Parkinson's Disease Rating Scale-III Research Articles

Cortical thinning is associated with disease stages and dementia in Parkinson's disease

ObjectiveTo investigate the pattern of cortical thinning in Parkinson's disease (PD) across different disease stages and to elucidate to what extent cortical thinning is related to cognitive impairment.DesignNinety-six subjects including...

Altered resting-state functional connectivity of the dentate nucleus in Parkinson's disease

We used functional magnetic resonance imaging (fMRI) to measure functional connectivity of the dentate nucleus (DN) between patients with Parkinson's disease (PD) and normal controls who were studied in a resting state. Images were acquired in 18 PD patients and in age- and sex-matched normal controls. Connectivity of the bilateral DN was calculated and compared between patients and controls, connectivity of the bilateral DN within the cerebellum was compared between rigidity and bradykinesia-dominant patients (PDAR) and tremor-dominant patients (PDT), and correlation analysis was performed between the connectivity strength and behavioral measures within the cerebellum. Some regions in the cerebellum showed enhanced connectivity with the bilateral DN in PD patients, and decreased connectivity of the DN with the bilateral cerebellar posterior lobe was observed in PDT as compared to PDAR. A set of regions consistent with the default mode network showed disrupted connectivity with the DN. Decreased connectivity between the inferior parietal lobule and the DN was also observed in PD patients. Additional analyses did not show any significant correlations between functional connectivity within the cerebellum and Unified Parkinson's Disease Rating Scale-III scores. Our findings suggest that connectivity of the DN in the resting state is disrupted in PD, and there may be a compensatory cerebellar connectivity mechanism in the resting state in PD. Further study of the cerebellum may clarify the pathophysiology of PD.

Cognitive performance of GBA mutation carriers with early-onset PD

To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age- and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p = 0.035), and on the memory (p = 0.017) and visuospatial (p = 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p < 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p < 0.001), and a clinical diagnosis of either MCI or dementia (p = 0.004). GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.

GBA-associated PD presents with nonmotor characteristics

To evaluate whether there exists distinct characteristics in glucocerebrosidase (GBA)-associated Parkinson disease (PD) with regard to motor and nonmotor symptoms as well as imaging characteristics assessed by transcranial sonography (TCS). Twenty patients with PD with heterozygous GBA mutations (N370S, L444P) (GBA-PD) in comparison to 20 patients with sporadic PD negative for GBA mutations (sPD) were included. We assessed motor impairment with the Unified Parkinson's Disease Rating Scale-III. Nonmotor symptoms were evaluated using the Montreal Cognitive Assessment, Neuropsychiatric Inventory, revised form of the Beck Depression Inventory, Parkinson Disease Sleep Scale, Sniffin' Sticks, and Unified Multiple System Atrophy Rating Scale items 9-12. TCS imaging was used to detect morphologic characteristics. Patients with GBA-PD more often had a variety of nonmotor symptoms, namely dementia, neuropsychiatric disturbances, and autonomic dysfunction, and had more severe cases, than patients with sPD. They also demonstrated a higher prevalence of a reduced echogenicity of the brainstem raphe assessed by TCS. Especially nonmotor symptoms seem to be very common in GBA-PD. Further studies are needed to validate these observations in order to better understand the pathogenesis of GBA-PD and develop specific therapeutic concepts.

Predicting Outcomes in Parkinson's Disease: Comparison of Simple Motor Performance Measures and the Unified Parkinson's Disease Rating Scale-III

The Unified Parkinson's Disease Rating Scale (UPDRS) part III is the principal motor assessment method for Parkinson's disease (PD), but has recognized limitations including subjectivity and insensitivity. Easy to administer, objective, quantitative tests that are good indicators of PD progression could offer advantages in both clinical and research settings. We administered four simple, motor performance measures--functional reach, timed hall walk, a timed block sort task, and timed dotting--as well as the UPDRS to 609 PD patients of a single neurologist. The unadjusted Spearman correlations of these performance measures with the UPDRS motor score (UPDRS III) ranged from 0.29 to 0.49. Moreover, these measures generally had high reliability on repeated testing. We defined specific outcomes in PD--overall disability, gait instability and falls, as well as non-motor outcomes of depression, dementia, and psychosis, and assessed the ability of the measures to predict these outcomes over the entire follow-up of the cohort (average: 2.4 years) and over the first year of follow-up. The associations between the measures and the outcomes were generally stronger and more precise for the performance measures than for the UPDRS III. A summary score of the performance measures was a particularly good predictor of the outcomes. These motor performance measures could provide a rapid, simple means of assessing PD progression that could benefit both clinical and research endeavors.

Pharmacokinetic-Pharmacodynamic Modeling of Levodopa in Patients With Advanced Parkinson Disease

The aims of the present study were to investigate the pharmacokinetic and pharmacodynamic (pk/pd) relationship of levodopa (l-dopa) in patients with advanced Parkinson disease (PD) and also to evaluate the effect of tolcapone on the pk/pd analysis of l-dopa in 1 patient with severe dyskinesias and fluctuations. The pharmacokinetics (plasma concentrations of l-dopa and 3-O-methyldopa [3-OMD]) and motor effects (global score of the Unified Parkinson's Disease Rating Scale-III) of a single dose of l-dopa (plus the peripheral decarboxylase inhibitor 1:4) were determined in 14 patients with advanced PD. Patients were classified into 2 groups according to Hoehn and Yahr scale (stages 2 and 3). In 1 patient with severe dyskinesias and fluctuations, pk/pd of l-dopa were evaluated before and after coadministration of tolcapone at 100 mg 2 times daily for 1 month. The pk/pd analysis was based on an estimate of the maximal response model with a semiparametric approach to effect site equilibrium. The highest levels of l-dopa and 3-OMD were observed in patients with stage 3 of Hoehn and Yahr scale. We showed differences in the pk/pd parameters after coadministration of tolcapone in 1 patient as well as the clinical improvement.Univariate analysis showed some significant correlations (P < 0.05) between l-dopa pk/pd parameters and patients' age, duration of l-dopa treatment, and duration of the disease. Multivariate analysis adjusted for patients' age, sex, duration of the disease, and Hoehn and Yahr stage showed that presence of diphasic (dyskinesia-improvement-dyskinesia [DID]) dyskinesias was the only independent predictor of larger threshold level - EC50 (mean concentration at half maximal effect) of l-dopa (P = 0.034). The motor complications during long treatment therapy in patients with advanced PD especially with stage 3 Hoehn and Yahr scale were correlated to the higher plasma concentrations of l-dopa. In the presented study, patients with motor complications, especially with DID dyskinesias, exhibited a larger threshold level (EC50). The clinical improvement of a patient who received l-dopa and tolcapone can be explained by tolcapone-induced changes of peripheral and central l-dopa pharmacokinetics, which led to a decrease of l-dopa EC50 and 3-OMD concentrations. Our data indicate that pk/pd analysis may be helpful for monitoring the efficiency of therapeutic strategy applied in PD patients.

Dopamine transporter imaging under high-dose transdermal nicotine therapy in Parkinson's disease: an observational study

Nicotine therapy might improve the course of Parkinson's disease. This observational study evaluated the performance of dopamine transporter imaging in follow-up patients under nicotine therapy. Six Hoehn and Yahr stage III patients underwent 123I-FP-CIT imaging prior to, 3 months, and 1 year after the onset of nicotine therapy. Nicotine was administered transdermally with increasing daily doses during 3 months (up to 105 mg/day) and decreased progressively. On co-registered magnetic resonance imaging, striatal regions of interest were drawn and binding potentials of 123I-FP-CIT were calculated.Changes in Unified Parkinson's Disease Rating Scale-III over time were compared with binding potentials using regression analysis. All patients improved motor scores at 3 months (-65 +/- 22% 'off', -89 +/- 12% 'on') and most received fewer dopaminergic drugs (-30% dosage in average). Motor improvement persisted to a lesser extent at 1 year(-39 +/- 31% 'off', -13 +/- 43% 'on'), partly because one patient stopped the treatment. Interestingly, the decrease in binding potentials (-4.0 +/- 10.5%) was slower than that expected in Parkinsonian patients (usually -10% per year) and was inversely correlated with Unified Parkinson's Disease Rating Scale-III improvement, r= 0.83 'off' and 0.91 'on'. This observational study emphasizes a potential effect of nicotine therapy on striatal dopamine transporter density, which may be interpreted as direct pharmacological effect or deceleration of neuronal loss.

Improved Motor Function And Cortical Activation In Parkinson'S Disease Patients Following Acute Forced-exercise

In previous studies, we have shown that a long-term lower extremity forced-exercise intervention (8 weeks) resulted in significant improvements in upper and lower extremity motor function of mild to moderate Parkinson's disease (PD) patients. The global nature of motor improvements suggest that forced-exercise may result in changes in central nervous system functioning. PURPOSE: To determine the motor and cortical effects of an acute bout of forced-exercise in a group of PD patients. METHODS: Motor function and functional magnetic resonance imaging (MRI) examinations were completed, in six mild to moderate PD patients, under two randomized conditions: no exercise and three hours after forced-exercise. The forced-exercise intervention consisted of one 40-minute session in which patients exercised on stationary tandem cycle with an able-bodied trainer. The trainer maintained a pedaling rate between 80-90 revolutions per minute which was approximately 35 percent faster than the patient's voluntary pedaling rate (60 revolutions per minute). Functional MRI analysis of changes in cortical activation volume was compared after forced-exercise to no exercise. RESULTS: Clinical motor function, assessed with the Unified Parkinson's disease Rating Scale-III, was nearly 40 percent better following forced-exercise compared to the no-exercise condition. During functional MRI scanning patients performed a force-tracking task in which they matched a projected sinusoidal or constant line. Motor performance was 35 percent better following forced-exercise compared to no exercise. Increases in cortical activation were most prominent in the supplementary motor area (SMA) after forced exercise in comparison to the no exercise state. This increase in activation was a general observation across tasks performed with each limb. CONCLUSION: Improvements in upper extremity function and increased levels of activation within cortical structures such as the SMA indicate that forced-exercise may facilitate central motor control processes in Parkinson's disease patients.

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 alpha 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. (c) 2008 Movement Disorder Society.

Brain 3D-SSP SPECT analysis in dementia with Lewy bodies, Parkinson's disease with and without dementia, and Alzheimer's disease

Objectives: Cerebral blood flow was compared among patients with dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Parkinson's disease without dementia (PD), and Alzheimer's disease (AD) using three-dimensional stereotactic surface projection (3D-SSP) analysis. Purpose: We attempt to clarify the difference of reduction pattern on SPECT among patients having DLB, PDD, PD, AD. Patients and Methods: Six patients with DLB, 7 patients with PDD who were matched with the DLB patients for age, unified Parkinson's disease rating scale-III (UPDRS-III) score, and degree of cognitive function disorders, 21 patients with PD who were matched with the DLB patients for age, UPDRS-III score, 12 patients with AD who were matched with the DLB patients for age and degree of cognitive function disorders, and 12 control subjects. All patients were examined by N-isopropyl- p[ 123I] iodoamphetamine single photon emission computed tomography ( 123I-IMP SPECT), and obtained images were analyzed with 3D-SSP using an image-analysis software, iSSP ver. 3.5. Results: Although DLB and PDD showed similar cerebral perfusion reduction pattern at the lateral parietal association and lateral temporal association and precuneus on SPECT by the pixel-by-pixel comparison, greater perfusion reduction was observed in DLB than in PDD. Cerebral perfusion was decreased at the occipital lobe of the DLB patients compared with the AD patients. Conclusions: The regional pattern of blood flow reduction in the brain was found to be different among DLB, PD, and AD. Greater blood flow reduction was observed in DLB, although DLB and PDD showed similar reduction pattern. These regional differences were considered to suggest different and disease-specific combinations of underlying pathological and neurochemical processes.