The Unified Parkinson's Disease Rating Scale (UPDRS): Status and recommendations

The Movement Disorder Society Task Force for Rating Scales for Parkinson's Disease prepared a critique of the Unified Parkinson's Disease Rating Scale (UPDRS). Strengths of the UPDRS include its wide utilization, its application across the clinical spectrum of PD, its nearly comprehensive coverage of motor symptoms, and its clinimetric properties, including reliability and validity. Weaknesses include several ambiguities in the written text, inadequate instructions for raters, some metric flaws, and the absence of screening questions on several important non‐motor aspects of PD. The Task Force recommends that the MDS sponsor the development of a new version of the UPDRS and encourage efforts to establish its clinimetric properties, especially addressing the need to define a Minimal Clinically Relevant Difference and a Minimal Clinically Relevant Incremental Difference, as well as testing its correlation with the current UPDRS. If developed, the new scale should be culturally unbiased and be tested in different racial, gender, and age‐groups. Future goals should include the definition of UPDRS scores with confidence intervals that correlate with clinically pertinent designations, “minimal,” “mild,” “moderate,” and “severe” PD. Whereas the presence of non‐motor components of PD can be identified with screening questions, a new version of the UPDRS should include an official appendix that includes other, more detailed, and optionally used scales to determine severity of these impairments. © 2003 Movement Disorder Society     

Comparative responsiveness of Parkinson's disease scales to change over time

The objective of the study is to examine the comparative responsiveness of outcome measures to assess progression over time in Parkinson's disease (PD). One hundred twenty‐eight patients participating in a clinic‐based naturalistic study of PD were assessed with the Hoehn and Yahr, UPDRS, MMSE, PDQ‐39, PDQL, EQ‐5D, and BDI scales at baseline and at 1 year. In addition, 82 patients in a community‐based study of patients with PD who had completed self‐rated Schwab and England, PDQ‐39, EQ‐5D, and BDI scales at baseline, were sent the same questionnaires at 1 and 4 years. Responsiveness was assessed using t‐tests, standardised effect size, and standardised response mean. In both samples, the Hr‐QoL measures were less responsive to change over time than the impairment and disability scales (Hoehn and Yahr, UPDRS, Schwab and England scales). In addition, in the clinic‐based sample, Hoehn and Yahr and UPDRS ADL scale (“on”) were more responsive to progression over time than UPDRS motor part and ADL part (“off”). Hr‐QoL measures are less responsive to change over time than measures of impairment and disability. Although this suggests that these measures are less accurate in detecting subtle changes, it may also indicate that the multifactorial subjective assessment of Hr‐QoL adapts to changes over time. Global assessment of overall impairment and disability (which incorporates motor and nonmotor features of PD), however, appeared relatively responsive to change over time in patients in a naturalistic setting. © 2009 Movement Disorder Society     

Determination of minimal clinically important change in early and advanced Parkinson's disease

Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in “off” time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo‐controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa‐treated subjects with motor fluctuations. An anchor‐based approach using clinical global impression of improvement (CGI‐I) was used to determine MCIC for UPDRS scores and daily “off” time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI‐I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I–III) in early PD was determined to be ?3.5 points based on mean scores and ?3.0 points based on ROC curves. In addition, we found an MCIC for reduction in “off” time of 1.0 hours as defined by mean reduction in “off” time in active treated subjects self‐rated as minimally improved on CGI‐I minus mean reduction in “off” time in placebo‐treated subjects self‐rated as unchanged (1.9–0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies. © 2011 Movement Disorder Society     

The effect of unilateral electrostimulation of the subthalamic nucleus on respiratory/phonatory subsystems of speech production in Parkinson's disease—a preliminary report

This paper reports findings on the respiratory/phonatory subsystems from an on‐going study investigating the effect of unilateral electrostimulation of the subthalamic nucleus (STN) on different speech subsystems in people with Parkinson's disease (PD). Speech recordings were made in the medication‐off state at baseline, three months post surgery with stimulation‐on, and with stimulation‐off, in six right‐handed PD patients. Subjects completed several speech tasks. Acoustic analyses of the maximally sustained vowel phonation were reported. The results were compared to the scores of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS‐III) obtained under the same conditions. Results showed that stimulation‐on improved UPDRS‐III scores in all six subjects. While mild improvement was observed for all subjects in the Stimulation‐on condition, three subjects received left‐STN stimulation showed a significant decline in vocal intensity and vowel duration from their baseline indicating the speech function was very susceptible to micro lesions due to the surgical procedure itself when the surgical site was in the dominant hemisphere.     

Comparison of orally dissolving carbidopa/levodopa (Parcopa) to conventional oral carbidopa/levodopa: A single‐dose,double‐blind,double‐dummy,placebo‐controlled,crossover trial

Levodopa use in fluctuating Parkinson's disease (PD) is complicated by an inconsistent and prolonged onset to clinical improvement. An orally dissolved carbidopa/levodopa (OD C/L) preparation (Parcopa UCB Pharma) is available in the United States. This offers potential advantages to shorten the duration from ingestion to clinical improvement. Surprisingly, this has never been clinically assessed. We tested 20 patients with fluctuating PD and a Unified Parkinson's Disease Rating Scale (UPDRS) “off” motor score of ≥25 in a 2‐day, single‐dose, double‐blind, double‐dummy, crossover study. Patients arrived in the morning in the practically defined “off” state and were randomly assigned to receive identical doses of either oral C/L and OD placebo or OD C/L and oral C/L placebo on 1st day and the reverse combination on a 2nd day. After training, patients underwent bilateral hand tapping at baseline and every 5 minutes for 60 minutes after dose ingestion. Stride length (SL) was recorded at 5‐minute intervals with an ambulatory gait monitor. Patients identified their subjective latency to “on” and noted drug preferences and adverse events. They also underwent a UPDRS motor examination at baseline and 60 minutes after dose. Twenty subjects [15 male, age 68.7 (9.7), PD duration 13.4 (6.8)] completed. There were no significant group differences in tapping speed, subjective time to “on,” latency of increased SL, or overall preference. However, all trends did favor OD C/L. Adverse events were similar. This small pilot study did not show significant group differences favoring OD C/L; however, larger studies may be justified, and individual patients may benefit. © 2010 Movement Disorder Society     

Comparison of a timed motor test battery to the Unified Parkinson's Disease Rating Scale‐III in Parkinson's disease

The most widely used scale currently available for the clinical evaluation of motor dysfunction in Parkinson's disease (PD)—the Unified Parkinson's Disease Rating Scale‐III (UPDRS‐III) —is time‐consuming, subjective, and has suboptimal sensitivity. A brief timed motor test (TMT) battery could possibly overcome these drawbacks. Two hundred eighty‐eight PD patients (disease duration 3.1 years; preceding dopaminergic treatment initiation) were assessed with the UPDRS‐III and nine TMTs based on aspects of (a) walking, (b) writing, (c) single and double‐handed pegboard performance, (d) finger tapping, and (e) rapid alternating forearm movements. We investigated validity, reliability, responsiveness, and feasibility. Completing the TMT battery took less than 5 minutes. The TMT correlated well with UPDRS‐III and disease duration. Two factors explained 61% of the TMT variance, the first represented mainly upper extremity function, the second mainly axial/lower extremity function. Cronbach's α was equal for the TMT and the UPDRS‐III (0.8). Test–retest reliability of the TMT sumscore was 0.93 to 0.89 for measurements separated by 3 up to 24 months, whereas UPDRS‐III correlations were 0.88 to 0.84. At group level, a trial using “change from baseline” as endpoint requires only 75% of the patients needed with the UPDRS‐III when applying the TMT battery, and 57% using the pegboard dexterity test. At patient level, TMT and UPDRS‐III were equally responsive. The TMT battery described here is valid, reliable, and feasible. Compared to the UPDRS‐III, it is more objective and more sensitive to change. Therefore, it could be a useful tool for both practical and scientific purposes. © 2008 Movement Disorder Society     

Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease

In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB‐q) is a measure designed to assess the impact of OAB symptoms on health‐related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB‐q short form. Possible correlations between the OAB‐q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB‐q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS‐III), Hoehn‐Yahr (H‐Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age‐matched healthy subjects. The OAB‐q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB‐q scores, UPDRS‐III scores, and H‐Y staging. A multiple linear regression analysis showed that OAB‐q values were significantly influenced by age and UPDRS‐III. No statistical correlations were found between OAB‐q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB‐q mainly correlates with UPDRS‐III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB‐q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD. © 2010 Movement Disorder Society     

Differential response of speed, amplitude, and rhythm to dopaminergic medications in Parkinson's disease

Although movement impairment in Parkinson's disease includes slowness (bradykinesia), decreased amplitude (hypokinesia), and dysrhythmia, clinicians are instructed to rate them in a combined 0–4 severity scale using the Unified Parkinson's Disease Rating Scale motor subscale. The objective was to evaluate whether bradykinesia, hypokinesia, and dysrhythmia are associated with differential motor impairment and response to dopaminergic medications in patients with Parkinson's disease. Eighty five Parkinson's disease patients performed finger‐tapping (item 23), hand‐grasping (item 24), and pronation–supination (item 25) tasks OFF and ON medication while wearing motion sensors on the most affected hand. Speed, amplitude, and rhythm were rated using the Modified Bradykinesia Rating Scale. Quantitative variables representing speed (root mean square angular velocity), amplitude (excursion angle), and rhythm (coefficient of variation) were extracted from kinematic data. Fatigue was measured as decrements in speed and amplitude during the last 5 seconds compared with the first 5 seconds of movement. Amplitude impairments were worse and more prevalent than speed or rhythm impairments across all tasks (P < .001); however, in the ON state, speed scores improved exclusively by clinical (P < 10^?6) and predominantly by quantitative (P < .05) measures. Motor scores from OFF to ON improved in subjects who were strictly bradykinetic (P < .01) and both bradykinetic and hypokinetic (P < 10^?6), but not in those strictly hypokinetic. Fatigue in speed and amplitude was not improved by medication. Hypokinesia is more prevalent than bradykinesia, but dopaminergic medications predominantly improve the latter. Parkinson's disease patients may show different degrees of impairment in these movement components, which deserve separate measurement in research studies. © 2011 Movement Disorder Society     

Helicobacter pylori infection and motor fluctuations in patients with Parkinson's disease

To investigate whether Helicobacter pylori (HP) infection affects the clinical response to levodopa and whether its eradication could improve motor fluctuation in patients with Parkinson's disease (PD). Using the [¹³C] urea breath test, we monitored HP infection in 65 patients with PD and motor fluctuations of the “wearing‐off” or delayed “on” types, with or without dyskinesia. We compared the clinical features and response to L ‐dopa between HP noninfected (n = 30) and HP infected patients (n = 35) by reviewing home diaries kept for 72 hours. Among HP infected patients, we compared the differences in L ‐dopa “onset” time, “on‐time” duration, and scores on the motor examination section of the Unified PD Rating Scale (UPDRS‐III) during the medication “on” phase before and after HP eradication. There were no differences in the age, disease duration, Hoehn and Yahr stage, UPDRS‐III score, L ‐dopa daily dose, and frequency of dyskinesia between HP noninfected and HP infected groups. However, L ‐dopa “onset” time was longer and “on‐time” duration was shorter in HP infected patients than in HP noninfected patients (78.4 ± 28.2 vs. 56.7 ± 25.1 and 210.0 ± 75.7 vs. 257.7 ± 68.9 min, respectively, P < 0.05). HP eradication improved the delay L ‐dopa “onset” time and short “on‐time” duration (to 58.1 ± 25.6 and to 234.4 ± 66.5 min, respectively, P < 0.05). These data demonstrated that HP infection could interfere with the absorption of L ‐dopa and provoke motor fluctuations. HP eradication can improve the motor fluctuations of HP infected patients with PD. © 2008 Movement Disorder Society     

A review of disease progression models of Parkinson's disease and applications in clinical trials

Quantitative disease progression models for neurodegenerative disorders are gaining recognition as important tools for drug development and evaluation. In Parkinson's disease (PD), several models have described longitudinal changes in the Unified Parkinson's Disease Rating Scale (UPDRS), one of the most utilized outcome measures for PD trials assessing disease progression. We conducted a literature review to examine the methods and applications of quantitative disease progression modeling for PD using a combination of key words including “Parkinson disease,” “progression,” and “model.” For this review, we focused on models of PD progression quantifying changes in the total UPDRS scores against time. Four different models reporting equations and parameters have been published using linear and nonlinear functions. The reasons for constructing disease progression models of PD thus far have been to quantify disease trajectories of PD patients in active and inactive treatment arms of clinical trials, to quantify and discern symptomatic and disease‐modifying treatment effects, and to demonstrate how model‐based methods may be used to design clinical trials. The historical lack of efficiency of PD clinical trials begs for model‐based simulations in planning for studies that result in more informative conclusions, particularly around disease modification. © 2016 International Parkinson and Movement Disorder Society     

Clinical measures of progression in Parkinson's disease

Despite all recent advances in symptomatic therapy Parkinson's disease (PD) continues to be a relentlessly progressive neurodegenerative disorder. Therefore therapies that will slow or hold disease progression are a major medical unmet need in PD. Clinical measures of disease progression that have been used in disease modification trials so far have focused on indices of progression of cardinal motor features like bradykinesia, rigidity, and tremor as captured by the UPDRS and the emerging need for effective dopaminergic symptomatic therapy. Progression of global disability in PD, however, is driven by additional factors beyond progressive nigrostriatal denervation leading to increasing severity of cardinal motor features. Progressive pathology in extranigral sites in the brain or peripheral autonomic nervous system contribute to poorly levodopa responsive motor symptoms like postural instability, freezing and falls or nonmotor symptoms. In addition treatment‐induced motor complications also impact on PD disability. Although it is widely accepted that clinical progression of PD is multidimensional and in addition includes effects of aging, there is no consensus how to best implement more clinically meaningful endpoints for disease progression trials that would reflect these complex interactions impacting on the evolution of global disability in PD. There is an urgent need for biomarkers for disease progression that would faithfully reflect advancing neurodegeneration and resulted clinical disability in PD and that could be used in shorter term clinical trials testing putative disease modifying agents. © 2009 Movement Disorder Society     

Gait function and locus coeruleus Lewy body pathology in 51 Parkinson's disease patients

IntroductionGait impairment in Parkinson's Disease (PD) is often severely disabling, yet frequently remains refractory to treatment. The locus coeruleus (LC) has diffuse noradrenergic projections that are thought to play a role in gait function. Enhancement of norepinephrine transmission may improve gait in some PD patients. We hypothesized that the severity of PD pathology, and more specifically, Lewy bodies and neuronal loss in the LC, would correlate with the severity of gait dysfunction in PD.MethodsAutopsy data from 51 patients, collected through the Morris K. Udall Parkinson's Disease Research Center, were correlated with clinical gait-related measures, including individual Unified Parkinson's Disease Rating Scale (UPDRS) Part II and III questions, total UPDRS Part III scores, and timed up-and-go speed (TUG).ResultsNeither the presence nor degree of Lewy body pathology in the LC on autopsy was associated with a higher UPDRS part III gait score. LC tau deposition and frontal Lewy body deposition were not correlated with any of the assessed gait measures. The degree of Lewy body pathology, independent of Braak stage, was positively associated with the severity of motor symptoms overall (UPDRS Part III total score).ConclusionNeither the degree of Lewy body nor tau pathology in the LC is associated with severity of gait disorders in PD. This finding may have implications for targeted noradrenergic therapies in patients with refractory gait disorders.     

A randomized controlled trial of movement strategies compared with exercise for people with Parkinson's disease

This randomized controlled clinical trial was conducted to compare the effects of movement rehabilitation strategies and exercise therapy in hospitalized patients with idiopathic Parkinson's disease. Participants were randomly assigned to a group that received movement strategy training or musculoskeletal exercises during 2 consecutive weeks of hospitalization. The primary outcome was disability as measured by the Unified Parkinson's Disease Rating Scale, UPDRS (motor and ADL components). Secondary outcomes were balance, walking speed, endurance, and quality of life. Assessments were carried out by blinded testers at baseline, after the 2 weeks of treatment and 3 months after discharge. The movement strategy group showed improvements on several outcome measures from admission to discharge, including the UPDRS, 10 m walk, 2 minute walk, balance, and PDQ39. However, from discharge to follow up there was significant regression in performance on the 2 minute walk and PDQ39. For the exercise group, quality of life improved significantly during inpatient hospitalization and this was retained at follow‐up. Inpatient rehabilitation produces short term reductions in disability and improvements in quality of life in people with Parkinson's disease. © 2008 Movement Disorder Society     

Intrajejunal levodopa infusion in Parkinson's disease: A pilot multicenter study of effects on nonmotor symptoms and quality of life

Switching from oral medications to continuous infusion of levodopa/carbidopa gel reduces motor complications in advanced Parkinson's disease (PD), but effects on nonmotor symptoms (NMSs) are unknown. In this prospective open‐label observational study, we report the effects of intrajejunal levodopa/carbidopa gel infusion on NMS in PD based on standard assessments utilizing the nonmotor symptoms scale (NMSS) along with the unified Parkinson's disease rating scale (UPDRS 3 motor and 4 complications) and quality of life (QoL) using the Parkinson's disease questionnaire (PDQ‐8). Twenty‐two advanced PD patients (mean age 58.6 years, duration of disease 15.3 years) were followed for 6 months. A statistically significant beneficial effect was shown in six of the nine domains of the NMSS: cardiovascular, sleep/fatigue, attention/memory, gastrointestinal, urinary, and miscellaneous (including pain and dribbling) and for the total score of this scale (NMSST) paralleling improvement of motor symptoms (UPDRS 3 motor and 4 complications in “best on” state) and dyskinesias/motor fluctuations. In addition, significant improvements were found using the Parkinson's disease sleep scale (PDSS) and the PDQ‐8 (QoL). The improvement in PDQ‐8 scores correlated highly significantly with the changes in NMSST, whereas a moderately strong correlation was observed with UPDRS changes. This is the first demonstration that a levodopa‐based continuous dopaminergic stimulation is beneficial for NMS and health‐related quality of life in PD in addition to the reduction of motor fluctuations and dyskinesias. © 2009 Movement Disorder Society     

Does auditory rhythmical cueing improve gait in people with Parkinson's disease and cognitive impairment? A Feasibility study

Gait and balance problems resulting from Parkinson's disease (PD) are more common in people with PD and dementia (PDD), yet, it is unknown whether the benefits of cueing therapy for mobility generalize to them. We aimed to determine the feasibility and effectiveness of auditory cues to improve gait in PD and cognitive impairment (PD‐CI). Nine participants with PD‐CI walked with and without auditory cues using two different strategies: (1) Cue with temporal instruction to “step in time to the beat,” (2) Cue with spatiotemporal instruction to “take a big step in time to the beat.” Cues were delivered with a metronome at preferred stepping frequency while on medication during single and dual‐task gait. Gait was assessed using GAITRite and walking speed, stride amplitude, step frequency, and variability (CV%) of step and double limb support time were measured. Data were analyzed in SPSS version 16 using fixed‐effect linear mixed models. An adjusted, P value of 0.01 was considered significant. Participants were men, aged 74.89 (±6.45) years with median MMSE of 22 (range 20.5–25) and UPDRS III score of 44 (35.5–47.0). Participants complied with testing and instructions. The cue that focused attention on both temporal and spatial parameters of gait significantly improved single and dual‐task walking speed and stride amplitude. This study provides evidence for the potential of cueing to improve gait in PD‐CI. Only individuals with mild CI were included, and the effect with increased CI and different types of dementia requires further evaluation. © 2009 Movement Disorder Society     

Comparing exercise in Parkinson's disease—the Berlin BIG Study

Physiotherapy is widely used in Parkinson's disease (PD), but there are few controlled studies comparing active interventions. Recently, a technique named “LSVT®BIG” has been introduced. LSVT®BIG is derived from the Lee Silverman Voice Treatment and focuses on intensive exercising of high‐amplitude movements. In the present comparative study, 60 patients with mild to moderate PD were randomly assigned to receive either one‐to‐one training (BIG), group training of Nordic Walking (WALK), or domestic nonsupervised exercises (HOME). Patients in training (BIG) and WALK received 16 hours of supervised training within 4 (BIG) or 8 (WALK) weeks. The primary efficacy measure was difference in change in Unified Parkinson's Disease Rating Scale (UPDRS) motor score from baseline to follow‐up at 16 weeks between groups. UPDRS scores were obtained by blinded video rating. ANCOVA showed significant group differences for UPDRS‐motor score at final assessment (P < 0.001). Mean improvement of UPDRS in BIG was ?5.05 (SD 3.91) whereas there was a mild deterioration of 0.58 (SD 3.17) in WALK and of 1.68 (SD 5.95) in HOME. LSVT®BIG was also superior to WALK and HOME in timed‐up‐and‐go and timed 10 m walking. There were no significant group differences for quality of life (PDQ39). These results provide evidence that LSVT®BIG is an effective technique to improve motor performance in patients with PD. © 2010 Movement Disorder Society     

The effect of cueing therapy on single and dual‐task gait in a drug naïve population of people with Parkinson's disease in northern Tanzania

The incidence of Parkinson's disease (PD) in sub‐Saharan Africa (SSA) is greater than thought however, is largely undiagnosed and untreated. This study aimed to evaluate a nonpharmacological approach using cueing therapy to improve gait in drug‐naïve PD and the feasibility of delivering rehabilitation in northern Tanzania. In this study, twenty‐one people with PD aged 76.4 years (12.9 SD) with varying disease severity participated. They received 9 × 30 min sessions of cueing therapy for gait problems over 3 weeks from a trained therapist delivered in their home environment. Cueing therapy consisted of walking in time to a metronome beat to correct step amplitude and step frequency during a range of functional activities. Gait was recorded on video before and after therapy, and videos were analyzed in the UK by an assessor not involved in data collection. Disease severity (UPDRS) and balance were also measured. Patients were assessed in their nearest clinic. Data were analyzed in Minitab and a P value of 0.05 was considered significant. Cueing therapy significantly improved single and dual task walking speed, step amplitude, and single task step frequency. There was also a significant improvement in motor impairment (UPDRS III) and activities of daily living (UPDRS II). The results provide promising evidence for the role of cueing therapy in PD for symptom management to reduce or delay medication onset. This study also supports the feasibility of rehabilitation in PD in community environments in SSA, which may be applicable to other developing regions. © 2010 Movement Disorder Society     

Clinical correlates of depressive symptoms in familial Parkinson's disease

Depression is one of the most common nonmotor complications of Parkinson's disease (PD) and has a major impact on quality of life. Although several clinical factors have been associated with depression in PD, the relationship between depression and stage of illness as well as between depression and degree of disability remains controversial. We have collected clinical data on 1,378 PD cases from 632 families, using the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II (activities of daily living) & III (motor), the Mini‐Mental State Exam, the Geriatric Depression Scale (GDS), and the Blessed Functional Activity Scale (Blessed). Analyses were performed using the 840 individuals with verified PD and without evidence of cognitive decline. Logistic regression was used to identify study variables that individually and collectively best predicted the presence of depressive symptoms (GDS ≥ 10). After correcting for multiple tests, depressive symptoms were significantly associated with Hoehn and Yahr stage and other clinical measures but not with any genetic variant (parkin, LRRK2, APOE). The Blessed score, education, presence of a first degree relative with signs of depression, and UPDRS Part II were found to best predict depressive symptomatology (R² = 0.33; P = 4 × 10^?48). Contrary to several reports, the results from this large study indicate that stage of illness, motor impairment, and functional disability are strongly correlated with depressive symptoms. © 2008 Movement Disorder Society     

Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature

Parkinson's disease (PD) is a progressive disorder characterized by the emergence of motor deficits. In light of the voluminous and conflicting findings in the literature, the aim of the present quantitative review was to examine the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) in the treatment of motor signs in PD. Studies meeting inclusion criteria were analyzed using meta‐analytic techniques and the Unified Parkinson's Disease Rating Scale (UPDRS) sections II and III were used as outcome measures. In order to determine the treatment effects of rTMS, the UPDRS II and III scores obtained at baseline, same day, to 1 day post rTMS treatment (short‐term follow‐up) and 1‐month post stimulation (long‐term follow‐up) were compared between the active and sham rTMS groups. Additionally, the placebo effect was evaluated as the changes in UPDRS III scores in the sham rTMS groups. A placebo effect was not demonstrated, because sham rTMS did not improve motor signs as measured by UPDRS III. Compared with sham rTMS, active rTMS targeting the M1 significantly improved UPDRS III scores at the short‐term follow‐up (Cohen's d of 0.27, UPDRS III score improvement of 3.8 points). When the long‐term follow‐up UPDRS III scores were compared with baseline scores, the standardized effect size between active and sham rTMS did not reach significance. However, this translated into a significant nonstandardized 6.3‐point improvement on the UPDRS III. No significant improvement in the UPDRS II was found. rTMS over the M1 may improve motor signs. Further studies are needed to provide a definite conclusion. © 2015 International Parkinson and Movement Disorder Society     

UPDRS activity of daily living score as a marker of Parkinson's disease progression

The activities of daily living (ADL) subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) captures the impact of Parkinson's disease (PD) on daily function and may be less affected than other subsections by variability associated with drug cycle and motor fluctuations. We examined UPDRS mentation, ADL and motor subscores in 888 patients with idiopathic PD. Multiple linear regression analyses determined the association between disease duration and UPDRS subscores as a function of medication status at examination and in a subset of patients with multiple examinations. Independent of medication status and across cross‐sectional and longitudinal analyses, ADL subscores showed a stronger and more stable association with disease duration than other UPDRS subscores after adjusting for age of disease onset. The association between disease duration and the motor subscore depended on medication status. The strong association between ADL subscore and disease duration in PD suggests that this measure may serve as a better marker of disease progression than signs and symptoms assessed in other UPDRS sections. © 2008 Movement Disorder Society