Non-motor Symptoms In Parkinson's Disease Patients Research Articles

Targeting protein-protein interactions for therapeutic intervention in Parkinson's disease to delay progression.

Background: Parkinson's disease (PD) is a neurodegenerative condition with few treatments to slow or stop development. Protein-protein interactions (PPIs) are intriguing therapeutic targets. This research examined the safety and effectiveness of a new Parkinson's disease medication targeting PPIs. Methods: After enrollment, 60 individuals were randomly assigned to the treatment and control groups. MDS-UPDRS Part III score change from baseline to week 12 was the main outcome measure. Secondary outcome measures were the Hoehn and Yahr scale, NMSS, and Montreal Cognitive Assessment. Study-wide adverse events were tracked. Results: Compared to the control group, the treatment group exhibited a substantial improvement in MDS-UPDRS Part III score (p < 0.001). Additionally, the therapy group showed substantial improvements in Hoehn and Yahr stage, NMSS score, and MoCA score compared to the control group (p < 0.001). No significant adverse effects were documented with the experimental medication. Conclusion: This research suggests that targeting PPIs may treat Parkinson's disease. No harmful side effects were detected with the experimental medication, which improved motor and non-motor symptoms in PD patients. These results require more study to determine the long-term safety and effectiveness of targeting PPIs in Parkinson's disease.

Relationship between increased serum neurofilament light chain and glial fibrillary acidic protein levels with non-motor symptoms in patients with Parkinson's disease.

This study set out to investigate the relationship between serum neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and various non-motor symptoms (NMSs) in patients with Parkinson's disease (PD). The study included 37 healthy controls (HCs) and 51 PD patients. Clinical assessments of PD symptoms were conducted for all PD patients. The NMSS was utilised to evaluate the NMS burden (NMSB) in individuals. Based on the severity of NMSB, we further categorised the PD group into two subgroups: mild-moderate NMSB group and severe-very severe NMSB group. The amounts of NFL and GFAP in the serum were measured using an extremely sensitive single molecule array (Simoa) method. Statistical analyses were performed on the collected data using SPSS 26.0 and R (version 3.6.3). Serum GFAP and NFL levels in the PD group with severe-very severe NMSB were significantly higher than those in the mild-moderate NMSB group (GFAP: P < 0.007; NFL: P < 0.009). Serum NFL and GFAP levels had positive correlations with NMSS total scores (GFAP: r = 0.326, P = 0.020; NFL: r = 0.318, P = 0.023) and multiple subdomains. The relationship between the attention/memory domains of NMSS and NFL levels is significantly positive (r = 0.283, P = 0.044). Similarly, the mood/apathy domains of NMSS are also significantly positively correlated with GFAP levels (r = 0.441, P = 0.001). Patients with emotional problems or cognitive impairment had higher GFAP or NFL levels, respectively. Furthermore, it has been demonstrated that NMSs play a mediating role in the quality of life of patients with PD. Moreover, the combination of NFL and GFAP has proven to be more effective than using a single component in identifying PD patients with severe-very severe NMSB. The severity of NMSs in PD patients, particularly cognitive and emotional symptoms, was found to be associated with the levels of serum NFL and GFAP. This study marks the first attempt to examine the connection between NMSs of PD and the simultaneous identification of NFL and GFAP levels.

Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

AbstractLipocalin‐2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme‐linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel‐based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Study of non-motor Symptoms in Parkinsons disease and its impact on their quality of life

Parkinson's disease (PD) is a neurodegenerative disorder characterised by the degeneration of dopaminergic nigrostriatal pathway. Its incidence ranges from 1 to 2 per 1000 in general population. Its a complex disorder characterised by motor and non-motor symptoms that can impair the quality of life (QoL). In the presence of effective symptomatic therapies for the motor symptoms of Parkinson's disease, the non-motor symptoms have become the major prognostic factors determining the overall disease burden and everyday function in Parkinson’s disease patients. Our study aimed at assessing the frequency and proportion of non-motor symptoms in PD patients and to assess their impact on QoL. A total of 88 PD patients visiting the outpatient department of Neurology at Goa Medical College were assessed for various non-motor symptoms using a semi – structured questionnaire and appropriate scales. Quality of life was assessed using PDQ-39 questionnaire. Patients satisfying the United Kingdom Parkinson’s Disease brain bank criteria for idiopathic Parkinson’s diseases were included in the study Single centre, Cross-sectional study. Mean age of study population was 68 years and mean duration of the disease was 5yrs. Attention and memory were the most frequently reported domain in the study population (52 patients, 59.75 percent) followed by mood and cognition (46 patients, 52.74 percent). The least reported symptom was perceptual problems including delusions and hallucinations (11.74%) and miscellaneous domain (10.93 percent) which included pain, olfactory dysfunction, increased perspiration and weight fluctuations. The mean UPDRS (part 3) score was found to be 33.24± 17.37 with values ranging from 3.57 (mild motor impairment) to 44.64 (severe motor impairment).The QoL assessment showed that impairment of Mobility had a major impact on QoL followed by activities of daily living and emotional well-being. Correlation between Non-motor symptoms and PDQ-39 revealed that mood, cognition and perceptual problems had an adverse outcome on their emotional well-being and deficit in attention and memory had significant outcomes on communication. This study highlights the fact that non-motor symptoms in PD significantly impair quality of life and we should incorporate screening tools to evaluate patients with autonomic, sensory or mood disturbances so that they are detected at the earliest as most of them precede motor symptoms by decades.

Diagnostic value of plasma SIRT1 levels and whole-brain gray matter volume in Parkinson's disease patients with cognitive impairment.

This study was designed to investigate the diagnostic value of plasma SIRT1 levels and whole-brain gray matter (GM) volume in Parkinson's disease (PD) patients with cognitive impairment. Automated enzymatic analysis was performed to measure plasma SIRT1 levels in 80 healthy controls and 77 PD patients. Motor symptoms and nonmotor symptoms in PD patients were assessed using the corresponding scales. A Siemens MAGNETOM Prisma 3T MRI scanner was used to acquire images in 35 of 77 PD patients. Plasma SIRT1 levels in PD patients were lower than those in healthy controls. Plasma SIRT1 levels were negatively correlated with the age, Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores, anxiety, depression, excessive daytime sleepiness (EDS), quality of life, and especially cognitive impairment. Thus, it showed that plasma SIRT1 levels were relevant to visuospatial/executive function, memory, and language. Receiver-operating characteristic (ROC) analysis confirmed that plasma SIRT1 levels had good diagnostic accuracy for PD with anxiety and EDS. Furthermore, plasma SIRT1 levels had a significant positive correlation with GM volume in the whole brain, and ROC analysis confirmed that plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment. This study showed that plasma SIRT1 levels were correlated with the nonmotor symptoms of anxiety, depression, EDS, and especially cognitive impairment as well as the total GM volume. Furthermore, the combination of plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment.

Obstructive Sleep Apnea and Other Vascular Risk factors' Impact on Non-Motor Symptoms in Parkinson's Disease.

Previous studies revealed an association between vascular comorbidities and obstructive sleep apnea (OSA) and the severity of motor and cognitive symptoms in Parkinson's disease (PD). However, there is a lack of studies assessing the entire spectrum of non-motor symptoms (NMS). To investigate the relationship between vascular comorbidities and NMS in PD patients. Patients were assessed at baseline and 4 years later with the Non-Motor Symptom Assessment Scale, Parkinson's Psychosis Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Apathy scale. After tetrachoric correlation matrix, we conducted linear regression models (adjusted for age, gender, disease duration, and UPDRS-III) to investigate the relationship between vascular comorbidities and NMS. In 73 PD patients, (mean disease duration 7.1 [5.3]), 57% had hypertension, 44% body mass index >25, 44% elevated cholesterol, 15% diabetes mellitus, 15% OSA, 14% cigarette-smoking history, 8% prior stroke, and 8% coronary disease. Cognition, psychotic symptoms, apathy, urinary function, and miscellaneous domains significantly worsened at the 4-year follow-up. OSA was significantly associated with higher severity of hallucinations/illusions at baseline and with a more severe deterioration of attention/memory, psychotic symptoms, and apathetic mood at the 4-year follow-up. At baseline, but not at follow-up, hypertension was negatively associated with miscellaneous domain scores and coronary disease with autonomic function scores (gastrointestinal tract and urinary function domains). Among PD-associated comorbidities, OSA was the main factor of decline. In addition to cognitive impairment, OSA might also potentially worsen psychotic symptoms and apathy. Treatment of OSA could be a strategy to improve these important NMS.

Insulin-like growth factor in Parkinson’s disease is related to nonmotor symptoms and the volume of specific brain areas

BackgroundInsulin-like growth factor 1 (IGF-1) plays a protective role in Parkinson's disease (PD). To date, studies on the relationship between plasma IGF-1 levels and nonmotor symptoms and brain gray matter volume in PD patients have been rare. MethodsA Siemens automatic chemical analyzer was used to determine plasma IGF-1 levels in 55 healthy controls and 119 PD patients, including those at the early (n = 67) and middle-late (n = 52) stages of the disease. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Image acquisition in 65 PD patients was performed using a Siemens MAGNETOM Prisma 3 T magnetic resonance imaging (MRI) scanner. ResultsPlasma IGF-1 levels in early-stage PD patients were higher than those in healthy controls, and plasma IGF-1 levels in early-stage PD patients were higher than those in middle-late-stage PD patients. Plasma IGF-1 levels were significantly negatively correlated with anxiety, depression and cognitive dysfunction. Receiver operating characteristic (ROC) curve assessment confirmed that plasma IGF-1 levels had good predictive accuracy for PD with anxiety, depression and cognitive dysfunction. Furthermore, plasma IGF-1 levels were significantly positively correlated with volumes in the insula, caudate and anterior cingulate. ConclusionsThis study shows that plasma IGF-1 levels were correlated with the nonmotor symptoms of anxiety, depression and cognitive dysfunction and the volume in specific brain areas. This is the first report examining the relationships between plasma IGF-1 and clinical manifestations and imaging features in PD patients.

Narcolepsy in Parkinson's disease with insulin resistance.

Background: Parkinson's disease (PD) is characterized by its progression of motor-related symptoms such as tremors, rigidity, slowness of movement, and difficulty with walking and balance. Comorbid conditions in PD individuals include insulin resistance (IR) and narcolepsy-like sleep patterns. The intersecting sleep symptoms of both conditions include excessive daytime sleepiness, hallucinations, insomnia, and falling into REM sleep more quickly than an average person. Understanding of the biological basis and relationship of these comorbid disorders with PD may help with early detection and intervention strategies to improve quality of life. Methods: In this study, an integrative genomics and systems biology approach was used to analyze gene expression patterns associated with PD, IR, and narcolepsy in order to identify genes and pathways that may shed light on how these disorders are interrelated. A correlation analysis with known genes associated with these disorders (LRRK2, HLA-DQB1, and HCRT) was used to query microarray data corresponding to brain regions known to be involved in PD and narcolepsy. This includes the hypothalamus, dorsal thalamus, pons, and subcoeruleus nucleus. Risk factor genes for PD, IR, and narcolepsy were also incorporated into the analysis. Results: The PD and narcolepsy signaling networks are connected through insulin and immune system pathways. Important genes and pathways that link PD, narcolepsy, and IR are CACNA1C, CAMK1D, BHLHE41, HMGB1, and AGE-RAGE. Conclusions:We have identified the genetic signatures that link PD with its comorbid disorders, narcolepsy and insulin resistance, from the convergence and intersection of dopaminergic, insulin, and immune system related signaling pathways. These findings may aid in the design of early intervention strategies and treatment regimes for non-motor symptoms in PD patients as well as individuals with diabetes and narcolepsy.

Clinical Characteristics of Minor Hallucinations in Chinese Parkinson's Disease Patients.

BackgroundPsychotic symptoms are common in Parkinson's disease (PD). However, the clinical characteristics of PD psychosis (PDP) have been rarely reported in Chinese PD patients. We aimed to categorize PDP in a PD cohort and its relationship to other clinical characteristics.MethodsA total of 149 Chinese PD patients were consecutively enrolled, and idiopathic PD patients were recruited in the study. The symptoms of PDP were assessed with the enhanced Scale for the Assessment of Positive Symptoms in PD. Then, the patients were classified into a PD-control group, isolated minor hallucination (MH) group, and complex MH group, and clinical and demographic data of different groups were compared.ResultsParkinson's disease psychosis was present in 40.3% (60/149) of our patients. The most common PDPs were MHs, present in 32.9% (49 of 149) of the cohort. Compared to patients without MHs, patients with MHs were older, had a longer disease duration, a higher levodopa equivalent daily dose, more severe motor symptoms, dyskinesia, a higher rate of rapid eye movement sleep behavior disorders, frontal lobe function impairments, and a higher percentage of cognitive impairment. Logistic regression analysis showed that advanced Hoehn-Yahr stage [odds ratio (OR): 2.697, p = 0.007)] and frontal lobe function impairment (OR: 0.684, p = 0.003) were independent risk factors for MHs.ConclusionMHs were frequent non-motor symptoms in PD patients. It was associated with increased motor and non-motor symptom burdens and reduced quality of life. MHs have been called “minor,” but they have major clinical and prognostic implications and need early screening.

Hippocampal volume is related to olfactory impairment in Parkinson's disease.

Recent evidence has suggested that hyposmia in patients with Parkinson's disease (PD) may be due to impaired central processing. Furthermore, the hippocampus has been regarded as a critical structure linking olfactory impairment and cognitive impairment in PD patients. This study aimed to identify significant structural alterations of the hippocampus in PD patients with hyposmia, and to determine whether these structural changes are significantly associated with olfactory impairment severity. Eighteen idiopathic PD patients with hyposmia and 18 age- and sex-matched PD patients without hyposmia were enrolled. Hippocampal volume and its subfields were measured using FreeSurfer software and compared between hyposmic and normosmic PD patients. We also compared hippocampal substructures' volumes and correlated the hippocampal volumes with hyposmia severity. PD patients with hyposmia had significantly smaller hippocampal volumes. Among the three components of the hippocampus, the hippocampal body showed a markedly lower volume, which correlated significantly with the cross-cultural smell identification test score that represents olfactory function status. Hippocampal subfield analysis showed that substructures (subiculum, molecular layer) that constitute the hippocampal body showed the most significant volume difference. We suggest that atrophy of the bilateral hippocampus implies underlying problems in the central olfaction process in PD patients. In particular, the hippocampus might not only play a critical role in olfaction but could also be important for elucidating possible mechanisms of broad nonmotor symptoms in PD patients.

Glucagon-Like Peptide-1 Receptor Agonist Ameliorates 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Neurotoxicity Through Enhancing Mitophagy Flux and Reducing α-Synuclein and Oxidative Stress.

Parkinson disease (PD) is the second most common neurodegenerative disease without known disease modification therapy to slow down disease progression. This disease has pathological features of Lewy bodies with α-synuclein aggregation being the major component and selective dopaminergic neuronal loss over the substantia nigra. Although the exact etiology is still unknown, mitochondrial dysfunction has been shown to be central in PD pathophysiology. Type 2 diabetes mellitus has recently been connected to PD, and anti-diabetic drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), have been shown to possess neuroprotective effects in PD animal models. The GLP-1RA liraglutide is currently under a phase 2 clinical trial to measure its effect on motor and non-motor symptoms in PD patients. In this study, we used an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to test the possible mechanism of the GLP-1RA liraglutide in the pathogenesis of PD. We show that the neurobehavioral and motor dysfunction caused by the mitochondrial complex I inhibitor, MPTP, can be partially reversed by liraglutide. The GLP-1RA can protect mice from apoptosis of substantia nigra neurons induced by MPTP. MPTP treatment led to imbalanced mitochondrial fusion and fission dynamics, altered mitochondrial morphology, impeded autophagy flux, increased α-synuclein accumulation, and elevated oxidative stress. Specifically, the normalizing of mitochondrial fusion-fission dynamic-related proteins and enhancement of autophagy flux after administration of liraglutide is associated with improving neuronal survival. This suggests that GLP-1RAs may provide potential beneficial effects for PD caused by mitochondrial dysfunction through improvement of mitochondrial morphology balance and enhancing damaged organelle degradation.

Frequency of Non-motor Symptoms in Parkinson's Patients With Motor Fluctuations.

Background: Non-motor symptoms (NMS), including neuropsychiatric, sleep, autonomic, and sensory domains, are an integral aspect of the clinical presentation of Parkinson disease (PD) and affect neurocognitive functioning as well as patients' and caregivers' well-being.Objective: To describe the occurrence of NMS in PD patients with motor fluctuations in real-life condition.Methods: The present study is a secondary analysis of a previous multinational, multicenter, retrospective-prospective cohort observational study (SYNAPSES). Patients with PD diagnosis and motor fluctuations aged ≥18 years were included. Data collected at the baseline visit were used for this study, and descriptive analyzes were conducted to describe the distribution of NMS in motor-fluctuating PD patients distributed according to different clinical characteristics.Results: Of the 1,610 patients enrolled, 1,589 were included for the analysis (978 males and 611 females), with a mean age of 68.4 (SD = 9.6). Most patients had at least one NMS (88.5%). Sleep problems and psychiatric symptoms were the most prevalent NMS in motor fluctuating PD patients in all H and Y stages. Psychiatric disorders were more frequent in older patients and in patients with a larger number of years of PD diagnosis, while sleep problems were more preeminent in younger patients and with inferior disease duration.Conclusions: The present findings further support the high prevalence of NMS in PD patients with motor fluctuations, thus reinforcing the need for assessing them for diagnostic accuracy and for delivering holistic care.

The effect of deep brain stimulation surgery on the non-motor symptoms in Parkinson's disease

Deep brain stimulation (DBS) has repeatedly been shown to be beneficial in controlling motor symptoms in Parkinson's disease (PD). For non-motor symptoms, a positive effect of DBS on mood, sleep disorders, impulse control disorders and psychotic experiences has been suggested. However, patients undergoing DBS often have a significant decrease in dopaminergic medication, which could also underlie changes in non-motor symptoms.The purpose of this study was to evaluate the effect of DBS surgery with corresponding change in medication on the psychiatric non-motor symptoms in PD patients.

Serum Uric Acid Levels and Non-Motor Symptoms in Parkinson's Disease.

Previous studies have identified low serum uric acid (SUA) levels as a risk factor for the development of Parkinson's disease (PD). Prodromal PD mainly manifests as a complex of non-motor features, but the association between SUA levels and nonmotor symptoms (NMS) burden level in advanced PD patients is poorly studied. To determine the association between SUA levels and NMS in PD patients. Data were gathered from an open label, cross sectional, study with analysis of SUA levels in 87 PD patients and were correlated to NMS through the NMS scale (NMSS). In addition, we examined the possible relation between SUA and NMS burden levels and motor scores. There was a moderate negative association between SUA levels and NMSS total score (ρ= -0.379, p < 0.001). In line with this, we observed that higher NMS burden was associated with lower SUA levels (p < 0.001). Within individual NMSS domains, a moderate negative correlation was observed between SUA levels and the cardiovascular/falls (ρ= -0.285, p = 0.008), sleep/fatigue (ρ= -0.299, p = 0.005), and miscellaneous domains (ρ= -0.318, p = 0.003). In this observational study we observed that SUA levels were negatively associated to NMS burden in PD patients with a specific link to miscellaneous, sleep/fatigue and cardiovascular domains of the NMSS. Interestingly, we did not find a clear relation between SUA and motor scores. Future large-scale prospective studies in de novo and advanced PD are needed to evaluate and establish these associations.

Nonmotor symptoms of 820 Taiwanese patients with Parkinson’s disease: an exploratory-comparative study

Nonmotor symptoms (NMSs) severely affect the daily quality of life of patients with Parkinson's disease (PD). Although many studies have documented the clinical characteristics of NMSs in PD patients, some issues remain unaddressed. The severity and gender distribution of NMSs in Asian and the Western patients differ. The correlations between clinical characteristics and NMS manifestations remain unclear. We studied these relationships in a large cohort of Taiwanese PD patients. Patients with PD were recruited from the outpatient clinic of a tertiary medical center and evaluated with standardized assessment protocols, including the NonMotor Symptoms Scale (NMSS), Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) scale, Mini-Mental Status Examination, and Montreal Cognitive Assessment. Among 820 patients enrolled, 41.8% were female. The prevalence of the NMSs was 96.5%, with attention/memory (79.51%) being the most frequently involved domain. The mean severity score on the NMSS was 36.48 ± 34.30. Male patients reported higher NMS prevalence and severity than female patients, mostly in the gastrointestinal tract and urinary domains. We found that the severity of NMSs was correlated with disease duration, UPDRS Part III score, and H&Y stage. Although they exhibited similar NMS prevalence, Taiwanese PD patients reported less intense NMSs compared with those reported by Western patients. Furthermore, the NMS items our patients emphasized and gender discrepancies were distinct from those in Western studies.

Non-motor symptoms depending on motor severity in Japanese patients with Parkinson's disease: A multicenter cross-sectional study

BackgroundAlthough non-motor symptoms (NMS) in patients with Parkinson's disease (PD) often worsen as the severity of motor symptoms (MS) increases, few studies have assessed the associated factors of non-motor symptoms. ObjectiveThis study aims to determine whether the presence of NMS in PD patients is associated with or independent from the severity of MS considering confounders. MethodsThe registry of PD patients from seven facilities in Japan was used. Multiple logistic regression was performed with each domain and item of the Non-motor Symptoms Scale (NMSS) as objective variables. Severity of motor symptoms was assessed by Hoehn & Yahr stage (HY stage) as an explanatory variable. The analysis was adjusted for sex, age, disease duration, presence/absence of wearing off and dyskinesia, clinical phenotypes and Levodopa equivalent daily dose. ResultsA total of 1037 patients were analyzed. Analysis by NMSS domain showed higher odds ratios (ORs) in patients with higher HY stages compared with patients with lower HY stages for domains D1 (cardiovascular), D2 (sleep/fatigue), D3 (mood/apathy), D4 (perceptual problems/hallucinations), D5 (attention/memory), and D6 (gastrointestinal) (ORs: 1.54–2.72, P < .05). However, only domains D7 (urinary) and D8 (sexual dysfunction) were not associated with HY stage. Item 2 (fainting) and Item 14 (delusions) showed higher ORs in the HY stage 4–5 (ORs: 9.95 and 5.92, P < .05). ConclusionsMost NMS worsened with exacerbation of MS in PD patients, however some NMS domains were also affected with other factors. These findings contribute to the understanding of the clinical picture of PD and may improve personalized medicine and research in PD.

The impact of subthalamic deep brain stimulation on sleep and other non-motor symptoms in Parkinson's disease

IntroductionThe non-motor symptoms have a major impact on quality of life in patients with Parkinson Disease (PD). We present results of the study on the impact of subthalamic deep brain stimulation (DBS-STN) on sleep and other non-motor symptoms in PD patients. Materials and methodsThirty-six patients with advanced PD were included into the study. Twenty four were evaluated with two-night polysomnography (PSG) before surgery and at 6 months after DBS programming. The whole group (n = 36) was assessed using motor, non-motor symptoms (sleep disturbances in particular) and quality of life measures (QoL), before surgery, 6 and 12 months after DBS programming. ResultsDBS-STN resulted in the significant deterioration of objective sleep parameters, as assessed by PSG, mostly in terms of total sleep time, sleep efficiency, duration of N1 and N2 sleep, wakefulness after sleep onset and sleep latency. At the same time, improvement in the subjective sleep measures, other non-motor symptoms (particularly fatigue, cardiovascular, gastrointestinal, and sexual symptoms) and QoL was identified. The subjective improvement of sleep, other non-motor symptoms and QoL was most prominent in the first 6 months after DBS-STN, diminished slightly (being still better than before surgery) after 12 months, in parallel to mood deterioration. ConclusionDBS-STN resulted in the subjective sleep quality improvement with worsening of objective (PSG) sleep parameters after 6 months. After 12 months all sleep clinical outcome measures were still better than before surgery, albeit worse when compared to the first follow-up visit. Subjective sleep quality correlated positively with mood.

Efficacy and safety of SQJZ herbal mixtures on nonmotor symptoms in Parkinson disease patients: Protocol for a randomized, double-blind, placebo-controlled trial.

Background:As a multisystemic neurodegenerative disorder, Parkinson disease (PD) has a broad spectrum of symptoms including motor and nonmotor symptoms (NMS). As shown in studies, NMS can also impact patient's quality of life, and many of them often go untreated. Chinese herbal medicines with multiconstituent may alleviate NMS in PD patients. This research is carried out to assess the efficacy and safety of a Chinese herbal formula for NMS, with its Chinese name acronym of SQJZ.Methods/design:It will be a multicenter, randomized, double-blind, placebo-controlled trial. Idiopathic PD with a Hoehn and Yahr scale score ≤4, aged 18 to 80 years, will be involved. About 240 patients will be randomly assigned to either SQJZ or placebo in a 2:1 ratio. There is a 2-week run-in period before the randomization, and the follow-up will be 24 weeks, including 12-week treatment period, with visit once every 4 weeks and 12-week washout follow-up. All participants are asked to maintain the regular medication schedule. SQJZ formula will consist of Chinese herbs with effects for insomnia, constipation, anxiety, and so on. The primary outcome will be measured using NMS scale, and secondary outcomes will include unified PD rating scale, PD sleep scale, the Parkinson fatigue scale, the constipation severity instrument, and PD Questionnaire-39. The primary efficacy analysis will be based on the intention-to-treat method, and mixed-model repeated-measures analyses will be used.Discussion:The findings from this research might provide evidence of the efficacy and safety of SQJZ Chinese herbal formula for treating NMS in PD patients. The results will sustain the broader use of SQJZ formula in PD.

A Randomized Controlled Trial of Chinese Medicine on Nonmotor Symptoms in Parkinson's Disease.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I–IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p = 0.019), mood/cognition (p = 0.005), and reduction in hallucinations (p = 0.024). In addition, post hoc analysis showed a significant reduction in constipation (p < 0.001). However, there was no evidence of improvement in MDS-UPDRS Part I total score (p = 0.216) at week 32. Adverse events (AEs) were mild and comparable between the two groups. In conclusion, long-term administration of JLT is well tolerated and shows significant benefits in improving NMS including mood, cognition, and constipation.

The impact of nonmotor symptoms on quality of life in patients with Parkinson's disease in Taiwan.

PurposeThe nonmotor symptoms (NMS) of Parkinson’s disease (PD) are important factors for quality of life (QoL). Few studies on NMS have been conducted in Asian PD patients. Additionally, effects of anti-PD drugs on risk of NMS are still controversial. We therefore conducted this hospital-based cross-sectional study to examine the clinical factors, including concomitant anti-PD medication use, on the occurrence of NMS and QoL in Taiwanese PD patients.Patients and methodsPD patients who received long-term follow-up in the movement disorders clinics were enrolled and received NMS questionnaire (NMSQuest) and the 39-item Parkinson’s Disease Questionnaire (PDQ-39). Spearman’s rank correlation coefficient was checked for the correlation between clinical factors and NMSQT/PDQSI. Multiple linear regressions were applied to assess the influence of clinical factors on NMSQT/PDQSI.ResultsA total of 210 PD patients (mean age 66.1±9.86 years, Hoehn and Yahr stage 2.2±0.9) were included in this study. Up to 98% of patients reported at least one symptom of NMS. The most prevalent symptom was urinary complaints (56%), followed by memory/apathy (30%) and depression/anxiety (28%). The correlation between NMSQT and PDQSI was strong (rs=0.667), especially the item of depression/anxiety (rs=0.607). The regression model for NMSQT indicated that disease duration and severity, but not pharmacological therapy, were major predictors of NMS.ConclusionOur data indicated a high prevalence rate of NMS in PD patients. Among symptoms of NMS, depression and anxiety had the greatest impact on QoL. Concomitant anti-PD medication use did not affect the occurrence of NMS and QoL.