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
An overview is presented of the literature dealing with sleep-like motility and concomitant neuronal activity patterns throughout the life cycle in vertebrates, ectothermic as well as endothermic. Spontaneous, periodi...An overview is presented of the literature dealing with sleep-like motility and concomitant neuronal activity patterns throughout the life cycle in vertebrates, ectothermic as well as endothermic. Spontaneous, periodically modulated, neurogenic bursts of non-purposive movements are a universal feature of larval and prenatal behavior, which in endothermic animals （i.e. birds and mammals） continue to occur periodically throughout life. Since the entire body musculature is involved in ever-shifting combinations, it is proposed that these spontaneously active periods be designated as ＇rapid-BODY-movement＇ （RBM） sleep. The term ＇rapid-EYE- movement （REM） sleep＇, characterized by attenuated muscle contractions and reduced tonus, can then be reserved for sleep at later stages of development. Mature stages of development in which sustained muscle atonia is combined with ＇paradoxical arousal＇ of cortical neuronal firing patterns indisputably represent the evolutionarily most recent aspect of REM sleep, but more research with ectothermic vertebrates, such as fish, amphibians and reptiles, is needed before it can be concluded （as many prematurely have） that RBM is absent in these species. Evidence suggests a link between RBM sleep in early development and the clinical condition known as ＇REM sleep behavior disorder （RBD）＇, which is characterized by the resurgence of periodic bouts of quasi-fetal motility that closely resemble RBM sleep. Early developmental neuromotor risk factors for RBD in humans also point to a relationship between RBM sleep and RBD.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
Purpose: Rapid eye movement sleep behavior disorder (RBD) and impulse control disorders (ICDs) are common in subjects with Parkinson’s disease. The association between these two conditions has been contradictory. The...Purpose: Rapid eye movement sleep behavior disorder (RBD) and impulse control disorders (ICDs) are common in subjects with Parkinson’s disease. The association between these two conditions has been contradictory. The aim of this study is to analyze the association between these two non-motor symptoms. Methods: Consecutive subjects with Parkinson’s disease attending the Movement Disorders Outpatient Clinic were included. The presence of ICDs was assessed using the Questionnaire for Impulse Control Disorders Rating Scale. RBD was diagnosed by an overnight, single night polysomnography. Results: Fifty-five consecutive subjects with Parkinson’s disease were included. The prevalence of ICDs and related behaviors was 23.6% (ICD in 14.5% and related behaviors in 9.1%). RBD was diagnosed in 47.2% of the patients. No differences were found in the frequency of ICDs and related behaviors when comparing subjects with and without RBD (23% versus 24.1%, p = 0.926, respectively). Conclusion: No association between the presence of RBD and the frequency of ICDs in subjects with Parkinson’s disease was found.展开更多
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
Sleep behaviors and physical activity(PA)are widely used to predict the risk of neurodegenerative disease.However,how sleep and PA interact to influence brain and cognitive health remains unknown.This study investigat...Sleep behaviors and physical activity(PA)are widely used to predict the risk of neurodegenerative disease.However,how sleep and PA interact to influence brain and cognitive health remains unknown.This study investigated independent,joint,and interacting associations of sleep behaviors and PA with brain structures and cognitive phenotypes using linear regression and generalized linear models among over 40,000 middle-aged and older participants in UK Biobank.We first found that unhealthy sleep patterns,abnormal sleep duration and high levels of PA were each associated with worse cognitive function and brain structure damage.Joint association analyses revealed that the group with long sleep duration and low levels of PA had the greatest prevalence of white matter hyperintensities(WMH;β=0.131,PFDR=0.013),a key metric of brain structural changes.Interestingly,interaction analysis suggested that a high level of PA significantly mitigates brain damage in relation to long sleep duration(i.e.,grey matter loss,βmoderate-long=-0.088,βhigh-long=-0.013,Pinteraction=0.024).In terms of cognitive phenotypes,a combination of long sleep and low levels of PA was similarly associated with worse cognitive performance(i.e.,symbol digit scores,β=-0.043,PFDR=0.018).Additionally,when stratified by PA levels,long sleep duration exhibited a negative impact on cognition compared to normal sleep duration among those with low PA,but this effect was smaller or insignificant for those engaging in moderate or high PA(i.e.,symbol digit scores,βlow-long=-0.047,PFDR=0.029;βmoderate-long=-0.022,PFDR=0.025;βhigh-long=-0.016,PFDR=0.239).Overall,maintaining a high PA level during late middle age could potentially mitigate the detrimental effects on brain structure associated with excessive sleep.Healthy sleep habits alongside an adequate PA level are essential for maintaining brain health during aging.展开更多
Background Dorsal nigral hyperintensity(DNH)abnormality associated with excessive iron deposition in the substantia nigra,is recognized as an imaging characteristic of Parkinson’s disease(PD)and can be effectively vi...Background Dorsal nigral hyperintensity(DNH)abnormality associated with excessive iron deposition in the substantia nigra,is recognized as an imaging characteristic of Parkinson’s disease(PD)and can be effectively visualized using 7T MRI.This study was aimed to develop and validate the optimal DNH assessment method as a biomarker for PD,idiopathic rapid eye movement sleep behavior disorder(iRBD),and Parkinson-plus syndromes,and to explore the nigral iron deposition patterns in these diseases.Methods Three-dimensional gradient-echo T2*-weighted images were acquired by 7T MRI from a total of 402 patients and 100 healthy controls(HCs)in two independent cohorts(development and validation cohorts).Seven methods,including four dichotomous methods and three DNH rating scales,were used to assess DNH and evaluate their diagnostic performance.R2*mapping and principal component analysis were performed to assess nigral iron deposition patterns.Results Bilateral DNH detection rates in the development cohort were 22.6%for early-stage PD,3.7%for advanced PD,93.5%for iRBD,5.7%for MSA-parkinsonian type,78.8%for MSA-cerebellar type,11.8%for progressive supranuclear palsy(PSP),and 100%for HC,with similar rates in the validation cohort.A cut-off of 6 on the 6-point visibility scale demonstrated a 100%accuracy for diagnosing early-stage PD in both the development and the validation cohorts.This scale exhibited moderate differential diagnostic performance between early-stage PD and iRBD(area under the curve[AUC]=0.940)or MSA-C(AUC=0.892).Iron deposition was predominantly in the dorsal and posterior substantia nigra of PD and PSP,the intermediate and posterior substantia nigra of MSA-P,and the ventral substantia nigra of MSA-C.Conclusion DNH may be preserved in approximately one-quarter of early-stage PD and most MSA-C cases.The 6-point visibility scale on 7T effectively distinguished PD from HC,iRBD,and MSA-C.The nigral iron deposition pattern in PD may help distinguish PD from MSA-P and MSA-C,although it overlaps with that of PSP.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
Objective： Rapid eye movement sleep behavior disorder （RBD） is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Pa...Objective： Rapid eye movement sleep behavior disorder （RBD） is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson＇s disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions. Data Sources： Using the combined keywords： ＂RBD＂, ＂neurodegenerative disease＂, ＂Parkinson disease＂, and ＂magnetic resonance imaging＂, the PubMed/MEDLINE literature search was conducted up to January 1, 2018. Study Selection： A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full. Results： Single-nucleotide polymorphisms in SCARB2 （rs6812193） and MAPT （rs12185268） were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings. Conclusions： More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatnaent trials to determine the effectiveness of interventions of RBD on preventing the conversion 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
Sleep disturbances are common in childhood and adolescence. Sleep problems in early infants tend to be persistent and prominent in preschool and school-aged children. Chronic sleep disorders, especially in young child...Sleep disturbances are common in childhood and adolescence. Sleep problems in early infants tend to be persistent and prominent in preschool and school-aged children. Chronic sleep disorders, especially in young children may lead to neurobehavioral problems and psycho-cognitive impairment. Sleep difficulties may be the result of underlying medical conditions, （breathing disorders） or psychological problems. Research studies have shown the association between sleep disorders and day time cognitive impairment, behavioral problems, poor school performance and inattention in children. Appropriate diagnosis and early management of sleep disorders in children lead to improvement of neurocognitive function and behavioral problems in these children.展开更多
Several reports suggest that college students often have atypical sleep patterns and experience poor sleep quality. We examined the effect of a cognitive behavioral therapy (CBT) based intervention program to improve ...Several reports suggest that college students often have atypical sleep patterns and experience poor sleep quality. We examined the effect of a cognitive behavioral therapy (CBT) based intervention program to improve sleep quality and overall mental health among college students. The intervention was delivered in the form of e-mail newsletters. Fifty-three students participated in the intervention group, and another 50 students participated in the control group. The intervention group received a lecture on sleep hygiene;once-weekly e-mail newsletters on sleep health topics (sleep hygiene, stimulus control, sleep restriction, sleep titration, and relapse prevention) and were asked to maintain a four-week sleep diary. The Pittsburgh Sleep Quality Index (PSQI), a measure of sleep quality, and the Kessler 6, a measure of psychological distress, were administered before the lecture (as the baseline measurement) and again 16 weeks later (follow-up measurement). PSQI and K6 scores were reduced in the intervention group compared with the control group. A CBT-based sleep health program utilizing e-mail newsletters may work to improve sleep quality and mental health. This program may represent a cost effective way for Japanese students to receive treatment for poor sleep and may also serve to prevent psychiatric problems.展开更多
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An overview is presented of the literature dealing with sleep-like motility and concomitant neuronal activity patterns throughout the life cycle in vertebrates, ectothermic as well as endothermic. Spontaneous, periodically modulated, neurogenic bursts of non-purposive movements are a universal feature of larval and prenatal behavior, which in endothermic animals （i.e. birds and mammals） continue to occur periodically throughout life. Since the entire body musculature is involved in ever-shifting combinations, it is proposed that these spontaneously active periods be designated as ＇rapid-BODY-movement＇ （RBM） sleep. The term ＇rapid-EYE- movement （REM） sleep＇, characterized by attenuated muscle contractions and reduced tonus, can then be reserved for sleep at later stages of development. Mature stages of development in which sustained muscle atonia is combined with ＇paradoxical arousal＇ of cortical neuronal firing patterns indisputably represent the evolutionarily most recent aspect of REM sleep, but more research with ectothermic vertebrates, such as fish, amphibians and reptiles, is needed before it can be concluded （as many prematurely have） that RBM is absent in these species. Evidence suggests a link between RBM sleep in early development and the clinical condition known as ＇REM sleep behavior disorder （RBD）＇, which is characterized by the resurgence of periodic bouts of quasi-fetal motility that closely resemble RBM sleep. Early developmental neuromotor risk factors for RBD in humans also point to a relationship between RBM sleep and RBD.
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.
文摘Purpose: Rapid eye movement sleep behavior disorder (RBD) and impulse control disorders (ICDs) are common in subjects with Parkinson’s disease. The association between these two conditions has been contradictory. The aim of this study is to analyze the association between these two non-motor symptoms. Methods: Consecutive subjects with Parkinson’s disease attending the Movement Disorders Outpatient Clinic were included. The presence of ICDs was assessed using the Questionnaire for Impulse Control Disorders Rating Scale. RBD was diagnosed by an overnight, single night polysomnography. Results: Fifty-five consecutive subjects with Parkinson’s disease were included. The prevalence of ICDs and related behaviors was 23.6% (ICD in 14.5% and related behaviors in 9.1%). RBD was diagnosed in 47.2% of the patients. No differences were found in the frequency of ICDs and related behaviors when comparing subjects with and without RBD (23% versus 24.1%, p = 0.926, respectively). Conclusion: No association between the presence of RBD and the frequency of ICDs in subjects with Parkinson’s disease was found.
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supported by National Key R&D Program of China(2021YFC2502200)The Young Top-notch Talent Cultivation Program of Hubei Province,and the China Postdoctoral Science Foundation(2024M751021).
文摘Sleep behaviors and physical activity(PA)are widely used to predict the risk of neurodegenerative disease.However,how sleep and PA interact to influence brain and cognitive health remains unknown.This study investigated independent,joint,and interacting associations of sleep behaviors and PA with brain structures and cognitive phenotypes using linear regression and generalized linear models among over 40,000 middle-aged and older participants in UK Biobank.We first found that unhealthy sleep patterns,abnormal sleep duration and high levels of PA were each associated with worse cognitive function and brain structure damage.Joint association analyses revealed that the group with long sleep duration and low levels of PA had the greatest prevalence of white matter hyperintensities(WMH;β=0.131,PFDR=0.013),a key metric of brain structural changes.Interestingly,interaction analysis suggested that a high level of PA significantly mitigates brain damage in relation to long sleep duration(i.e.,grey matter loss,βmoderate-long=-0.088,βhigh-long=-0.013,Pinteraction=0.024).In terms of cognitive phenotypes,a combination of long sleep and low levels of PA was similarly associated with worse cognitive performance(i.e.,symbol digit scores,β=-0.043,PFDR=0.018).Additionally,when stratified by PA levels,long sleep duration exhibited a negative impact on cognition compared to normal sleep duration among those with low PA,but this effect was smaller or insignificant for those engaging in moderate or high PA(i.e.,symbol digit scores,βlow-long=-0.047,PFDR=0.029;βmoderate-long=-0.022,PFDR=0.025;βhigh-long=-0.016,PFDR=0.239).Overall,maintaining a high PA level during late middle age could potentially mitigate the detrimental effects on brain structure associated with excessive sleep.Healthy sleep habits alongside an adequate PA level are essential for maintaining brain health during aging.
基金supported by the National Natural Science Foundation of China(No.82271459 and No.82071422).
文摘Background Dorsal nigral hyperintensity(DNH)abnormality associated with excessive iron deposition in the substantia nigra,is recognized as an imaging characteristic of Parkinson’s disease(PD)and can be effectively visualized using 7T MRI.This study was aimed to develop and validate the optimal DNH assessment method as a biomarker for PD,idiopathic rapid eye movement sleep behavior disorder(iRBD),and Parkinson-plus syndromes,and to explore the nigral iron deposition patterns in these diseases.Methods Three-dimensional gradient-echo T2*-weighted images were acquired by 7T MRI from a total of 402 patients and 100 healthy controls(HCs)in two independent cohorts(development and validation cohorts).Seven methods,including four dichotomous methods and three DNH rating scales,were used to assess DNH and evaluate their diagnostic performance.R2*mapping and principal component analysis were performed to assess nigral iron deposition patterns.Results Bilateral DNH detection rates in the development cohort were 22.6%for early-stage PD,3.7%for advanced PD,93.5%for iRBD,5.7%for MSA-parkinsonian type,78.8%for MSA-cerebellar type,11.8%for progressive supranuclear palsy(PSP),and 100%for HC,with similar rates in the validation cohort.A cut-off of 6 on the 6-point visibility scale demonstrated a 100%accuracy for diagnosing early-stage PD in both the development and the validation cohorts.This scale exhibited moderate differential diagnostic performance between early-stage PD and iRBD(area under the curve[AUC]=0.940)or MSA-C(AUC=0.892).Iron deposition was predominantly in the dorsal and posterior substantia nigra of PD and PSP,the intermediate and posterior substantia nigra of MSA-P,and the ventral substantia nigra of MSA-C.Conclusion DNH may be preserved in approximately one-quarter of early-stage PD and most MSA-C cases.The 6-point visibility scale on 7T effectively distinguished PD from HC,iRBD,and MSA-C.The nigral iron deposition pattern in PD may help distinguish PD from MSA-P and MSA-C,although it overlaps with that of PSP.
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Objective： Rapid eye movement sleep behavior disorder （RBD） is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson＇s disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions. Data Sources： Using the combined keywords： ＂RBD＂, ＂neurodegenerative disease＂, ＂Parkinson disease＂, and ＂magnetic resonance imaging＂, the PubMed/MEDLINE literature search was conducted up to January 1, 2018. Study Selection： A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full. Results： Single-nucleotide polymorphisms in SCARB2 （rs6812193） and MAPT （rs12185268） were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings. Conclusions： More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatnaent trials to determine the effectiveness of interventions of RBD on preventing the conversion 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Sleep disturbances are common in childhood and adolescence. Sleep problems in early infants tend to be persistent and prominent in preschool and school-aged children. Chronic sleep disorders, especially in young children may lead to neurobehavioral problems and psycho-cognitive impairment. Sleep difficulties may be the result of underlying medical conditions, （breathing disorders） or psychological problems. Research studies have shown the association between sleep disorders and day time cognitive impairment, behavioral problems, poor school performance and inattention in children. Appropriate diagnosis and early management of sleep disorders in children lead to improvement of neurocognitive function and behavioral problems in these children.
文摘Several reports suggest that college students often have atypical sleep patterns and experience poor sleep quality. We examined the effect of a cognitive behavioral therapy (CBT) based intervention program to improve sleep quality and overall mental health among college students. The intervention was delivered in the form of e-mail newsletters. Fifty-three students participated in the intervention group, and another 50 students participated in the control group. The intervention group received a lecture on sleep hygiene;once-weekly e-mail newsletters on sleep health topics (sleep hygiene, stimulus control, sleep restriction, sleep titration, and relapse prevention) and were asked to maintain a four-week sleep diary. The Pittsburgh Sleep Quality Index (PSQI), a measure of sleep quality, and the Kessler 6, a measure of psychological distress, were administered before the lecture (as the baseline measurement) and again 16 weeks later (follow-up measurement). PSQI and K6 scores were reduced in the intervention group compared with the control group. A CBT-based sleep health program utilizing e-mail newsletters may work to improve sleep quality and mental health. This program may represent a cost effective way for Japanese students to receive treatment for poor sleep and may also serve to prevent psychiatric problems.
