Disorder Society-Unified Parkinson's Disease Research Articles

Assessment of the psychometric properties of the Italian version of the New Freezing of Gait Questionnaire (NFOG-Q-IT) in people with Parkinson disease: a validity and reliability study.

Freezing of gait (FOG) in Parkinson's disease (PD) is a challenging clinical symptom to assess, due to its episodic nature. A valid and reliable tool is the New FOG Questionnaire (NFOG-Q) used worldwide to measure FOG symptoms in PD. The aim of this study was to translate, to culturally adapt, and to test the psychometric characteristics of the Italian version of the NFOG-Q (NFOG-Q-It). The translation and cultural adaptation was based on ISPOR TCA guidelines to finalize the 9-item NFOG-Q-It. Internal consistency was assessed in 181 Italian PD native speakers who experienced FOG using Cronbach's alpha. Cross-cultural analysis was tested using the Spearman's correlation between the NFOG-Q-It and the Modified Hoehn-Yahr Scale (M-H&Y). To assess construct validity, correlations among NFOG-Q-It, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Falls Efficacy Scale-International (FES-I), the 6-min Walking Test (6MWT), the Mini Balance Evaluation System Test (Mini-BESTest) and the Short Physical Performance Battery (SPPB) were investigated. The Italian N-FOGQ had high internal consistency (Cronbach's α = 0.859). Validity analysis showed significant correlations between NFOG-Q-IT total score and M-H&Y scores (r = 0.281 p < 0.001), MDS-UPDRS (r = 0.359 p < 0.001), FES-I (r = 0.230 p = 0.002), Mini BESTest (r = -0.256 p = 0.001) and 6MWT (r = -0.166 p = 0.026). No significant correlations were found with SPPB, MOCA and MMSE. The NFOG-It is a valuable and reliable tool for assessing FOG symptoms, duration and frequency in PD subjects. Results provide the validity of NFOG-Q-It by reproducing and enlarging previous psychometric data.

The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study.

Autonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated. We aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment. Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively. Follow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = -0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004). Autonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis.

Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study.

Parkinson disease (PD) presents relevant sex-related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as the experimental models suggest; however, human-based evidence is scarce. Here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical-pathological features in male PD patients. A cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total α-synuclein, amyloid-β-42, amyloid-β-40, total tau, and phosphorylated-181 tau levels. A subgroup of 47 PD patients underwent brain volumetry by 3-T magnetic resonance imaging for further correlations. A control group of 56 age-matched individuals was enrolled for comparative analyses. Male PD patients had higher estradiol and testosterone levels than controls. Estradiol had independent inverse associations with Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF α-synuclein and right globus pallidus volume. FSH and LH had age-dependent correlations with cognitive impairment and CSF amyloid-β-42/amyloid-β-40 ratio. The study suggested that sex hormones could differentially contribute to clinical-pathological features of PD in male patients. Whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. Gonadotropins instead might mediate age-dependent phenomena of amyloidopathy and cognitive decline.

Vision-based estimation of MDS-UPDRS scores for quantifying Parkinson's disease tremor severity.

Parkinson's disease (PD) is a common neurodegenerative movement disorder among older individuals. As one of the typical symptoms of PD, tremor is a critical reference in the PD assessment. A widely accepted clinical approach to assessing tremors in PD is based on part III of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). However, expert assessment of tremor is a time-consuming and laborious process that poses considerable challenges to the medical evaluation of PD. In this paper, we proposed a novel model, Global Temporal-difference Shift Network (GTSN), to estimate the MDS-UPDRS score of PD tremors based on video. The PD tremor videos were scored according to the majority vote of multiple raters. We used Eulerian Video Magnification (EVM) pre-processing to enhance the representations of subtle PD tremors in the videos. To make the model better focus on the tremors in the video, we proposed a special temporal difference module, which stacks the current optical flow to the result of inter-frame difference. The prediction scores were obtained from the Residual Networks (ResNet) embedded with a novel module, the Global Shift Module (GSM), which allowed the features of the current segment to include the global segment features. We carried out independent experiments using PD tremor videos of different body parts based on the scoring content of the MDS-UPDRS. On a fairly large dataset, our method achieved an accuracy of 90.6% for hands with rest tremors, 85.9% for tremors in the leg, and 89.0% for the jaw. An accuracy of 84.9% was obtained for postural tremors. Our study demonstrated the effectiveness of computer-assisted assessment for PD tremors based on video analysis. The latest version of the code is available at https://github.com/199507284711/PD-GTSN.

Olfactory Impairment Is the Main Predictor of Higher Scores at REM Sleep Behavior Disorder (RBD) Screening Questionnaire in Parkinson's Disease Patients.

Olfactory impairment and REM sleep behavior disorder (RBD) are common non-motor symptoms in Parkinson's disease (PD) patients, often preceding the onset of the specific motor symptoms and, thus, crucial for strategies directed to anticipate PD diagnosis. In this context, the specific interaction between olfactory impairment and RBD has not been clearly defined. The aim of this study was to determine the possible role of olfactory impairment and other clinical characteristics as possible predictors of higher scores at RBD screening questionnaire (RBDSQ) in a large population of PD patients. In this study, 590 PD patients were included from the Parkinson's Progression Markers Initiative. Demographic and clinical features were registered. All participants completed motor and non-motor evaluations at the baseline visit. For motor assessments, the disease severity was evaluated by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pars III. Regarding non-motor symptoms assessment, Montreal Cognitive Assessments (MoCA), University of Pennsylvania Smell Identification Test (UPSIT) and RBD screening questionnaire (RBDSQ) were registered. Among 590 PD patients included in this study, 111 patients with possible RBD were found (18.8%). RBD was less frequent in female PD patients (p ≤ 0.011). Among patients with or without possible RBD diagnosis, statistically significant differences in MDS-UPDRS III (23.3 ± 11.4 vs. 19.7 ± 9.1, respectively, p ≤ 0.002) and in UPSIT score (19.7 ± 8.3 vs. 22.6 ± 8.0, respectively, p ≤ 0.001) were found. Moreover, significant correlations between RBDSQ versus UPDRS III score and versus UPSIT score were observed. Multivariate linear regression analysis showed that UPSIT was the most significant predictor of higher scores at RBDSQ, while the other significant predictors were UPDRS III and age. The severity of olfactory impairment appears tightly correlated to RBD symptoms, highlighting the role of these biomarkers for PD patients. Additionally, according to this large study, our data confirmed that RBD in PD patients exhibits peculiar gender differences.

Identifying clinical features and blood biomarkers associated with mild cognitive impairment in Parkinson's Disease using machine learning.

A broad list of variables associated with mild cognitive impairment (MCI) in Parkinson's Disease (PD) has been investigated separately. However, there is no study including all of them to assess variable importance yet. Shapley variable importance cloud (ShapleyVIC) can robustly assesses variable importance while accounting for correlation between variables. 1) To prioritise the important variables associated with PD-MCI; 2) To explore new blood biomarkers related to PD-MCI. ShapleyVIC-assisted variable selection was used to identify a subset of variables from 41 variables potentially associated with PD-MCI in a cross-sectional study. Backward selection was used to further identify the variables that associated with PD-MCI. Relative risk was used to quantify the association of final predictors and PD-MCI in the final multivariable log-binomial regression model. Among 41 variables analysed, 22 variables were identified as significantly important variables associated with PD-MCI and 8 variables were subsequently selected in the final model, indicating shorter education year, history of hypertension, higher MDS-UPDRS motor score, higher levels of TG, APOA1, and SNCA rs6826785 non-carrier were associated with increased risk of PD-MCI (p<0.05). Our study highlighted the strong association between TG, APOA1, SNCA rs6826785 and PD-MCI by machine learning approach. Screening and management of high TG and ApoA1 levels might help prevent the cognitive impairment in early PD patients. SNCA rs6826785 could be a novel therapeutic target for PD-MCI. ShapleyVIC-assisted variable selection is a novel and robust alternative to traditional approaches for future clinical study to prioritize the variables of interests.

Emotional symptoms and cognitive function outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts and the volume of tissue activated.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), that can improve patients' motor and non-motor symptoms. However, there are differences in the improvement of patients' emotional symptoms and cognitive function. To investigate the impact of active contact location and the volume of tissue activated (VTA) on patients' emotional symptoms and cognitive function in STN-DBS in PD. A total of 185 PD patients were included in this study. We evaluated them using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination (MMSE) scales at the preoperative, 1- and 12-month postoperative time points. Leads were positioned in standard space using the Lead-DBS toolbox, and VTA was calculated for analysis. When the lead active contact was closer to the ventral side of the STN, the patients' HAM-A improvement rate was higher, and when the active contact was closer to the anterior and dorsal sides of the STN, the patients' MoCA improvement rate was higher. Stimulation of the sensorimotor zone was more favorable to the improvement of HAM-A and HAM-D in patients. And, the stimulation of the associative zone was more favorable to the improvement of MoCA in patients. Our results provide evidence that the 12-month outcomes of cognitive function and emotional symptoms in PD patients with STN-DBS were closely related to the specific location of the active contacts in the STN and influenced by the VTA.

Rapid eye movement sleep behavior disorder is associated with decreased quality of life and stigma in people with Parkinson’s disease

Individuals with Parkinson's disease (PD) may present with rapid eye movement sleep behavior disorder (RBD). We therefore investigated the association between RBD and quality of life (QOL) in people with PD. Individuals with PD and a Mini-Mental State Examination score ≥ 24 were divided into two groups using the RBD screening questionnaire (RBDSQ): those with an RBDSQ score ≥ 5 were assigned to the "probable RBD" (pRBD) group, and those with a score < 5 to the "non-pRBD" group. Participants were then evaluated for motor symptoms (Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III and modified Hoehn and Yahr Scale), cognitive functions (Montreal Cognitive Assessment and Frontal Assessment Battery [FAB]), anhedonia (Snaith-Hamilton Pleasure Scale), and QOL (Parkinson's Disease Questionnaire [PDQ]-39 total and subscores for mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort). Each measure was compared between the two groups (Mann-Whitney U test/χ2 test). Multiple regression analyses were performed to identify factors contributing to the total score and the subscore of the stigma domain of the PDQ-39. Ninety-three individuals with PD were recruited (mean ± standard deviation age, 67.0 ± 10.6years). The pRBD group exhibited a longer disease duration (P = 0.006), worse FAB (P = 0.015) and PDQ-39 total (P = 0.032) scores. RBDSQ scores correlated with higher scores in the PDQ-39 stigma domain (B = 2.44, P = 0.033). RBD is associated with worse QOL andstigma in people with PD. The RBDSQ is a useful tool for the prediction of such disturbances in QOL.

RehaBEElitation: the architecture and organization of a serious game to evaluate motor signs in Parkinson's disease.

The use of serious games (SG) has received increasing attention in health care, and can be applied for both rehabilitation and evaluation of motor signs of several diseases, such as Parkinson's disease (PD). However, the use of these instruments in clinical practice is poorly observed, since there is a scarcity of games that, during their development process, simultaneously address issues of usability and architectural design, contributing to the non-satisfaction of the actual needs of professionals and patients. Thus, this study aimed to present the architecture and usability evaluation at the design stage of a serious game, so-called RehaBEElitation, and assess the accessibility of the game. The game was created by a multidisciplinary team with experience in game development and PD, taking into consideration design guidelines for the development of SG. The user must control the movements of a bee in a 3D environment. The game tasks were designed to mimic the following movements found in the gold-standard method tool-Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-for the assessment of individuals with PD: hand opening and closing, hand extension and flexion, hand adduction and abduction, finger tapping, and forearm supination and pronation. The user interacts with the game using a wearable interface device that embeds inertial and tactile sensors. The architecture of RehaBEElitation was detailed using the business process model (BPM) notation and the usability of the architecture was evaluated using the Nielsen-Shneiderman heuristics. Game accessibility was evaluated by comparing the overall scores of each phase between 15 healthy participants and 15 PD patients. The PD group interacted with the game in both the ON and OFF states. The system was modularized in order to implement parallel, simultaneous and independent programming at different levels, requiring less computational effort and enabling fluidity between the game and the control of the interface elements in real time. The developed architecture allows the inclusion of new elements for patient status monitoring, extending the functionality of the tool without changing its fundamental characteristics. The heuristic evaluation contemplated all the 14 heuristics proposed by Shneiderman, which enabled the implementation of improvements in the game. The evaluation of accessibility revealed no statistically significant differences (p<0.05) between groups, except for the healthy group and the PD group in the OFF state of medication during Phase 3 of the game. The proposed architecture was presented in order to facilitate the reproduction of the system and extend its application to other scenarios. In the same way, the heuristic evaluation performed can serve as a contribution to the advancement of the SG design for PD. The accessibility evaluation revealed that the game is accessible to individuals with PD.

Wrist-worn sensor-based measurements for drug effect detection with small samples in people with Lewy Body Dementia

IntroductionFew late-stage clinical trials in Parkinson's disease (PD) have produced evidence on the clinical validity of sensor-based digital measurements of daily life activities to detect responses to treatment. The objective of this study was to assess whether digital measures from patients with mild-to-moderate Lewy Body Dementia demonstrate treatment effects during a randomized Phase 2 trial. MethodsSubstudy within a 12-week trial of mevidalen (placebo vs 10, 30, or 75 mg), where 70/344 patients (comparable to the overall population) wore a wrist-worn multi-sensor device. ResultsTreatment effects were statistically significant by conventional clinical assessments (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] sum of Parts I-III and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC] scores) in the full study cohort at Week 12, but not in the substudy. However, digital measurements detected significant effects in the substudy cohort at week 6, persisting to week 12. ConclusionsDigital measurements detected treatment effects in a smaller cohort over a shorter period than conventional clinical assessments. Trial registrationclinicaltrials.gov, NCT03305809

Accurate Detection of α-Synuclein Seeds in Cerebrospinal Fluid from Isolated Rapid Eye Movement Sleep Behavior Disorder and Patients with Parkinson's Disease in the DeNovo Parkinson (DeNoPa) Cohort.

Misfolded α-synuclein (αSyn) aggregates (αSyn-seeds) in cerebrospinal fluid (CSF) are biomarkers for synucleinopathies such as Parkinson's disease (PD). αSyn-seeds have been detected in prodromal cases with isolated rapid eye movement sleep behavior disorder (iRBD). The objective of this study was to determine the accuracy of the αSyn-seed amplification assay (αS-SAA) in a comprehensively characterized cohort with a high proportion of PD and iRBD CSF samples collected at baseline. We used a high-throughput αS-SAA to analyze 233 blinded CSF samples from 206 participants of the DeNovo Parkinson Cohort (DeNoPa) (113 de novo PD, 64 healthy controls, 29 iRBD confirmed by video polysomnography). Results were compared with the final diagnosis, which was determined after up to 10 years of longitudinal clinical evaluations, including dopamine-transporter-single-photon emission computed tomography (DAT-SPECT) at baseline, CSF proteins, Movement Disorder Society-Unified Parkinson's Disease Rating Scale, and various cognitive and nonmotor scales. αS-SAA detected αSyn-seeds in baseline PD-CSF with 98% accuracy. αSyn-seeds were detected in 93% of the iRBD cases. αS-SAA results showed higher agreement with the final than the initial diagnosis, as 14 patients were rediagnosed as non-αSyn aggregation disorder. For synucleinopathies, αS-SAA showed higher concordance with the final diagnosis than DAT-SPECT. Statistically significant correlations were found between assay parameters and disease progression. Our results confirm αS-SAA accuracy at the first clinical evaluation when a definite diagnosis is most consequential. αS-SAA conditions reported here are highly sensitive, enabling the detection of αSyn-seeds in CSF from iRBD just months after the first symptoms, suggesting that αSyn-seeds are present in the very early prodromal phase of synucleinopathies. Therefore, αSyn-seeds are clear risk markers for synuclein-related disorders, but not for time of phenoconversion. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Bradykinesia in Neurodegenerative Disorders: A Blinded Video Analysis of Pathology-Proven Cases.

Bradykinesia is a cardinal feature in parkinsonisms. No study has assessed the differential features of bradykinesia in patients with pathology-proven synucleinopathies and tauopathies. We examined whether bradykinesia features (speed, amplitude, rhythm, and sequence effect) may differ between pathology-proven synucleinopathies and tauopathies. Forty-two cases who underwent autopsy were included and divided into synucleinopathies (Parkinson's disease and dementia with Lewy bodies) and tauopathies (progressive supranuclear palsy). Two raters blinded to the diagnosis retrospectively scored the Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III and Modified Bradykinesia Rating Scale on standardized videotaped neurological examinations. Bradykinesia scores were compared using the Mann-Whitney test and logistic regression models to adjust for disease duration. Demographic and clinical parameters were similar between synucleinopathies and tauopathies. There were no differences between speed, amplitude, rhythm, and sequence effect in synucleinopathies and tauopathies in unadjusted comparisons and adjusted models (all P > 0.05). Clinical bradykinesia features do not distinguish the underlying neuropathology in neurodegenerative parkinsonisms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Utility of movement disorder society-unified Parkinson's disease rating scale for evaluating effect of subthalamic nucleus deep brain stimulation.

The Movement Disorders Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS) is increasingly used to assess motor dysfunction before and after subthalamic nucleus deep brain stimulation (STN-DBS). We, therefore, investigated whether the MDS-UPDRS can detect longitudinal changes in motor function after STN-DBS in the same way as UPDRS. We examined 21 patients with Parkinson's disease (PD) (mean age 59.2 ± 10.6 years, mean disease duration 12.0 ± 3.0 years) who underwent STN-DBS and whose motor functions were assessed by the UPDRS and MDS-UPDRS before, 3 months after, and 1 year after STN-DBS. We then evaluated the consistency between the scores of Parts II and III of the UPDRS and MDS-UPDRS during the off phase using Lin's concordance coefficient (LCC) and a Bland-Altman plot. The scores of Parts II and III of both the UPDRS and MDS-UPDRS were significantly decreased 3 months and 1 year after STN-DBS during the off phase. Scores of the UPDRS and MDS-UPDRS showed significant positive correlations before and after STN-DBS. We calculated estimated MDS-UPDRS scores from the UPDRS scores using a regression line and calculated the LCC between the MDS-UPDRS and the estimated MDS-UPDRS scores. The LCC value was 0.59-0.91, which suggests a relatively high consistency between the UPDRS and MDS-UPDRS. The Bland-Altman plot showed that differences between both scores were basically within ±1.96 standard deviations of the difference. The present preliminary study indicated that the utility of the MDS-UPDRS in evaluating motor function before and after STN-DBS demonstrates its potential equivalency to the UPDRS.

Unveiling the Impact of Outpatient Physiotherapy on Specific Motor Symptoms in Parkinson's Disease: A Prospective Cohort Study.

Understanding how outpatient physiotherapy impacts on specific motor symptoms in Parkinson's disease (PD) is important for multidisciplinary care, but these points have not been clarified. We investigated the impact of outpatient physiotherapy on individual motor symptoms in PD patients. Fifty-five PD patients participated in the prospective cohort study, which examined the changes in motor symptoms after 90 min of outpatient physiotherapy program (1×/week for 10 weeks) and at 3 months follow-up. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score and tremor, rigidity, bradykinesia, and axial scores were assessed and compared pre-intervention, post-intervention, and at follow-up. Significant level was set at 0.05. Their MDS-UPDRS motor score and axial score significantly decreased post-intervention and at the follow-up. In the analysis differentiating effects based on the severity of motor symptoms according to the MDS-UPDRS motor score, only the moderate-severe group showed significant decreases in their MDS-UPDRS motor score, bradykinesia, and axial scores post-intervention, as well as in their MDS-UPDRS motor score, rigidity, bradykinesia, and axial scores at the follow-up. These findings suggest the outpatient physiotherapy might provide benefits, particularly in managing axial symptoms and bradykinesia, for community dwelling PD patients with moderate-severe motor symptoms within a multidisciplinary care framework.

Can Gait Features Help in Differentiating Parkinson's Disease Medication States and Severity Levels? A Machine Learning Approach.

Parkinson's disease (PD) is one of the most prevalent neurological diseases, described by complex clinical phenotypes. The manifestations of PD include both motor and non-motor symptoms. We constituted an experimental protocol for the assessment of PD motor signs of lower extremities. Using a pair of sensor insoles, data were recorded from PD patients, Elderly and Adult groups. Assessment of PD patients has been performed by neurologists specialized in movement disorders using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-Part III: Motor Examination, on both ON and OFF medication states. Using as a reference point the quantified metrics of MDS-UPDRS-Part III, severity levels were explored by classifying normal, mild, moderate, and severe levels of PD. Elaborating the recorded gait data, 18 temporal and spatial characteristics have been extracted. Subsequently, feature selection techniques were applied to reveal the dominant features to be used for four classification tasks. Specifically, for identifying relations between the spatial and temporal gait features on: PD and non-PD groups; PD, Elderly and Adults groups; PD and ON/OFF medication states; MDS-UPDRS: Part III and PD severity levels. AdaBoost, Extra Trees, and Random Forest classifiers, were trained and tested. Results showed a recognition accuracy of 88%, 73% and 81% for, the PD and non-PD groups, PD-related medication states, and PD severity levels relevant to MDS-UPDRS: Part III ratings, respectively.

Effects of monotherapy with a monoamine oxidase B inhibitor on motor symptoms in Parkinson's disease are dependent on frontal function.

Monotherapy with monoamine oxidase B (MAO-B) inhibitors enhances the level of endogenous dopamine in treatment for Parkinson's disease (PD) and provides some benefits. Certain neuropsychiatric functions are also regulated by central dopaminergic activity. To investigate the relationship of the efficacy of monotherapy with MAO-B inhibitors on motor symptoms in PD with baseline cognitive function. Outcomes were examined for 27 consecutive drug-naïve PD patients who received initial treatment with a MAO-B inhibitor (selegiline: 11, rasagiline: 16). Selegiline was titrated to an optimal dose. The dose of rasagiline was fixed at 1mg/day. Motor symptoms were assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III before treatment and after the efficacy reached a plateau within 19weeks after drug initiation, and the % improvement in motor symptoms was calculated. Pre-treatment cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). Correlations of % improvement in motor symptoms and baseline cognitive assessments were examined using Spearman correlation coefficients and multiple regression analysis. In all patients, the mean % improvement in motor symptoms was 46.5% (range 0-83.3%). Spearman correlation coefficients showed the % improvement in motor symptoms was correlated with FAB (r = 0.631, p < 0.001). In multiple regression analysis with patient background factors as independent variables, only FAB was associated with improvement in motor symptoms in the MAO-B group. Better FAB scores predict a significant improvement in motor symptoms with treatment with MAO-B inhibitors, suggesting high activity of endogenous dopamine.

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease

Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. ISRCTN Identifier: 16108482.

Clinically important change on the Unified Dyskinesia Rating Scale among patients with Parkinson's disease experiencing dyskinesia.

The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)-the smallest change in a treatment outcome that a patient considers important-remains undefined for the UDysRS. To utilize pivotal amantadine delayed-release/extended-release (DR/ER) trial data to derive MCICs for the UDysRS total score in patients with PD experiencing dyskinesia. Pivotal trials included PD patients with ≥1 h daily ON time with troublesome dyskinesia and baseline scores ≥2 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, item 4.2. Patients randomized to amantadine DR/ER or placebo completed two consecutive 24-h diaries before each clinic visit and were evaluated during ON time with dyskinesia using the UDysRS, MDS-UPDRS, and Clinician Global Impression of Change (CGI-C). The UDysRS changes from baseline to week 12 were anchored to corresponding changes in MDS-UPDRS item 4.2 scores. A minimal clinically important improvement in the CGI-C and diary-reported ON time with troublesome dyskinesia (≥0.5 h) were supportive anchors. Receiver operating characteristic curves determined the UDysRS change values optimizing sensitivity and specificity to at least minimal improvement on each anchor. The analyses included 196 patients. Week 12 UDysRS total score reduction of ≥8 points corresponded to at least minimal MDS-UPDRS item 4.2 improvement. UDysRS reduction of ≥9 points corresponded to decreased ON time with troublesome dyskinesia of ≥0.5 h per patient diaries, and UDysRS reduction of ≥10 points corresponded to at least minimal improvement on the CGI-C. Anchored to the MDS-UPDRS Part IV, item 4.2, an 8-point reduction in the UDysRS total score can be considered an MCIC for PD patients with dyskinesia.

Effects of nordic walking exercise on gait, motor/non-motor symptoms, and serum brain-derived neurotrophic factor in individuals with Parkinson's disease

ObjectiveThe primary purpose of this study was to investigate the immediate and long-term effects of Nordic Walking (NW) exercise on walking function, motor/non-motor Parkinson's Disease (PD) symptoms, and serum brain-derived neurotrophic factor (BDNF) in persons with idiopathic PD.MethodsTwelve community-dwelling participants with mild to moderate idiopathic PD and varied degrees of gait dysfunction were recruited for this prospective, repeated measures design that examined clinical measures and BDNF levels at baseline (T0), post-intervention (T1) and 3-month follow-up (T2). Participants engaged in 6 weeks of supervised NW exercise training with individualized instruction, followed by 14 weeks of independent NW exercise with remote coaching. Outcome measurements included daily step counts, 6-Minute Walk Test (6-MinWT), 10-Meter Walk Test (10MWT), spatiotemporalparameters, Timed Up and Go Test (TUG), dual-task TUG, Revised-Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Revised-Freezing of Gait Questionnaire, MDS-Nonmotor Symptom scale (NMS), Parkinson's Fatigue Scale, and serum BDNF levels. The Friedman test with post hoc Wilcoxon sign-ranked pairwise comparisons were used to compare baseline to T1, baseline to T2, and T1 to T2 timepoints with a Benjamini-Hockberg correction applied.ResultsStatistically significant improvements found post-training and retained at 3-month follow-up included 6-MinWT, daily step count, 10mWT, MDS-UPDRS, and TUG with effect sizes of 0.57 to 1.03. Serum BDNF at T2 was significantly greater than T0 and T1. Although no statistically significant improvements were observed in the MDS-NMS, 9 of 12 participants had improved non-motor symptoms. There was good adherence, sustained independent exercise engagement, and no adverse events over the 5-month study duration.ConclusionsThis study demonstrated that NW exercise was a safe, feasible, and sustainable mode of aerobic exercise for this sample of participants with varied Parkinson's disease duration and severity. Following an individualized and progressive NW training intervention, significant improvements in walking function, daily activity level, and motor function were observed. Following the supervised NW training phase, independent three-month engagement in NW exercise was sustained with long-term retention of these clinical improvements and an increase in serum BDNF levels over this five-month NW exercise trial.ImpactNordic walking exercise may be a safe, feasible and sustainable mode of independent exercise for improving daily ambulatory activity, gait and motor function, and serum BDNF in individuals with mild to moderate PD with varied gait abilities.Clinical Trials Registry ID20-101-H

Join us on an amazing journey towards next-generation treatments for CNS disorders: Launch of Neuroprotection, a new high-quality journal in translational neuroscience.

Join us on an amazing journey towards next-generation treatments for CNS disorders: Launch of Neuroprotection, a new high-quality journal in translational neuroscience.