Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study

Iranzo, Álex; Tolosa, Eduard; Gelpí, Ellen; Molinuevo, José Luís; Valldeoriola, Francesc; Serradell, Mónica; Sánchez‐Valle, Raquel; Vilaseca, Isabel; Lomeña, Francisco; Vilas, Dolores; Lladó, Albert; Gaig, Carles; Santamaría, Joan

doi:10.1016/s1474-4422(13)70056-5

Cited by 621 publications

(429 citation statements)

References 66 publications

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“…The second phase of the study was to apply these analytical conditions and cutoff criteria to a set of confirmatory in vivo CSF samples from 20 patients with clinically diagnosed PD, 15 control patients and three patients with REM sleep behavior disorder (RBD) recognized to be at high risk of developing future alpha‐synucleinopathies,17 obtained from the large prospective, OPDC Discovery cohort 17. These CSF samples were coded, analyzed, and reported without prior knowledge of the final diagnosis.…”

Section: Resultsmentioning

confidence: 99%

“…The control population was recruited from spouses and friends of patients taking part in the study, as well as the general public. The at‐risk group comprised patients with REM sleep behavior confirmed on overnight polysomnography,16 80% of which have shown to develop Lewy body disorder over time 17. Demographic information is given in Table 1.…”

Section: Methodsmentioning

confidence: 99%

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Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies

Fairfoul

McGuire

Pal

et al. 2016

Ann Clin Transl Neurol

441

288

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We have developed a novel real‐time quaking‐induced conversion RT‐QuIC‐based assay to detect alpha‐synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha‐synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT‐QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha‐synucleinopathies.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies

Fairfoul

McGuire

Pal

et al. 2016

Ann Clin Transl Neurol

441

288

View full text Add to dashboard Cite

show abstract

“…Animal studies and few observations in humans indicate that the locus subcoeruleus sublaterodorsal nucleus, the precoeruleus complex and the magnocellular reticular formation regulate atonia in REM sleep [13], while dysfunction of basal ganglia circuitries is believed to underlie motor problems in PD. Thus, RBD and RWA might reflect more widespread, more pronounced alpha-synuclein neuropathology, in terms of a propagation of adjacent brainstem nuclei [7].…”

Section: Discussionmentioning

confidence: 99%

“…RBD consists of two features: loss of atonia during REM sleep, so called REM sleep without atonia (RWA) and acting out of dreams, most often of violent content [6]. In this line, it would be important to know whether RBD and RWA not only heralds the occurrence of PD [7], but also predicts the pace of disease progression. As RBD is associated with higher doses of levodopa, occurrence of hallucinations and higher burden of autonomic failure [8], RBD may reflect a more widespread neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

Revisiting the impact of REM sleep behavior disorder on motor progression in Parkinson's disease

Sommerauer¹,

Valko²,

Werth³

et al. 2014

Parkinsonism & Related Disorders

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BACKGROUND Estimation of progression in Parkinson's disease (PD) is useful to guide clinical decisions and to enable patients to plan and manage their life with PD. Rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia (RWA) are recognized as early harbingers of neurodegeneration and may precede motor symptoms by years. However, their impact on motor progression remains elusive. METHODS We retrospectively analyzed polysomnographic and clinical data of 59 PD patients, grouping them into patients with RBD (n = 15), RWA (n = 22) and those with normal muscle atonia (n = 22). We compared the three groups with regard to motor progression, defined as changes in Unified Parkinson's Disease Rating Scale (UPDRS) III values per year, and selected PD specific characteristics. RESULTS Motor disability at first visit and time interval between first and last visits were similar between groups. We observed a significantly faster motor progression in PD patients with RBD and RWA than in those with preserved REM sleep atonia. CONCLUSION Our findings suggest that impaired muscle atonia during REM sleep might represent a marker of faster motor progression in PD.

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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.…”

mentioning

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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Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study

Cited by 621 publications

References 66 publications

Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies

Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies

Revisiting the impact of REM sleep behavior disorder on motor progression in Parkinson's disease

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

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