Movement Disorder Society-sponsored Revision Of The Unified Parkinson's Disease Rating Scale Research Articles

Effectiveness and Safety of Meridian Activation Remedy System for Alleviating Motor Symptoms in Parkinson's Disease: an Observational Study.

Parkinson's disease (PD) lacks disease-modifying drugs or sustainable interventions, creating an unmet treatment need. Investigating complementary and alternative medicines aims to improve PD patients' quality of life by alleviating symptoms and delaying the course of the disease. In this single-center, prospective, observational, single-arm study, we aimed to assess the effectiveness and safety of acupuncture combined with exercise therapy and the Meridian Activation Remedy System (MARS). From March to October 2021, 13 PD patients with Hoehn and Yahr stages 1 to 3 were recruited. For 8 weeks, MARS intervention was carried out twice a week. T-statistics were used to evaluate functional near-infrared spectroscopy (fNIRS) and GAITRite outcomes. All of the remaining outcome variables were evaluated using the Wilcoxon signed-rank test. The MARS intervention significantly reduced PD patients' Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDSUPDRS) Part III score (from 20.0 ± 11.8 to 8.8 ± 5.5, p = 0.003), 10-meter walk test speed (from 9.5 ± 1.8 to 8.7 ± 1.3 seconds, p = 0.040), and timed up and go time (from 9.8 ± 1.8 to 8.9 ± 1.4 seconds, p = 0.040). Moreover, the MDS-UPDRS Part II, fNIRS hemodynamics, 360-degree turn test, fall efficacy scale, and Parkinson's Disease Questionnaire 39 scores improved but not significantly. All participants completed the 8-week intervention without any adverse reactions. An 8-week MARS intervention improved motor symptoms in PD patients. In particular, improvements in UPDRS Part III scores exhibited large clinically important differences. The findings are encouraging, and a randomized controlled trial will be conducted to determine the efficacy and cost-effectiveness of MARS intervention.

The greatest loss of unpleasant smells may be related to the risk of more severe PD symptoms.

Limited research has explored the relationship between the valence of olfactory dysfunction and PD clinical symptoms. This study aimed to investigate correlations between the emotional valence of olfactory impairment and different domains of PD symptoms. PD patients who fulfilled the clinically probable PD diagnostic criteria of the International Parkinson and Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease were recruited from the Center for Parkinson and Movement Disorders at Taichung Veterans General Hospital between October 2016 and April 2022. Demographic data and serial clinical assessments were collected, including the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC) and Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Thirty-five odors from the UPSIT-TC were classified into neutral, pleasant or unpleasant groups. Group comparisons, correlation analyses, and linear regression analyses were conducted to examine the relationship between olfactory impairment of UPSIT-TC odors, considering emotional valence, and MDS-UPDRS subscores across various domains. A total of 176 PD patients were recruited for analysis. Patients in the predominantly neutral/unpleasant odor impairment groups had higher MDS-UPDRS part III scores compared to those in the predominantly pleasant odor impairment group (pleasant vs. neutral vs. unpleasant odor impairment groups: 26.79 ± 13.59 vs. 35.33 ± 16.36 vs. 31.57 ± 12.37, p = 0.009). This trend was also noted in MDS-UPDRS rigidity, bradykinesia, and akinetic-rigid subscores (p = 0.003, p = 0.012, and p = 0.001, respectively). Correlation analysis revealed a weak but significant correlation between rigidity/akinetic-rigid subscores and misidentification numbers for neutral/unpleasant odors (all p < 0.05), with age, gender, LEDD, and disease duration as covariates. All significances were retained in the linear regression analysis. Our results emphasize the link between olfactory impairment of specific emotional valence, neutral/unpleasant odors, and PD severity, particularly with respect to akinetic-rigid symptoms. A concise olfactory test that focuses on both neutral and unpleasant odors may offer deeper insights into PD symptoms.

Comprehensive analysis of clinical and biological features in Parkinson's disease associated with the LRRK2 G2019S mutation: Data from the PPMI study.

The Parkinson's Progression Marker Initiative (PPMI) aims to identify biomarkers for Parkinson's disease (PD) risk, onset, and progression. This study focuses on the G2019S missense mutation in the LRRK2 gene, which is associated with hereditary and sporadic PD. Utilizing data from the PPMI database, we conducted an analysis of baseline clinical characteristics, as well as serum and cerebrospinal fluid levels in two groups: patients with PD with the G2019S mutation (PD + G2019S) and patients with PD without the mutation (PD-G2019S). Multiple linear regression and longitudinal analysis were performed, controlling for confounding factors. Compared to the PD-G2019S group, the PD + G2019S group showed more obvious initial motor dysfunction-higher baseline Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) scores (false discovery rate [FDR]-adjusted p < 0.001), but progressed more slowly. Mechanism of Coordinated Access and activities of daily living (ADL) scores were lower at baseline (FDR-adjusted p < 0.001), whereas Scales for Outcomes of Parkinson's Disease (SCOPA)-Thermoregulatory (FDR-adjusted p = 0.015) scores were higher, emphasizing the increase of non-motor symptoms associated with LRRK2-G2019S mutation. During the follow-up period, the motor and non-motor symptoms changed dynamically with time, and there were longitudinal differences in the scores of MDS-UPDRS (FDR-adjusted PI = 0.013, PII = 0.008, PIV < 0.001), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (FDR-adjusted p = 0.027), SCOPA-Thermoregulatory (FDR-adjusted p = 0.021), and ADL (FDR-adjusted p = 0.027) scale scores. PD associated with the LRRK2 G2019S mutation demonstrated more severe symptoms at baseline but slower progression. Motor complications and thermoregulatory disorders were more pronounced.

Embedding Patient Input in Outcome Measures for Long-Term Disease-Modifying Parkinson Disease Trials.

Clinical trials of disease-modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients. The objective is to select a patient-centered primary outcome measure for disease-modification trials over three or more years. Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures. A larger PPIE group provided input on their key considerations for such an endpoint. Feasibility, clinimetric properties, and relevance to patients were assessed and synthesized. Although initial considerations favored the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in Off, feasibility, PPIE input, and clinimetric properties supported the MDS-UPDRS Part II. However, PPIE input also highlighted the importance of nonmotor symptoms, especially in the longer term, leading to the selection of the MDS-UPDRS Parts I + II sum score. The MDS-UPDRS Parts I + II sum score was chosen as the primary outcome for large 3-year disease-modification trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa.

Impaired movement vigor (bradykinesia) is a cardinal feature of Parkinson's disease (PD) and hypothesized to result from abnormal motivational processes-impaired motivation-vigor coupling. Dopamine replacement therapy (DRT) improves bradykinesia, but the response to DRT is multifaceted, comprising a short-duration response (SDR) and a long-duration response (LDR) only manifesting with chronic treatment. Prior experiments assessing motivation-vigor coupling in PD used chronically treated subjects, obscuring the roles of the SDR and LDR. To disambiguate the SDR and LDR, 11 de novo PD subjects (6 male [M]:5 female [F]; mean age, 67) were studied before treatment, after an acute levodopa (l-dopa) dose, and in both the practical "off" (LDR) and "on" (LDR + SDR) states after chronic stable treatment. At each visit, subjects were characterized with a standard battery including the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and an incentivized joystick task to assess motor performance in response to varying rewards. l-Dopa induced a robust SDR and LDR, with further improvement in the combined SDR + LDR state. At baseline, after acute treatment (SDR), and after LDR induction, subjects did not exhibit the normal increase in movement speed with increasing reward. Only in the combined SDR + LDR state was there restoration of motivation-vigor coupling. Although consistent with prior results in chronically treated PD subjects, the significant improvement in motor performance observed with the SDR and LDR suggests that bradykinesia is not solely secondary to deficient modulation of motivational processes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Associations of Apolipoprotein ε4 Genotypes with Motor and Nonmotor Symptoms in Parkinson's Disease: A Cross-Sectional Study.

The apolipoprotein E (APOE) ε4 allele has been associated with cognitive decline in Parkinson's disease (PD), but little is known about its relationship with motor and other nonmotor symptoms and whether APOE ε4 retains an influence on cognition when other factors are considered. To investigate the impact of APOE ε4 on motor/nonmotor symptoms and its relationship with other factors affecting cognition in individuals with PD. We analyzed data from 7616 individuals, comparing motor/nonmotor symptoms in different APOE genotypes using binary logistic regression. Multivariate logistic regression examined factors associated with cognitive impairments, including APOE ε4, Geriatric Depression Scale (GDS) score, Non-motor Symptom Questionnaire (NMS) score, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score, and physical activity level. APOE ε4 heterozygosity was modestly associated with lower cognitive scores (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.87-0.99), whereas no significant association was found for any other nonmotor and motor symptoms. However, in multivariate analysis, cognitive impairment was associated with higher GDS (OR, 1.28; 95% CI, 1.23-1.34), NMS (OR, 1.22; 95% CI, 1.19-1.25), and MDS-UPDRS Part II (OR, 1.07; 95% CI, 1.06-1.09) scores, whereas physical activity was negatively associated (OR, 0.99; 95% CI, 0.98-0.99). APOE ε4 was no longer significant after adjusting for these factors. There is a link between cognition and APOE ε4 in patients with PD; however, when considering multiple factors, APOE ε4 plays a subordinate role. Other factors, such as depression, physical activity, and other nonmotor symptoms, demonstrate a stronger influence on cognitive impairment.

The Emergence and Progression of Motor Dysfunction in Individuals at Risk of Parkinson's Disease.

PREDICT-PD is a United Kingdom population-based study aiming to stratify individuals for future Parkinson's disease (PD) using a risk algorithm. A randomly selected, representative sample of participants in PREDICT-PD were examined using several motor assessments, including the motor section of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III, at baseline (2012) and after an average of 6 years of follow-up. We checked for new PD diagnoses in participants seen at baseline and examined the association between risk scores and incident sub-threshold parkinsonism, motor decline (increasing ≥5 points in MDS-UPDRS-III) and single motor domains in the MDS-UPDRS-III. We replicated analyses in two independent datasets (Bruneck and Parkinson's Progression Markers Initiative [PPMI]). After 6 years of follow-up, the PREDICT-PD higher-risk group (n = 33) had a greater motor decline compared with the lower-risk group (n = 95) (30% vs. 12.5%, P = 0.031). Two participants (both considered higher risk at baseline) were given a diagnosis of PD during follow-up, with motor signs emerging between 2 and 5 years before diagnosis. A meta-analysis of data from PREDICT-PD, Bruneck, and PPMI showed an association between PD risk estimates and incident sub-threshold parkinsonism (odds ratio [OR], 2.01 [95% confidence interval (CI), 1.55-2.61]), as well as new onset bradykinesia (OR, 1.69 [95% CI, 1.33-2.16]) and action tremor (OR, 1.61 [95% CI, 1.30-1.98]). Risk estimates using the PREDICT-PD algorithm were associated with the occurrence of sub-threshold parkinsonism, including bradykinesia and action tremor. The algorithm could also identify individuals whose motor examination experience a decline over time. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Deep brain stimulation for Parkinson's disease: experience, benefits and limitations in a center in Latin America

Parkinson's disease is poorly studied in Colombia. It is pharmacologically managed, but for refractory cases, surgery is a therapeutic option, positively impacting on quality of life. To determine the impact of deep brain stimulation as management in the control of progression in patients with Parkinson's disease attended our institution between the years 2014 to 2020. Descriptive retrospective study, with patients collected between 2014 and 2020 undergoing deep brain stimulation surgery. The MDS-UPDRS (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale) was applied in the pre- and postoperative period, and the results were compared. 21 patients were included and the UPDRS was applied, finding a decrease in scores in the postoperative period. One patient had an operative site infection. There was an improvement in the MDS-UPDRS score, with a low rate of complications. The procedure time was prolonged from the preoperative evaluation. Deep brain stimulation is the management of choice for refractory Parkinson's disease. The patients in this series showed improvement in their symptoms. Unfortunately, there are limitations to perform this procedure in Colombia, such as the delay in the authorization of the procedure.

Feasibility for evaluating motor aspects of Parkinson's disease through video consultations in a resource-limited setting in Southern Brazil.

Performing motor evaluations using videoconferencing for patients with Parkinson's disease (PD) is safe and feasible. However, the feasibility of these evaluations is not adequately studied in resource-limited settings. To evaluate the feasibility of performing motor evaluations for patients with PD in a resource-limited setting. The examiners rated motor aspects of parkinsonism of 34 patients with PD from the Brazilian public healthcare system through telemedicine with the patient's own means by using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) rating scale. Quality measures of the video meeting were also obtained. The feasibility of rating the motor aspects was the primary outcome whereas the rating of individual motor aspects, video meeting quality and predictors of a complete evaluation served as secondary outcomes. The least assessable parameters were freezing of gait (52.9%), gait (70.6%), leg agility, and rest tremor (both 76.5%). Complete MDS-UPDRS part III was possible in 41.2% of patients and 62 out of 374 motor aspects evaluated (16.6%) were missed. Available physical space for a video evaluation was the worst quality measure. Incomplete evaluations were directly associated with disability (p = 0.048, r = 0.34) and inversely with available physical space (p = 0.003, r = 0.55). A significant portion of the MDS-UPDRS part III is unable to be performed during telemedicine-based evaluations in a real-life scenario of a resource-limited setting.

Associations of striatal dopamine transporter binding with motor and non-motor symptoms in early Parkinson's disease.

Dopamine transporter (DAT) imaging is an in vivo tool to assess presynaptic dopaminergic function in the clinical practices of Parkinson's disease (PD). Current clinical practices focused on qualitatively visual interpretation of DAT imaging, whereas quantitative analyses are potentially more helpful when monitoring the progression of PD. Previous cross-sectional studies indicated certain motor and non-motor features were associated with striatal DAT binding, whereas limited data were reported in terms of the longitudinal correlation between clinical features of PD with striatal DAT binding. The purpose of our study is to clarify current and longitudinal correlations between striatal DAT binding and clinical measures. A total of 352 untreated PD individuals and 167 healthy controls with complete baseline clinical measures and neuroimaging data were identified from the Parkinson's Progression and Markers Initiative (PPMI) database. Patients with PD underwent DAT imaging at the screening visit and following months 12, 24, and 48. Multiple linear regression models and linear mixed-effect models were respectively conducted to investigate the cross-sectional and longitudinal correlation between clinical characteristics and DAT binding. Associations between changes in clinical characteristics and changes in DAT binding were further evaluated and the Spearman rank correlation coefficients were reported. In the cross-sectional analysis, baseline striatal DAT binding was significantly associated with the Hoehn and Yahr scale, the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) scores, the rigidity scores, and the axial scores in PD individuals (false discovery rate [FDR]-adjusted p=0.0017 for all above). Patients who developed freezing of gait had lower striatal DAT binding (FDR-adjusted p=0.0161). Healthy controls who had higher tremor scores and suffered more severe olfactory dysfunction had lower striatal DAT binding (FDR-adjusted p=0.0257 for all above). Longitudinal analysis indicated that baseline severity of rapid-eye-movement sleep behavior disorder was significantly associated with longitudinal striatal DAT binding in patients with PD (FDR-adjusted p=0.0120). Furthermore, changes in MDS-UPDRS scores and the State-Trait Anxiety Inventory (STAI) scores demonstrated significant correlations with changes in striatal DAT binding over 4 years (p=0.005 and p=0.032, respectively). Our findings clarified quantitative associations between certain motor and non-motor features with current and future striatal dopamine binding, suggesting the feasibility of using DAT images as a progression predictive marker for PD. Further studies are needed to investigate correlations between different regional dopamine binding with specific clinical features.

It Is as It Was: MDS-UPDRS Part III Scores Cannot Be Combined with Other Parts to Give a Valid Sum.

Original clinimetric analyses by the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) developers did not confirm the validity of summing the scores of its parts. Recent studies used the summed score of Part III and other parts as efficacy outcomes. The aim of this study was to establish whether summing scores of MDS-UPDRS parts can be recommended. Using 7466 full MDS-UPDRS scores, we applied two-step factor analysis as in the original article to reassess the validity analysis with the threshold criterion set at comparative fit index ≥0.9. All comparative fit indexes of any combination including Part III were lower than 0.90. Summing Part III MDS-UPDRS scores with other parts is not clinimetrically sound. The MDS-UPDRS is a validated four-part scale with corresponding individual part scores and needs to be used within the limits originally presented. © 2022 International Parkinson and Movement Disorder Society.

The safety and effectiveness of α-synuclein immunotherapy vs. placebo for the treatment of Parkinson's disease: a systematic review and meta-analysis.

There is no consensus on the efficacy of using α-synuclein as the primary immunotherapy site for Parkinson's disease (PD). The present study sought to investigate the safety and effectiveness of α-synuclein immunotherapy for treating PD. The databases of CNKI, CBM, Cochrane Library, PubMed, Web of Science, and Embase were searched for randomized controlled trials (RCTs). Cochrane Collaboration's bias assessment tool was used to assess the risk of bias in the included articles, and the included PD patients older than 18 years adopted immunotherapy. Stata 15.0 was employed for statistical analysis. A total of 6 RCTs were eligible for the present study, involving 606 immunotherapy recipients (using alpha-synuclein immunotherapy) and 254 control individuals (placebo). Our meta-analysis found no statistical difference in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score [weighted mean difference (WMD): -0.72, 95% confidence interval (CI): -1.56 to 0.13, P=0.099], adverse event incidence [relative risk (RR): 1.06, 95% CI: 0.98 to 1.15, P=0.150], headache incidence (RR: 0.95, 95% CI: 0.67 to 1.34, P=0.773), and constipation incidence (RR: 1.47, 95% CI: 0.77 to 2.78, P=0.242). However, the infection rate in the immunotherapy group was higher than in the control group (RR: 2.29, 95% CI: 1.40 to 3.74, P=0.003). The above results indicate that immunotherapy is significantly different from placebo in MDS-UPDRS and adverse event incidence, but it can reduce the incidence of infection rate. Existing results showed that α-synuclein immunotherapy had no significant effect on PD. high-quality, multi-center, and large-scale clinical studies are desired to corroborate our findings.

A tree-structure-guided graph convolutional network with contrastive learning for the assessment of parkinsonian hand movements.

Bradykinesia is one of the core motor symptoms of Parkinson's disease (PD). Neurologists typically perform face-to-face bradykinesia assessment in PD patients according to the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). As this human-expert assessment lacks objectivity and consistency, an automated and objective assessment scheme for bradykinesia is critically needed. In this paper, we propose a tree-structure-guided graph convolutional network with contrastive learning scheme to solve the challenge of difficulty in fine-grained feature extraction and insufficient model stability, finally achieving the video-based automated assessment of Parkinsonian hand movements, which represent a vital MDS-UPDRS component for examining upper-limb bradykinesia. Specifically, a tri-directional skeleton tree scheme is proposed to achieve effective fine-grained modeling of spatial hand dependencies. In this scheme, hand skeletons are extracted from videos, and then the spatial structures of these skeletons are constructed through depth-first tree traversal. Afterwards, a tree max-pooling module is employed to establish remote exchange between outer and inner nodes, hierarchically gather the most salient motion features, and hence achieve fine-grained mining. Finally, a group-sparsity-induced momentum contrast is also developed to learn similar motion patterns under different interference through contrastive learning. This can promote stable learning of discriminative spatial-temporal features with invariant motion semantics. Comprehensive experiments on a large clinical video dataset reveal that our method achieves competitive results, and outperforms other sensor-based and RGB-depth methods. The proposed method leads to accurate assessment of PD bradykinesia through videos collected by low-cost consumer cameras of limited capabilities. Hence, our work provides a convenient tool for PD telemedicine applications with modest hardware requirements.

What Is the Role of Dopamine Transporter Imaging in Parkinson Prevention Clinical Trials?

Recent advances in the understanding of the natural course of brain pathophysiology in the major neurodegenerative disorders including Alzheimer disease and Parkinson disease (PD) have led to therapeutic approaches targeting abnormal brain protein deposition. In PD in particular, there is a need for reliable biomarkers to assess and quantify the clinical consequences of this pathology and support clinical evaluation of the efficacy of new therapeutic strategies. Some clinical measures tracked longitudinally can provide evidence for the efficacy of the therapeutic intervention. These include both motor and non-motor assessments like the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDSUPDRS), quality of life measures, and attaining clinical milestones (e.g., need for medication, onset of falling). Unfortunately, these measures were not developed for tracking the slow rate of clinical change and its high variability between PD patients, nor the resulting difficulty in measuring a reduction in the rate of change of these outcomes. Furthermore, many current trials seek eligibility determinations for trial enrollment in early disease, especially in identifying premotor PD and at-risk individuals for whom, theoretically, the treatment may delay or even prevent the onset of some clinical manifestations of early PD.1,2 In this context, CSF, blood and tissue biomarkers, genomics, and imaging have all been proposed as potential tools to aid in clinical trial eligibility determinations, as well as monitoring the natural course of illness and measuring the efficacy of treatment on slowing disease progression.3,4 Imaging is of value in providing a phenotypic snapshot in living human brain of specific pathologic processes that would otherwise only be obtainable at postmortem.5,6

Short-Latency Afferent Inhibition Correlates with Stage of Disease in Parkinson's Patients.

Sensory-motor decoupling at the cortical level involving cholinergic circuitry has also been reported in Parkinson's Disease (PD). Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been used previously to probe cortical cholinergic circuits in well-characterised subgroups of patients with PD. In the current study, we compared SAI in a cohort of PD patients at various stages of disease and explored correlations between SAI and various clinical measures of disease severity. The modified Hoehn and Yahr (H&Y) scale was used to stage disease in 22 patients with PD. Motor and cognitive function were assessed using the MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale) part III and MoCA (Montreal Cognitive Assessment) score, respectively. Objective gait assessment was performed using an electronic walkway (GAITRite®). SAI was measured as the average percentage inhibition of test motor-evoked potentials (MEPs) conditioned by electrical stimulation of the contralateral median nerve at the wrist. SAI was significantly reduced in patients with advanced PD (H&Y stage 3) compared to early PD patients (H&Y stage 1) on pairwise comparison. The visuospatial executive function and orientation domains of cognition demonstrated significant negative associations with SAI. Cortical sensory-motor integration is progressively diminished as disease progresses. The observation that a reduction in SAI is associated with a reduction in cognitive function possibly reflects the progressive involvement of cortical cholinergic circuits in PD with increasing motor stage. Future longitudinal studies are necessary to confirm this preliminary result.

Evaluation of curcumin as add-on therapy in patients with Parkinson's disease: A pilot randomized, triple-blind, placebo-controlled trial

Background and objectivePreclinical studies suggest that curcumin might be a potential neuroprotective agent in Parkinson's disease (PD). This clinical trial aimed to evaluate the efficacy of adding nanomicelle curcumin on improving the motor and non-motor symptoms of PD patients and their quality of life. Material and methodsIdiopathic PD patients aged ≥30≥ 30 whose symptoms were under control were included in this pilot, randomized, triple-blind, placebo-controlled, add-on trial. Eligible patients were randomly assigned to either the curcumin (n = 30, 80 mg/day) or placebo (n = 30) groups and were followed for nine months. Primary outcomes were the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Parkinson's Disease Questionnaire (PDQ-39). These variables, along with demographic data, drug history, and possible side effects of curcumin, were gathered at the beginning of the study and every three months. A mixed effects model was used to compare the group-by-time interaction, followed by post hoc analysis. ResultsAlthough the mean MDS-UPDRS and PDQ-39 scores were not significantly different between the curcumin and placebo groups at any time points, MDS-UPDRS part III (P = 0.04) showed a significant difference in its overall trend between the study groups. However, post hoc analysis failed to spot this difference at study time points. The most common side effects of curcumin were nausea and vomiting (P = 0.25) and gastroesophageal reflux (P = 0.42). ConclusionWhile curcumin is a well-tolerated natural compound, this trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients.

An Automatic Evaluation Method for Parkinson's Dyskinesia Using Finger Tapping Video for Small Samples

PurposeThe assessment of dyskinesia in Parkinson's disease (PD) based on Artificial Intelligence technology is a significant and challenging task. Based on the representative action of finger tapping, this paper designs an automatic evaluation method by deep learning technology to provide big data screening and preliminary evaluation for potential patients with PD. Presently, doctors use the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) to assess the severity of patients. This method is time-consuming and laborious, and there are subjective differences. The evaluation method based on sensor equipment is also widely used, but it is expensive and needs professional guidance, which is not suitable for remote evaluation and patient self-examination. Additionally, it is difficult to collect patient data for medical research, so it is important to find an objective and automatic assessment method for Parkinson's dyskinesia based on small samples.MethodsIn this study, we designed an automatic evaluation method combining manual features and convolutional neural network (CNN) suitable for small sample classification. Based on the finger tapping video of Parkinson's patients, we used the pose estimation model to obtain the action skeleton information and calculated the feature data. We then use the 5-folds cross validation training model to achieve an optimum trade-off between bias and variance, and finally make a multi-class prediction through fully connected network (FCN).ResultsOur proposed method achieves the current optimal accuracy of 79.7% in this research. We have compared with the latest methods of related research, and our method is superior to them in terms of accuracy, number of parameters and floating point operations (FLOPs).ConclusionThe proposed method does not require patients to wear sensor devices and has clear advantages in providing early screening and remote clinical evaluation for patients with PD. Simultaneously, the proposed method using motion feature data to train the CNN model obtains the optimal accuracy, effectively solves the problem of limited data acquisition in medicine and provides a novice proposal for a small sample size classification.

Multichannel Transcranial Direct Current Stimulation Combined With Treadmill Gait Training in Patients With Parkinson's Disease: A Pilot Study.

BackgroundGait problems are critical impairments in Parkinson's disease (PD) and are related to increased risk of fall and negatively impact activities of daily life. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modify the cortical excitability of gait-related brain regions. In this study, we investigated whether multichannel tDCS with simultaneous treadmill gait training could improve gait in PD.MethodsTwenty-four patients with PD were assigned randomly to a real or sham tDCS group. Before intervention, one patient of the real tDCS group was dropped out, leaving 23 patients to be analyzed in this study. Each patient underwent 30 min of treadmill gait training for 10 sessions over four consecutive weeks. Multichannel 4x1 tDCS was applied using five 6-cm-diameter round electrodes. One anode was placed on the CZ, and four cathodes were positioned symmetrically over the FZ, C5, C6, and PZ. Anodal tDCS (2mA) and sham tDCS were delivered for 20 min. The secondary outcomes were gait performance, as measured by the timed up and go test (TUG) and freezing of gait questionnaire (FOG-Q), and balance was assessed using the dynamic gait index (DGI), Berg balance scale (BBS), and functional reach test (FRT). Motor and non-motor performance of patients with PD were assessed using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Participants were assessed before the intervention, immediately after the intervention, and 4 weeks after completion of the intervention.ResultsThe real tDCS group showed a significant improvement in the 10-m walk test, but the sham group did not. Among the secondary outcome measures, MDS-UPDRS part II, TUG, and BBS were improved only in the real tDCS group. Particularly, MDS-UPDRS part II showed a significant group*time interaction effect, indicating that real tDCS demonstrated a better effect on the activities of daily living patients with PD.ConclusionsThe results of this pilot study suggest that multichannel tDCS applied on the leg motor cortex during treadmill gait training is a safe and effective means to improve gait velocity in patients with PD. Additional rigorous, large-sample, multicenter, randomized controlled trials are needed to confirm the effect of tDCS as a therapeutic adjunct for gait rehabilitation of patients with PD.

Comorbid alpha synucleinopathies in idiopathic normal pressure hydrocephalus.

This study aimed to determine the prevalence and clinical features of Parkinson's disease (PD)/PD dementia (PD/PDD) or dementia with Lewy bodies (DLB) in idiopathic normal pressure hydrocephalus (iNPH). Patients with iNPH who were admitted to the Department of Neurology, Juntendo University School of Medicine over the past 10years have been retrospectively analyzed. The diagnosis of iNPH and concomitant PD/PDD or DLB was established using diagnostic criteria. Motor symptoms were assessed by the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III. 123I-ioflupane single-photon emission computed tomography (DaT-SPECT) and cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC)-based assay were performed for alpha synuclein aggregation. Overall, 79 patients met the criteria for iNPH, of which 34 developed iNPH without accompanying disorders (iNPHa; 43%), 23 developed iNPH with comorbid PD/PDD (iNPHc + PD/PDD; 29.1%), and 8 developed iNPH with comorbid DLB (iNPHc + DLB; 10.1%). Significant differences in facial expansion and upper-limb parkinsonism were observed with a comorbidity of either PD/PDD or DLB. The specific binding ratio (SBR) of DaTscan was reduced in iNPHa (p = 0.02), but it reduced further with comorbid PD/PDD (p < 0.01) or DLB (p < 0.01). RT-QuIC was positive for all 13 comorbid PD/PDD and negative for all 19 iNPHa. These results highlight that synucleinopathies coexist with iNPH. These can be differentiated by performing DaTscan and RT-QuIC, which can affect its clinical features.

Characteristics of sagittal spinopelvic alignment in patients with Parkinson's disease.

IntroductionThe aim of this study was to characterize the associations between sagittal spinopelvic alignment and motor symptoms in patients with Parkinson's disease (PD).MethodsThe study included patients with idiopathic PD (aged <80 years and with abnormal posture). All patients underwent whole‐spine lateral and coronal radiography. Sagittal spinopelvic alignment was evaluated using nine parameters. Motor symptoms were evaluated using the Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III score—with bradykinesia and axial motor sub‐scores. Multivariate analysis was used to analyze associations between motor symptoms and sagittal spinopelvic alignment in PD patients according to sex.ResultsThe study subjects were 79 PD patients (39 men, 40 women; median age, 70 years). Clear sex‐related differences were noted. In male patients, the MDS‐UPDRS part III score correlated significantly with cervical sagittal vertical axis (SVA), and bradykinesia and axial motor scores correlated significantly with SVA, cervical SVA, and T1 slope. In female patients, the MDS‐UPDRS part III score correlated significantly with thoracic kyphosis, bradykinesia score correlated significantly with cervical SVA and thoracic kyphosis, and the axial motor score correlated significantly with SVA, cervical SVA, T1 slope, sacral slope, and pelvic tilt.ConclusionOur results showed clear correlations among various motor symptoms and sagittal global alignment in PD patients and that these correlations are different in female PD patients and their male counterparts.