Movement Disorder Society-Unified Parkinson's Disease Rating Scale Research Articles

Weak association between total alpha‐synuclein reflex tear levels and non‐motor symptoms burden in Parkinson's disease

AbstractBackgroundAlpha‐synuclein (αSyn) is critical to the pathogenesis of Parkinson's disease (PD). Recognition of non‐motor symptoms as clinical manifestations of PD suggests aggregation of αSyn in extranigral areas.AimThis study aimed to evaluate the association between total αSyn levels in reflex tears with non‐motor symptoms.MethodsThis cross‐sectional study included 25 people living with PD (PwP) and 38 age‐matched healthy controls (HC). Total αSyn reflex tear levels were measured using an enzyme‐linked immunosorbent assay. PwP were evaluated using the Non‐Motor Symptoms Scale (NMSS), the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), Hoehn and Yahr Stage (HY), and Montreal Cognitive Assessment (MoCA).ResultsTotal αSyn reflex tear levels were significantly higher in PwP when compared with HC (1.77 pg/mL [IQR 1.75–1.79] vs. 1.73 pg/mL [IQR 1.70–1.75], p < 0.001). The urinary domain was negatively correlated with total αSyn levels in tears (r = −0.416, p = 0.048). No correlation was observed between total αSyn levels in reflex tears with MDS‐UPDRS, HY, or MoCA.ConclusionsTotal αSyn levels in reflex tears can differentiate PD from HC. In addition, total αSyn reflex tear levels were associated with the urinary domain of NMSS but are not associated with motor and cognitive symptoms, nor HY. Therefore, our findings suggest that it does not reflect ongoing dopaminergic neurodegeneration.

Safety and efficacy of adipose-derived mesenchymal stem cell therapy in elderly Parkinson's disease patients: an intermediate-size expanded access program

ObjectiveThis intermediate-size expanded access program aimed to evaluate safety and clinical efficacy of multiple intravenous infusions of autologous, Hope Biosciences adipose-derived mesenchymal stem cell (HB-adMSC) therapy in elderly patients with Parkinson's disease (PD). MethodsTen eligible participants (aged 76–95 years) received six intravenous infusions each with 200MM autologous HB-adMSCs over 18 weeks, with the end of study (EOS) at week 26. Safety was assessed through adverse events (AEs) and serious adverse events (SAEs). Efficacy was measured through improvements in both motor and non-motor symptoms, utilizing scales including Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I-IV, Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's disease Fatigue Scale (PFS-16), Patient Health Questionnaire-9 (PHQ-9), and Visual Analog Scale (VAS). Analysis employed paired t-tests and Minimal Clinically Important Difference (MCID) thresholds for the patient-reported outcomes. ResultsMost AEs (37 out of 46) were mild in severity, with 5 SAEs reported, none attributed to the drug. No deaths occurred. Despite lack of statistical significance across the efficacy endpoints, modest yet clinically meaningful improvements with effect size > 0.3 were observed in several secondary efficacy endpoints (MDS-UPDRS part I & III, PDQ-39, and PHQ-9) at the EOS, nearing or surpassing the established MCID values. ConclusionsThe administration of autologous 200MM HB-adMSCs was found to be safe and well-tolerated in the elderly PD population. Although not achieving statistical significance, modest clinical improvements were noted across multiple secondary endpoints. These findings underscore the safety profile of the treatment in elderly patients and highlight the importance of evaluating clinical relevance alongside statistical measures for meaningful patient outcomes. Further investigation with a larger, randomized, placebo-controlled design is warranted to validate these observations.

Validation of computer vision technology for analyzing bradykinesia in outpatient clinic videos of people with Parkinson's disease

BackgroundCurrent diagnosis and monitoring of Parkinson's disease (PD) is based on subjective clinical assessments. Objective measures of motor functioning could support clinical acumen. Computer vision (CV) technology is a promising contactless technique but requires further validation. AimTo investigate the performance of CV analysis of clinic-based videos of finger-tapping. Our goals were (i) to distinguish PD from healthy controls (HC), when compared to human raters, (ii) to measure the severity of bradykinesia, and (iii) detect ON/OFF medication state. MethodsVideos of thirty-one persons with PD and forty-nine HC were collected during clinical outpatient visits. Videos were analysed using CV to produce speed, amplitude, rhythm and composite bradykinesia measures. All videos were independently rated by three raters using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Modified Bradykinesia Rating Scale (MBRS). Twenty video pairs were conducted in ON and OFF states. Classification accuracy for PD/HC state and ON/OFF state were measured using the Area under Receiver Operating characteristic curve and a confusion matrix. CV and clinical measures were correlated using Spearman coefficients. ResultsCV classified disease state with higher accuracy than clinical raters (91 % sensitivity; 97 % specificity). CV measures of bradykinesia correlated significantly with clinical ratings: R = 0.740 for MDS-UPDRS, 0.715 for MBRS speed, 0.714 for amplitude and 0.504 for rhythm. CV classified ON/OFF state as accurately as clinical raters. DiscussionCV can provide a valid, objective and contactless bradykinesia assessment based on clinically collected videos, which offers promise as a new clinical outcome, including in remote settings.

In‐Home Remote Assessment of the MDS‐UPDRS Part III: Multi‐Cultural Development and Validation of a Guide for Patients

AbstractBackgroundThe shift toward virtualized care introduces challenges in assessing the motor severity of Parkinson's disease (PD). The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part III, the most used rating scale in PD, lacks validation for synchronous remote administration.ObjectiveOur goal was to validate the usability of a patient guide to allow an accurate video‐based MDS‐UDPRS part III remote examination.MethodsWe conducted a multi‐stage mixed methods study that included a team consensus for the concept of the guide, cognitive pretesting, and usability (system usability scale, [SUS]) testing in five sites (total n = 25 participants) with distinct linguistic and cultural contexts.ResultsA multi‐language (English, Portuguese, Spanish, and traditional Chinese) largely pictograph guide of the MDS‐UPDRS part III remote examination reached benchmark for usability (SUS score ≥68) in 25 participants who completed the synchronous remote assessment.ConclusionsThe MDS‐UDPRS part III remote examination guide can be used remotely accurately, and facilitate clinical practice and research in a paradigm of telemedicine.

Long-Term Dementia Risk in Parkinson Disease.

It is widely cited that dementia occurs in up to 80% of patients with Parkinson disease (PD), but studies reporting such high rates were published over two decades ago, had relatively small samples, and had other limitations. We aimed to determine long-term dementia risk in PD using data from two large, ongoing, prospective, observational studies. Participants from the Parkinson's Progression Markers Initiative (PPMI), a multisite international study, and a long-standing PD research cohort at the University of Pennsylvania (Penn), a single site study at a tertiary movement disorders center, were recruited. PPMI enrolled de novo, untreated PD participants and Penn a convenience cohort from a large clinical center. For PPMI, a cognitive battery is administered annually, and a site investigator makes a cognitive diagnosis. At Penn, a comprehensive cognitive battery is administered either annually or biennially, and a cognitive diagnosis is made by expert consensus. Interval-censored survival curves were fit for time from PD diagnosis to stable dementia diagnosis for each cohort, using cognitive diagnosis of dementia as the primary end point and Montreal Cognitive Assessment (MoCA) score <21 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I cognition score ≥3 as secondary end points for PPMI. In addition, estimated dementia probability by PD disease duration was tabulated for each study and end point. For the PPMI cohort, 417 participants with PD (mean age 61.6 years, 65% male) were followed, with an estimated probability of dementia at year 10 disease duration of 9% (site investigator diagnosis), 15% (MoCA), or 12% (MDS-UPDRS Part I cognition). For the Penn cohort, 389 participants with PD (mean age 69.3 years, 67% male) were followed, with 184 participants (47% of cohort) eventually diagnosed with dementia. The interval-censored curve for the Penn cohort had a median time to dementia of 15 years (95% CI 13-15); the estimated probability of dementia was 27% at 10 years of disease duration, 50% at 15 years, and 74% at 20 years. Results from two large, prospective studies suggest that dementia in PD occurs less frequently, or later in the disease course, than previous research studies have reported.

Thalamic-limbic circuit dysfunction and white matter topological alteration in Parkinson's disease are correlated with gait disturbance.

Limbic structures have recently garnered increased attention in Parkinson's disease (PD) research. This study aims to explore changes at the whole-brain level in the structural network, specifically the white matter fibres connecting the thalamus and limbic system, and their correlation with the clinical characteristics of patients with PD. Between December 2020 and November 2021, we prospectively enrolled 42 patients with PD and healthy controls at the movement disorder centre. All participants underwent diffusion tensor imaging (DTI), 3D T1-weighted imaging (3D-T1WI), and routine brain magnetic resonance imaging on a 3.0 T MR scanner. We employed the tract-based spatial statistical (TBSS) analytic approach, examined structural network properties, and conducted probabilistic fibre tractography to identify alterations in white matter pathways and the topological organisation associated with PD. In patients with PD, significant changes were observed in the fibrous tracts of the prefrontal lobe, corpus callosum, and thalamus. Notably, the fibrous tracts in the prefrontal lobe and corpus callosum showed a moderate negative correlation with the Freezing of Gait Questionnaire (FOG-Q) scores (r = -0.423, p = 0.011). The hippocampus and orbitofrontal gyrus exhibited more fibre bundle parameter changes than other limbic structures. The mean streamline length between the thalamus and the orbitofrontal gyrus demonstrated a moderate negative correlation with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (r = -0.435, p = 0.006). Topological parameters, including characteristic path length (L p), global efficiency (E g), normalised shortest path length (λ) and nodal local efficiency (N le), correlated moderately with the MDS-UPDRS, HAMA, MoCA, PDQ-39, and FOG-Q, respectively. DTI is a valuable tool for detecting changes in water molecule dispersion and the topological structure of the brain in patients with PD. The thalamus may play a significant role in the gait abnormalities observed in PD.

Rest Tremor in Parkinson's Disease Is Associated with Ipsilateral Striatal Dopamine Transporter Binding.

The cardinal motor symptoms of Parkinson's disease (PD) include rigidity, bradykinesia, and rest tremor. Rigidity and bradykinesia correlate with contralateral nigrostriatal degeneration and striatal dopamine deficit, but association between striatal dopamine function and rest tremor has remained unclear. The aim of this study was to investigate the possible link between dopamine function and rest tremor using Parkinson's Progression Markers Initiative dataset, the largest prospective neuroimaging cohort of patients with PD. Clinical, [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT), and structural magnetic resonance imaging data from 354 early PD patients and 166 healthy controls were included in this study. We employed a novel approach allowing nonlinear registration of individual scans accurately to a standard space and voxelwise analyses of the association between motor symptoms and striatal dopamine transporter (DAT) binding. Severity of both rigidity and bradykinesia was negatively associated with contralateral striatal DAT binding (PFWE < 0.05 [FWE, family-wise error corrected]). However, rest tremor amplitude was positively associated with increased ipsilateral DAT binding (PFWE < 0.05). The association between rest tremor and binding remained the same controlling for Hoehn & Yahr stage, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, bradykinesia-rigidity score, or motor phenotype. The association between rest tremor and binding was independent of bradykinesia-rigidity and replicated using 2-year follow-up data (PFWE < 0.05). In agreement with the existing literature, we did not find a consistent association between rest tremor and contralateral dopamine defect. However, our results demonstrate a link between rest tremor and increased or less decreased ipsilateral DAT binding. Our findings provide novel information about the association between dopaminergic function and parkinsonian rest tremor. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Assessing gait dysfunction severity in Parkinson’s Disease using 2-Stream Spatial-Temporal Neural Network

Parkinson’s Disease (PD), a neurodegenerative disorder, significantly impacts the quality of life for millions of people worldwide. PD primarily impacts dopaminergic neurons in the brain’s substantia nigra, resulting in dopamine deficiency and gait impairments such as bradykinesia and rigidity. Currently, several well-established tools, such as the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Hoehn and Yahr (H&Y) Scale, are used for evaluating gait dysfunction in PD. While insightful, these methods are subjective, time-consuming, and often ineffective in early-stage diagnosis. Other methods using specialized sensors and equipment to measure movement disorders are cumbersome and expensive, limiting their accessibility. This study introduces a hierarchical approach to evaluating gait dysfunction in PD through videos. The novel 2-Stream Spatial-Temporal Neural Network (2S-STNN) leverages the spatial–temporal features from the skeleton and silhouette streams for PD classification. This approach achieves an accuracy rate of 89% and outperforms other state-of-the-art models. The study also employs saliency values to highlight critical body regions that significantly influence model decisions and are severely affected by the disease. For a more detailed analysis, the study investigates 21 specific gait attributes for a more nuanced quantification of gait disorders. Parameters such as walking pace, step length, and neck forward angle are found to be strongly correlated with PD gait severity categories. This approach offers a comprehensive and convenient solution for PD management in clinical settings, enabling patients to receive a more precise evaluation and monitoring of their gait impairments.

Scale consistance in cognitive status awareness of patients with Parkinson’s disease

Objectives: This study aimed to investigate the relationship between patients’ awareness of their cognitive symptoms and the presence of cognitive involvement according to neuropsychological tests. Patients and methods: In this cross-sectional study, 539 patients (276 males, 263 females; mean age: 64.3±11.0 years; range, 19 to 88 years) were assessed between September 2020 and June 2023. The Mini-Mental Status Examination (MMSE) scores were recorded in addition to age, sex, education level, and chronic diseases. Patients were classified as having cognitive disorders if their MMSE scores were &lt;26, while those with scores ≥26 were classified as cognitively healthy. The relationship between the frequency of cognitive involvement according to a related question from the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the frequency of cognitive disorders according to the MMSE scores was evaluated. Results: No relationship was detected between the frequency of cognitive disorders according to the MMSE scores and the frequency of cognitive involvement according to the corresponding question in the nonmotor component of the MDS-UPDRS (p&lt;0.001). Conclusion: The findings indicate that the cognitive impairment inquiry in the nonmotor section of the MDS-UPDRS is not an effective method for detecting cognitive involvement in Parkinson’s disease.

Long-term outcomes of subthalamic nucleus deep brain stimulation for Parkinson's disease in Singapore.

Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson's disease (PD), reducing dyskinesia and time spent in the "OFF" state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore. We conducted a retrospective review of Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery. A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the "OFF" state by 36.9% at 1 year (P=0.034) and 40.9% at 5 years (P=0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years (P<0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild. STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.

Dual-task performance and brain morphologic characteristics in Parkinson's disease.

Introduction Parkinson's disease (PD) reduces an individual's capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual-tasks (DT) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics. Methods Data were obtained from 34 individuals with PD and 47 healthy older adults including: 1) demographics (age, sex), 2) disease severity (Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn &amp; Yahr, levodopa equivalent daily dose (LEDD)), 3) cognition (Montreal Cognitive Assessment), 4) Levodopa Equivalent Daily Dose, 5) single task- and DT- performance during a DT-Timed-Up-and-Go test utilizing a serial-subtraction task, and 6) Cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT-effect was greater than the previously determined mean value for healthy older adults (μ=74.2). Nonparametric testing using Quade's ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT-effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion. Results The highDT group had thicker cortices than the lowDT group in the right primary somatosensory (p=0.001), bilateral primary motor (p=&lt;0.001, left; p=0.002, right), bilateral supplementary motor area (p=0.001, left; p&lt;0.001, right), and mean of the bilateral hemispheres (p=0.001, left; p&lt;0.001, right). Of note, left primary cortex thickness (p=0.002), left prefrontal cortex thickness (p&lt;0.001), and right supplementary motor area thickness (p=0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT-effect (p=0.011) beyond the influence of covariates. Conclusions These results suggest regions underlying dual-task performance; specifically, a convergence of neural control relying sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD.

The diabetic parkinsonian – the association of diabetes mellitus comorbidity and symptoms of Parkinson’s disease

Introduction and objective: Many studies have investigated the interplay between Parkinson’s disease and diabetes mellitus, suggesting that glucose metabolism impairment may worsen the clinical course of Parkinson’s disease. This study aimed to explore the association between diabetes mellitus and the course of Parkinson’s disease. Materials and methods: A retrospective study was performed by analysing the clinical data of patients diagnosed with Parkinson’s disease who were hospitalised in University Clinical Centre of the Medical University of Silesia from 2019 to 2021. The study group comprised 241 patients selected according to the study’s inclusion and exclusion criteria. Their clinical conditions were assessed using body mass index, the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Hoehn–Yahr scale, Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT) and Beck Depression Inventory (BDI). Data were collected on current anti-parkinsonian treatment, fasting glycaemia, lipid panel, and thyroid stimulating hormone, homocysteine and vitamin D3 levels. Results: The study group included 31 patients diagnosed with diabetes mellitus and 240 patients without glucose metabolism impairment. Both groups were matched by considering age, disease duration, and gender distribution. Diabetic patients displayed a higher MDS-UPDRS part III OFF rating (42 [31–55] vs. 48 [39–59]; p = 0.0043), higher MDS-UPDRS part III ON rating (17 [11–26] vs. 26.5 [19–32]; p = 0.0009) and higher BDI score (7 [4–11] vs. 11 [9–16]; p = 0.0013). As expected, patients with diabetes mellitus had a higher fasting glycaemia, total cholesterol, lower high-density lipoprotein cholesterol and higher body mass index. Conclusions: Our study confirms the relationship between diabetes mellitus and a worse clinical course for Parkinson’s disease.

Factors Associated with Quality of Life in Patients with Dementia with Lewy Bodies: Additional Analysis of a Cross-Sectional Study.

Quality of life (QOL) and treatment needs of patients with dementia with Lewy bodies (DLB) and their caregivers are important factors to consider when developing treatment strategies. To investigate factors associated with QOL in patients with DLB, and to examine factors associated with activities of daily living (ADL) if ADL was associated with QOL. We previously conducted a questionnaire survey study to investigate the treatment needs of patients with DLB and their caregivers. This pre-specified additional analysis evaluated the Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form-8 for QOL, and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II total score for ADL. In total, 231 patient- caregiver pairs and 38 physicians were included. Multivariable analysis of QOL showed that the MDS-UPDRS Part II total score (standard regression coefficient [β], - 0.432) was associated with the PCS, and presence of depression (β, - 0.330) was associated with the MCS. The severity of postural instability/gait disorder (PIGD) (β, 0.337) and rigidity (β, 0.266), presence of hallucinations (β, 0.165), male sex (β, 0.157), and use of "short stay" or "small-scale, multifunctional home care" (β, 0.156) were associated with worsened ADL. In patients with DLB, QOL was negatively impacted by severity of ADL disability and depression, and ADL was negatively impacted by severity of PIGD and rigidity, hallucinations, male sex, and use of "short stay" or "small-scale, multifunctional home care."

Khảo sát tình hình điều trị thuốc cho người bệnh parkinson tại Bệnh viện Đại học Y dược TP. Hồ Chí Minh

Background: Parkinson's disease is one of the most common progressive neurodegenerative disorders. There's currently no cure for Parkinson's disease. Current therapies only help patients relieve the symptoms and improve their quality of life. Objectives: To determine the rate of drugs prescribed to treat Parkinson's disease motor symptoms, the rate of the types of drug combinations, and the frequency of drug-induced motor complications in Parkinson's disease patients. Methods: This cross-sectional study was conducted at the University Medical Center HCMC, Ho Chi Minh City. The patient was diagnosed with Parkinson's disease based on the criteria of the International Parkinson's Disease and Movement Disorder Society (IPMDS). Patients' demographic data, information about Parkinson's disease, and medications used to treat Parkinson's disease were collected. Rating scales include MDS-UPRRS (Movement Disorder Society-Unified Parkinson's Disease Rating Scale), and Hoehn &amp; Yahr. Results: Among 218 Parkinson's patients, 33 (15.1%) patients received levodopa monotherapy, 126 (57.8%) patients received combination therapy of levodopa and dopamine agonists, 07 (3.2%) ) patients received combination therapy of levodopa and trihexyphenidyl, 1 (0.5%) patient received combination therapy of dopamine agonist and trihexyphenidyl, and 51 (23.4%) patients received combination therapy of both levodopa, dopamine agonist and trihexyphenidyl. A total of 217 patients were prescribed levodopa at a median dose of 375 mg. The median daily levodopa equivalent dose was 500 mg. A total of 177 patients (81.2%) used the dopamine agonist (pramipexole) with a median dose of 0.75 mg. 27.9 % of patients used an anticholinergic drug (trihexyphenidyl) with a median dose of 2 mg. The proportion of Parkinson's disease patients with motor complications was 32.6%. Conclusion: Levodopa was the medication most commonly prescribed to treat motor symptoms in patients with Parkinson's disease. The combination of levodopa and dopamine agonist was most popularly used. Drug-induced motor complications were common in Parkinson’s disease.

Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson's Disease.

The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid β (Aβ) from the brain. Higher Aβ levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging-along the perivascular space (DTI-ALPS) is an imaging measure proposed to indirectly measure glymphatic function. Evaluate differences in DTI-ALPS-index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI-ALPS. PD participants were classified as PD-normal cognition (PD-NC; n = 20) or PD-mild cognitive impairment (PD-MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). PD participants had lower DTI-ALPS-index compared to HC. PD participants classified as PD-MCI had significantly lower DTI-ALPS-index compared to PD-NC. Lower DTI-ALPS-index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. Glymphatic clearance, as measured with DTI-ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.

User-centred design, validation and clinical testing of an anti-choking mug for people with Parkinson’s disease

Oropharyngeal dysphagia, or difficulty initiating swallowing, is a frequent problem in people with Parkinson’s disease (PD) and can lead to aspiration pneumonia. The efficacy of pharmacological options is limited. Postural strategies, such as a chin-down manoeuvre when drinking, have had some degree of success but may be difficult for people who have other limitations such as dementia or neck rigidity, to reproduce consistently. Using a user-centred design approach and a multidisciplinary team, we developed and tested an anti-choking mug for people with PD that helps angle the head in the optimum position for drinking. The design reflected anthropometric and ergonomic aspects of user needs with features including regulation of water flow rate and sip volume, an inner slope, a thickened handle and a wide base, which promoted a chin-down posture when used. Prototype testing using digital technology to compare neck flexion angles (the primary outcome), plus clinical outcomes assessed using standard tools (Swallowing Clinical Assessment Score in Parkinson’s Disease (SCAS-PD) and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III), found significant improvements in a range of parameters related to efficient swallowing and safe drinking when using the anti-choking mug versus a sham mug.

Dual-task gait has prognostic value for cognitive decline in Parkinson’s disease

IntroductionCognitive decline frequently occurs in individuals with Parkinson’s disease (PD), but the clinical methods to predict the onset of cognitive changes are limited. Given preliminary evidence of the link between gait and cognition, the purpose of this study was to determine if dual task (DT) gait was related to declines in cognition over two years in PD. MethodsA retrospective two-year longitudinal study of 48 individuals with PD using data from the Parkinson’s Progression Markers Initiative of the Michael J. Fox Foundation. The following data were extracted at baseline: spatiotemporal gait (during single and DT), demographics (age, sex), PD disease duration (time since diagnosis), motor function (Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)), and cognition (Montreal Cognitive Assessment (MoCA)), with MoCA scores also extracted after two years. ResultsA binomial logistic regression was conducted, with all covariates (above) in block 1 and DT effect (DTE) of gait characteristics in block 2 entered in a stepwise fashion. The final model was statistically significant (χ2(6) = 23.20, p < 0.001) and correctly classified 78.7 % of participants by cognitive status after two years. Only DTE of arm swing asymmetry (ASA) (p = 0.030) was included in block 2 such that a 1 % decline in DTE resulted in 1.6 % increased odds of cognitive decline. ConclusionsIndividuals with greater change in arm swing asymmetry from single to DT gait may be more likely to experience a decline in cognition within two years. These results suggested that reduced automaticity or poor utilization of attentional resources may be indicative of subtle changes in cognition and indicate that DT paradigms may hold promise as a marker of future cognitive decline.

The effects of myofascial release in combined with task-oriented circuit training on balance in people with Parkinson’s disease: a randomized pilot trial

ABSTRACT Objectives Task-oriented circuit training (TOCT) has been used to improve balance in people with Parkinson’s disease (pwPD). To investigate the effectiveness of TOCT on balance, quality of life, and disease symptoms when combined with myofascial release in pwPD. Methods Twenty-six pwPD were randomized into two groups for this randomized controlled study. The groups received TOCT three days a week for eight weeks. At the end of each session, the myofascial release was applied to the neck, trunk, and lumbar region with three sets of 60-s foam rolling body weight (Intervention group-IG) and perceived discomfort level 0/10 (Control group-CG) using a numeric rating scale. Primary outcome measures were measured by the Berg Balance Scale (BBS), Parkinson’s Disease Questionnaire (PDQ-8), and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Secondary outcome measures included posturographic assessment, timed-up and go test (TUG), Trunk Impairment Scale (TIS), and rolling time. Results Data obtained from 26 pwPDs in equal numbers in both groups were analyzed. All groups reported a significant change in MDS-UPDRS, MDS-UPDRS-III, PDQ-8, TIS, and rolling time after treatment compared to pretreatment. Post-hoc analyses showed that IG significantly improved motor symptoms, TUG, and TIS dynamics compared to CG. The mediolateral limits of stability and anterioposterior limits of stability distances of IG increased (p < 0.05). Discussion Myofascial release, when combined with TOCT, may help to reduce disease-related motor symptoms and improve dynamic balance in pwPD. These findings suggest that myofascial release can be a beneficial addition to TOCT programs for pwPD. Clinical Trial Number: NCT05900934 (ClinicalTrials.gov).

Motor and non-motor outcome in tremor dominant Parkinson’s disease after MR-guided focused ultrasound thalamotomy

Background and objectivesMagnetic Resonance-guided Focused Ultrasound (MRgFUS) is an emerging technique for the treatment of severe, medication-refractory tremor syndromes. We here report motor and non-motor outcomes 6 and 12 months after unilateral MRgFUS thalamotomy in tremor-dominant Parkinson’s disease (tdPD).Methods25 patients with tdPD underwent neuropsychological evaluation including standardized questionnaires of disability, quality of life (QoL), mood, anxiety, apathy, sleep disturbances, and cognition at baseline, 6 and 12 months after MRgFUS. Motor outcome was evaluated using the Clinical Rating Scale for Tremor (CRST) and Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). In addition, side effects and QoL of family caregivers were assessed.Results12 months after MRgFUS significant improvements were evident in the tremor subscores. Patients with concomitant rest and postural tremor showed better tremor outcomes compared to patients with predominant rest tremor. There were no differences in the non-motor assessments. No cognitive decline was observed. Side effects were mostly transient (54%) and classified as mild (62%). No changes in the caregivers' QoL could be observed.ConclusionWe found no changes in mood, anxiety, apathy, sleep, cognition or persistent worsening of gait disturbances after unilateral MRgFUS thalamotomy in tdPD. Concomitant postural tremors responded better to treatment than predominant rest tremors.

Safinamide as adjunctive therapy to levodopa monotherapy for patients with Parkinson's disease with wearing-off: The Japanese observational J-SILVER study

BackgroundSafinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. MethodsThis multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. ResultsIn total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change −7.0 [p = 0.012], −2.4 [p = 0.007] and − 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. ConclusionSafinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. Study registrationUniversity Hospital Medical Information Network in Japan; study ID: UMIN000044341.