scholarly journals Serum metabolic biomarkers for synucleinopathy conversion in isolated REM sleep behavior disorder

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ariadna Laguna ◽  
Helena Xicoy ◽  
Eduardo Tolosa ◽  
Mònica Serradell ◽  
Dolores Vilas ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Predictive Models ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Protein Glycosylation ◽  
Serum Samples ◽  
Sleep Behavior ◽  
Control Serum ◽  
Metabolic Biomarkers

AbstractIsolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of Lewy-type synucleinopathies (LTS), which can present either with an initial predominant parkinsonism (Parkinson’s disease (PD)) or dementia (dementia with Lewy bodies (DLB)). To provide insights into the underlying pathogenic mechanisms, the lipoprotein and protein glycosylation profile of 82 iRBD patients, collected before and/or after their conversion to an overt LTS, and 29 matched control serum samples were assessed by nuclear magnetic resonance (NMR) spectroscopy. Data were statistically analyzed to identify altered metabolites and construct predictive models. Univariant analysis detected no differences between iRBD patients with an LTS compared to controls. However, significant differences were found when the analysis distinguished between iRBD patients that manifested initially predominant parkinsonism (pre-PD) or dementia (pre-DLB). Significant differences were also found in the analysis of paired iRBD samples pre- and post-LTS diagnosis. Predictive models were built and distinguished between controls and pre-DLB patients, and between pre-DLB and pre-PD patients. This allowed a prediction of the possible future clinical outcome of iRBD patients. We provide evidence of altered lipoprotein and glycosylation profiles in subgroups of iRBD patients. Our results indicate that metabolic alterations and inflammation are involved in iRBD pathophysiology, and suggest biological differences underlying the progression of LTS in iRBD patients. Our data also indicate that profiling of serum samples by NMR may be a useful tool for identifying short-term high-risk iRBD patients for conversion to parkinsonism or dementia.

Severe Brain Metabolic Decreases Associated with REM Sleep Behavior Disorder in Dementia with Lewy Bodies

2016 ◽  
Vol 52 (3) ◽  
pp. 989-997 ◽  
Author(s):  
Leonardo Iaccarino ◽  
Sara Marelli ◽  
Sandro Iannaccone ◽  
Giuseppe Magnani ◽  
Luigi Ferini-Strambi ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Sleep Behavior

scholarly journals REM Sleep Behavior Disorder (RBD) in Dementia with Lewy Bodies (DLB)

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Po-Chi Chan ◽  
Hsun-Hua Lee ◽  
Chien-Tai Hong ◽  
Chaur-Jong Hu ◽  
Dean Wu
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Dementia With Lewy Bodies ◽  
Clinical Manifestations ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Rapid Eye Movement ◽  
Sleep Behavior ◽  
Neurologic Disorders

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia, with abnormal dream-enacting behavior during the rapid eye movement (REM) sleep. RBD is either idiopathic or secondary to other neurologic disorders and medications. Dementia with Lewy bodies (DLB) is the third most common cause of dementia, and the typical clinical presentation is rapidly progressive cognitive impairment. RBD is one of the core features of DLB and may occur either in advance or simultaneously with the onset of DLB. The association between RBD with DLB is widely studied. Evidences suggest that both DLB and RBD are possibly caused by the shared underlying synucleinopathy. This review article discusses history, clinical manifestations, possible pathophysiologies, and treatment of DLB and RBD and provides the latest updates.

scholarly journals Smaller pineal gland is associated with rapid eye movement sleep behavior disorder in Alzheimer’s disease

2020 ◽  
Author(s):  
Jeongbin Park ◽  
Seung Wan Suh ◽  
Grace Eun Kim ◽  
Subin Lee ◽  
Jun Sung Kim ◽  
...  
Keyword(s):  
Pineal Gland ◽  
Eye Movement ◽  
Rem Sleep ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Rapid Eye Movement ◽  
Sleep Behavior ◽  
Gland Volume

Abstract Background: To investigate the association between pineal gland volume and symptoms of rapid eye movement (REM) sleep behavior disorder (RBD) in Alzheimer’s disease (AD) patients without any feature of dementia with Lewy bodies.Methods: We enrolled 296 community-dwelling probable AD patients who did not meet the diagnostic criteria for possible or probable dementia with Lewy bodies. Among them, 93 were amyloid beta (Aβ) positive on 18F-florbetaben amyloid brain positron emission tomography. We measured RBD symptoms using the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) and defined probable RBD (pRBD) as the RBDSQ of 5 or higher. We manually segmented pineal gland on 3T structural T1-weighted brain magnetic resonance imaging.Results: The participants with pRBD had smaller pineal parenchyma volume (VPP) than those without pRBD (p < 0.001). The smaller the VPP, the more severe the RBD symptoms (p < 0.001). VPP was inversely associated with risk of prevalent pRBD (odds ratio = 0.909, 95% confidence interval [CI] = 0.878–0.942, p < 0.001). Area under the receiver operator characteristic curve for pRBD of VPP was 0.80 (95% CI = 0.750–0.844, p < 0.0001). These results were not changed when we analyzed the 93 participants with Aβ-positive AD separately.Conclusions: In AD patients, reduced pineal gland volume may be associated with RBD.

REM sleep behavior disorder

2017 ◽  
Author(s):  
Ronald B. Postuma
Keyword(s):  
Rem Sleep ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Clinical History ◽  
Final Diagnosis ◽  
Acting Out ◽  
Sleep Behavior ◽  
Rem Atonia

A diagnosis of REM sleep behavior disorder (RBD), a disorder characterized by “acting out” of dreams during REM sleep, has critical implications for a patient’s future. Aside from being a treatable parasomnia, usually managed with melatonin or clonazepam, RBD is the most powerful risk factor for Parkinson disease and dementia with Lewy bodies yet discovered. Over 70% of patients with idiopathic RBD will develop a neurodegenerative synucleinopathy. Moreover, the disease course is more severe in patients with RBD than those without. Numerous screens have been developed to aid detection, and clinical history can help distinguish RBD from NREM parasomnia. However, final diagnosis relies on polysomnographic documentation of REM atonia loss. Given the profound implications of idiopathic RBD, patients need careful counseling and the offer of neurological follow-up to detect and treat prodromal disease symptoms. Recognition of RBD is also a means to discover and test protective therapies against neurodegenerative disease.

REM sleep behavior disorder and degenerative dementia

Neurology ◽  
1998 ◽  
Vol 51 (2) ◽  
pp. 363-370 ◽  
Author(s):  
B. F. Boeve ◽  
M. H. Silber ◽  
T. J. Ferman ◽  
E. Kokmen ◽  
G. E. Smith ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Clinical Laboratory ◽  
Neuropsychological Testing ◽  
Age At Onset ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Sleep Behavior ◽  
Diagnosis Of Dementia ◽  
Degenerative Dementia

Background:REM sleep behavior disorder (RBD) has been reported with various neurodegenerative disorders, most frequently in disorders with Lewy body pathology. RBD often precedes the onset of PD, and a recent prospective study showed that 38% of patients with RBD eventually developed PD.Methods:We identified 37 patients with degenerative dementia and a history of bursts of vigorous movement of the arms and legs with vocalization during sleep and associated with dream recall. Patients with and without two or more signs of parkinsonism were compared. Clinical, laboratory, and neuropsychometric features were analyzed, and criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) were applied to all patients.Results:Thirty-four of the 37 patients were male with mean age at onset of 61.5 years for RBD and 68.1 years for cognitive decline. RBD commenced before or concurrently with dementia in all patients but two. Parkinsonism (two or more signs) occurred in 54% of the sample (20/37), with a mean age at onset of 69.1 years. Polysomnography (PSG) confirmed RBD in all patients studied. Neuropsychological testing demonstrated impaired perceptual-organizational skills, verbal fluency, and marked constructional dyspraxia in more than one-half the patients. There were no statistically significant differences in the frequency of clinical features or in neuropsychological performance between patients with and without parkinsonism. Thirty-four patients (92%) met criteria for clinically possible or probably DLB. Three patients were autopsied; all had limbic with or without neocortical Lewy bodies.Conclusions:We report a group of predominantly male patients with a characteristic association of RBD and degenerative dementia. The clinical and neuropsychometric features of the groups of patients with and without parkinsonism are similar. We hypothesize that the underlying pathology in these patients is DLB.

How does dementia with Lewy bodies start? prodromal cognitive changes in REM sleep behavior disorder

2018 ◽  
Vol 83 (5) ◽  
pp. 1016-1026 ◽  
Author(s):  
Daphné Génier Marchand ◽  
Ronald B. Postuma ◽  
Frédérique Escudier ◽  
Jessie De Roy ◽  
Amélie Pelletier ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Cognitive Changes ◽  
Sleep Behavior

Novel biomarker signatures for idiopathic REM sleep behavior disorder

Neurology ◽  
2018 ◽  
Vol 91 (18) ◽  
pp. e1710-e1715 ◽  
Author(s):  
Stefania Mondello ◽  
Firas Kobeissy ◽  
Yehia Mechref ◽  
Jingfu Zhao ◽  
Farid R. Talih ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Clinical Decision Making ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Clinical Decision ◽  
Serum Levels ◽  
Serum Samples ◽  
Proteomics Analysis ◽  
Sleep Behavior ◽  
Altered Expression

ObjectiveTo perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes.MethodsSerum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography–mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD.ResultsWe identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology.ConclusionsOur results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.

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