Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study.
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ABSTRACT:
SUBMITTER: Postuma RB
PROVIDER: S-EPMC5769479 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Publications
Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study.
Postuma Ronald B RB Iranzo Alex A Hogl Birgit B Arnulf Isabelle I Ferini-Strambi Luigi L Manni Raffaele R Miyamoto Tomoyuki T Oertel Wolfgang W Dauvilliers Yves Y Ju Yo-El YE Puligheddu Monica M Sonka Karel K Pelletier Amelie A Santamaria Juan J Frauscher Birgit B Leu-Semenescu Smaranda S Zucconi Marco M Terzaghi Michele M Miyamoto Masayuki M Unger Marcus M MM Carlander Bertrand B Fantini Maria-Livia ML Montplaisir Jacques Y JY
Annals of neurology 20150313 5
<h4>Objective</h4>To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD).<h4>Methods</h4>Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication ...[more]
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Project description:Idiopathic REM sleep behavior disorder (iRBD) is now considered a prodromal stage of an α-synucleinopathy-related to neurodegenerative disease such as Parkinson's diseases. Emerging evidence has shown that post-translational modification or glycosylation are implicated in dynamic disease mechanisms and the onset of many pathological conditions. We hypothesized that the characterization of the glycosylation pattern of patients with RBD would be of great value to understand the pathophysiology and underlying mechanisms and represent potentially useful biomarkers for disease-associated molecular changes. To test this hypothesis, we assessed the serum glycome of patients with RBD and compared to that of healthy controls. NanoRPLC-MS was used to generate quantitative N-glycan profiles while high-temperature PGC-LC-MS platform was employed to generate quantitative isomeric N-glycan profiles. By analyzing permethylated glycans derived from human blood sera on C18-LC-MS/MS, we identified 59 N-glycan structures in healthy (control) cohort, 56 N-glycans in RBD cohort. Sixteen N-glycans structures were found to be significantly altered in the RBD cohort (p < 0.05). N-glycans with the composition of HexNAc4 Hex5 Fuc1 , HexNAc5 Hex5 , and HexNAc4 Hex5 Fuc1 NeuAc1 presented the most substantial difference between controls and RBD patients (p < 0.01). HexNAc4 Hex5 Fuc1 NeuAc1 showed a relatively high abundance (3.1 ± 0.7% in the control cohort versus 4 ± 3% in the idiopathic RBD cohort). These N-glycans can be potential diagnostic biomarker candidates and provide a window into underlying neurodegenerative processes in patients with idiopathic RBD. In addition, 7 N-glycan isomers were significantly different between controls and RBD patients (p < 0.05). HexNAc4 Hex5 Fuc1 NeuAc1 (4511-2) and HexNAc4 Hex5 Fuc1 NeuAc2 (4512-2) showed the most substantial difference between the control and idiopathic RBD cohorts (p < 0.001). Levels of both these two isomeric structures were higher in the idiopathic RBD cohort. Further larger studies are required to assess the reproducibility of these findings and to elucidate the role played by the changes in glycan structures in the pathogenetic mechanisms of RBD. This information will be instrumental in developing molecular therapeutic targets to promote neuroprotection and prevention of neurodegeneration.
| S-EPMC6625764 | biostudies-literature
Project description:Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus (SLD) of the dorsal pons are critical for generation for REM sleep atonia. Descending projections from SLD glutamatergic neurons activate inhibitory premotor neurons in the ventromedial medulla (VMM) and in the spinal cord to antagonize the glutamatergic supraspinal inputs on the motor neurons during REM sleep. REM sleep behavior disorder (RBD) consists of simple behaviors (i.e., twitching, jerking) and complex behaviors (i.e., defensive behavior, talking). Animal research has lead to the hypothesis that complex behaviors in RBD are due to SLD pathology, while simple behaviors of RBD may be due to less severe SLD pathology or dysfunction of the VMM, ventral pons, or spinal cord.
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Project description:Study objectivesRapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia and elaborate motor activity in association with dream mentation. The melatonin receptor agonist ramelteon has been documented as being effective in two patients with secondary RBD. However, there are no reports on ramelteon treatment for idiopathic RBD.MethodsIn an open-labeled trial, we treated 12 consecutive patients with idiopathic RBD for at least 4 w with 8 mg ramelteon given within 30 min before bedtime.ResultsRamelteon treatment did not have a clear effect on REM sleep without atonia or an RBD severity scale measured by video-supported polysomnography. However, clinical assessment using a visual analog scale showed a trend toward significance and there were also definitely positive changes in some individual cases. Ramelteon was well tolerated in most patients, with minor side effects.ConclusionsConsidering that ramelteon is associated with few side effects, further study may ascertain whether patients with RBD could be effectively treated by ramelteon, especially when clonazepam may not be suitable due to its side effects.CommentaryA commentary on this article appears in this issue on page 643.
| S-EPMC4865555 | biostudies-literature
Project description:Objective: In this study we investigate cortical and subcortical gray matter structure in patients with Idiopathic REM-sleep behavior disorder (IRBD), and their relation to cognitive performance. Methods: This study includes a sample of 20 patients with polysomnography-confirmed IRBD and 27 healthy controls that underwent neuropsychological and T1-weighted MRI assessment. FreeSurfer was used to estimate cortical thickness, subcortical volumetry (version 5.1), and hippocampal subfields segmentation (version 6.0). FIRST, FSL's model-based segmentation/registration tool was used for hippocampal shape analysis. Results: Compared with healthy subjects, IRBD patients showed impairment in facial recognition, verbal memory, processing speed, attention, and verbal naming. IRBD patients had cortical thinning in left superior parietal, post-central, and fusiform regions, as well as in right superior frontal and lateral occipital regions. Volumetric and shape analyses found right hippocampal atrophy in IRBD, specifically in posterior regions. Hippocampal subfields exploratory analysis identified significant differences in the right CA1, molecular layer, granule cell layer of dentate gyrus, and CA4 of this patients. No correlations were found between cognitive performance and brain atrophy. Conclusion: This work confirms the presence of posterior based cognitive dysfunction, as well as cortical and right hippocampal atrophy in IRBD patients.
| S-EPMC6459930 | biostudies-literature
Project description:Idiopathic rapid eye movement sleep behavior disorder (iRBD) is often a precursor to neurodegenerative disease. However, voxel-based morphological studies evaluating structural abnormalities in the brains of iRBD patients are relatively rare. This study aimed to explore cerebral structural alterations using magnetic resonance imaging and to determine their association with clinical parameters in iRBD patients. Brain structural T1-weighted MRI scans were acquired from 19 polysomnogram-confirmed iRBD patients (male:female 16:3; mean age 66.6 ± 7.0 years) and 20 age-matched healthy controls (male:female 5:15; mean age 63.7 ± 5.9 years). Gray matter volume (GMV) data were analyzed based on Statistical Parametric Mapping 8, using a voxel-based morphometry method and two-sample t-test and multiple regression analysis. Compared with controls, iRBD patients had increased GMV in the middle temporal gyrus and cerebellar posterior lobe, but decreased GMV in the Rolandic operculum, postcentral gyrus, insular lobe, cingulate gyrus, precuneus, rectus gyrus, and superior frontal gyrus. iRBD duration was positively correlated with GMV in the precuneus, cuneus, superior parietal gyrus, postcentral gyrus, posterior cingulate gyrus, hippocampus, lingual gyrus, middle occipital gyrus, middle temporal gyrus, and cerebellum posterior lobe. Furthermore, phasic chin electromyographic activity was positively correlated with GMV in the hippocampus, precuneus, fusiform gyrus, precentral gyrus, superior frontal gyrus, cuneus, inferior parietal lobule, angular gyrus, superior parietal gyrus, paracentral lobule, and cerebellar posterior lobe. There were no significant negative correlations of brain GMV with disease duration or electromyographic activity in iRBD patients. These findings expand the spectrum of known gray matter modifications in iRBD patients and provide evidence of a correlation between brain dysfunction and clinical manifestations in such patients. The protocol was approved by the Ethics Committee of Huashan Hospital (approval No. KY2013-336) on January 6, 2014. This trial was registered in the ISRCTN registry (ISRCTN18238599).
| S-EPMC6375045 | biostudies-literature
Project description:Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia that is an important risk factor for Parkinson's disease (PD) and Lewy body dementia. Its prevalence is unknown. One barrier to determining prevalence is that current screening tools are too long for large-scale epidemiologic surveys. Therefore, we designed the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q), a screening question for dream enactment with a simple yes/no response.Four hundred and eighty-four sleep-clinic-based participants (242 idiopathic RBD patients and 242 controls) completed the screen during a multicenter case-control study. All participants underwent a polysomnogram to define gold-standard diagnosis according to standard criteria.We found a sensitivity of 93.8% and a specificity of 87.2%. Sensitivity and specificity were similar in healthy volunteers, compared to controls or patients with other sleep diagnoses.A single-question screen for RBD may reliably detect disease, with psychometric properties favorably comparable to those reported for longer questionnaires.
| S-EPMC4043389 | biostudies-literature
Project description:BackgroundIncreasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD.ObjectivesTo compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals.MethodsMicrobiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed.ResultsDifferentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms.ConclusionOur study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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Project description:Study objectivesTo determine the mortality and its risk factors in patients with rapid eye movement (REM) sleep behavior disorder (RBD).MethodsA total of 205 consecutive patients with video-polysomnography confirmed RBD (mean age = 66.4 ± 10.0 y, 78.5% males) were recruited. Medical records and death status were systematically reviewed in the computerized records of the health care system. Standardized mortality ratio (SMR) was used to calculate the risk ratio of mortality in RBD with reference to the general population.ResultsForty-three patients (21.0%) died over a mean follow-up period of 7.1 ± 4.5 y. The SMR was not increased in the overall sample, SMR (95% confidence interval [CI]) = 1.00 (0.73-1.33). However, SMR (95% CI) increased to 1.80 (1.21-2.58) and 1.75 (1.11-2.63) for RBD patients in whom neurodegenerative diseases and dementia, respectively, eventually developed. In the Cox regression model, mortality risk was significantly associated with age (hazard ratio [HR] = 1.05; 95% CI, 1.01-1.10), living alone (HR = 2.04; 95% CI, 1.39-2.99), chronic obstructive pulmonary disease (HR = 3.38; 95% CI, 1.21-9.46), cancer (HR = 10.09; 95% CI, 2.65-38.42), periodic limb movements during sleep (HR = 3.06; 95% CI, 1.50-6.24), and development of neurodegenerative diseases (HR = 2.84; 95% CI, 1.47-5.45) and dementia (HR = 2.66; 95% CI, 1.39-5.08).ConclusionsPatients with RBD have a higher mortality rate than the general population only if neurodegenerative diseases develop. Several risk factors on clinical and sleep aspects are associated with mortality in RBD patients. Our findings underscore the necessity of timely neuroprotective interventions in the early phase of RBD before the development of neurodegenerative diseases.
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Project description:ObjectiveTo systematically examine the association between alcohol intake and likelihood of having probable rapid eye movement sleep behavior disorder (pRBD) 6 years later.MethodsThe study included 11,905 participants (mean age: 47.7 years) of the Kailuan Study, free of stroke, cancer, Parkinson disease, dementia, and head injury in 2006. We determined pRBD using a validated RBD questionnaire-Hong Kong in 2012. Amounts and types of alcohol intake were collected with questionnaire. Participants were categorized into: nondrinkers, light (women: 0-0.4 servings/day; men: 0-0.9 servings/day), moderate (women: 0.5-1.0 servings/day; men: 1-2 servings/day), and heavy drinkers(women: >1 serving/day; men: >2 servings/day). To examine the alcohol-pRBD relationship, we used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for demographic characteristics, smoking, hypertension, diabetes, physical activity, body mass index, and plasma concentrations of lipids and urate.ResultsCompared with nondrinkers, current drinkers had a 23% higher likelihood of having pRBD (adjusted OR 1.23, 95% CI 1.07-1.59). Both moderate (adjusted OR: 1.53, 95% CI 1.01-2.30) and heavy drinkers (adjusted OR: 1.29, 95% CI 1.00-1.66), but not light drinkers (adjusted OR: 1.16, 95% CI 0.94-1.44), had a significantly higher likelihood of having pRBD, relative to nondrinkers. There was a nonsignificant trend between consumption of each individual alcoholic beverages (i.e., beer, wine, or hard liquor) and higher likelihood of having pRBD (adjusted ORs ranged from 1.11 to 1.49).ConclusionsAlcohol consumption was associated with a higher likelihood of having pRBD. Future prospective studies with clinically confirmed RBD, large sample size for information on types of alcoholic beverage are warranted.
| S-EPMC6186943 | biostudies-literature
Project description:BackgroundMelanopsin retinal ganglion cell (mRGC)-mediated pupillary light reflex (PLR) abnormalities have been documented in several neurodegenerative disorders including Parkinson's disease. Overall, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) represents the strongest prodromal risk factor for impending α-synucleinopathies.ObjectivesTo quantitatively compare PLR and mRGC-mediated contribution to PLR in 16 iRBD patients and 16 healthy controls.MethodsiRBD and controls underwent extensive neuro-ophthalmological evaluation and chromatic pupillometry. In iRBD, PLR metrics were correlated with clinical variables and with additional biomarkers including REM atonia index (RAI), DaTscan, and presence of phosphorylated-α-synuclein (p-α-syn) deposition in skin biopsy.ResultsWe documented higher baseline pupil diameter and decreased rod-transient PLR amplitude in iRBD patients compared to controls. PLR rod-contribution correlated with RAI. Moreover, only iRBD patients with evidence of p-α-syn deposition at skin biopsy showed reduced PLR amplitude compared to controls.ConclusionThe observed PLR abnormalities in iRBD might be considered as potential biomarkers for the risk stratification of phenoconversion of the disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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