Transcranial Direct Current Stimulation: Effects on Motor and Non-Motor Symptoms of Parkinson’s Disease

Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson’s disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2 mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg and arm cramps at night and distressing dreams). There was also an improvement in the rate of errors and successes for congruent and incongruent stimuli of the Stroop Test. The beneficial effects on motor function were decreased rigidity, improved gait, and greater agility in the finger-tapping test. Conclusion: Three tDCS sessions showed positive results for participants with PD, producing significant improvements in various motor and non-motor functions, including sleep quality, cognition, and EFs. Additionally, the present results indicate that tDCS neuromodulation of the left dorsolateral prefrontal cortex region is feasible, safe, and provides significant objective benefits for PD patients.

Clinical Characteristics of Sleep Disorders in Patients with Parkinson's Disease

In order to investigate the sleep quality and influencing factors in patients with Parkinson＇s disease（PD）, 201 PD patients were enrolled and underwent extensive clinical evaluations. Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index（PSQI）, and the Epworth Sleepiness Scale（ESS）. It was found that poor sleep quality（77.11%） and excessive daytime sleepiness（32.34%） were commonly seen in PD patients and positively correlated with disease severity. Then 70 out of the 201 PD patients and 70 age- and sex-matched controls underwent a polysomnographic recording. The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed. The results showed that sleep efficiency（SE） was significantly decreased（P〈0.01）, and sleep latency（SL） and the arousal index（AI） were increased（P〈0.05） in the PD group as compared with those in the control group. SE and total sleep time（TST） were positively correlated with the Hoehn and Yahr（H＆Y） stage. There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group（P〈0.05）. Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder, which may be correlated with the disease severity. Respiratory function and oxygen supply are also affected to a certain degree in PD patients.

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.

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.

Health-related quality of life in Parkinson's disease patients in northeastern Sicily, Italy An ecological perspective

Parkinson＇s disease has a negative impact on health-related quality of life in Parkinson＇s disease patients. Depression, cognitive impairment, coping strategies, dyskinesia, gait disorders and complications of dopaminergic drugs are the variables that most affect health-related quality of life. The ecological model of human development focuses attention on both individual and social environmental factors as targets for health interventions. From this perspective, the aim of this cross-sectional survey was to evaluate the influence of gender, family size and perceived autonomy on health-related quality of life in Parkinson＇s disease patients in nOrtheastern Sicily, Italy. Ninety Parkinson＇s disease patients, attending the Movement Disorders Clinic at IRCCS Centro Neurolesi ＂Bonino-Pulejo＂ （Messina）, were consecutively enrolled. The Unified Parkinson Disease Rating Scale motor subscale （UPDRS-Ⅲ） scores, the Parkinson Disease Questionnaire-39 Item scores （as a disease-specific measure of health-related quality of life）, scores on the Short Form （36） Health Survey Questionnaire （as a generic measure）, and answers to a brief checklist were recorded. A total of 85 Parkinson＇s disease patients （49% males and 51% females; mean age 70.8 ± 8.6 years mean UPDRS-Ⅲ 24.15 ± 6.55; mean disease duration 5.52 ± 4.65 years） completed the booklet of questionnaires. In the multivariate regression analysis, we included clinical and social variables as independent predictors of health-related quality of life. Our results suggest a potential compounding effect of ecological intrapersonal and interpersonal levels on health-related quality of life outcomes. Gender, self-evaluated autonomy and family size significantly impacted health-related quality of life. If quality of life is used as an indicator of treatment outcomes, an ecological perspective of the case history will be important to disclose relevant prognostic information and trigger personalized health care interventions.

Parkinson’s Disease: Examining the Role of the Pedunculopontine Nucleus via Animal Models

Parkinson’s disease is a neurodegenerative disease that spreads rapidly through the brain, and can influence a number of vital systems. The cause of this disease appears to be brought on by the progressive inability to produce adequate dopamine in the brain. People that suffer with Parkinson’s have reported REM sleep disruption at the onset of the condition. This paper reviews several animal model lesion studies related to the Pedunculopontine Nucleus, and how it plays a role in sleep regulation following a decline in dopamine production in those with parkinsonian conditions. The goal of this paper is to elucidate the functioning of the PPN and explain the nuclei’s possible role in the onset and progression of parkinsonian conditions in animal models.

Properties of the Apathy Scale(AS)for use on Parkinson’s patients

Parkinson’s disease is a neurodegenerative disorder characterized by motor, autonomic, and neuropsychiatric symptoms, among the latter, apathy has been found to be present in up to 70% of patients. The main objective of the present study was to assess the psychometric properties of the Apathy Scale for evaluation of Ecuadorian patients with Parkinson’s. This was a cross sectional study, with re-test. There were 73 women (34.5%) in the final sample of 211 patients. Mean age was 67.5 ± 10.2 years, mean length of illness was 7.1 ± 5.5 years, and the mean ldopa dose was 656.1 ± 292.7 mg/day. The mean Apathy Scale score was 12.7 ± 7.1. Reliability: The Guttman’s λ obtained was 0.89. The SEM was 2.34 for the AS. The ICC using an absolute agreement definition was: ICC = 0.78 [(95% IC 0.73?- 0.82) f = 4.96;p ≤ 0.000]. Discriminative validity, analyzed with the Kruskal-Wallis statistic and using H&Y stages as segmentation variable registered an X(2) value of p 0.0001. In conclusion the Apathy Scale proved to have suitable metric attributes in this specific PD patient sample: internal consistency, reliability, stability, and convergent and known-groups validity.

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).

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.

Increased Serum Cystatin C in Early Parkinson’s Disease with Objective Sleep Disturbances

Background：Sleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson’s disease （PD） patients. Cystatin C （CysC） is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD.Methods：We recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients.Results：The mean serum level of CysC was significantly higher in patients with early PD （1.03 ± 0.19 mg/L） compared to controls （0.96 ± 0.15 mg/L, P = 0.009）. There were significantly positive correlations between serum CysC levels and age （r = 0.334, P 〈 0.001）, gender （r = 0.264, P = 0.013）, and creatinine levels （r = 0.302, P = 0.018） in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index （AHI） （r = 0.231, P = 0.017）, especially hypopnea index （r = 0.333, P 〈 0.001）. In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index （r = 0.223, P = 0.021）, percentage of time spent at oxygen saturation （SaO2） 〈90% （r = 0.644, P 〈 0.001）, arousal with respiratory event during sleep （r = 0.247, P = 0.013）. On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO2 （r = ？0.323, ？0.315, both P = 0.001） in PD patients.Conclusions：The level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.

Excessive Daytime Sleepiness in Parkinson＇s Disease： Clinical Implications and Management

Objective：Excessive daytime sleepiness （EDS） is one of the most common sleep abnormalities in patients with Parkinson’s disease （PD）, yet its multifactorial etiology complicates its treatment. This review summarized recent studies on the epidemiology, etiology, clinical implications, associated features, and evaluation of EDS in PD. The efficacy of pharmacologic and non-pharmacologic treatments for EDS in PD was also reviewed.Data Sources：English language articles indexed in PubMed and Cochrane databases and Chinese-language papers indexed in Wanfang and National Knowledge Infrastructure databases that were published between January 1987 and November 2017 were located using the following search terms： ＂sleepiness＂ , ＂sleep and Parkinson’s disease＂ , and ＂Parkinson’s disease and treatment＂ .Study Selection：Original research articles and critical reviews related to EDS in PD were selected.Results：EDS is a major health hazard and is associated with many motor and nonmotor symptoms of PD. Its causes are multifactorial. There are few specific guidelines for the treatment of EDS in PD. It is first necessary to identify and treat any possible factors causing EDS. Recent studies showed that some nonpharmacologic （i.e., cognitive behavioral therapy, light therapy, and repetitive transcranial magnetic stimulation） and pharmacologic （i.e., modafinil, methylphenidate, caffeine, istradefylline, sodium oxybate, and atomoxetine） treatments may be effective in treating EDS in PD.Conclusions：EDS is common in the PD population and can have an immensely negative impact on quality of life. Its causes are multifactorial, which complicates its treatment. Further investigations are required to determine the safety and efficacy of potential therapies and to develop novel treatment approaches for EDS in PD.

Sleep Disorders in Parkinson＇s Disease： Present Status and Future Prospects

INTRODUCTION Parkinson＇s disease （PD） is the second most common neurodegenerative disorder in the world. In China, approximately 48-89% of Chinese patients with PD have been shown to be affected by sleep disorders, in recent decades, there have been major advances in our understanding of the relationship between sleep disorders and PD, yet many questions remain unanswered.

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.

Altered Motor Performance,Sleep EEG,and Parkinson’s Disease Pathology Induced by Chronic Sleep Deprivation in Lrrk2^(G2019S) Mice

Parkinson’s disease(PD)is a multifaceted disease in which environmental variables combined with genetic predisposition cause dopaminergic(DAergic)neuron loss in the substantia nigra pars compacta.The mutation of leucine-rich repeat kinase 2(Lrrk2)is the most common autosomal dominant mutation in PD,and it has also been reported in sporadic cases.A growing body of research suggests that circadian rhythm disruption,particularly sleep-wake abnormality,is common during the early phase of PD.Our present study aimed to evaluate the impact of sleep deprivation(SD)on motor ability,sleep performance,and PD pathologies in Lrrk2^(G2019S) transgenic mice.After two months of SD,Lrrk2^(G2019S) mice at 12 months of age showed an exacerbated PD-like phenotype with motor deficits,a reduced striatal DA level,degenerated DAergic neurons,and altered sleep structure and biological rhythm accompanied by the decreased protein expression level of circadian locomotor output cycles kaput Lrrk2 gene in the brain.All these changes persisted and were even more evident in 18-month-old mice after 6 months of follow-up.Moreover,a significant increase inα-synuclein aggregation was found in SD-treated transgenic mice at 18 months of age.Taken together,our findings indicate that sleep abnormalities,as a risk factor,may contribute to the pathogenesis and progression of PD.Early detection of sleep disorders and improvement of sleep quality may help to delay disease progression and provide long-term clinical benefits.

Tremor and clinical fluctuation are related to sleep disorders in Chinese patients with Parkinson’s disease

Objective:To study the relationship between sleep disturbances and symptoms in patients with Parkinson’s disease(PD).Methods:The Parkinson’s Disease Sleep Scale-Chinese Version(PDSS-CV)was used to evaluate the sleep disturbances of PD patients in a cross sectional study.The Unified Parkinson’s Disease Rating Scale(UPDRS)parts II-IV,and the Hoehn&Yahr(H&Y)stage were used to determine the level of motor function in PD and the severity of PD.The Spearman correlation and a multiple regression analysis were used to identify the relationship between sleep disturbances and symptoms of PD.The quantities derived from the UPDRS and the H&Y stage and disease duration were compared between groups of patients either with or without sleep disturbances identified by the PDSS.This study was conducted from December 2011 to March 2012 at the First Affiliated Hospital of Sun Yat-sen University,in Guangzhou.Results:A total of 136 PD patients were included in this study.The overall total PDSS score in PD patients was 107.58±23.35 points(range:30–146).There were significant differences in the disease duration,the H&Y stage,and the UPDRS section subscores between groups of patients either with or without sleep disturbances(Kruskal-Wallis Test,p<0.05).There were significant negative correlations between PDSS scores and the UPDRS subscores,the H&Y stage and the disease duration(Spearman correlation,p<0.05).The multiple regression analysis indicated that sleep disturbances identified by the PDSS were only associated with daily life activity,tremor intensity and clinical fluctuation(R2=0.22,F(3,132)=12.4,p<0.001).The correlations were also significant when the contribution of the other two factors was excluded using partial correlations.Conclusions:The level of daily life activity and the occurrences of tremor and clinical fluctuation are likely to be important factors that lead to PD patients’sleep disturbances.This study may elucidate an important clue for the relationship between sleep disturbances and PD symptoms.

Progressive changes of orexin system in a rat model of 6-hydroxydopamine-induced Parkinson’s disease

Objective Sleep disturbance,which is characterized by excessive daytime sleepiness and sleep attacks,is frequently observed in patients with Parkinson’s disease（PD）.Loss of orexin neurons in hypothalamus and the resultant decreased level of orexin in cerebrospinal fluid（CSF）found in narcolepsy patients may also play an essential role in the pathogenesis of sleep disturbance.The present study aimed to investigate the possible changes in the orexin system during PD progression.Methods After the establishment of a rat PD model by injecting 6-hydroxydopamine（6-OHDA）into the medial forebrain bundle,the numbers of orexin-A-and tyrosine hydroxylase（TH）-positive neurons,and the levels of orexin-A fibers and orexin-A in CSF were examined by immunohistochemistry and ELISA assay,respectively.Results Compared to the TH-containing neurons that exhibited fast degeneration in response to 6-OHDA,orexin-A-containing neurons were less sensitive to 6-OHDA.The number of orexin-A-positive neurons began to decrease at day 21 after operation,and at day 49,it decreased by 30%of the initial level.The orexin-A level in CSF of PD rats did not show any obvious fluctuations compared to the control,and there was no obvious reduction in the density of orexin-A-positive fibers in brain areas such as tuberomammillary nucleus.Conclusion These results reveal for the first time the dynamic changes of orexin system during the progression of PD.This may provide valuable information for drug development to reverse the loss of orexin neurons and sleep disturbance in PD patients.

滋肾平颤汤联合多巴丝肼片对老年帕金森病伴失眠症病人PSQI评分、TESS评分及生活质量的影响

目的探讨滋肾平颤汤联合多巴丝肼片对老年帕金森病伴失眠症病人匹茨堡睡眠质量指数量表(PSQI)评分、不良反应量表(TESS)评分及生活质量的影响。方法选取2015年8月-2017年9月西安医学高等专科学校附属医院收治的老年帕金森病伴失眠症病人96例,随机分为治疗组与对照组,每组48例。两组均给予基础治疗,在此基础上对照组应用多巴丝肼片,治疗组在对照组基础上联合滋肾平颤汤治疗。比较两组临床疗效、PSQI评分、日常生活能力、运动功能、生活质量及TESS评分。结果治疗后,治疗组总有效率为91.67%,高于对照组的72.92%,差异有统计学意义(P<0.05);治疗后两组PSQI各因子评分均低于治疗前(P<0.05),且治疗组均低于对照组(P<0.05);治疗后两组统一帕金森病评定量表第二分量表(UPDRSⅡ)、第三分量表(UPDRSⅢ)评分均低于治疗前(P<0.05),且治疗组均较对照组低(P<0.05);两组治疗后39项帕金森病生存质量调查问卷(PDQ-39)评分均低于治疗前(P<0.05),且治疗组较对照组低(P<0.05);治疗组TESS评分明显较对照组低(P<0.05)。结论滋肾平颤汤联合多巴丝肼片治疗老年帕金森病伴失眠症,可明显改善病人失眠症状,有效提高病人生活质量,并能增强其日常生活活动能力、运动功能。

A New Perspective for Parkinson's Disease:Circadian Rhythm

Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei （SCN） in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson＇s disease （PD） exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative conse- quences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.