How non-rapid eye movement sleep and Alzheimer pathology are linked

Alzheimer's disease(AD)is a multifactorial neurodegenerative disorder characterized by the presence of senile plaques and neurofibrillary tangles.Research attempts to identify characteristic factors that are associated with the presence of the AD pathology on the one hand and that increase the risk of developing AD on the other.Changes in non-rapid eye movement(NREM)sleep may meet both requirements for various reasons.First,NREM-sleep is important for optimal memory function.In addition,studies report that the presence of AD pathology is associated with NREM-sleep changes.Finally,more and more results appear to suggest that sleep problems are not only a symptom of AD but can also increase the risk of AD.Several of these studies suggest that it is primarily a lack of NREM-sleep that is responsible for this increased risk.However,the majority investigated sleep only through subjective reporting,as a result of which NREMsleep could not be analyzed separately.The aim of this literature study is therefore to present the results of the studies that relate the AD pathology and NREM-sleep(registered by electroencephalography).Furthermore,we try to evaluate whether NREM-sleep analysis could be used to support the diagnosis of AD and whether NREM-sleep deficiency could be a causal factor in the development of AD.

Assessing gray matter volume in patients with idiopathic rapid eye movement sleep behavior disorder

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).

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.

Gender Differences in Rapid Eye Movement-Related Sleep Disordered Breathing

Sleep disordered breathing (SDB) is an independent risk factor for cardiovascular disease. It is known to be associated more frequently with men than women, particularly in the premenopausal age range. The goal of this study is to evaluate gender differences among Korean patients diagnosed with SBD. This study included 309 patients who visited our Sleep Clinic due to sleep-related symptoms and were diagnosed with SDB by overnight polysomnography (PSG). We analyzed age, gender, body mass index, various PSG indices including sleep stages, apnea-hypopnea index (AHI) and AHI ratio in rapid eye movement (REM) versus non-REM (NREM) sleep stages (R:N ratio). Of those 309 patients diagnosed with obstructive sleep apnea, 217 (70.2%) were men (mean age 51.05 ± 12.64 years) and 92 (29.8%) were women (mean age 64.53 ± 10.43 years). The mean AHI during total sleep time was 30.34 ± 21.17 in men and 21.47 ± 17.14 in women (P P P = 0.402). REM SDB with R:N ratio higher than 2.0 was more frequently observed in women than in men, 34.8% (32/92) of women, compared with 11.9% (26/217) in men (P 60 years old. These findings suggest the possibility of different pathophysiologic mechanisms of SDB between genders and also between NREM versus REM sleep, which can be partly explained by the influence of female sex hormones.

Effect of Sleep Deprivation on Eye Movement Behavior in Flight Simulation

To examine the effect of sleep deprivation （SD） on eye movement be- havior in flight task, four subjects who were skilled in flight simulator participated in the experiment, which were asked to perform a level flight task in a flight simulator. Eye movement data and flight performance data were measured at the following hours： 11：00, 15：00, 04：00, 11：00, 15：00. The subjects workload and fatigue were assessed with the method of national aeronautics and space administration-task load index （NASA-TLX） and rating of perceived exertion （RPE）. Eye movement indices of average pupil area, av- erage saceade amplitude and average saccade velocity decreased during the 32 h of SD and they all showed significantly change in the final SD while the index of average fixa- tion time increased in the final SD. Flight performance deteriorated during the 32 h of SD, but not significantly. The feeling of fatigue and workload reported by subjects both increased during the 32 h of SD. Daily rhythm effects on the measured indices were also found, there were a obviously change at the hour of 04：00. 32 h of SD has obvious effect on eye movement behaviors which have close relation to fatigue because of SD. The eye movement measurement can be served as a tool to continually monitor fatigue online.

Sleep disorders in Alzheimer’s disease:the predictive roles and potential mechanisms

Sleep disorders are common in patients with Alzheimer’s disease,and can even occur in patients with amnestic mild cognitive impairment,which appears before Alzheimer’s disease.Sleep disorders further impair cognitive function and accelerate the accumulation of amyloid-βand tau in patients with Alzheimer’s disease.At present,sleep disorders are considered as a risk factor for,and may be a predictor of,Alzheimer’s disease development.Given that sleep disorders are encountered in other types of dementia and psychiatric conditions,sleep-related biomarkers to predict Alzheimer’s disease need to have high specificity and sensitivity.Here,we summarize the major Alzheimer’s disease-specific sleep changes,including abnormal non-rapid eye movement sleep,sleep fragmentation,and sleep-disordered breathing,and describe their ability to predict the onset of Alzheimer’s disease at its earliest stages.Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer’s disease.This paper therefore explores some potential mechanisms that may contribute to sleep disorders,including dysregulation of the orexinergic,glutamatergic,andγ-aminobutyric acid systems and the circadian rhythm,together with amyloid-βaccumulation.This review could provide a theoretical basis for the development of drugs to treat Alzheimer’s disease based on sleep disorders in future work.

Memory consolidation during sleep and adult hippocampal neurogenesis

In anticipation of the massive burden of neurodegenerative disease within super-aged societies, great efforts have been made to utilize neural stem and progenitor cells for regenerative medicine. The capacity of intrinsic neural stem and progenitor cells to regenerate damaged brain tissue remains unclear, due in part to the lack of knowledge about how these newly born neurons integrate into functional circuitry. As sizable integration of adult-born neurons naturally occurs in the dentate gyrus region of the hippocampus, clarifying the mechanisms of this process could provide insights for applying neural stem and progenitor cells in clinical settings. There is convincing evidence of functional correlations between adult-born neurons and memory consolidation and sleep; therefore, we describe some new advances that were left untouched in our recent review.

Polysomnographic sleep aspects in liver cirrhosis: A case control study

AIM: To study sleep aspects and parameters in cirrhotic patients and assess the role of liver dysfunction severity in polysomnographic results. METHODS: This was a case-control study. Patients with a diagnosis of liver cirrhosis were consecutively enrolled in the study. Clinical examinations and laboratory liver tests were performed in all patients, and disease severity was assessed using the Child-Pugh score. The control group consisted of ageand gender-matched healthy volunteers. All individuals answered a questionnaire about habits, behaviors, and complaints related to sleep and were submitted to polysomnography. Sleep parameters were compared between the two groups, and separate analyses were performed among classesof Child-Pugh classification in the cirrhotic group. RESULTS: Forty-two cirrhotic patients and forty-two controls were enrolled. Compared to the control group, the cirrhotic group exhibited lower sleep efficiency (mean ± SD: 73.89% ± 14.99% vs 84.43% ± 8.55%, P < 0.01), increased latency (151.27 ± 93.24 min vs 90.62 ± 54.74 min, P < 0.01) and a lower percentage of rapid eye movement (REM) sleep (14.04% ± 5.64% vs 20.71% ± 6.77%, P < 0.05) as well as a higher frequency of periodic limb movements (10.56 ± 2.85/h vs 2.79 ± 0.61/h, P < 0.01). The comparison of sleep parameters among Child A, B and C cirrhotic patients revealed a significant reduction of REM sleep stage occurrence in individuals with severe liver disease (Child C patients) compared to Child A/B patients (polysomnography percentage of REM sleep stage of patients Child A: 16.1% ± 1.2%; Child B: 14.9% ± 1.2%; Child C: 8.6% ± 1.6%, P < 0.05). CONCLUSION: Cirrhosis was associated with shorter sleep time, reduced sleep efficiency, increased sleep latency, increased REM latency and reduced REM sleep. Additionally, disease severity influences sleep parameters.

Modifi cation of sleep architecture in an animal model of experimental cirrhosis

AIM： To analyze the polygraphic sleep patterns during cirrhosis progression in a rat model by repeated CCh administration. METHODS： Male Wistar rats received three weekly injections of CCl4 for 11 wk, and were analyzed before and during the induction of cirrhosis. Rats were im- planted with electrodes to record their sleep patterns. Polygraph recordings were made weekly over 11 wk for 8 h, during the light period. After a basal recording, rats received three weekly injections of CCl4. Histological confirmation of cirrhosis was performed after 11 wk. RESULTS： The results showed a progressive decrease in total wake time that reached statistical significance from the second week of treatment. In addition, there was an increase in total time of slow wave sleep （SWS）Ⅱ and rapid eye movement sleep （REM sleep） in most of the 11 wk. SWS I showed no significant variations. During the final weeks, a significant increase in REM sleep frequency was also observed. Histological analyses of the livers showed unequivocal signs of cirrhosis. CONCLUSION： These data suggest that hepatic failure produced by CCh administration is capable of modifying the sleep pattern even after only a few doses.

Sleep Paralysis - Cultural Significance and Its Management

Sleep paralysis (SP) is a benign,transient episode of immobility and it lasts a few seconds to a few minutes.It can occur while falling asleep or on awakening.It is a condition of unknown etiology and all the skeletal muscles are almost ‘paralyzed’.It leads to an inability to speak or move but individual remains conscious.This review summarizes the existential clinical literature on sleep paralysis most relevant to practitioners;also summarizes the many historical and artistic manifestations of SP in different cultures.It also throws light on the available Arabic literature and others as per the aim of the review.For this review,literature search using engines was carried out,and review papers and original research articles were analyzed.We start with a review which summarizes the collection of symptoms,prevalence rate,risk factors and etiological theories,characteristics and classification of the SP over the past years up to the present time,also the management in the form of psychotherapy and pharmacotherapy as well as the cultural significances in different countries.SP plays an important role in the genesis and maintenance of many supernatural beliefs such as nocturnal alien abductions,demonic and ghost attacks in individuals with intact reality testing.

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.

Increased Arousal Levels and Decreased Sleep by Brain Music in Rats

More and more studies have been reported on whether music and other types of auditory stimulation would improve the quality of sleep. Many of these studies have found significant results, but others argue that music is not significantly better than the tones or control conditions in improving sleep. For further understanding the relationship between music and sleep or music and arousal, the present study therefore examines the effects of brain music on sleep and arousal by means of biofeedback. The music is from the transformation of rapid eye movement （REM） sleep electroencephalogram （EEG） of rats using an algorithm in the Chengdu Brain Music （CBM） system. When the brain music was played back to rats, EEG data were recorded to assess the efficacy of music to induce or improve sleep, or increase arousal levels by sleep staging, etc. Our results demonstrate that exposure to the brain music increases arousal levels and decreases sleep in rats, and the underlying mechanism of decreased non-rapid eye movement （NREM） and REM sleep may be different.

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.

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.

CSF Aβ1-42 level is associated with cognitive decline in early Parkinson’s disease with rapid eye movement sleep behavior disorder

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.

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.

Auditory evoked potentials recorded in monkeys with hallucinatory-like behaviors induced by bromocriptine

Objective Bromocriptine and other dopamine D2 receptor agonists can affect a range of behaviors in nonhuman primates, particularly those behaviors associated with motor and mental function, such as suppressant behaviors and hallucinatory-like behaviors in monkeys. Besides bromocriptine, the dysfunction of the rapid eye movement sleep （REM） mechanism may also contribute to hallucinations. Dissociation of wakefulness, REM, and non-REM （NREM） can cause a series of psychotic symptoms. Methods In present study, we simultaneously recorded auditory evoked potentials （AEP） from five cerebral regions in monkeys during normal and psychotomimetic states to investigate and compare state-dependent changes in AEE Results Phase reversal of peak-to-baseline amplitude of 250 ms component （PBA250） in dorsolateral prefrontal cortex was common characteristic of hallucinatory-like and REM, and that hallucinatory-like and REM shared the equivalent modulatory orderliness of the PBA250 in dorsolateral prefrontal cortex. This result suggests that hallucinatory-like and REM share an equivalent electrophysiological modulatory in dorsolateral prefrontal cortex. Conclusion Our results reveal that emergence of the N250 in dorsolateral prefrontal cortex is an exclusive marker that may help to discern whether hallucinatory-like behaviors is exhibited, which suggests that dorsolateral prefrontal cortex may be the most pivotal region for exhibition of hallucinatory-like 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.

Longitudinal evolution of cortical thickness signature reflecting Lewy body dementia in isolated REM sleep behavior disorder:a prospective cohort study

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.