Unified Parkinson's Disease Rating Scale Motor Research Articles

A meta-analysis on transcranial magnetic stimulation for Parkinson's disease

Objective To systematically review findings on the effectiveness and safety of transcranial magnetic stimulation (TMS) for treating Parkinson's disease. Methods Foreign and Chinese databases were searched to find relevant trials. The searches were supplemented by searching the reference lists of the published trials. The studies were separated into two groups: those applying TMS at frequencies higher than 1 Hz, and those at 1 Hz or lower. Meta-analysis was performed with the aid of RevMan 5.0 software. Results Both low-frequency and highfrequency TMS can significantly reduce total scores on the Unified Parkinson's Disease Rating Scale (UPDRS) compared with sham stimulations. High-frequency TMS can significantly reduce UPDRS motor scores compared with sham stimulations. On the other hand, low-frequency TMS studies showed no significant overall improvement in motor scores, mental scores or in the activities of daily living (ADL) UPDRS scores. Low-frequency and high-frequency TMS studies also showed no significant overall improvement in Schwab and England ADL scores. Conclusions TMS therapy is safe and partially effective for treating Parkinson's disease. Key words: Transcranial magnetic stimulation; Parkinson's disease; Meta-analysis

Effects of a short duration, high dose contact improvisation dance workshop on Parkinson disease: A pilot study

This study explored the feasibility and possible benefits of contact improvisation (CI) as an exercise intervention for individuals with PD. This was an uncontrolled pilot study. Eleven people with PD (H&Y=2.4 ± 0.4) participated in a workshop of 10 1.5-h CI classes over 2 weeks, dancing with previously trained student CI dancers. Measures of disease severity, balance, functional mobility, and gait were compared 1 week before and after the workshop. Participants demonstrated improvements on the Unified Parkinson Disease Rating Scale-Motor Subsection and Berg balance scores, along with increased swing and decreased stance percentages during walking. Backward step length also increased. Participants expressed a high level of enjoyment and interest in taking future CI classes. This pilot study supports the feasibility of CI as an intervention to address mobility limitations associated with PD.

Effects of five years of chronic STN stimulation on muscle strength and movement speed

This study examined the long-term effects of chronic subthalamic nucleus (STN) deep brain stimulation (DBS) using both clinical evaluation and laboratory motor control measures. Over a 5-year time period, changes in the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) and movement speed and strength at the ankle joint were evaluated on and off STN DBS in eight patients with Parkinson's disease (PD). Four patients were also studied at the elbow joint. Patients with PD originally received unilateral STN DBS between years 2001 and 2003. They were re-evaluated after 5 years of long-term STN DBS between years 2006-2008. At baseline (year 0) and after 5 years, patients with PD were tested off treatment and on STN DBS. In each testing condition, patients performed ballistic, single degree of freedom ankle dorsiflexion and ankle plantarflexion movements and peak velocity was calculated. Patients also performed maximal voluntary contractions at the ankle joint in both directions, and peak torque was calculated. Results showed increased motor UPDRS scores from year 0 to year 5, but STN DBS was efficacious in reducing them. In contrast to the increase in motor UPDRS scores, motor control results showed a marked improvement in peak velocity and peak torque over the 5-year time period in the off treatment condition, and STN DBS was efficacious by improving both peak velocity and peak torque. The current findings suggest that 5 years of chronic STN DBS can have beneficial effects on the motor system over the long term in discrete motor tasks in which maximal effort and maximal neural output is required.

Enlarged hyperechogenic substantia nigra is related to motor performance and olfaction in the elderly

Enlarged substantia nigra hyperechogenicity (SN+) assessed by transcranial sonography (TCS) may be associated with Parkinson's disease (PD) risk markers such as impaired motor performance and hyposmia. The aim of this multicenter cross-sectional study was to define the association between SN+ and these risk markers in a large population older than 50 years without the diagnosis of PD. In three centers (Tuebingen, Homburg, and Innsbruck), 1,839 individuals were examined. The echostatus of the SN was assessed by TCS, motor performance by the Unified Parkinson's Disease Rating Scale (UPDRS) motor score, and olfactory function with Sniffin' Sticks. From the 1,603 subjects included in the analysis, 16.2% were SN+, 23.0% scored above zero in the UPDRS motor section, and 28.0% were hyposmic as defined by less than 75% correctly classified Sniffin' Sticks. SN+ was associated with a UPDRS motor score above zero (OR 1.45, 95% CI 1.08-1.96) and with a lower odor identification capability (OR 1.48, 95% CI 1.12-1.96). The combination of these two features (OR 1.98, 95% CI 1.25-3.15) and UPDRS motor scores >or=3 lead to higher OR. It is concluded that SN+, impaired motor performance, and hyposmia are frequently observed in the elderly and in isolation are unspecific and of limited use to predict a subject's risk for PD. Whether the association of SN+ with both impaired motor performance and hyposmia as seen in this study predicts an increased risk for the development of PD needs to be evaluated in the follow-up investigations.

Autonomic and cognitive functions in Parkinson's disease (PD)

We performed this study to evaluate the relationship between the stages of PD and autonomic dysfunction, and to find an association between the autonomic dysfunction and cognitive impairment in PD. Sixty-three patients who met the criteria of the United Kingdom PD Society Brain Bank were enrolled prospectively. Clinical stages were using the Hoehn and Yahr (H&Y) staging and unified PD rating scale motor scores. Cognitive functions were evaluated using the mini-mental state examination (MMSE) and the modified MMSE (3MS) test. The scale for outcome in PD-autonomic (SCOPA-AUT) was used to evaluate autonomic symptoms. Severities of autonomic dysfunction were classified using the composite autonomic scoring scale (CASS). Fifty-four of the 63 patients (86%) had shown abnormalities on CASS. H&Y stages correlated with SCOPA-AUT ( p < 0.05) and 3MS and MMSE scores ( p < 0.05). H&Y stages were positively related with autonomic dysfunction, heart rate ratios during deep breathing and the quantitative sudomotor axon reflex test (QSART) scores. Autonomic dysfunction may be present from disease onset, whereas the rate of cognitive decline increases with disease progression. We recommend that both qualitative and quantitative autonomic evaluation from the early stage of disease and regular cognitive screening with disease progression might be useful to facilitate optimal management in PD.

Camptocormia in Parkinson's Disease

Objectives. Abnormalities of posture represent one of the main features of Parkinson's disease (PD). Among them, camptocormia has been considered as rare in PD. We investigated frequency and clinical features of camptocormia in PD patients. Methods. 153 PD patients (mean 68.5 ± 10.7 years old, duration 5.9 ± 2.4 years) outpatiently recruited. After neurologic examination, patients were rated on the Unified PD Rating Scale motor scale (UPDRS Part III), minimental state examination (MMSE). Also we evaluated patients with camptocormia by MRI. Of the 153 PD patients, 27 had camptocormia (mean age, 67.9 ± 7.9 years old; disease duration, 6.1 ± 3.9 years). For further evaluation, we recruited age- and sex-matched 27 PD patients without camptocormia (11 men and 16 women; mean age ± SD, 69.2 ± 10.1 years, duration 6.0 ± 2.7 years) These selected 54 patients completed several self-assessments. Lumbar and thoracic paraspinal muscles were studied by EMG. Results. There were no significant differences in age, duration, severity, and drug dose between patients with and without camptocormia. Analysis of NMSS subitems indicated that PD patients tended to show lower scores for sleep/fatigue, attention/memory, and miscellaneous items. Conclusions. We found significant differences concerning nonmotor signs and symptoms evaluated by FAB, PDQ-8, FSQ, VAS-F, and NMSS between patients with and without camptocormia. Our findings indicate that camptocormia is a relatively common sign in PD and that patients with camptocormia scores on the PDQ-8 compared with PD patients without camptocormia. This suggests that improvements in camptocormia of PD patients may improve their QOL.

The Clinically Important Difference on the Unified Parkinson's Disease Rating Scale

To determine the estimates of minimal, moderate, and large clinically important differences (CIDs) for the Unified Parkinson's Disease Rating Scale (UPDRS). Cross-sectional analysis of the CIDs for UPDRS total and motor scores was performed on patients with Parkinson disease (PD) using distribution- and anchor-based approaches based on the following 3 external standards: disability (10% on the Schwab and England Activities of Daily Living Scale), disease stage (1 stage on the Hoehn and Yahr Scale), and quality of life (1 SD on the 12-Item Short Form Health Survey). University of Maryland Parkinson Disease and Movement Disorders Center, Patients Six hundred fifty-three patients with PD. A minimal CID was 2.3 to 2.7 points on the UPDRS motor score and 4.1 to 4.5 on the UPDRS total score. A moderate CID was 4.5 to 6.7 points on the UPDRS motor score and 8.5 to 10.3 on the UPDRS total score. A large CID was 10.7 to 10.8 points on the UPDRS motor score and 16.4 to 17.8 on the UPDRS total score. Concordance among multiple approaches of analysis based on subjective and objective data show that reasonable estimates for the CID on the UPDRS motor score are 2.5 points for minimal, 5.2 for moderate, and 10.8 for large CIDs. Estimates for the UPDRS total score are 4.3 points for minimal, 9.1 for moderate, and 17.1 for large CIDs. These estimates will assist in determining clinically meaningful changes in PD progression and response to therapeutic interventions.

The influence of subthalamic nucleus deep brain stimulation on physical, emotional, cognitive functions and daily living activities in patients with parkinson's disease

To describe effectiveness of deep brain stimulation of subthalamic nucleus (DBS STN) on physical, emotional, cognitive functions and daily activities in Parkinson's patients. Ten patients (51.20 ±10.20 yr.) were assessed three times. The Time Up and Go Test, 12 m Walking Test and Chair Stand Test were used to assess mobility and balance. Purdeu Pegboard and hand writing tests were used to evaluate hand function. The Hospital Anxiety and Depression Scale (HAD) was used to detect depressive symptoms and anxiety score. The Unified Parkinson\'s Disease Rating Scale (UPDRS) and Hoehn &Yahr Scale were also used. The Schwab and England Test was used to evaluate the daily activities (ADL). The results showed that all the patients' mobility and balance ability improved after surgery (p < 0.05). Depressive symptoms / anxiety scores were found to be lower than before surgery (p < 0.05). There were differences in terms of ADL and UPDRS scores after surgery (p < 0.05). At six month after surgery; depressive symptoms decreased by 78%. ADL and UPDRS motor and total scores improved by 190%, 72%, and 78% respectively. STN DBS is an effective treatment to improve physical functioning, emotional status and daily activities in Parkinson's patients. However, it did not show any positive effect on cognitive function.

QUETIAPINE IMPROVES VISUAL HALLUCINATIONS IN PARKINSON DISEASE BUT NOT THROUGH NORMALIZATION OF SLEEP ARCHITECTURE: RESULTS FROM A DOUBLE-BLIND CLINICAL-POLYSOMNOGRAPHY STUDY

Polysomnographic studies of Parkinson's disease (PD) patients with visual hallucinations (VH) usually reveal short, fragmented rapid eye movement (REM) sleep, with lower sleep efficiency and reduced total REM sleep. Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD. To confirm quetiapine's efficacy in improving VH, and to determine whether the mechanism was due to its effect on REM sleep architecture, we performed a pilot, double-blind, placebo-controlled study. Sixteen PD patients experiencing VH were recruited. Eight patients were randomized to quetiapine and eight patients to placebo. Patients underwent pre- and post-treatment polysomnography. The Clinical Global Impression Scale (CGIS), Brief Psychiatric Rating Scale (BPRS), and Unified Parkinson Disease Rating Scale (UPDRS) motor subscale were obtained. There were no differences in baseline characteristics between the treatment arms except that the placebo group had more sleep in stage REM (74.7 min vs. 40.1 min; p < .001). Data were imputed for all patients who prematurely discontinued (four quetiapine and one placebo) in an intention-to-treat analysis. The average quetiapine dose was 58.3 mg/day. While there was no significant difference in the change in REM duration pre- vs. post-treatment in either arm, patients randomized to quetiapine improved on the CGIS (p = .03) and the hallucination item of the BPRS (p = .02). No difference was noted in the UPDRS motor scores. Despite the small sample, this is the first double-blind trial to show quetiapine's efficacy over placebo in controlling VH in the PD population. However, normalization of sleep architecture was not supported as the mechanism.

Six-Minute Walk Distance in Persons With Parkinson Disease: A Hierarchical Regression Model

Falvo MJ, Earhart GM. Six-minute walk distance in persons with Parkinson disease: a hierarchical regression model. Objectives To determine the six-minute walk distance (6MWD) in subjects with Parkinson disease (PD) and to determine the impairments that contribute to walking capacity. Design Descriptive cross-sectional study of subjects with PD. Setting University laboratory. Participants Subjects with PD (N=75; 65.0±9.5y) of mild to moderate severity, as defined by an average Hoehn and Yahr (HY) rating of 2.0±0.4 and Unified Parkinson Disease Rating Scale (UPDRS) motor score of 27±8.9, were tested on medication. Interventions Not applicable. Main Outcome Measures Subjects were administered the motor subsection of the UPDRS and completed the following tests: Berg Balance Scale (BBS), Timed Up & Go (TUG), and six-minute walk test. In addition, they also provided self-reports of freezing of gait and number of falls in the past 6 months. Results The average 6MWD was 391.6±99.9m. All of the aforementioned tests, with the exception of fall number ( P=.07), correlated significantly with 6MWD ( r range, −.64 to .55). By using a hierarchical regression model, we entered age, HY, and UPDRS motor score into the first block (ie, set of independent variables) to represent parkinsonian characteristics, which explained a significant amount of variability in 6MWD ( R 2=.196, P<.001). The second block entered (eg, functional measures scores, self-reports) explained a significant amount of additional variability ( R 2 change=.355, P<.001). The TUG, BBS, and number of falls contributed independently in the presence of all independent variables. Conclusions The 6MWD in subjects with PD is explained in part by disease-specific characteristics and perhaps to a greater extent by impaired balance and predisposition to falling. Training targeted at improving balance and reducing falling risk factors may increase 6MWD (ie, walking capacity) in subjects with PD.

Depressive Symptoms in Parkinson Disease Correlate With Impaired Global and Specific Cognitive Performance

Consecutive patients in a Movement Disorders Center with Parkinson disease (PD) were offered to undergo complete neuropsychological testing and to complete the Beck Depression Inventory (BDI), regardless of their cognitive and behavioral status. A total of 82 patients were included in this cross-sectional study and had a mean age of 67.7 years, formal education of 14.8 years, PD duration of 101 months, Unified Parkinson Disease Rating Scale-Motor ''off'' score of 36.96, Mini-Mental State Examination (MMSE) score of 27.8 (range 19-30), and BDI score of 10.23 (SD 8.65). Beck Depression Inventory scores did not correlate with disease duration or motor scores but inversely correlated with the MMSE scores (r = -0.40; P < .001) and total Dementia Rating Scale (DRS) scores (r = -0.33; P < .01). Using a univariate regression analysis controlling for age, gender, education, and total Unified Parkinson Disease Rating Scales (UPDRS) score, the BDI scores had a significant and unique relationship with MMSE scores. However, when the BDI scores were correlated with specific cognitive domains, only the Boston Naming Test and the Hopkins Verbal Learning Test (HVLT) delayed recall remained significant after Bonferroni correction. Similarly, when comparing the cognitive performance of patients with PD who scored >14 on the BDI versus those who scored <14, only the mean score of the Boston Naming Test was different between the 2 groups. Our study shows that while depressive symptoms correlated with global cognitive performance, naming, verbal memory, and language are the most susceptible cognitive domains affected with depressive symptoms.

Staged bilateral deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease

Several investigators have described the efficacy and safety of unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the treatment of Parkinson's disease (PD). Some patients who underwent unilateral STN DBS required additional surgery on the contralateral side because the unilateral treatment was insufficient. The goal of this study was to assess the efficacy and safety of staged bilateral STN DBS compared to the simultaneous bilateral procedure. Ten patients with medically intractable PD underwent staged bilateral STN DBS, and 12 patients underwent a simultaneous bilateral procedure. Clinical assessments were performed preoperatively and 6 months after the last surgery using the Unified Parkinson's Disease Rating Scale (UPDRS), motor and activity of daily living (ADL) subscores, and Hoehn and Yahr stages. Both the staged and simultaneous groups experienced significant improvement in the UPDRS motor and ADL scores, and the Hoehn and Yahr stages. There were no statistical differences between the two groups in the percent improvement in UPDRS scores. The rate of adverse events in the staged group (20%) was less than that of the simultaneous group (42%), although the difference was not statistically significant. Both the staged bilateral STN DBS and the simultaneous bilateral procedure are effective and safe treatment options, but the staged bilateral procedure may be regarded as the preferred choice for the treatment of some patients.

Towards an understanding of fatigue in Parkinson disease

Objectives: To gain an improved understanding of fatigue in Parkinson disease (PD) by exploring possible predictors among a wide range of motor and non-motor aspects of PD. Methods: 118 consecutive...

Clinically deployable Kinesia™ technology for automated tremor assessment

The objective was to design, build, and assess Kinesia, a wireless system for automated assessment of Parkinson's disease (PD) tremor. The current standard in evaluating PD is the Unified Parkinson's Disease Rating Scale (UPDRS), a qualitative ranking system typically completed during an office visit. Kinesia integrates accelerometers and gyroscopes in a compact patient-worn unit to capture kinematic movement disorder features. Objectively quantifying PD manifestations with increased time resolution should aid in evaluating efficacy of treatment protocols and improve patient management. In this study, PD subjects performed the tremor subset of the UPDRS motor section while wearing Kinesia. Quantitative kinematic features were processed and highly correlated to clinician scores for rest tremor (r(2) = 0.89), postural tremor (r(2) = 0.90), and kinetic tremor (r(2) = 0.69). The quantitative features were used to develop a mathematical model that predicted tremor severity scores for new data with low errors. Finally, PD subjects indicated high clinical acceptance.

Clinical and cerebral activity changes induced by subthalamic nucleus stimulation in advanced Parkinson's disease: A prospective case-control study

Background High-frequency stimulation of the subthalamic nucleus (STN-DBS) improves motor symptoms in advanced Parkinson's disease (PD), but the mechanisms are still unclear. Functional imaging evidenced pathological overactivity in motor cortical areas in advanced PD that can be normalized by effective therapies. Patients and methods We studied resting state cerebral blood flow pre-operatively and 12 months after surgery in 40 patients with advanced PD using ECD-SPECT. SPECT scans were also acquired 1 year apart in 21 matched PD controls who did not undergo surgery. Statistical analysis was performed using statistical parametric mapping (SPM2) software. In addition, we correlated brain perfusion changes after surgery with clinical improvement, assessed using the unified PD rating scale motor score (UPDRS-III). Results Patients showed marked motor improvement and medication reduction after surgery. Stimulated PD patients revealed bilateral rCBF decrements in motor cortical areas and prefrontal cortex bilaterally compared to pre-surgical condition as well as versus PD controls ( p < .01 FDR corrected). Perfusion increases were found in cerebellum, temporal and occipital lobes. Clinical improvement was associated with perfusion decrements in primary motor and premotor cortices. Conclusions Effective STN-DBS is associated with neuronal activity changes in brain regions implicated in movement programming and performance. We hypothesize that clinical benefit might be associated with stimulation-induced normalization of the abnormal overactivity within the cortico-basal ganglia-thalamo-cortical motor loop in advanced PD.

Ropinirole 24-hour prolonged release and ropinirole immediate release in early Parkinson's disease: a randomized, double-blind, non-inferiority crossover study

ABSTRACTObjective: This study compares once-daily ropinirole 24-h prolonged release and three-times-daily ropinirole immediate release in patients with early Parkinson's disease.Methods: This multicentre, double-blind, non-inferiority crossover study involved 161 patients randomized to one of four formulation sequences: (1) immediate release–immediate release–prolonged release; (2) immediate release–prolonged release–prolonged release; (3) prolonged release–prolonged release–immediate release; (4) prolonged release–immediate release–immediate release. During a 12-week dose-titration period, ropinirole immediate release was titrated according to the approved labelling; titration of ropinirole 24-h prolonged release started at a higher dose and was more rapid. Patients then entered three consecutive, flexible-dose, 8-week maintenance periods. At the end of the first maintenance period, half of the patients in each formulation group switched to the same or closest dose of the alternative formulation; remaining patients switched at the end of the second maintenance period.Results: At the end of titration, before the first dose switch, there were substantial reductions in mean Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. During maintenance periods, both groups showed similar efficacy on the UPDRS motor score. Overall mean (standard error) change from period baseline was −0.1 (0.28) for ropinirole 24-h prolonged release, and 0.6 (0.30) for ropinirole immediate release (adjusted mean treatment difference −0.7; 95% confidence interval [CI]: −1.51, 0.10; p = 0.0842). The upper limit of the 95% CI was less than the predefined threshold of 3 points for non-inferiority. Ropinirole 24-h prolonged release was well-tolerated when titrated more rapidly than ropinirole immediate release; overnight switching between formulations was also well-tolerated. Study limitations included complexity of the non-inferiority study design and the forced dose-titration schedule.Conclusion: Ropinirole 24-h prolonged release was effective and well-tolerated in patients with early Parkinson's disease.

Clinical correlation of the binding potential with 123I-FP-CIT in de novo idiopathic Parkinson’s disease patients

The aim of this study was to evaluate the accuracy of different single-photon emission computed tomography (SPECT) reconstruction techniques in measuring striatal N-omega-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]iodophenyl-nortropane ((123)I-FP-CIT) binding in de novo Parkinson's disease (PD) patients, in order to find a correlation with clinical scales of disease severity in the initial phases of disease. Thirty-six de novo PD patients underwent (123)I-FP-CIT SPECT and MRI scan. SPECT data were reconstructed with filtered back projection (FBP), with an iterative algorithm (ordered subset expected maximization, OSEM) and with a method previously developed in our institution, called least-squares (LS) method. The ratio of specific to non-specific striatal (123)I-FP-CIT binding (binding potential, BP) was used as the outcome measure with all the reconstruction methods (BP(FBP), BP(OSEM), BP(LS)). The range of values of striatal BP(LS) was significantly greater than BP(FBP) and BP(OSEM). For all striatal regions, estimates of BP(FBP) correlated well with BP(OSEM) (r = 0.84) and with BP(LS) (r = 0.64); BP(OSEM) correlated significantly with BP(LS) (r = 0.76). A good correlation was found between putaminal BP(LS) and Hoen and Yahr, Unified PD Rating Scale (UPDRS) and lateralized UPDRS motor scores (r = -0.46, r = -0.42, r = -0.39, respectively). Neither putaminal BP(FBP) nor putaminal BP(OSEM) correlated with any of these motor scores. In de novo PD patients, (123)I-FP-CIT BP values derived from FBP and OSEM reconstruction techniques do not permit to differentiate PD severity. The LS method instead finds a correlation between striatal BP and disease severity scores. The results of this study support the use of (123)I-FP-CIT BP values estimated with the LS method as a biomarker of PD severity.

Evaluation of ActiTrac® (ambulatory activity monitor) in Parkinson's Disease

At present, the evaluation of Parkinson's Disease (PD) relies mainly on Unified Parkinson's Disease Rating Scale (UPDRS). Other objective measures have been proposed, including functional studies, timed tests and ambulatory activity monitors (AAM). We carried out a prospective study to analyze the utility and correlation of the AAM: ActiTrac with UPDRS scores and timed tests in patients with PD. We studied 28 patients with idiopathic PD (age: 62 +/- 11 years; duration of illness: 7.7 +/- 4.4 years; clinical stage 2.3 +/- 0.39). Motor evaluation included UPDRS and five timed tests: Purdue Pegboard test and those proposed in CAPIT protocol, pronation-supination (PS), finger dexterity (FD), movement between two points (MTP) and walking test (WT). Clinical evaluation was performed in off condition, at 9 a.m., (12h off their medication). Finally, ActiTrac was placed on the wrist (more affected side) continuously for at least 72h. ActiTrac activity was correlated (Spearman) with total UPDRS (r: - 0.53, p < 0.005) and motor UPDRS (r:- 0.46, p: 0.01); UPDRS rigidity subscore (r:- 0.52, p < 0.01); UPDRS bradykinesia subscore (r:- 0.48; p:0.01); FD (r: - 0.47 p: 0.01), WT (r: - 0.49, p < 0.01) and Purdue test (r:0.54; p < 0.01). ActiTrac seems to be a reasonably accurate method to evaluate motor activity in PD.

Placebo response in Parkinson's disease: Comparisons among 11 trials covering medical and surgical interventions

Placebo-associated improvements have been previously documented in small series of Parkinson's disease (PD) patients. Using a strict definition of placebo-associated improvement, we examined rates and timing of placebo responses to identify patient- and study-based characteristics, predicting positive placebo response in several PD clinical trials. We collected individual patient data from the placebo groups of 11 medical and surgical treatment trials involving PD patients with differing PD severities and placebo-assignment likelihoods. We defined a positive placebo response as > or = 50% improvement in total Unified Parkinson's Disease Rating Scale motor (UPDRSm) score or a decrease by > or = 2 points on at least two UPDRSm items compared to baseline. We calculated positive placebo response rates at early (3-7 weeks), mid (8-18 weeks), and late (23-35 weeks) stages of follow-up. Odds ratios for patient- and study-based characteristics were obtained from a model fitted using generalized estimating equations. There were 858 patients on placebo who met inclusion criteria for analysis. Three studies involved patients without need of symptomatic treatment, two involved patients without motor fluctuations needing symptomatic treatment, and six (three medical and three surgical) involved patients with motor fluctuations. The overall placebo response rate was 16% (range: 0-55%). Patients with higher baseline UPDRSm scores and studies that focused on PD with motor fluctuations, surgical interventions, or those with a higher probability of placebo assignment showed increased odds of positive placebo response. Placebo responses were temporally distributed similarly during early, mid, and late phases of follow-up. Placebo-related improvements occur in most PD clinical trials and are similarly distributed across all 6 months of follow-up. Recognition of factors that impact placebo response rates should be incorporated into individual study designs for PD clinical trials.

Cognitive decline tracks motor progression and not disease duration in Parkinson patients

We performed an analysis of prospectively-acquired cross sectional data on 106 Parkinson disease (PD) patients who underwent comprehensive neuropsychological testing and the Unified Parkinson Disease Rating Scale (UPDRS) motor scale. A significant correlation between the UPDRS motor and neuropsychological tests in all cognitive domains except for general intelligence and visuo-spatial function was seen. In this study, cognitive decline within this PD cohort correlated with motor impairment but not disease duration. Our findings suggest that overall cognitive impairment (except visuospatial dysfunction) may track motor progression in PD more than duration of disease. Longitudinal studies are needed to confirm our results.