Parkinson's Disease Severity at 3 Years Can Be Predicted from Non-Motor Symptoms at Baseline.
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ABSTRACT:
SUBMITTER: Ayala A
PROVIDER: S-EPMC5674937 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson's disease (PD) compared with healthy controls (HC).MethodsParkinson's Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging.Results423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1-42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy.ConclusionsThis study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1-42 level is an important finding that will have to be replicated in other cohorts.Trial registrationClinicalTrials.gov identifier: NCT01141023.
| S-EPMC5732865 | biostudies-literature
Project description:The nature of the inflammatory response in Parkinson's disease (PD) remains to be better understood. Here, we used highly sensitive Single Molecule Array (SIMOA) technology to measure the levels of the inflammatory mediators Interleukin 6 (IL-6), Interleukin 17A (IL-17A), Tumour Necrosis Factor α (TNFα) and Transforming Growth Factor β (TGFβ) in plasma from PD patients and age- and gender-matched healthy controls. We report that IL-17A correlates with non-motor symptoms (NMS) scores, while IL-6 positively correlates with motor scores. We found no correlations between cytokines and disease duration suggesting that IL-6 and IL-17A are associated with disease severity rather than disease duration in this cohort, furthermore IL-17A may be involved in the underlying pathophysiology of NMS in PD.
| S-EPMC6839458 | biostudies-literature
Project description:OBJECTIVE:The objective of this study was to assess the efficacy and safety of nabilone, a synthetic tetrahydrocannabinol analogue, as a treatment for non-motor symptoms (NMS) in Parkinson's disease (PD). METHODS:This was a phase II placebo-controlled, double-blind, parallel-group, enriched enrollment randomized withdrawal trial conducted at the Medical University Innsbruck. A random sample of 47 patients with PD with stable motor disease and disturbing NMS defined by a score of ?4 points on the Movement Disorder Society - Unified PD Rating Scale-I (MDS-UPDRS-I) underwent open-label nabilone titration (0.25 mg once daily to 1 mg twice daily, phase I). Responders were randomized 1:1 to continue with nabilone or switch to placebo for 4?weeks (phase II). The primary efficacy criterion was the change of the MDS-UPDRS-I between randomization and week 4. Safety was analyzed in all patients who received at least one nabilone dose. RESULTS:Between October 2017 and July 2019, 19 patients received either nabilone (median dose = 0.75 mg) or placebo. At week 4, mean change of the MDS-UPDRS-I was 2.63 (95% confidence interval [CI] 1.53 to 3.74, p =?0.002, effect size = 1.15) in the placebo versus 1.00 (95% CI -0.16 to 2.16, p =?0.280, effect size = 0.42) in the nabilone-group (difference: 1.63, 95% CI 0.09 to 3.18, p =?0.030, effect size = 0.66). Seventy-seven percent of patients had adverse events (AEs) during open-label titration, most of them were transient. In the double-blind phase, similar proportions of patients in each group had AEs (42% in the placebo group and 32% in the nabilone group). There were no serious AEs. INTERPRETATION:Our results highlight the potential efficacy of nabilone for patients with PD with disturbing NMS, which appears to be driven by positive effects on anxious mood and night-time sleep problems. TRIAL REGISTRY:ClinicalTrials.gov (NCT03769896) and EudraCT (2017-000192-86). ANN NEUROL 2020;88:712-722.
| S-EPMC7540547 | biostudies-literature
Project description:Nonmotor symptoms (NMSs) cause major burden in patients with Parkinson's disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4-6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.
| S-EPMC8292315 | biostudies-literature
Project description:Parkinson's disease is now considered a complex, multi-peptide, central, and peripheral nervous system disorder with considerable clinical heterogeneity. Non-motor symptoms play a key role in the trajectory of Parkinson's disease, from prodromal premotor to end stages. To understand the clinical heterogeneity of Parkinson's disease, this study used cluster analysis to search for subtypes from a large, multi-center, international, and well-characterized cohort of Parkinson's disease patients across all motor stages, using a combination of cardinal motor features (bradykinesia, rigidity, tremor, axial signs) and, for the first time, specific validated rater-based non-motor symptom scales. Two independent international cohort studies were used: (a) the validation study of the Non-Motor Symptoms Scale (n = 411) and (b) baseline data from the global Non-Motor International Longitudinal Study (n = 540). k-means cluster analyses were performed on the non-motor and motor domains (domains clustering) and the 30 individual non-motor symptoms alone (symptoms clustering), and hierarchical agglomerative clustering was performed to group symptoms together. Four clusters are identified from the domains clustering supporting previous studies: mild, non-motor dominant, motor-dominant, and severe. In addition, six new smaller clusters are identified from the symptoms clustering, each characterized by clinically-relevant non-motor symptoms. The clusters identified in this study present statistical confirmation of the increasingly important role of non-motor symptoms (NMS) in Parkinson's disease heterogeneity and take steps toward subtype-specific treatment packages.
| S-EPMC5611404 | biostudies-literature
Project description:BackgroundsSleep disorders are the most common and disabling symptoms in patients with Parkinson's disease (PD). Understanding the associations between sleep characteristics and motor and non-motor symptoms (NMSs) in PD can provide evidence to guide therapeutic interventions and nursing strategies. We aimed to investigate the association between sleep characteristics and motor function and NMSs in PD using multiple approaches.MethodsA total of 328 participants were included, and all participants underwent Pittsburgh Sleep Quality Index (PSQI) evaluation and clinical assessments of PD symptoms. We conducted Spearman's correlation to evaluate the associations between sleep and PD symptoms, nonlinear regression to assess the relationships between sleep habits and PD, and mediated analyses to test the effects of NMSs on global PSQI and PD severity, quality of life, and motor symptoms.ResultsPoor sleep was associated with more severe PD symptoms. In addition, the reflection point for bedtime was around 21:52, associated with motor symptoms, and insufficient and excessive total time spent in bed and nocturnal sleep duration were correlated with higher NMS burdens. The optimal points were 8-9.2 and 6.2-6.9 h, respectively. It was also discovered that NMSs played the mediating roles in global sleep with the quality of life, PD stages, and motor symptoms to a varying range of 6.8-95.4%.ConclusionsSleep disorders have a significant effect on the burden of PD symptoms. The current findings provide new insights into the monitoring and management of sleep and PD and need to be further explored in the future studies.
| S-EPMC9226540 | biostudies-literature
Project description:Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have different rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.
| S-EPMC5560285 | biostudies-other
Project description:BackgroundNon-motor symptoms (NMS) are frequent in Parkinson's disease (PD).ObjectivesTo estimate the prevalence of NMS and of non-motor fluctuations (NMF) using the Movement Disorders Society-Non-Motor Rating Scale (MDS-NMS) and other scales assessing NMS, and their relationship with sex and PD severity.MethodsCross-sectional study with a sample of 402 PD patients. The Hoehn and Yahr staging system (HY), Clinical Impression of Severity Index for PD (CISI-PD), MDS-NMS (including NMF- subscale), Non-Motor Symptoms scale (NMSS), and MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) were applied. A NMS was considered present when scored ≥1. Differences in scores by sex and HY, CISI-PD, and MDS-UPDRS severity levels were calculated using Fisher's exact and chi-squared tests.ResultsUsing the MDS-NMS, NMS were present in 99.7% of patients and the mean number of NMS was 16.13 (SD: 9.36). The most prevalent NMS was muscle, joint or back pain (67.4% of the sample) and the least prevalent was dopamine dysregulation syndrome (2.2%). Feeling sad or depressed was significantly more prevalent in women. Using the MDS-NMS revealed more NMS than the other scales assessing NMS. NMF were present in 41% of the sample, with fatigue being the most prevalent symptom (68.5% patients with NMF), and no differences by sex. Patients with greater PD severity had higher prevalence of NMS than patients with lower severity.ConclusionsAlmost all patients with PD experience NMS, and many experience NMF. Prevalence rates for NMS using the MDS-NMS are higher than on other scales used and increase with higher disease severity.
| S-EPMC7853195 | biostudies-literature
Project description:Background and purposeThe prevalence and duration of non-motor symptoms (NMS) in prodromal Parkinson's disease (PD) has not been extensively studied. The aim of this study was to determine the prevalence and duration of prodromal NMS (pNMS) in a cohort of patients with recently diagnosed PD.MethodsWe evaluated the prevalence and duration of pNMS in patients with early PD (n = 154). NMS were screened for using the Non-Motor Symptom Questionnaire (NMSQuest). We subtracted the duration of the presence of each individual NMS reported from the duration of the earliest motor symptom. NMS whose duration preceded the duration of motor symptoms were considered a pNMS. Individual pNMS were then grouped into relevant pNMS clusters based on the NMSQuest domains. Motor subtypes were defined as tremor dominant, postural instability gait difficulty (PIGD) and indeterminate type according to the Movement Disorder Society Unified Parkinson's Disease Rating Scale revision.ResultsProdromal NMS were experienced by 90.3% of patients with PD and the median number experienced was 4 (interquartile range, 2-7). A gender difference existed in the pNMS experienced, with males reporting more sexual dysfunction, forgetfulness and dream re-enactment, whereas females reported more unexplained weight change and anxiety. There was a significant association between any prodromal gastrointestinal symptoms [odds ratio (OR), 2.30; 95% confidence interval (CI), 1.08-4.89, P = 0.03] and urinary symptoms (OR, 2.54; 95% CI, 1.19-5.35, P = 0.016) and the PIGD phenotype. Further analysis revealed that total pNMS were not significantly associated with the PIGD phenotype (OR, 1.10; 95% CI, 0.99-1.21, P = 0.068).ConclusionsProdromal NMS are common and a gender difference in pNMS experienced in prodromal PD may exist. The PIGD phenotype had a higher prevalence of prodromal gastrointestinal and urinary tract symptoms.
| S-EPMC6563450 | biostudies-literature
Project description:Background and objectiveSex plays a role in Parkinson's disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD.Patients and methodsPD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used.ResultsAt baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression (p < 0.0001), fatigue (p < 0.0001), and pain (p < 0.00001) were more frequent and/or severe in females, whereas other symptoms such as hypomimia (p < 0.0001), speech problems (p < 0.0001), rigidity (p < 0.0001), and hypersexuality (p < 0.0001) were more noted in males. Women received a lower levodopa equivalent daily dose (p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (p = 0.001).ConclusionThe present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed.
| S-EPMC9960095 | biostudies-literature