Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.
ABSTRACT: Background:The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Objective:Determine progression rates of MDS-UPDRS scores in de novo PD. Methods:362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. Results:MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. Conclusions:The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.
Project description:<h4>Objective</h4>To 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).<h4>Methods</h4>Parkinson'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.<h4>Results</h4>423 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 A?1-42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy.<h4>Conclusions</h4>This 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 A?1-42 level is an important finding that will have to be replicated in other cohorts.<h4>Trial registration</h4>ClinicalTrials.gov identifier: NCT01141023.
Project description:PURPOSE:The aim of this work was to allow combination of information from recent and historical trials in Parkinson's Disease (PD) by developing bridging methodology between two versions of the clinical endpoint. METHODS:A previously developed Item Response Model (IRM), that described longitudinal changes in Movement Disorder Society (MDS) sponsored revision of Unified Parkinson's Disease Rating Scale (UPDRS) [MDS-UPDRS] data from the De Novo PD cohort in Parkinson's Progression Markers Initiative, was first adapted to describe baseline UPDRS data from two clinical trials, one in subjects with early PD and another in subjects with advanced PD. Assuming similar IRM structure, items of the UPDRS version were mapped to those in the MDS-UPDRS version. Subsequently, the longitudinal changes in the placebo arm of the advanced PD study were characterized. RESULTS:The parameters reflecting differences in the shared items between endpoints were successfully estimated, and the model diagnostics indicated that mapping was better for early PD subjects (closer to De Novo cohort) than for advanced PD subjects. Disease progression for placebo in advanced PD patients was relatively shallow. CONCLUSION:An IRM able to handle two variants of clinical PD endpoints was developed; it can improve the utilization of data from diverse sources and diverse disease populations.
Project description:Background:The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS-UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD. Methods:For this cross-sectional study, demographic data and MDS-UPDRS scores were collected, including HY stage. Subscores on MDS-UPDRS Parts I through IV were analyzed using 1-way analyses of variance for each HY stage and in 5-year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states. Results:The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0-5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS-UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5-year increments of disease duration, MDS-UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states. Conclusions:MDS-UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5-year increments of disease duration in the first 15 years of the disease.
Project description:Background:Nonmotor symptoms (NMSs) of Parkinson's disease (PD) impair health-related quality of life. Objectives:To identify changes in NMSs during 52?weeks in Japanese PD patients exhibiting motor fluctuations. Methods:In PD patients with ?1 NMS and wearing-off, changes in total/subscore of the Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part I and 8-item PD Questionnaire were assessed. Group-based trajectory models were used to characterize longitudinal patterns of MDS-UPDRS Part I. Results:Data from 996 patients were analyzed. MDS-UPDRS Part I subscores for cognitive function decreased linearly over time. Total and subscores for apathy and lightheadedness on standing significantly deteriorated with fluctuations, whereas other subscores fluctuated without significant deterioration. Changes in the MDS-UPDRS Part I total score correlated with changes in the 8-item PD Questionnaire total score. Based on group-based trajectory models, longitudinal pattern analysis of MDS-UPDRS Part I scores yielded the following 3 separate groups: unchanged (63.8%), deteriorated (20.1%), and improved (16.2%). The improved group had significantly more NMSs at baseline, significantly higher MDS-UPDRS Part I/8-item PD Questionnaire total scores, and modified Hoehn and Yahr scores, and had received treatment for NMSs. The multivariate analysis revealed significant associations between severe motor disability and receiving any treatment for NMSs at baseline and improvement of MDS-UPDRS Part I total scores. Conclusions:Changes in MDS-UPDRS Part I scores were variable and related to changes in health-related quality of life in PD patients with motor fluctuations.
Project description:Phosphorylated ?-synuclein accounts for more than 90% of ?-synuclein found in Lewy bodies of Parkinson's disease (PD). We aimed to examine whether plasma Ser129-phosphorylated ?-synuclein (pS129-?-synuclein) is a surrogate marker of PD progression. This prospective study enrolled 170 participants (122 PD patients, 68 controls). We measured plasma levels of total and pS129-?-synuclein using immunomagnetic reduction-based immunoassay. PD patients received evaluations of motor and cognition at baseline and at a mean follow-up interval of three years. Changes in the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale motor score (MDS-UPDRS part III) and Mini-Mental State Examination (MMSE) score were used to assess motor and cognition progression. Our results showed that plasma levels of total and pS129-?-synuclein were significantly higher in PD patients than controls (total: 1302.3 ± 886.6 fg/mL vs. 77.8 ± 36.6 fg/mL, p < 0.001; pS129-?-synuclein: 12.9 ± 8.7 fg/mL vs. 0.8 ± 0.6 fg/mL, p < 0.001), as was the pS129-?-synuclein/total ?-synuclein ratio (2.8 ± 1.1% vs. 1.1 ± 0.6%, p = 0.01). Among PD patients, pS129-?-synuclein levels were higher with advanced motor stage (p < 0.001) and correlated with MDS-UPDRS part III scores (r = 0.27, 95% CI: 0.09-0.43, p = 0.004). However, we found no remarkable difference between PD patients with and without dementia (p = 0.75). After a mean follow-up of 3.5 ± 2.1 years, PD patients with baseline pS129-?-synuclein > 8.5 fg/mL were at higher risk of motor symptom progression of at least 3 points in the MDS-UPDRS part III scores than those with pS129-?-synuclein < 8.5 fg/mL (p = 0.03, log rank test). In conclusion, our data suggest that plasma pS129-?-synuclein levels correlate with motor severity and progression, but not cognitive decline, in patients with PD.
Project description:OBJECTIVE:To assess effects of caffeine on Parkinson disease (PD). METHODS:In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life. RESULTS:Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo). CONCLUSION:Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects. CLINICALTRIALSGOV IDENTIFIER:NCT01738178. CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.
Project description:Cardiovascular comorbidities associate with neurodegeneration in the elderly and may contribute to extranigral pathologies and medically refractory axial motor features in Parkinson disease (PD).We explored differences in the estimated rate of axial motor feature accrual between patients with PD with and without elevated cardiovascular risk factors as estimated by the Framingham General Cardiovascular Disease risk-scoring algorithm in a cross-sectional cohort study. All participants underwent motor evaluations with the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS), [(11)C]dihydrotetrabenazine (DTBZ) monoaminergic brain PET imaging, and MRI.Participants with PD with elevated Framingham risk (FR) scores (n = 63, 74.1%) showed higher unadjusted rates of total MDS-UPDRS (t = 3.60, p = 0.0006) and axial motor scores (t = 3.98, p = 0.0001) per estimated year of motor symptoms compared to participants with normal-range risk scores (n = 22, 25.9%). After controlling for sex, Montreal Cognitive Assessment score, frontal leukoaraiosis severity, and striatal DTBZ activity, elevated risk factor status was associated with the rate of accrual of axial motor impairments (R(2) = 0.206; t = 2.62, p = 0.011) but not with total MDS-UPDRS motor score (R(2) = 0.198; t = 1.51, p = 0.135). Frontal leukoaraiosis was associated with the rate of axial and total MDS-UPDRS scores per year of symptoms and also with elevated systolic blood pressure (R(2) = 0.291; t = 2.30, p = 0.024) in a separate risk-factor model.Cardiovascular risk factors may contribute to axial motor features in PD. Early modification of cardiovascular risk factors, including hypertension, deserves further study as a novel disease-modifying strategy in PD.