavior Disorder in Mice

FDG PET, dopamine transporter SPECT, and olfaction: Combining biomarkers in REM sleep behavior disorder

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