Parkinson's Disease Sleep Scale Research Articles

Thyrotroph embryonic factor polymorphism predicts faster progression of Parkinson's disease in a longitudinal study.

The thyrotroph embryonic factor gene is a circadian clock-controlled gene. The rs738499 polymorphism of this gene has been suggested to be associated with depression and sleep disturbance in Parkinson's disease in previous cross-sectional studies. We aimed to investigate whether this single nucleotide polymorphism is associated with the progression rates of various motor and non-motor symptoms in patients with Parkinson's disease. We recruited 186 patients with Parkinson's disease for a longitudinal study. Motor and non-motor symptoms were assessed at baseline and follow-up, and 170 Parkinson's disease patients completed the clinical evaluation twice with an average follow-up period of 3.3 ± 1.1 years. A stepwise linear regression model was used to validate factors associated with Parkinson's disease symptoms' annual progression rates. Faster annual worsening rates of sleep quality and Hoehn-Yahr stage were found in carriers with the homozygous dominant (TT). After adjustment for related clinical factors, the rs738499 polymorphism showed a contribution of 3.1% to the annual decline rate on the Parkinson's Disease Sleep Scale score and a contribution of 5.5% to the annual increase rate of the Hoehn-Yahr stage. Additionally, anxiety and axial symptoms predicted the progression of sleep disturbances and motor staging. The TT genotype of rs738499 might be a potential predictor of rapid deterioration in sleep quality and Hoehn-Yahr stage in patients with Parkinson's disease and may advance the understanding of the genetic contributions to Parkinson's disease.

Pingchan granule for depressive symptoms in parkinson’s disease: A randomized, double-blind, placebo-controlled trial

BackgroundDepression in Parkinson’s disease (dPD) is closely related to quality of life. Current studies have suggested that Pingchan Granule (PCG) might be effective for treating dPD. ObjectiveThis study determines the efficacy of PCG for depressive symptoms in Parkinson’s disease (PD). Design, setting, participants and interventionsThis was a randomized, double-blind, placebo-controlled trial, conducted in Longhua Hospital, Shanghai, China. Patients diagnosed with idiopathic PD and clinically significant depressive symptoms (defined by a 24-item Hamilton Rating Scale for Depression [HAM-D] score ≥ 8) were included in this study, randomly assigned to PCG or placebo group in a 1:1 ratio and followed for 24 weeks. Main outcome measuresThe primary outcome was the change from baseline to week 24 in HAM-D score among the set of patients who completed the study following the treatment protocol (per-protocol set). Secondary outcomes included changes in scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) part 2 (UPDRS-II), UPDRS part 3 (UPDRS-III), Parkinson’s Disease Sleep Scale (PDSS) and Hamilton Rating Scale for Anxiety (HAM-A), between baseline and week 24. ResultsEighty-six patients were enrolled, and 85 patients were included in the per-protocol set. HAM-D scores decreased by an adjusted mean of 11.77 (standard error [SE] 0.25) in the PCG group and 3.86 (SE 0.25) in the placebo group (between-group difference = 7.91, 95% confidence interval [7.22, 8.80], P < 0.001), in the multivariable linear regression. Improvements in scores on the UPDRS-II, UPDRS-III, PDSS, and HAM-A scales were also observed. ConclusionTreatment with PCG was well tolerated and improved depressive symptoms and motor and other non-motor symptoms in PD. Trial registrationChinese Clinical Trial Register: ChiCTR-INR-17011949.

Sleep Disturbances in Seniors with Parkinson’s Disease

introduction:The prevalence of sleep disturbances in patients with Parkinson's disease is very high. It is one of the factors that significantly affects the health care, nursing care and also quality of life of patients and their family members. design: For the purpose of the research, design of a prospective quantitative study was chosen based on an assessment scale. aim: The research aim was to map out the prevalence of sleep disturbances in patients with Parkinson's disease and to find out the influence of sex (gernder) and stage of the disease on the sleep disturbances prevalence. methods: We used the Parkinson's Disease Sleep Scale PDSS2 to assess the symptoms of sleep disturbances. We statistically computed the results using the chi-square test and Mann- Whitney U test. The research sample consisted of 220 respondents diagnosed with Parkinson's disease, who were included in the sample on the basis of deliberate selection. results: Out of the total respondents, 115 (52.3%) show mildly severe sleep disorder according to the score of the sleep scale from 0 to 20; 67 (30.5%) respondents show moderate sleep disorder; 38 (17.3%) show severe sleep disorder according to the score of the sleep scale from 21 to 40. The median score was higher in women (20.5) compared to men (19) with no statistical significance (p=0.646). When comparing sleep disturbances by the stage of the disease, the median score was 10.5 at an early stage while 10.0 at advance stage, this difference was not significant (p value= 0.477). conclusion: The issue of the sleep disorders prevalence in patients with Parkinson's disease is highly urgent. In conclusion, we can state that neither sex (gender) nor the stage of the disease has a clear effect on the manifestations of sleep disturbances in patients with Parkinson's disease.

Association between MMP16 rs60298754 and clinical phenotypes of Parkinson's disease in southern Chinese.

The aim was to investigate the association between MMP16 rs60298754 and symptoms of Parkinson's disease (PD) in southern Chinese. Seven hundred forty-five PD patients were recruited in this study. All patients were evaluated by Brief Pain Inventory (BPI), Hamilton anxiety rating scale and Hamilton depression rating scale, 39-item Parkinson's disease Questionnaire (PDQ-39), and MDS-Unified PD Rating Scale (MDS-UPDRS). Symptoms were also recorded. The difference of BPI and Parkinson's disease sleep scale (PDSS) between two groups was showed (BPI: MMP16 wildtypes: 14.73 ± 14.45; MMP16 carriers: 10.95 ± 10.67, p 0.002; PDSS: MMP16 wildtypes: 117.80 ± 21.45; MMP16 carriers: 108.40 ± 23.95, p < 0.001). The association of apathy, nocturia, and sensitive to light were found (apathy: p 0.001, OR: 0.49, 0.32-0.76; nocturia: p < 0.001, OR: 3.57, 1.90-7.26; sensitive to light: p < 0.001, OR: 3.99, 2.01-7.74). MMP16 rs60298754 was associated with the presence of apathy, pain, nocturia, and sensitive to light.

Effects of sleep quality and mood of patients with Parkinson's disease on their caregivers

Objectve: To evaluate the relationship of Parkinson's disease(PD) patients' sleep quality and depression with burden, quality of life, and depression of their caregivers. Methods: A total of 120 PD patients (68 males and 52 females) and their caregivers (48 males and 72 females) from Changshu Hospital Affiliated to Nanjing University of Chinese Medicine between January 2017 and June 2019 were recruited. Patients' sleep quality, depression and quality of life was evaluated. Burden, quality of life, quality of sleep, and depression of caregivers were assessed by the Caregivers Burden Questionnaire (CBI), Health Survey Brief (SF-36), Pittsburgh Sleep Quality Index (PQS1) and Hamilton Depression Scale (HAMD), meanwhile, the correlation between relevant factors was analyzed. Results: The CBI of caregivers was positively correlated with the unified Parkinson's disease rating scale (UPDRS)-Ⅲ scores of PD patients (r=0.436, P<0.05). The CBI, SF-36GH, SF-36MH, HAMD and PSQI scores of caregivers were positively correlated with Parkinson's disease sleep scale (PDSS) scores of PD patients (r=0.546, 0.762, 0.528, 0.562 and 0.522, respectively, all P<0.01). The caregiver's CBI score was positively correlated with PD patients' Epworth sleepiness score (ESS) score (r=0.442, P<0.05), and caregiver's CBI, SF-36GH, SF-36MH, HAMD, PSQI scores were positively correlated with PD patients' HAMD scores (r=0.765, 0.813, 0.635, 0.884 and 0.601, respectively, all P<0.01). The caregiver's CBI score was positively correlated with the PDQ-39 score of PD patients (r=0.834, 0.452, 0.463, 0.421 and 0.387, respectively, all P<0.05). Multiple regression analysis indicated that the caregiver's CBI score was significantly correlated with the patient's PDQ-39, PDSS and HAMD scores (r=0.512, 0.645 and 0.635, respectively, all P<0.01), and the caregiver's SF-36GH score was significantly correlated with the patient's PDQ-39, PDSS and HAMD scores (r=0.452, 0.682 and 0.506, respectively, all P<0.01). The caregiver's SF-36MH score was significantly correlated with the patient's PDQ-39, PDSS and HAMD scores (r=0.426, 0.608 and 0.598, respectively, all P<0.01). There was significant correlations between the caregiver's HAMD score and the patient's PDSS and HAMD scores (r=0.568 and 0.496, both P<0.01), and the PSQI score of the caregiver was significantly correlated with the PDSS and HAMD scores of the patient (r=0.532 and 0.461, both P<0.01). Conclusions: This current study underscores the presence of a significant relationship of patient's sleep quality with caregiver's burden, quality of life, depression and sleep quality. Specifically, sleep quality and depression of the patients are independent predictors for burden, quality of life and sleep quality of the caregivers.

Sleep-related symptoms in multiple system atrophy: determinants and impact on disease severity.

Background:Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity.Methods:This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS).Results:The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA.Conclusions:Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

Association of sleep disturbance and freezing of gait in Parkinson disease: prevention/delay implications.

Freezing of gait (FOG) severely impairs life quality of Parkinson disease (PD) patients. The relationship between sleep disturbance and FOG in PD remains unclear, so in this study, we aimed to investigate that relationship. First, we assessed clinical characteristics of freezers and nonfreezers among PD patients. Next, we assessed clinical characteristics of PD patients with different PDSS1 scores (score on first item of Parkinson's Disease Sleep Scale). Finally, we prospectively followed a cohort of nonfreezers from a baseline clinical visit and to a maximum of 18 months and performed a Cox regression analysis to further investigate the relationship between PDSS1 score and FOG in PD. A total of 163 participants with PD were included in the baseline analysis. The freezers had significantly worse sleep compared with the nonfreezers. The proportion of freezers in the patients with low PDSS1 score (PDSS1 < 6) was significantly higher than that in the patients with high PDSS1 score (PDSS1 ≥ 6). A total of 52 nonfreezers were prospectively followed. During a maximum 18-month follow-up, FOG incidence (73%) in the PDSS1 < 6 group was significantly higher than that (24%) in the PDSS1 ≥ 6 group (P = .008). Low PDSS1 score (hazard ratio = 4.23, 95% CI 1.64-10.92, P = .003) and high levodopa equivalent daily dose (hazard ratio = 4.18, 95% CI 1.62-10.75, P = .003) were significantly associated with an increased hazard of FOG. Our study indicated that low PDSS1 score may be a risk indicator for the development of FOG and provided important insights into potential targets for the prevention/delay of FOG in PD.

A quantitative analysis of the effect of bilateral subthalamic nucleus-deep brain stimulation on subjective and objective sleep parameters in Parkinson's disease

ObjectiveTo explore how subjective and objective sleep parameters respond to bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). MethodsThirty DBS sleep studies were included by searching PubMed, Embase, and the Cochrane Library, and only 21 prospectively designed studies, including 541 patients, were eligible for the main analysis. We evaluated sleep disturbance using 1 objective measurement, polysomnography (PSG), and 4 subjective scales, including PD Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and restless legs syndrome (RLS). We pooled data using the standard mean difference (SMD). The primary outcome was a change in sleep parameters 6 months postoperatively. Outcomes from <12 months to ≥12 months follow-up were compared in the subgroup analysis. Meta-regression was further conducted. ResultsSTN-DBS significantly improved all 4 subjective sleep scales in the 6-month follow-up: ESS (SMD = 0.234), PDSS (SMD = 0.724), PSQI (SMD = 1.374) and RLS (SMD = 1.086), while most PSG parameters remained unchanged, except for shortened rapid eye movement sleep latency (RSL) (SMD = 0.520). In the over-12-month follow-up, improvement persisted in PDSS but not in ESS. Dopamine drug reduction (p = 0.009) and motor improvement (p = 0.036) were correlated with ESS improvement and PDSS improvement, respectively. ConclusionsBilateral STN-DBS continuously improved subjective nocturnal sleep, while its effect on ESS lasted for only 1 year. Medication reduction and motor improvement may contribute to improved daytime sleepiness and better subjective nocturnal sleep, respectively. Except for a shortened RSL, STN-DBS did not change PSG parameters, including sleep efficiency and sleep architecture. RegistrationOpen Science Framework: DOI 10.17605/OSF.IO/3EGRC.

The role of Therapeutic Repetitive Transcranial Magnetic Stimulation in Treatment of Sleep Disorders in Parkinson’s disease Patients

Background: Parkinson’s disease (PD) is the most common movement disorder and represents the second most common degenerative disease of the central nervous system. Objective: To measure the effect of repetitive transcranial magnetic stimulation (rTMS) as therapeutic treatment on sleep disorders in patients with Parkinson’s disease (PD). Patients and methods: This double-blinded study included 20 PD patients (10 received real rTMs and 10 received sham rTMs) patients recruited from Inpatient and Outpatient Clinic of Neuropsychiatric Department of Aswan University Hospital. Our patients were divided into 2 groups (10 patients each). Results: As regards the effect of rTMs on PDSS and sleep latency, our study results found no significant change in Parkinson disease sleep scale between both groups but there was significant change in sleep latency that it decreased in the group received real rTMS in comparison with the SHAM group. In addition, there were significant changes in wake stage and rapid eye movement stage that both decreased in response to rTMS while there was no significant changes in non-rapid eye movement stage. Awakening after being asleep on both studied groups showing significant decrease in wake after sleep onset and wake after persistent sleep as both of them decrease wit rTMS. Conclusion: The main finding of this study was that 10 sessions of 20–Hz rTMS applied over both parietal area improved the subjective as well as the objective sleep quality as reflected by a decrease of frequency in arousal from sleep and in Non-REM–1 stage sleep.

Does gender differences have a role in determining sleep quality in Parkinson's disease?

Sleep disturbances in Parkinson's disease (PD) are common. Non -motor symptoms including sleep disturbance have gender difference in PD. The objective is to determine gender differences in PD in relation to the sleep quality. 156 patients with PD with males (n = 119) and females (n = 37) were included. The sleep quality and sleep disturbances were assessed using Pittsburgh sleep quality index (PSQI), Parkinson's disease Sleep Scale (PDSS) and Epworth Sleep Scale (ESS). Females with PD had higher frequency with insomnia (56.7%) as compared to males with PD (44.5%) (p = 0.05), nightmares (32.4%) as compared to males with PD (16.8%) (p = 0.04), greater PSQI component score of habitual sleep efficiency (p = 0.008), sleep disturbance (p = 0.03) and daytime dysfunction (p = 0.02), greater global PSQI score (p = 0.03), higher percentage of patients with global PSQI score > 5 (64.8%) than males with PD (41.1%) (p = 0.01), suggesting poor quality of sleep in females with PD. Higher total ESS score (p = 0.03), higher frequency of females with PD with total ESS score > 10 (45.9%) than in males with PD (26.9%) (p = 0.02), and lower total PDSS score (p = 0.009). On correlation analysis, the global PSQI score in females with PD had strong positive correlation with duration of PD, HAM-A and HAM-D scores and negative correlation with MMSE scores. Females with PD had a poor sleep quality with higher frequency of insomnia, nightmares, and daytime sleepiness. The longer duration of PD, higher scores of anxiety and depression scale and lower MMSE scores are associated with poor sleep quality in females with PD.

Study on the Clinical Features of Parkinson's Disease With Probable Rapid Eye Movement Sleep Behavior Disorder.

Objective: To investigate the clinical features and factors associated with Parkinson's disease (PD) patients with probable rapid eye movement sleep behavior disorder (PD-pRBD).Methods: A total of 2,440 patients with clinically established or clinically probable PD were divided into two groups: PD-pRBD and PD without pRBD (PD-NRBD), according to the RBD questionnaire—Hong Kong. Data collection included demographic data, basic clinical history, and motor and non-motor symptoms. Based on the onset time of pRBD and the motor symptoms in PD, PD-pRBD patients were further divided into the pRBD prior to PD (PD-prRBD) group and the pRBD posterior to PD (PD-poRBD) group. Clinical features were compared between the PD-pRBD and PD-NRBD groups, as well as the PD-prRBD and PD-poRBD groups. The associated factors of pRBD were also explored.Results: The prevalence of pRBD was 41.4% (1,010 out of the total of 2,440) in our PD cohort. Further, compared with the PD-NRBD group, the PD-pRBD group had longer disease duration and more severe motor symptoms. Moreover, the PD-pRBD group had significantly higher levodopa equivalent daily dose and a higher ratio of dyskinesia, wearing-off, and offset of the Hoehn–Yahr stage. The scores on the non-motor symptom rating scale (NMSS), cognitive impairment, Parkinson's disease sleep scale (PDSS), excessive daytime sleepiness, constipation, hyposmia, depression, and the 39-item Parkinson's disease questionnaire also appeared worse in the PD-pRBD group. Significant differences in the educational level, disease duration, disease progression, Unified Parkinson's Disease Rating Scale (UPDRS)-II, UPDRS-III, tremor, rigidity, bradykinesia, posture gait, frozen gait, levodopa equivalent daily dose, dyskinesia, wearing-off, Hoehn–Yahr stage, NMSS-6, PDSS, and communication score widely existed between the PD-prRBD and PD-poRBD groups. Late-onset PD, long disease duration, high UPDRS-I score, high NMSS-4 score, low PDSS score, constipation, and hyposmia were all identified as the risk factors for PD-pRBD.Conclusions: Compared with the PD-NRBD group, the PD-pRBD group may have more severe motor symptoms, motor complications, and non-motor symptoms as well as a substandard quality of life. Further, late-onset PD, long disease duration, high UPDRS-I score, high NMSS-4 score, low PDSS score, constipation, and hyposmia can be risk factors for RBD in PD. Differences also occurred between the PD-prRBD and PD-poRBD groups.

Therapeutic Effect of Levodopa/Carbidopa/Entacapone on Sleep Disturbance in Patients with Parkinson's Disease.

Objective To investigate the efficacy of levodopa/carbidopa/entacapone (LCE) at bedtime for treating sleep disturbance in patients with Parkinson’s disease (PD) with motor fluctuations.Methods Participants included 128 PD patients with motor fluctuations. All patients were assessed for motor, nonmotor, and sleep-specific symptoms using the United Parkinson’s Disease Rating Scale (UPDRS), the Korean version of the Nonmotor Symptom Scale, the Parkinson’s Disease Sleep Scale (PDSS), the Epworth Sleepiness Scale, and the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ). We compared the baseline characteristics of patients with sleep disturbance (PDSS score < 120) and those without sleep disturbance (PDSS score ≥ 120). Thirty-nine patients with sleep disturbance who agreed to take LCE at bedtime completed 3-month follow-ups. We analyzed changes in the scores of motor, nonmotor, and sleep symptom scales over the 3 months.Results PD patients with sleep disturbance were at more advanced disease stages and had more severe motor, nonmotor, and sleep symptoms than those without sleep disturbance. Patients who took LCE at night showed improvements in motor (UPDRS part III, p = 0.007) and sleep symptoms (total PDSS, p < 0.001). Sleep features that benefitted from LCE included not only nocturnal motor components but also insomnia (PDSS items 2 and 3, p = 0.005 and p < 0.001) and rapid eye movement behavior disorder (PDSS item 6, p = 0.002; and RBDSQ, p < 0.001).Conclusion The use of LCE at bedtime may be a useful treatment for sleep disturbance in advanced PD patients with motor fluctuations.

Predictors of fatigue severity in early, de novo Parkinson disease patients: A 1-year longitudinal study

IntroductionFatigue is one of the most common and disabling nonmotor symptom in Parkinson's disease (PD). The aim of the present study was to investigate the 1-year course of fatigue in a consecutive sample of de novo drug-naïve patients with PD, and at systematically searching for baseline motor and nonmotor predictors associated with fatigue severity over time. MethodsFifty-five consecutive de novo PD patients (age: 64.71 ± 7.74 years) underwent a comprehensive examination, including Parkinson Fatigue Scale, Epworth Sleepiness Scale, Parkinson's Disease Sleep Scale, Beck Depression Inventory, Parkinson's Anxiety Scale, Apathy Evaluation Scale, and an extensive neuropsychological evaluation. Bivariate and multiple regression analyses were performed to identify baseline predictors independently related to fatigue severity at 1-year follow-up. ResultsPrevalence rate of fatigue (defined by PFS cut-off) increased from 22% at baseline to 38% at 1-year follow-up. A similar increase in prevalence was observed for excessive daytime sleepiness, and apathy. Among patients with fatigue at baseline, 91% had fatigue at follow-up too (i.e., persistent fatigue). Multivariate regression analysis identified fatigue (p < 0.01), daytime sleepiness (p < 0.01), and emotional apathy (p < 0.01) as the main baseline variables significantly predicting fatigue severity at 1-year follow-up. ConclusionIn early PD, fatigue increases and persists over time, and its severity is related to higher baseline levels of fatigue, excessive daytime sleepiness, and emotional apathy. These results warrant to monitor fatigue since the early stage of disease, and suggest that treating excessive daytime sleepiness and emotional apathy might prevent its worsening.

Subthalamic nucleus deep brain stimulation improves sleep in Parkinson's disease patients: a retrospective study and a meta-analysis

BackgroundMost Parkinson's patients suffered from sleep problems. There is increasing evidence that Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has a positive effect on several sleep parameters, improving overall sleep quality in patients with PD. However, the results are controversial. MethodsWe performed a retrospective study and meta-analysis to assess the Parkinson's disease sleep scale (PDSS) in Parkinson's patients. ResultsWe reviewed our data of patients who underwent STN-DBS, and then extracted five other trials to perform a meta-analysis. The pooled results showed an advantage on post-operative PDSS in both our medical center and pooled results (MD = 20.41, 95% CI = [13.03, 27.79], I2 = 61%, P < 0.001). There was a significant difference in Unified Parkinson's Disease Rating Scale (UPDRS)-Ⅲ score between pre and post-operation (MD = −12.59, 95% CI = [−14.70, −10.49], I2 = 90%, P < 0.001). What's more, Parkinsonian medication was significantly lower in the post-operative groups after DBS (MD = −314.71, 95% CI = [−468.13, −161.28], I2 = 53%, P < 0.001). ConclusionIn the retrospective study and meta-analysis of 6 trials, we found that DBS can significantly increase sleep quality. Furthermore, motor function improved and Parkinsonian medication was significantly decreased postoperatively. The sample size was enough and no further investigations would change the conclusion.

A randomized double-blind placebo-controlled multicenter trial of Bushen Yisui and Ziyin Jiangzhuo formula for constipation in Parkinson disease.

Introduction:Constipation is a common nonmotor symptom of Parkinson disease (PD). Constipation can also impact patient's quality of life. Chinese herbal medicines have been used for the treatment of constipation in PD. This trial will evaluate the efficacy and safety of a Chinese herbal formula Bushen Yisui and Ziyin Jiangzhuo (BYZJ) for the treatment of constipation in PD.Methods and analysis:This randomized, double-blind, placebo-controlled, multicenter clinical trial will involve 4 hospitals in Beijing, China. The study will aim to recruit 90 PD patients with constipation between 30 and 80 years-of age with a score of 1 – 4 on the Hoehn and Yahr scale. Once recruited, Patients will be randomized into a BYZJ group or a placebo group in a 2:1 ratio. The trial will include a 1-week run-in period, a 4-week double-blind treatment period, a 4-week and a 12-week follow-up period. All patients will be educated about PD-related constipation during the run-in period. BYZJ granules and simulated granules will be administered twice daily for 4 weeks to the BYZJ group and the placebo group respectively. Assessments will be performed during run-in period, before the start of treatment (baseline, week 0), and at 4, 8, and 16 weeks. The primary outcome will be measured with the Constipation Severity Instrument, and secondary outcomes will be evaluated with the Patient Assessment of Constipation Quality of Life questionnaire, Bristol Stool Form Scale, Movement Disorders–Unified Parkinson Disease Rating Scale, Nonmotor Symptoms Scale, PD Sleep Scale, Parkinson Fatigue Scale-16. Laxative use (dose and frequency) will also be recorded. Intention-to-treat and per-protocol set analyses will be used to compare symptom improvement between the 2 groups. Any adverse events will be recorded.Discussion:If found effective and safe, BYZJ formula will be one of Chinese herb to treat constipation and even other nonmotor or motor symptoms in PD patients. The results will sustain the broader use of BYZJ formula in PD.

Smartwatch-based Activity Analysis During Sleep for Early Parkinson's Disease Detection.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder with the non-motor symptoms preceding the motor impairment that is needed for clinical diagnosis. In the current study, an angle-based analysis that processes activity data during sleep from a smartwatch for quantification of sleep quality, when applied on controls and PD patients, is proposed. Initially, changes in their arm angle due to activity are captured from the smartwatch triaxial accelerometry data and used for the estimation of the corresponding binary state (awake/sleep). Then, sleep metrics (i.e., sleep efficiency index, total sleep time, sleep fragmentation index, sleep onset latency, and wake after sleep onset) are computed and used for the discrimination between controls and PD patients. A process of validation of the proposed approach when compared with the PSG-based ground truth in an in-the-clinic setting, resulted in comparable state estimation. Moreover, data from 15 early PD patients and 11 healthy controls were used as a test set, including 1,376 valid sleep recordings in-the-wild setting. The univariate analysis of the extracted sleep metrics achieved up to 0.77 AUC in early PD patients vs. healthy controls classification and exhibited a statistically significant correlation (up to 0.46) with the clinical PD Sleep Scale 2 counterpart Items. The findings of the proposed method show the potentiality to capture non-motor behavior from users' nocturnal activity to detect PD in the early stage.

1121 Nonmotor Symptoms Affect Sleep Quality in Early-Stage Parkinson’s Disease Patients With or Without Cognitive Dysfunction

Abstract Introduction Parkinson’s disease (PD) patients frequently present with sleep disorders. This study was designed to assess the impact of nonmotor symptoms (NMSs) on subjective sleep quality in early-stage PD patients with and without cognitive dysfunction. Methods A sample of 389 early-stage PD patients (Hoehn and Yahr score ≤2.5, duration ≤5 years) was recruited for the present study. The Non-Motor Symptoms Questionnaire (NMS-Quest) was used to screen for global NMSs. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAMD). PD motor symptoms were measured with the Unified PD Rating Scale (UPDRS), part III. The Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive status, and the PD Sleep Scale (PDSS) was used to quantify sleep quality. Logistic regression models were built to identify factors associated with sleep disturbances. Results In our sample, approximately one-quarter of the PD patients suffered from sleep disturbances (23.7%). Our results also confirmed the high prevalence of cognitive dysfunction in patients with PD (39.8%). In total, the patients who suffered from NMSs, such as depressive symptoms, anxiety symptoms, urinary tract symptoms and hallucinations/delusions, had poorer sleep quality. Better cognition may protect against sleep disorders. In patients with cognitive dysfunction, the NMS-Hallucinations/delusions score was the most important risk factor for sleep disorders. In patients without cognitive dysfunction, NMSs such as anxiety and cognition and medication were related to sleep disorder. Conclusion NMSs in early-stage PD are highly associated with and are determinants of subjective sleep quality. Future studies should focus on elucidating the pathophysiology of these symptoms. Support Special Funds of the Jiangsu Provincial Key Research and Development Projects (grant No. BE2018610)

Depressive symptoms effect subjective sleep quality in Chinese patients with Parkinson’s disease

ObjectivesThe objective of this paper was aimed to estimate the influence of depressive symptoms on subjective sleep quality in Chinese PD patients. Patients and MethodsA sample of 491 PD patients was collected and studied in the present study. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAMD). PD severity was assessed using Hoehn and Yahr (H–Y) staging, and motor symptoms were measured with the Unified PD Rating Scale (UPDRS) part III. The Montreal Cognitive Assessment (MOCA) was used to evaluate the global Cognitive status and PD Sleep Scale (PDSS) was used to quantify sleep quality. Three linear regression models were built to check factors associated with caregiver burden, one for the total sample and two for subgroups stratified by the presence of cognitive disturbance. ResultsIn our sample, 29.9% of patients suffer from sleep disturbance. The most frequent depressive symptoms were helplessness (81.5%), depressed mood (57.8%), and general somatic symptoms (55.4%) for entire sample. Patients with cognitive disturbance (n = 274; 55.8% of sample) presented more depressive symptoms than patients without cognitive disturbance. Patients suffer poorer sleep quality when patients experience depression with cognitive disturbance. On linear regression models, the main determinants of subjective quality for the total sample were NMS-depression/anxiety/anhedonia, HAMD-anxiety/somatization, disease severity, age and HAMD-loss of weight. For patients with cognitive disturbance, the significant determinants were NMS-depression/anxiety/anhedonia, HAMD-anxiety/somatization, motor symptoms, HAMD-loss of weight and gender. For patients without cognitive disturbance, the significant determinants were NMS-depression/anxiety/anhedonia, disease severity and HAMD-anxiety/somatization. ConclusionDepressive symptoms in PD are highly associated with and are determinants of subjective sleep quality, and are more prevalent in patients with cognitive disturbance. Detailed assessment and specific interventions aimed at depression and dementia could alleviate sleep disorder.

Elevated Plasma Melatonin Levels Are Correlated With the Non-motor Symptoms in Parkinson's Disease: A Cross-Sectional Study.

ObjectiveMelatonin is the major hormone produced and secreted at night by the pineal gland into the cerebrospinal fluid (CSF) and circulation. The relationship between plasma melatonin levels and Parkinson’s disease is not clear. The aim of the current study was to assess plasma melatonin levels in Parkinson’s disease (PD) patients and to analysis the relationship between plasma melatonin levels and non-motor symptoms.Participants and MethodsIn this cross-sectional study, we evaluated 61 patients with idiopathic PD [males n = 30 (49.2%), average age 62.4 years (range: 46–73 years)] and a total of 58 healthy volunteers [males n = 30 (51.7%), average age 64.3 years (range: 45–70 years)] who participated in the study. Plasma melatonin levels were measured using an enzyme-linked immunosorbent assay. The severity of disease in PD patients was scored by the Unified Parkinson’s Disease Rating Scale and the Hoehn and Yahr Staging scale. The quality of life in PD patients was assessed by the 39-item Parkinson’s Disease Questionnaire. The non-motor symptoms were assessed by the 14-item Hamilton Anxiety Rating Scale, the 24-item Hamilton Depression Rating Scale, the Parkinson Disease Sleep Scale, the Epworth Sleepiness Scale and the Non-Motor Symptoms Scale for PD.ResultsCompared with the healthy controls, the plasma melatonin levels were significantly higher in PD patients (12.82 ± 4.85 vs. 19.40 ± 4.23, P < 0.001). Plasma melatonin levels were significantly associated with the levodopa equivalent daily dose (r = −0.262, P < 0.05, n = 61). Higher plasma melatonin concentrations were detected in the negative cardiovascular symptom group than in the cardiovascular symptom group (20.13 ± 3.74 vs. 16.93 ± 3.74, P < 0.05). Higher plasma melatonin concentrations were detected in the non-sleep-disorders group than in the sleep disorders group (22.12 ± 5.93 vs. 18.86 ± 3.66, P < 0.05). In addition, the plasma melatonin concentration was higher in the group without gastrointestinal dysfunction than in the gastrointestinal dysfunction group (21.71 ± 4.44 vs. 18.35 ± 3.74, P < 0.05).ConclusionThis study revealed that the plasma melatonin levels in PD patients were significantly higher than those in healthy controls. Non-motor symptoms that were significantly negatively correlated with plasma melatonin levels were cardiovascular symptoms, sleep disorders, and gastrointestinal dysfunction. Plasma melatonin levels have the closest relationship with sleep disorders. There was a correlation between plasma melatonin levels and sleep quality in patients with PD. The remaining non-motor symptoms were not related to plasma melatonin levels.

Nonmotor Symptoms Affect Sleep Quality in Early-Stage Parkinson's Disease Patients With or Without Cognitive Dysfunction

Purpose: Parkinson's disease (PD) patients frequently present with sleep disorders. This study was designed to assess the impact of nonmotor symptoms (NMSs) on sleep quality in early-stage PD patients with and without cognitive dysfunction.Materials and Methods: A sample of 389 early-stage PD patients (modified Hoehn and Yahr score ≤ 2.5, duration ≤ 5 years) was recruited for the present study. The Non-Motor Symptoms Questionnaire (NMS-Quest) was used to screen for global NMSs. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAMD). PD motor symptoms were measured with the Unified PD Rating Scale (UPDRS), part III. The Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive status, and the PD Sleep Scale (PDSS) was used to quantify sleep quality. Polysomnography (PSG) was used for objective assessment of sleep.Results: In our sample, approximately one-quarter of the PD patients suffered from sleep disturbances (23.7%). Our results also confirmed the high prevalence of cognitive dysfunction in patients with PD (39.8%). In patients with cognitive dysfunction, higher percentage of sleep disorders (34.8 vs. 16.2%, P < 0.01) was observed. They also with lower PDSS score, sleep efficiency (SE) and longer sleep lantency (SL) and wake after sleep onset (WASO) (All P < 0.05). In total, the patients who suffered from NMSs, such as depressive symptoms, anxiety symptoms, urinary tract symptoms and hallucinations/delusions, had poorer sleep quality. Better cognition may predict better sleep quality. In patients with cognitive dysfunction, the NMS-Hallucinations/delusions score was the most important risk factor for sleep disorders. In patients without cognitive dysfunction, NMSs such as anxiety and cognition and medication were related to sleep disorder.Conclusions: NMSs in early-stage PD are highly associated with and are determinants of subjective sleep quality. Future studies should focus on elucidating the pathophysiology of these symptoms.