Empirically supported psychological treatments:The challenges of comorbid psychiatric and behavioral disorders in people with intellectual disability

This paper reviews the current state of knowledge on psychological interventions with empirical evidence of efficacy in treating common psychiatric and behavioral disorders in people with intellectual disability(ID)at all stages of their life.We begin with a brief presentation of what is meant by psychiatric and behavioral disorders in this population,along with an explanation of some of the factors that contribute to the increased psychosocial vulnerability of this group to present with these problems.We then conduct a review of empirically supported psychological therapies used to treat psychiatric and behavioral disorders in people with ID.The review is structured around the three generations of therapies:Applied behavior analysis(e.g.,positive behavior support),cognitive behavioral therapies(e.g.,mindfulness-based cognitive therapy),and contextual therapies(e.g.,dialectical behavior therapy).We conclude with some recommendations for professional practice in the fields of ID and psychiatry.

Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance

Objective This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016(CNBS-R2016)for Autism Spectrum Disorder(ASD)screening in the presence of developmental surveillance.Methods All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules(GDS).Spearman’s correlation coefficients and Kappa values were obtained.Taking GDS as a reference assessment,the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic(ROC)curves.The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule,Second Edition(ADOS-2).Results In total,150 children aged 12–42 months with ASD were enrolled.The developmental quotients of the CNBS-R2016 were correlated with those of the GDS(r=0.62–0.94).The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays(Kappa=0.73–0.89),except for Fine Motor.There was a significant difference between the proportions of Fine Motor,delays detected by the CNBS-R2016 and GDS(86.0%vs.77.3%).With GDS as a standard,the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor,which was 0.70.In addition,the positive rate of ASD was 100.0%and 93.5%when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used,respectively.Conclusion The CNBS-R2016 performed well in developmental assessment and screening for children with ASD,especially by Communication Warning Behaviors subscale.Therefore,the CNBS-R2016 is worthy of clinical application in children with ASD in China.

Lack of Association between Impulse Control Disorders and REM Sleep Behavior Disorder in Patients with Parkinson’s Disease

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.

Current Evidence and Diverse Perspectives on Attention-Deficit/Hy­peractivity Disorder:A Systematic Review

Introduction:ADHD is one of the most common neurodevelopmental disorders in childhood and adolescence.Although the disorder starts to manifest early in childhood,a significant proportion of cases often persists into adulthood.ADHD negatively and significantly impacts social and occupational functioning and academic performance.A number of extant theories and scientific evidence provide insight into the genesis and manifestations of ADHD and the attendant challenges of significant dysfunction that individuals may encounter at home,school,and the workplace.Method:This systematic review was conducted through a literature search for published peer-reviewed articles using standard PRISMA guidelines.The goal of the study was to explore current theories,models,concepts,and risk factors about ADHD published in peer-reviewed literature.We made use of use several online databases-including PsycINFO,PubMed,Web of Science,ScienceDirect,and Medline in the process of searching for relevant studies.Relevant peer-reviewed publications since the 1980s when the term Attention-Deficit/Hyperactivity Disorder(ADHD)was introduced in DSM-III-R were included.Non-peer-reviewed publications,including dissertations,editorials,commentaries,and materials published in languages other than English were excluded.Results and Discussion:The results of the review indicated that ADHD is characterized by a behavioral reaction that interferes with personal and social functioning.The factors associated with ADHD fall into several major thematic areas,including genetic and hereditary factors;dietary and nutritional factors;parenting and behavioral factors;adverse early life events,and high-risk environmental factors,crystallized by a number of developmental and behavioral theories.The review also identified a number of extant models and theories that attempt to explain the diverse perspectives associated with ADHD.Conclusions:This study has attempted to identify the major risk factors and diverse models and theories associated with ADHD.The thematic risk factors include genetic and hereditary factors;dietary and nutritional factors;parenting and behavioral factors;adverse early life events,and high-risk environmental factors.The most prominent models identified include the biomedical model and the bio-psycho-social models,the latter being a more holistic approach which aims to treat both the patient and the disease.This review would provide an additional evidence base to individuals,families,and educators to make informed choices and decisions in the best interest of the affected children,including their personal growth,healthcare,and medical needs,academic performance,and social skills development.

Effect of gluten free diet on gastrointestinal and behavioral indices for children with autism spectrum disorders:a randomized clinical trial

Background:Genetic and environmental factors are both responsible for the etiology of autism spectrum disorders(ASD).Although epidemiological studies have been conducted to clarify the association between restriction diets and ASD,the conclusion remains unclear.This study was undertaken to investigate the effect of gluten free diet(GFD)on gastrointestinal symptoms and behavioral indices in children with ASD.Methods:In this randomized clinical trial,80 children diagnosed with ASD by the Autism Diagnostic Interview-Revised(ADI-R)were assigned into GFD(n=40)and regular diet(RD)(n=40)groups for 6 weeks.At the beginning and end of the intervention,the ROMEШquestionnaire for evaluating gastrointestinal symptoms and Gilliam Autism Rating Scale 2 questionnaire(GARS-2)for assessing psychometric properties were completed.Results:Of the 80 children,53.9%had gastrointestinal abnormalities.In the GFD group,the prevalence of gastrointestinal symptoms decreased significantly(P<0.05)after intake of GFD(40.57%vs.17.10%)but increased insignificantly in the RD group(42.45%vs.44.05%).GFD intervention resulted in a significant decrease in behavioral disorders(80.03±14.07 vs.75.82±15.37,P<0.05)but an insignificant increase in the RD group(79.92±15.49 vs.80.92±16.24).Conclusion:This study suggested that GFD may be effective in controlling gastrointestinal symptoms and ASD behaviors.

Development of a depression in Parkinson's disease prediction model using machine learning

BACKGROUND It is important to diagnose depression in Parkinson’s disease(DPD)as soon as possible and identify the predictors of depression to improve quality of life in Parkinson’s disease(PD)patients.AIM To develop a model for predicting DPD based on the support vector machine,while considering sociodemographic factors,health habits,Parkinson's symptoms,sleep behavior disorders,and neuropsychiatric indicators as predictors and provide baseline data for identifying DPD.METHODS This study analyzed 223 of 335 patients who were 60 years or older with PD.Depression was measured using the 30 items of the Geriatric Depression Scale,and the explanatory variables included PD-related motor signs,rapid eye movement sleep behavior disorders,and neuropsychological tests.The support vector machine was used to develop a DPD prediction model.RESULTS When the effects of PD motor symptoms were compared using“functional weight”,late motor complications(occurrence of levodopa-induced dyskinesia)were the most influential risk factors for Parkinson's symptoms.CONCLUSION It is necessary to develop customized screening tests that can detect DPD in the early stage and continuously monitor high-risk groups based on the factors related to DPD derived from this predictive model in order to maintain the emotional health of PD patients.

Treatment of acute ischemic stroke by minimally manipulated umbilical cord-derived mesenchymal stem cells transplantation:A case report

BACKGROUND Stroke is one of the major causes of disability and death worldwide.Some treatments for stroke exist,but existing treatment methods have limitations such as difficulty in the regeneration of damaged neuronal cells of the brain.Recently,mesenchymal stem cells(MSCs)have been studied as a therapeutic alternative for stroke,and various preclinical and case studies have been reported.CASE SUMMARY A 55-year-old man suffered an acute stroke,causing paralysis in the left upper and lower limbs.He intravenously transplanted the minimally manipulated human umbilical cord-derived MSCs(MM-UC-MSCs)twice with an 8-d interval.At 65 wk after transplantation,the patient returned to his previous occupation as a veterinarian with no adverse reactions.CONCLUSION MM-UC-MSCs transplantation potentially treats patients who suffer from acute ischemic stroke.

Chemogenetic activation of sublaterodorsal tegmental glutamatergic neurons alleviates rapid eye movement sleep behavior disorder symptoms in a chronic rat model of Parkinson disease

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.

Sleep Disturbance in Parkinson’s Disease Varies with Age of Onset and Family History

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.

Genetic heterogeneity on sleep disorders in Parkinson’s disease: a systematic review and meta-analysis

A growing amount of evidence has indicated contributions of variants in causative genes of Parkinson’s disease (PD) to the development of sleep disturbance in PD and prodromal PD stages. In this article, we aimed to investigate the role of genetics in sleep disorders in PD patients and asymptomatic carriers at prodromal stage of PD. A systematic review and meta-analysis of observational studies was conducted based on the MEDLINE, EMBASE and PsychINFO databases. A pooled effect size was calculated by odds ratio (OR) and standard mean difference (SMD). Forty studies were selected for quantitative analysis, including 17 studies on glucocerebrosidase (GBA), 25 studies on Leucine-rich repeat kinase 2 (LRRK2) and 7 on parkin (PRKN) genes, and 3 studies on alpha-synuclein gene (SNCA) were used for qualitative analysis. Patients with PD carrying GBA variants had a significantly higher risk for rapid-eye-movement behavior disorders (RBD) (OR, 1.82) and higher RBD Screening Questionnaire scores (SMD, 0.33). Asymptomatic carriers of GBA variants had higher severity of RBD during follow-up. Patients with PD carrying the LRRK2 G2019S variant had lower risk and severity of RBD compared with those without LRRK2 G2019S. Variants of GBA, LRRK2 and PRKN did not increase or decrease the risk and severity of excessive daytime sleepiness and restless legs syndrome in PD. Our findings suggest that the genetic heterogeneity plays a role in the development of sleep disorders, mainly RBD, in PD and the prodromal stage of PD.

Clinical Significance of REM Sleep Behavior Disorders and Other Non-motor Symptoms of Parkinsonism

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.

Effect of Rapid Eye Movement Sleep Behavior Disorder on Obstructive Sleep Apnea Severity and Cognition of Parkinson＇s Disease Patients

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.

The Mechanism of Cortico-Striato-Thalamo-Cortical Neurocircuitry in Response Inhibition and Emotional Responding in Attention Deficit Hyperactivity Disorder with Comorbid Disruptive Behavior Disorder

The neurocircuitries that constitute the corticostriato-thalamo-cortical（CSTC） circuit provide a framework for bridging gaps between neuroscience and executive function in attention deficit hyperactivity disorder（ADHD）, but it has been difficult to identify the mechanisms for regulating emotional problems from the understanding of ADHD comorbidity with disruptive behavior disorders（DBD）. Research based on ＂cool＇＇ and ＂hot＇＇executive functional theory and the dual pathway models,which are thought of as applied response inhibition and delay aversion, respectively, within the neuropsychological view of ADHD, has shed light on emotional responding before and after decontextualized stimuli, while CSTC circuit-related domains have been suggested to explain the different emotional symptoms of ADHD with or without comorbid DBD. This review discusses the role of abnormal connections in each CSTC circuit, especially in the emotion circuit, which may be responsible for targeted executive dysfunction at the neuroscience level. Thus, the two major domains – abstract thinking（cool） and emotional trait（hot） – trigger the mechanism of onset of ADHD.

Premotor Diagnosis of Parkinson's Disease

Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder and depression may antecede these motor symp- toms for years. It would be ideal, if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinson＇s disease （PD）. Thus, it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD, if there is a high amour of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein. This would be of relevance if we would have available means to stop the propagation of abnormal alpha-synuclein which is otherwise one of the reasons of this spreading disease PD.

Rapid Eye Movement Sleep Behavior Disorder Symptoms Correlate with Domains of Cognitive Impairment in Parkinson＆#39;s Disease

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.

Clinical features of Parkinson’s disease with and without rapid eye movement sleep behavior disorder

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.

Recent Progress in Non-motor Features of Parkinson’s Disease with a Focus on Circadian Rhythm Dysregulation

Parkinson’s disease(PD)is the second most common neurodegenerative disease,which manifests with both motor and non-motor symptoms.Circadian rhythm dysregulation,as one of the most challenging non-motor features of PD,usually appears long before obvious motor symptoms.Moreover,the dysregulated circadian rhythm has recently been reported to play pivotal roles in PD pathogenesis,and it has emerged as a hot topic in PD research.In this review,we briefly introduce the circadian rhythm and circadian rhythm-related genes,and then summarize recent research progress on the altered circadian rhythm in PD,ranging from clinical features to the possible causes of PD-related circadian disorders.We believe that future comprehensive studies on the topic may not only help us to explore the mechanisms of PD,but also shed light on the better management of PD.

Comparison Study of Polysomnographic Features in Multiple System Atrophy-cerebellar Types Combined with and without Rapid Eye Movement Sleep Behavior Disorder

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.

Perchance to dream? Primordial motor activity patterns in vertebrates from fish to mammals: their prenatal origin, postnatal persistence during sleep, and pathological reemergence during REM sleep behavior disorder

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.

Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases： Clinical Assessments, Biomarkers, and Treatment

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.