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 patie...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).展开更多
Rapid eye movement(REM)sleep behavior disorder(RBD)is a parasomnia that is featured by elevated motor behaviors and dream enactments during REM sleep.Clinical observations show that RBD bears significant relevance wit...Rapid eye movement(REM)sleep behavior disorder(RBD)is a parasomnia that is featured by elevated motor behaviors and dream enactments during REM sleep.Clinical observations show that RBD bears significant relevance with several synucleinopathies such as Lewy body dementia and Parkinson disease(PD),and often develops prior to their diagnosis.Being a potential biomarker of PD,investigating the relationship of RBD symptoms and their emergence in developing PD would provide insight intoits pathogenesis.Here,in a chronic model of PD,rats with daily rotenone treatment exhibited key RBD features,including elevated sleep muscle tone,sleep fragmentation and EEG slowing at different time points.Based on detectedearly alpha synuclein aggregation and neural apoptosis in the sublaterodorsal tegmental nucleus(SLD),an area known to promote REM sleep and maintain sleep muscle atonia,the possible involvement of SLD glutamatergic neurons was interrogated.Via chemogenetic activation of SLD glutamatergic neurons,key RBD symptoms and EEG slowing in REM sleep were alleviated.These results are consistent with a progressive degeneration in REM sleep promoting pathways.Our findings provide a foundation for further studies into RBD and its relationship to neurodegenerative diseases.展开更多
Background The isolated rapid-eye-movement sleep behavior disorder(iRBD)is a prodromal condition of Lewy body disease including Parkinson’s disease and dementia with Lewy bodies(DLB).We aim to investigate the longitu...Background The isolated rapid-eye-movement sleep behavior disorder(iRBD)is a prodromal condition of Lewy body disease including Parkinson’s disease and dementia with Lewy bodies(DLB).We aim to investigate the longitudinal evolution of DLB-related cortical thickness signature in a prospective iRBD cohort and evaluate the possible predictive value of the cortical signature index in predicting dementia-first phenoconversion in individuals with iRBD.Methods We enrolled 22 DLB patients,44 healthy controls,and 50 video polysomnography-proven iRBD patients.Participants underwent 3-T magnetic resonance imaging(MRI)and clinical/neuropsychological evaluations.We characterized DLB-related whole-brain cortical thickness spatial covariance pattern(DLB-pattern)using scaled subprofile model of principal components analysis that best differentiated DLB patients from age-matched controls.We analyzed clinical and neuropsychological correlates of the DLB-pattern expression scores and the mean values of the whole-brain cortical thickness in DLB and iRBD patients.With repeated MRI data during the follow-up in our prospective iRBD cohort,we investigated the longitudinal evolution of the cortical thickness signature toward Lewy body dementia.Finally,we analyzed the potential predictive value of cortical thickness signature as a biomarker of phenoconversion in iRBD cohort.Results The DLB-pattern was characterized by thinning of the temporal,orbitofrontal,and insular cortices and relative preservation of the precentral and inferior parietal cortices.The DLB-pattern expression scores correlated with attentional and frontal executive dysfunction(Trail Making Test-A and B:R=−0.55,P=0.024 and R=−0.56,P=0.036,respectively)as well as visuospatial impairment(Rey-figure copy test:R=−0.54,P=0.0047).The longitudinal trajectory of DLB-pattern revealed an increasing pattern above the cut-off in the dementia-first phenoconverters(Pearson’s correlation,R=0.74,P=6.8×10−4)but no significant change in parkinsonism-first phenoconverters(R=0.0063,P=0.98).The mean value of the whole-brain cortical thickness predicted phenoconversion in iRBD patients with hazard ratio of 9.33[1.16-74.12].The increase in DLB-pattern expression score discriminated dementia-first from parkinsonism-first phenoconversions with 88.2%accuracy.Conclusion Cortical thickness signature can effectively reflect the longitudinal evolution of Lewy body dementia in the iRBD population.Replication studies would further validate the utility of this imaging marker in iRBD.展开更多
Background：Rapid eye movement （REM） sleep behavior disorder （RBD） and obstructive sleep apnea （OSA） are the most common sleep disorders in Parkinson’s disease （PD）. The aim of this study was to identify whet...Background：Rapid eye movement （REM） sleep behavior disorder （RBD） and obstructive sleep apnea （OSA） are the most common sleep disorders in Parkinson’s disease （PD）. The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment.Methods：From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography （PSG）. We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression.Results：We grouped participants as follows： PD only （n = 53）, PD ＋ OSA （n = 29）, PD ＋ RBD （n = 61）, and PD ＋ RBD ＋ OSA （n = 31）. Minimum oxygen saturation （SaO2） during whole sleep and in REM sleep was higher in PD ＋ RBD ＋ OSA patients than that in PD ＋ OSA patients. PD ＋ RBD patients had worse Mini-Mental Status Examination and Montreal Cognitive Assessment （MoCA） scores than those in the PD group （P 〈 0.001）, especially in visuospatial/executive, attention, and memory functions. The PD ＋ OSA group performed worse than the PD group in the delayed recall domain. After adjusting for age, sex, body mass index, education, disease severity, and other sleep disorders, MoCA was negatively associated with OSA （β = ？0.736, P = 0.043） and RBD （β = ？2.575, P 〈 0.001）. The severity of RBD （tonic/phasic electromyography activity） and OSA （apnea-hypopnea index/oxygen desaturation index/minimum SaO2） were also associated with MoCA. The adjusted β values of RBD-related parameters were higher than that for OSA.Conclusions：We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD.展开更多
Background： Rapid eye movement （REM） sleep behavior disorder （RBD） may be a risk factor for cognitive impairment in patients with Parkinson＆#39;s disease （PD）.However, little is known regarding the relation be...Background： Rapid eye movement （REM） sleep behavior disorder （RBD） may be a risk factor for cognitive impairment in patients with Parkinson＆#39;s disease （PD）.However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment.The aim of this study was： （1） to investigate the domains of cognitive impairment in patients with PD and RBD, and （2） to explore risk factors for PD-mild cognitive impairment （PD-MCI） and the relationship between RBD severity and impairment in different cognitive domains in PD.Methods： The participants were grouped as follows： PD without RBD （PD-RBD;n =42）, PD with RBD （PD ＋ RBD;n =32）, idiopathic RBD （iRBD;n =15）, and healthy controls （HCs;n =36）.All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function.The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD ＋ RBD groups.Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong （RBDQ-HK） and the RBD Screening Questionnaire （RBDSQ）, then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.Results： Compared to PD-RBD subjects, PD ＋ RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher （P 〈 0.05）.During neuropsychological testing, PD ＋ RBD patients performed worse than PD-RBD patients, including delayed memory function, especially.The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD ＋ RBD, iRBD, and HC groups, respectively.RBD was an important factor for the PD-MCI variance （odds ratio =5.204, P =0.018）.During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B （errors） and Auditory Verbal Learning Test （delayed recall） and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure （copy） results.Conclusions： When PD-RBD and PD ＋ RBD patients have equivalent motor symptoms, PD ＋ RBD patients still have more olfactory dysfunction and worse daytime somnolence.RBD is an important risk factor for MCI, including delayed memory.Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.展开更多
Background:Rapid eye movement sleep behavior disorder(RBD)and Parkinson’s disease(PD)are two distinct clinical diseases but they share some common pathological and anatomical characteristics.This study aims to confir...Background:Rapid eye movement sleep behavior disorder(RBD)and Parkinson’s disease(PD)are two distinct clinical diseases but they share some common pathological and anatomical characteristics.This study aims to confirm the clinical features of RBD in Chinese PD patients.Methods:One hundred fifty PD patients were enrolled from the Parkinson`s disease and Movement Disorders Center in Department of Neurology,Shanghai General Hospital from January 2013 to August 2014.This study examined PD patients with or without RBD as determined by the REM Sleep Behavior Disorder Screening Questionnaire(RBDSQ),assessed motor subtype by Unified PD Rating Scale(UPDRS)III at“on”state,and compared the sub-scale scores representing tremor,rigidity,appendicular and axial.Investigators also assessed the Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),Mini-Mental State Examination(MMSE),Clinical Dementia Rating(CDR),and Parkinson’s disease Sleep Scale(PDSS).Results:One hundred fourty one PD patients entered the final study.30(21.28%)PD patients had probable RBD(pRBD)diagnosed with a RBDSQ score of 6 or above.There were no significant differences for age,including age of PD onset and PD duration,gender,smoking status,alcohol or coffee use,presence of anosmia or freezing,UPDRS III,and H-Y stages between the pRBD+and pRBD−groups.pRBD+group had lower MMSE scores,higher PDSS scores,and pRBD+PD patients had more prominent proportion in anxiety,depression,constipation,hallucination and a greater prevalence of orthostatic hypotension.Conclusion:pRBD+PD patients exhibited greater changes in non-motor symptoms.However,there was no increase in motor deficits.展开更多
Background： The brain stem is found to be impaired in multiple system atrophy-ccrcbellar types （MSA-C）. Rapid eye movement （REM） sleep behavior disorder （RBD） is reported as a marker of progressive brain stem d...Background： The brain stem is found to be impaired in multiple system atrophy-ccrcbellar types （MSA-C）. Rapid eye movement （REM） sleep behavior disorder （RBD） is reported as a marker of progressive brain stem dysfunction. Few systematic studies about the sleep disturbances in MSA-C patients combined with or without RBD were reported. This study aimed to explore the polysomnographic （PSG） features of sleep disturbances between MSA-C patients with and without RBD. Methods： Totally, 46 MSA-C patients （23 with RBD, and 23 without RBD） were enrolled in this study. All patients underwent a structured interview for their demographic data, history of sleep pattern, and movement disorders; and then, overnight video-PSG was performed in each patient. All the records were evaluated by specialists at the Sleep Medicine Clinic for RBD and the Movement Disorder Clinic for MSA-C. The Student＇s t-test, Mann-Whitney U-test for continuous variables, and the Chi-square test for categorical variables were used in this study. Results： MSA-C patients with RBD had younger visiting age （52.6 ± 7.4 vs. 56.7 ± 6.0 years, P = 0.046） and shorter duration of the disease （12.0 [12.0, 24.0] vs. 24.0 [14.0, 36.0] months, P 0.009） than MSA-C patients without RBD. MSA-C with RBD had shorter REM sleep latency （111.7 ± 48.2 vs. 157.0 ± 68.8 rain, P = 0.042）, higher percentage of REM sleep （14.9% ±4.0% vs. 10.0% ± 3.2%, P = 0.019）, and lower Stage 1 （9.5% ±7.2% vs. 15.9% ±8.0%, P= 0.027） than MSA-C without RBD. Moreover, MSA-C patients with RBD had more decreased sleep efficiency （52.4% ±12.6% vs. 65.8% ±15.9%, P = 0.029） than that without RBD. Conclusions： In addition to the RBD, MSA-C patients with RBD had other more severe sleep disturbances than those without RBD. The sleep disorders of MSA patients might be associated with the progress of the disease.展开更多
Background:Rapid eye movement sleep behavior disorder(RBD)is associated with cognitive decline in early Parkinson’s disease(PD).However,the underlyling basis for this association remains unclear.Methods:Parkinson’s ...Background:Rapid eye movement sleep behavior disorder(RBD)is associated with cognitive decline in early Parkinson’s disease(PD).However,the underlyling basis for this association remains unclear.Methods:Parkinson’s Progression Marker’s Initiative(PPMI)subjects underwent baseline RBD testing with RBD sleep questionnaire(RBDSQ).Serial assessments included measures of motor symptoms,non-motor symptoms(NMS),neuropsychological assessment,blood and cerebrospinal fluid(CSF)biomarkers.Up to three years follow-up data were included.We stratified early PD subjects into PD with RBD(RBDSQ score>5)and PD without RBD groups.Then,we evaluated baseline biomarkers in each group as a predictor of cognitive decline using Montreal Cognitive Assessment(MoCA)score changes over three years in regression models.Results:Four hundred twenty-three PD subjects were enrolled at baseline,and a total of 350 PD subjects had completed 3 years of study follow-up with completely serial assessments.We found that at baseline,only CSF β-amyloid 1–42(Aβ1–42)was significantly lower in PD subjects with RBD.On three years follow-up analysis,PD subjects with RBD were more likely to develop incident mild cognitive impairment(MCI)and presented greater cognitive decline in MoCA score.Lower baseline CSF Aβ1–42 predicted cognitive decline over 3 years only in PD subjects with RBD(β=−0.03,P=0.003).A significant interaction between Aβ1–42 and the 2 groups confirmed that this effect was indeed higher in PD with RBD than the other individual(β=−2.85,P=0.014).Conclusion:These findings indicate that CSF Aβ1–42 level is associated with global cognitive decline in early PD with RBD.The addition of CSF Aβ1–42 to RBD testing increase the likelihood of identifying those at high risk for cognitive decline in early PD.展开更多
报道1例表现为多系统萎缩小脑型的脊髓小脑性共济失调8型(spinocerebellar ataxia type 8,SCA8)患者。该患者为57岁男性,病程4年,以头晕、共济失调为首发症状,后出现自主神经功能障碍、快速眼动睡眠障碍等表现。神经系统查体提示自主神...报道1例表现为多系统萎缩小脑型的脊髓小脑性共济失调8型(spinocerebellar ataxia type 8,SCA8)患者。该患者为57岁男性,病程4年,以头晕、共济失调为首发症状,后出现自主神经功能障碍、快速眼动睡眠障碍等表现。神经系统查体提示自主神经功能障碍、眼球震颤、构音障碍、共济失调,颅脑核磁共振见脑干、小脑对称性萎缩及脑桥“十字征”。基因检测结果显示ATXN8OS的两个等位基因CTA/CTG重复次数异常增多,确诊为SCA8。治疗上予以改善共济失调、自主神经功能障碍等对症治疗后患者反应良好。SCA8为罕见的运动障碍性疾病,临床异质性高。本报道旨在提示临床医师,SCA8也可表现为自主神经功能障碍、共济失调、脑桥“十字征”等类似多系统萎缩小脑型的特点,临床工作中要避免误诊、漏诊。展开更多
Rapid eye movement sleep behavior disorder （RBD） is one of the most common non-motor symptoms of parkinsonism, and it may serve as a prodromal marker of neurodegenerative disease. The mechanism underlying RBD is unc...Rapid eye movement sleep behavior disorder （RBD） is one of the most common non-motor symptoms of parkinsonism, and it may serve as a prodromal marker of neurodegenerative disease. The mechanism underlying RBD is unclear. Several prospective studies have reported that specific non-motor symptoms predict a conversion risk of developing a neurodegenerative disease, including olfactory dysfunction, abnormal color vision, autonomic dysfunction, excessive daytime sleepiness, depression, and cognitive impairment. Parkinson＇s disease （PD） with RBD exhibits clinical heterogeneity with respect to motor and non-motor symptoms compared with PD without RBD. In this review, we describe the main clinical and pathogenic features of RBD, focusing on its association with other non-motor symptoms of parkinsonism.展开更多
Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-...Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-motor symptoms. Sleep disturbances, such as rapid eye movement (REM) behavior disorder (RBD), are common in patients with PD and may precede onset of PD. Methods: Data was collected on patients with PD (358 subjects)in a movement disorders clinic at a safety net hospital. In this retrospective database analysis, the association of PD complications with age of onset was evaluated using chi-square tests and logistic regression. Results: Of the PD complications analyzed, there was a significant difference in sleep disturbances by age. Among the 358 PD patients, 120 individuals (33.5%) had information regarding the presence or absence of sleep disturbances. There was a significant difference between the early (onset < 50) and later onset (≥50) groups (p = 0.03) with the odds of having a sleep disorder for the early group 1.6 times that of the late group. Those subjects with siblings who also had PD had 2.0 times the odds of having a sleep disorder compared those without (p = 0.02). Conclusion: Non-motor symptoms such as sleep disorders are a useful predictor of early onset PD. Genetic components of PD impact both motor and non-motor aspects of the disease.展开更多
发作性睡病(narcolepsy,NT)是与快速眼动睡眠期(rapid eye movement,REM)相关的一种中枢性嗜睡疾病,好发于儿童与青少年,临床表现为日间过度思睡和猝倒,还可伴有异常的快速眼动表现,如入睡幻觉、睡眠麻痹、夜间睡眠紊乱以及其他快速眼...发作性睡病(narcolepsy,NT)是与快速眼动睡眠期(rapid eye movement,REM)相关的一种中枢性嗜睡疾病,好发于儿童与青少年,临床表现为日间过度思睡和猝倒,还可伴有异常的快速眼动表现,如入睡幻觉、睡眠麻痹、夜间睡眠紊乱以及其他快速眼动睡眠行为障碍(REM sleep behavior disorder,RBD)等;其发病率较低,为0.02%~0.05%不等[1],发病年龄有两个高峰,分别为15岁和35岁。国际睡眠障碍分类第3版(The International Classification of Sleep Disorders-Third Edition,ICSD-3)将NT分为1型发作性睡病(narcolepsy type 1,NT1:伴猝倒/下丘脑分泌素缺乏)和2型发作性睡病(narcolepsy type 2,NT2:无猝倒和下丘脑分泌素缺乏),其中NT1所占比例为75%~80%。NT1和NT2均有日间过度思睡的临床症状,NT1表现为脑脊液分泌素1(hypocretin-1,hcrt-1)水平下降以及猝倒,这表明NT1与下丘脑hcrt-1密切相关;NT2的发病原因目前认为可能是下丘脑损害不完全,因此脑脊液中hcrt-1水平低下或略低,部分NT2患者后期又可发展为NT1[2]。NT的诊断通常具有滞后性,可达10年以上[1],严重影响患者学习和工作,甚至带来心理上的焦虑与抑郁,因此该疾病应早发现、早诊断,并采取及时的干预措施。展开更多
基金supported by the China-US Biomedical Collaborative Research Program,No.81361120393(to CTZ)the National Natural Science Foundation of China,No.81401135(to PW),81671239(to CTZ)the Shanghai Sailing Program,No.18YF1403100(to JJG)
文摘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).
基金The project supported by the HKGRCGRF gran(t14111715)
文摘Rapid eye movement(REM)sleep behavior disorder(RBD)is a parasomnia that is featured by elevated motor behaviors and dream enactments during REM sleep.Clinical observations show that RBD bears significant relevance with several synucleinopathies such as Lewy body dementia and Parkinson disease(PD),and often develops prior to their diagnosis.Being a potential biomarker of PD,investigating the relationship of RBD symptoms and their emergence in developing PD would provide insight intoits pathogenesis.Here,in a chronic model of PD,rats with daily rotenone treatment exhibited key RBD features,including elevated sleep muscle tone,sleep fragmentation and EEG slowing at different time points.Based on detectedearly alpha synuclein aggregation and neural apoptosis in the sublaterodorsal tegmental nucleus(SLD),an area known to promote REM sleep and maintain sleep muscle atonia,the possible involvement of SLD glutamatergic neurons was interrogated.Via chemogenetic activation of SLD glutamatergic neurons,key RBD symptoms and EEG slowing in REM sleep were alleviated.These results are consistent with a progressive degeneration in REM sleep promoting pathways.Our findings provide a foundation for further studies into RBD and its relationship to neurodegenerative diseases.
基金supported by a research grant of National Research Foundation(NRF)funded by the Ministry of Education,Science and Technology(MEST)in Korea(NRF-2018R1C1B3008971,2018R2A5A2025974,2021R1C1C1011077,NRF-2020R1I1A1A01054095)the Korea government(MSIT)Ministry of Science and ICT(NRF-2022R1A2C4001834).
文摘Background The isolated rapid-eye-movement sleep behavior disorder(iRBD)is a prodromal condition of Lewy body disease including Parkinson’s disease and dementia with Lewy bodies(DLB).We aim to investigate the longitudinal evolution of DLB-related cortical thickness signature in a prospective iRBD cohort and evaluate the possible predictive value of the cortical signature index in predicting dementia-first phenoconversion in individuals with iRBD.Methods We enrolled 22 DLB patients,44 healthy controls,and 50 video polysomnography-proven iRBD patients.Participants underwent 3-T magnetic resonance imaging(MRI)and clinical/neuropsychological evaluations.We characterized DLB-related whole-brain cortical thickness spatial covariance pattern(DLB-pattern)using scaled subprofile model of principal components analysis that best differentiated DLB patients from age-matched controls.We analyzed clinical and neuropsychological correlates of the DLB-pattern expression scores and the mean values of the whole-brain cortical thickness in DLB and iRBD patients.With repeated MRI data during the follow-up in our prospective iRBD cohort,we investigated the longitudinal evolution of the cortical thickness signature toward Lewy body dementia.Finally,we analyzed the potential predictive value of cortical thickness signature as a biomarker of phenoconversion in iRBD cohort.Results The DLB-pattern was characterized by thinning of the temporal,orbitofrontal,and insular cortices and relative preservation of the precentral and inferior parietal cortices.The DLB-pattern expression scores correlated with attentional and frontal executive dysfunction(Trail Making Test-A and B:R=−0.55,P=0.024 and R=−0.56,P=0.036,respectively)as well as visuospatial impairment(Rey-figure copy test:R=−0.54,P=0.0047).The longitudinal trajectory of DLB-pattern revealed an increasing pattern above the cut-off in the dementia-first phenoconverters(Pearson’s correlation,R=0.74,P=6.8×10−4)but no significant change in parkinsonism-first phenoconverters(R=0.0063,P=0.98).The mean value of the whole-brain cortical thickness predicted phenoconversion in iRBD patients with hazard ratio of 9.33[1.16-74.12].The increase in DLB-pattern expression score discriminated dementia-first from parkinsonism-first phenoconversions with 88.2%accuracy.Conclusion Cortical thickness signature can effectively reflect the longitudinal evolution of Lewy body dementia in the iRBD population.Replication studies would further validate the utility of this imaging marker in iRBD.
文摘Background：Rapid eye movement （REM） sleep behavior disorder （RBD） and obstructive sleep apnea （OSA） are the most common sleep disorders in Parkinson’s disease （PD）. The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment.Methods：From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography （PSG）. We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression.Results：We grouped participants as follows： PD only （n = 53）, PD ＋ OSA （n = 29）, PD ＋ RBD （n = 61）, and PD ＋ RBD ＋ OSA （n = 31）. Minimum oxygen saturation （SaO2） during whole sleep and in REM sleep was higher in PD ＋ RBD ＋ OSA patients than that in PD ＋ OSA patients. PD ＋ RBD patients had worse Mini-Mental Status Examination and Montreal Cognitive Assessment （MoCA） scores than those in the PD group （P 〈 0.001）, especially in visuospatial/executive, attention, and memory functions. The PD ＋ OSA group performed worse than the PD group in the delayed recall domain. After adjusting for age, sex, body mass index, education, disease severity, and other sleep disorders, MoCA was negatively associated with OSA （β = ？0.736, P = 0.043） and RBD （β = ？2.575, P 〈 0.001）. The severity of RBD （tonic/phasic electromyography activity） and OSA （apnea-hypopnea index/oxygen desaturation index/minimum SaO2） were also associated with MoCA. The adjusted β values of RBD-related parameters were higher than that for OSA.Conclusions：We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD.
文摘Background： Rapid eye movement （REM） sleep behavior disorder （RBD） may be a risk factor for cognitive impairment in patients with Parkinson＆#39;s disease （PD）.However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment.The aim of this study was： （1） to investigate the domains of cognitive impairment in patients with PD and RBD, and （2） to explore risk factors for PD-mild cognitive impairment （PD-MCI） and the relationship between RBD severity and impairment in different cognitive domains in PD.Methods： The participants were grouped as follows： PD without RBD （PD-RBD;n =42）, PD with RBD （PD ＋ RBD;n =32）, idiopathic RBD （iRBD;n =15）, and healthy controls （HCs;n =36）.All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function.The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD ＋ RBD groups.Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong （RBDQ-HK） and the RBD Screening Questionnaire （RBDSQ）, then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.Results： Compared to PD-RBD subjects, PD ＋ RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher （P 〈 0.05）.During neuropsychological testing, PD ＋ RBD patients performed worse than PD-RBD patients, including delayed memory function, especially.The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD ＋ RBD, iRBD, and HC groups, respectively.RBD was an important factor for the PD-MCI variance （odds ratio =5.204, P =0.018）.During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B （errors） and Auditory Verbal Learning Test （delayed recall） and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure （copy） results.Conclusions： When PD-RBD and PD ＋ RBD patients have equivalent motor symptoms, PD ＋ RBD patients still have more olfactory dysfunction and worse daytime somnolence.RBD is an important risk factor for MCI, including delayed memory.Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(81171205,81371410)the Biomedical Multidisciplinary Program of Shanghai Jiao Tong University(YG2014MS31,YG2015QN21,YG2016QN25).
文摘Background:Rapid eye movement sleep behavior disorder(RBD)and Parkinson’s disease(PD)are two distinct clinical diseases but they share some common pathological and anatomical characteristics.This study aims to confirm the clinical features of RBD in Chinese PD patients.Methods:One hundred fifty PD patients were enrolled from the Parkinson`s disease and Movement Disorders Center in Department of Neurology,Shanghai General Hospital from January 2013 to August 2014.This study examined PD patients with or without RBD as determined by the REM Sleep Behavior Disorder Screening Questionnaire(RBDSQ),assessed motor subtype by Unified PD Rating Scale(UPDRS)III at“on”state,and compared the sub-scale scores representing tremor,rigidity,appendicular and axial.Investigators also assessed the Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),Mini-Mental State Examination(MMSE),Clinical Dementia Rating(CDR),and Parkinson’s disease Sleep Scale(PDSS).Results:One hundred fourty one PD patients entered the final study.30(21.28%)PD patients had probable RBD(pRBD)diagnosed with a RBDSQ score of 6 or above.There were no significant differences for age,including age of PD onset and PD duration,gender,smoking status,alcohol or coffee use,presence of anosmia or freezing,UPDRS III,and H-Y stages between the pRBD+and pRBD−groups.pRBD+group had lower MMSE scores,higher PDSS scores,and pRBD+PD patients had more prominent proportion in anxiety,depression,constipation,hallucination and a greater prevalence of orthostatic hypotension.Conclusion:pRBD+PD patients exhibited greater changes in non-motor symptoms.However,there was no increase in motor deficits.
文摘Background： The brain stem is found to be impaired in multiple system atrophy-ccrcbellar types （MSA-C）. Rapid eye movement （REM） sleep behavior disorder （RBD） is reported as a marker of progressive brain stem dysfunction. Few systematic studies about the sleep disturbances in MSA-C patients combined with or without RBD were reported. This study aimed to explore the polysomnographic （PSG） features of sleep disturbances between MSA-C patients with and without RBD. Methods： Totally, 46 MSA-C patients （23 with RBD, and 23 without RBD） were enrolled in this study. All patients underwent a structured interview for their demographic data, history of sleep pattern, and movement disorders; and then, overnight video-PSG was performed in each patient. All the records were evaluated by specialists at the Sleep Medicine Clinic for RBD and the Movement Disorder Clinic for MSA-C. The Student＇s t-test, Mann-Whitney U-test for continuous variables, and the Chi-square test for categorical variables were used in this study. Results： MSA-C patients with RBD had younger visiting age （52.6 ± 7.4 vs. 56.7 ± 6.0 years, P = 0.046） and shorter duration of the disease （12.0 [12.0, 24.0] vs. 24.0 [14.0, 36.0] months, P 0.009） than MSA-C patients without RBD. MSA-C with RBD had shorter REM sleep latency （111.7 ± 48.2 vs. 157.0 ± 68.8 rain, P = 0.042）, higher percentage of REM sleep （14.9% ±4.0% vs. 10.0% ± 3.2%, P = 0.019）, and lower Stage 1 （9.5% ±7.2% vs. 15.9% ±8.0%, P= 0.027） than MSA-C without RBD. Moreover, MSA-C patients with RBD had more decreased sleep efficiency （52.4% ±12.6% vs. 65.8% ±15.9%, P = 0.029） than that without RBD. Conclusions： In addition to the RBD, MSA-C patients with RBD had other more severe sleep disturbances than those without RBD. The sleep disorders of MSA patients might be associated with the progress of the disease.
基金This Study was funded by Chinese National Natural Science Foundation(No.81571234)Key research and development plan of Shandong Province(2018GSF118235)+1 种基金Shandong Province medical science and technology development projects(2014WS0260)Yantai Science and Technology Development Project(2014WS035,2016WS037).
文摘Background:Rapid eye movement sleep behavior disorder(RBD)is associated with cognitive decline in early Parkinson’s disease(PD).However,the underlyling basis for this association remains unclear.Methods:Parkinson’s Progression Marker’s Initiative(PPMI)subjects underwent baseline RBD testing with RBD sleep questionnaire(RBDSQ).Serial assessments included measures of motor symptoms,non-motor symptoms(NMS),neuropsychological assessment,blood and cerebrospinal fluid(CSF)biomarkers.Up to three years follow-up data were included.We stratified early PD subjects into PD with RBD(RBDSQ score>5)and PD without RBD groups.Then,we evaluated baseline biomarkers in each group as a predictor of cognitive decline using Montreal Cognitive Assessment(MoCA)score changes over three years in regression models.Results:Four hundred twenty-three PD subjects were enrolled at baseline,and a total of 350 PD subjects had completed 3 years of study follow-up with completely serial assessments.We found that at baseline,only CSF β-amyloid 1–42(Aβ1–42)was significantly lower in PD subjects with RBD.On three years follow-up analysis,PD subjects with RBD were more likely to develop incident mild cognitive impairment(MCI)and presented greater cognitive decline in MoCA score.Lower baseline CSF Aβ1–42 predicted cognitive decline over 3 years only in PD subjects with RBD(β=−0.03,P=0.003).A significant interaction between Aβ1–42 and the 2 groups confirmed that this effect was indeed higher in PD with RBD than the other individual(β=−2.85,P=0.014).Conclusion:These findings indicate that CSF Aβ1–42 level is associated with global cognitive decline in early PD with RBD.The addition of CSF Aβ1–42 to RBD testing increase the likelihood of identifying those at high risk for cognitive decline in early PD.
文摘目的快速眼动睡眠行为障碍(rapid eye movement sleep behavior disorder,RBD)是帕金森病(Parkinson's disease,PD)常见的非运动症状且是重要预后因素。本研究通过静息态功能磁共振成像,利用度中心度(degreecentrality,DC)和低频振幅(amplitudes of low-frequency fluctuation,ALFF)分析PD伴RBD和不伴有RBD患者组以及健康对照组三组间DC值和ALFF值,探索PD伴RBD患者脑功能活动特征及RBD特异性脑区,探究RBD发生的病理机制。材料与方法招募20例伴有RBD的PD患者(PD-RBD组)、40例无RBD的PD患者(PD-nonRBD组)和44例年龄性别匹配的健康对照(健康对照组),三组被试均接受磁共振扫描。利用静息态数据计算DC值和ALFF值,探测脑功能特征。结果方差分析结果显示三组间DC值主效应脑区为右侧中央前回、颞上回、小脑、额中回(P<0.05,FDR校正);ALFF值主效应脑区为左侧海马旁回、楔叶、舌回(P<0.05,FDR校正)。进一步分析发现相比于PD-nonRBD组,PD-RBD患者表现为右侧额中回DC值升高(t=4.02;P=0.007,FDR校正);左侧楔前叶DC值降低(t=5.30;P=0.009,FDR校正)。相比于健康对照组,PD-RBD患者表现为左侧额上回、小脑、右侧颞上回、左侧颞中回、额中回的DC值升高(P<0.05,FDR校正);左侧中央前回、颞上回和颞中回的DC值降低(P<0.05,FDR校正);右侧楔叶ALFF值降低(P<0.05,FDR校正)。结论PD-RBD在DC和ALFF上有独特的影像学特征,特别是右侧额中回、左侧楔前叶的功能异常可能与PD患者RBD的发生密切相关。
文摘报道1例表现为多系统萎缩小脑型的脊髓小脑性共济失调8型(spinocerebellar ataxia type 8,SCA8)患者。该患者为57岁男性,病程4年,以头晕、共济失调为首发症状,后出现自主神经功能障碍、快速眼动睡眠障碍等表现。神经系统查体提示自主神经功能障碍、眼球震颤、构音障碍、共济失调,颅脑核磁共振见脑干、小脑对称性萎缩及脑桥“十字征”。基因检测结果显示ATXN8OS的两个等位基因CTA/CTG重复次数异常增多,确诊为SCA8。治疗上予以改善共济失调、自主神经功能障碍等对症治疗后患者反应良好。SCA8为罕见的运动障碍性疾病,临床异质性高。本报道旨在提示临床医师,SCA8也可表现为自主神经功能障碍、共济失调、脑桥“十字征”等类似多系统萎缩小脑型的特点,临床工作中要避免误诊、漏诊。
基金supported by the National Natural Science Foundation of China (91649114)the Jiangsu Provincial Special Program of Medical Science, China (BL2014042)+3 种基金a Jiangsu Provincial Medical Key Discipline Projectthe Suzhou Clinical Research Center of Neurological Disease (Szzx201503)Jiangsu Province Ordinary University Professional Degree Graduate Practice Innovation, China (SJZZ16-0242)the Priority Academic Program Development of Jiangsu Higher Education Institutions, China
文摘Rapid eye movement sleep behavior disorder （RBD） is one of the most common non-motor symptoms of parkinsonism, and it may serve as a prodromal marker of neurodegenerative disease. The mechanism underlying RBD is unclear. Several prospective studies have reported that specific non-motor symptoms predict a conversion risk of developing a neurodegenerative disease, including olfactory dysfunction, abnormal color vision, autonomic dysfunction, excessive daytime sleepiness, depression, and cognitive impairment. Parkinson＇s disease （PD） with RBD exhibits clinical heterogeneity with respect to motor and non-motor symptoms compared with PD without RBD. In this review, we describe the main clinical and pathogenic features of RBD, focusing on its association with other non-motor symptoms of parkinsonism.
文摘Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-motor symptoms. Sleep disturbances, such as rapid eye movement (REM) behavior disorder (RBD), are common in patients with PD and may precede onset of PD. Methods: Data was collected on patients with PD (358 subjects)in a movement disorders clinic at a safety net hospital. In this retrospective database analysis, the association of PD complications with age of onset was evaluated using chi-square tests and logistic regression. Results: Of the PD complications analyzed, there was a significant difference in sleep disturbances by age. Among the 358 PD patients, 120 individuals (33.5%) had information regarding the presence or absence of sleep disturbances. There was a significant difference between the early (onset < 50) and later onset (≥50) groups (p = 0.03) with the odds of having a sleep disorder for the early group 1.6 times that of the late group. Those subjects with siblings who also had PD had 2.0 times the odds of having a sleep disorder compared those without (p = 0.02). Conclusion: Non-motor symptoms such as sleep disorders are a useful predictor of early onset PD. Genetic components of PD impact both motor and non-motor aspects of the disease.
文摘发作性睡病(narcolepsy,NT)是与快速眼动睡眠期(rapid eye movement,REM)相关的一种中枢性嗜睡疾病,好发于儿童与青少年,临床表现为日间过度思睡和猝倒,还可伴有异常的快速眼动表现,如入睡幻觉、睡眠麻痹、夜间睡眠紊乱以及其他快速眼动睡眠行为障碍(REM sleep behavior disorder,RBD)等;其发病率较低,为0.02%~0.05%不等[1],发病年龄有两个高峰,分别为15岁和35岁。国际睡眠障碍分类第3版(The International Classification of Sleep Disorders-Third Edition,ICSD-3)将NT分为1型发作性睡病(narcolepsy type 1,NT1:伴猝倒/下丘脑分泌素缺乏)和2型发作性睡病(narcolepsy type 2,NT2:无猝倒和下丘脑分泌素缺乏),其中NT1所占比例为75%~80%。NT1和NT2均有日间过度思睡的临床症状,NT1表现为脑脊液分泌素1(hypocretin-1,hcrt-1)水平下降以及猝倒,这表明NT1与下丘脑hcrt-1密切相关;NT2的发病原因目前认为可能是下丘脑损害不完全,因此脑脊液中hcrt-1水平低下或略低,部分NT2患者后期又可发展为NT1[2]。NT的诊断通常具有滞后性,可达10年以上[1],严重影响患者学习和工作,甚至带来心理上的焦虑与抑郁,因此该疾病应早发现、早诊断,并采取及时的干预措施。
