Parkinson's Disease Rating Scale Research Articles

Temporal sequence of incident mild cognitive impairment, incident parkinsonism, and risk of death in unimpaired community-dwelling older adults.

Mild cognitive impairment (MCI) and parkinsonism affect many older adults. The objective of this study was to determine the sequence of their occurrence and associated risk of death. 1,255 community-dwelling unimpaired participants from two epidemiological cohorts were examined annually. MCI was based on neuropsychological testing, and parkinsonism was based on the motor portion of the modified Unified Parkinson's Disease Rating Scale. A multi-state Cox proportional hazards model simultaneously examined incidences of MCI, parkinsonism, and death. Average age at baseline was 76.5 years (SD = 7.2) and 73% were female. Incident MCI occurred almost as commonly as incident parkinsonism, yet compared to no impairment, risk of death was higher for MCI (HR = 1.82, 95%CI=1.34, 2.47), but it was not different for parkinsonism (HR = 1.29; 95%CI = 0.95, 1.75). Risk of death for participants with incident MCI who progressed to parkinsonism (40%) was not significantly different from those with MCI alone (HR = 1.25, 95%CI = 0.93, 1.69). However, risk of death for participants with incident parkinsonism who progressed to MCI (51%) was significantly higher than those who did not progress (HR = 1.67, 95%CI = 1.27, 2.18), indicating that risk of death is highest with incidence of MCI. The varied patterns of sequential occurrence of cognitive and motor impairment and associated risk of death suggests much greater heterogeneity than previously recognized. Further work is needed to determine the biology underlying the temporal evolution of these phenotypes, and if identification of the various subtypes improves risk stratification.

Efficacy and safety of safinamide in Parkinson's disease patients with motor fluctuations without levodopa dosage escalation over 18 weeks: KEEP study.

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with≥1.5 h of "off" time daily, who took levodopa≥3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson's Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale, MDS-UPDRS part 3 and part 4; King's Parkinson's Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily "off" time (-1.3±2.4 h, p<0.001) and quality of life (QoL) based on PDQ-39 summary index (-2.7±10.3, p<0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily "on" time without dyskinesia (all p<0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022.

The effects of free dance versus hatha yoga on quality of life and motor and non-motor symptoms in people with Parkinson's disease: protocol study for a randomized clinical trial

Objective: To describe a protocol comparing the effects of free dance, hatha yoga, and a control group on quality of life, motor and non-motor symptoms in people with Parkinson's disease (PwP). Methods: This is a randomized three-arm study. Inclusion criteria will be people with clinically diagnosed Parkinson's disease (PD), ≥ 45 years old, and in stages I to IV of the Hoehn and Yahr Disability Scale (HY). Who do not reach the cut-off point of the Montreal Cognitive Assessment (MoCA) and classified in stage V of the HY will be excluded. The interventions will last 60 minutes, twice a week, progressing from light to vigorous intensity. The primary outcome will be quality of life assessed by the Parkinson's Disease Questionnaire (PDQ39). Secondary outcomes will include the Unified Parkinson's Disease Rating Scale (UPDRS), the evaluation of motor and physical function such as shoulder and hip range of motion (goniometer), cardiorespiratory fitness (six-minute walk test), balance (MiniBESTest), as well as non-motor aspects such as anxiety (Beck Anxiety Inventory), self-esteem (Rosenberg Self-Esteem Scale), cognition (MoCA), hope (Herth Hope Scale), fecal incontinence (Fecal Incontinence Quality of life), urinary incontinence (International Consultation on Incontinence Questionnaire - Short Form), and depressive symptoms (Beck Depression Inventory). Data will be collected at baseline and post-intervention. Discussion: If study interventions are deemed effective compared to standard of care (i.e. control group), the present study will advance current knowledge on non-pharmacological therapeutic strategies for People with Parkinson. Study registered RBR-54s92mh on 02/29/24.

A single-blind, randomised control trial on the effectiveness of a structured multi component training module for family caregiver of persons with Parkinson's disease: A study protocol.

Parkinson disease (PD), a neurodegenerative disorder that progresses over time, is steadily growing in number and prevalence worldwide. PD in Malaysia is expected to increase five-fold by 2040 from the existing estimate of 20,000 patients in 2018. Treatment program of PD in Malaysia is rather unstructured, and there is no known comprehensive PD family caregiver training program available to date. To ensure the quality of a program, it must be tested for feasibility, effectiveness and sustainability. This paper describes the protocol of a study that evaluates the effectiveness of a structured, comprehensive training program of family caregiver to persons with PD in comparison to usual care. A total of 60 pairs of persons with PD of stage II and III, and their primary family caregiver will be recruited and allocated into either an experimental or a control group for 12 weeks of intervention. The experimental group will undergo initial training from multi-disciplinary healthcare providers and will be given a physical module containing weekly tasks that must be practised at home. While the control group will receive a usual care. Both groups will be assessed in terms of physical functions, functional mobility, quality of life (QoL), caregiver burden and knowledge using standardised assessment tools namely Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Timed Up and Go (TUG) test, Parkinson's Disease Questionnaire (PDQ-39), European Quality of Life five-dimensions (EQ-5D), Malay version of Zarit Burden Interview (MZBI) and Knowledge of Parkinson Disease Questionnaire (KPDQ). In addition, the feasibility and sustainability of the interventions will be evaluated, alongside its cost-effectiveness based on the average and incremental cost effectiveness ratio. All data will be analysed using descriptive and inferential statistics, particularly mixed model ANOVA. There is a significant gap in the literature pertaining family caregiver training programs for people with PD. Documented programs are lacking in term of comprehensiveness of content, application approach and the measurement of training outcomes including the program cost-effectiveness. The feasibility and effectiveness of such training program in a Malaysian setting also requires investigation due to differences in living environment, support system and population's perception. This study will assist to fulfil the existing literature gap and demonstrate the potential benefit of caregiver involvement in mediating the care and therapy for PD in the home setting. Optimum knowledge and skills gained through the training are expected to enhance the confidence and ability of the family caregivers and may possibly reduce their perceived caregiving burden. The protocol of this study is registered in the Australian-New Zealand Clinical Trial Registry (ANZCTR) with a registration number ACTRN12623000336684.

Efficacy of acupuncture in ameliorating anxiety in Parkinson's disease: a systematic review and meta-analysis with trial sequential analysis

BackgroundAlthough numerous studies have explored acupuncture for alleviating Parkinson's disease (PD) symptoms, specific methods focusing on reducing anxiety in these patients are lacking. Preliminary research indicates that acupuncture may improve anxiety in patients with Parkinson's; however, high-quality evidence is lacking. Therefore, we conducted a meta-analysis and trial sequential analysis (TSA) to assess the efficacy of acupuncture in managing anxiety symptoms in PD.MethodsWe systematically searched eight databases for randomized controlled trials (RCTs) evaluating the efficacy of acupuncture for the treatment of anxiety in patients with PD. Primary outcomes were measured using the Hamilton Anxiety Scale (HAMA) and the Self-Rating Anxiety Scale (SAS). Secondary outcomes included the Parkinson's Disease Questionnaire-39 (PDQ-39) and the Unified Parkinson's Disease Rating Scale (UPDRS). Risk of bias was assessed using the Cochrane RoB 2.0 tool, and certainty of evidence was assessed using the GRADE system. The Trial Sequential Analysis (TSA) was used to assess the sufficiency of the evidence.ResultsOur meta-analysis included 14 studies. The Manual acupuncture (MA) + routine drug treatment (RDT) group improved more than the RDT alone group. MA was more effective than sham acupuncture. MA+ traditional Chinese medicine (TCM) was also more effective than TCM. Auricular therapy (AT) was not as effective as control therapy (CT). The Electroacupuncture (EA) + routine drug treatment (RDT) group was not as effective as RDT. PDQ-39 and UPDRS subgroup analysis showed that the acupuncture group had better clinical efficacy than CT. The GRADE assessment rated the overall certainty of evidence for anxiety outcomes as low, PDQ-39 as very low and UPDRS as low. TSA results indicate insufficient evidence; further high-quality RCTs are needed to substantiate these findings.ConclusionOur analysis suggests that MA combined with RDT may help ameliorate anxiety in PD patients, although the evidence is weak due to low quality RCTs. EA and AT showed no significant effects, highlighting the need for more rigorous studies with better controls and longer follow-up. The potential of acupuncture for PD-related anxiety should be considered with caution until stronger evidence becomes available.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.

Evaluating efficacy and safety of Saffron add-on treatment in improvement of motor and depressive symptoms of patients with Parkinson’s disease: a randomized, double-blind, placebo-controlled clinical trial

AimEvidence has highlighted neuroprotective effects of saffron in animal models of Parkinson’s disease (PD). The present study investigated the efficacy and safety of add-on saffron on motor and depressive symptoms of patients with PD. MethodsThis study was an 8-week, randomized, double-blind, and parallel-group clinical trial. Known cases of PD with depression were randomized to receive either a routine treatment (levodopa or levodopa-equivalent dose of a dopamine agonist) plus saffron capsule (15 mg bid) or routine treatment plus placebo. All participants were assessed using the Hamilton Depression Rating Scale (HAMD), Geriatric Depression Scale-30 (GDS-30), item 3 of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 1, MDS-UPDRS part 3, and H and Y scale at baseline and at week 8. ResultsA total of 52 patients (25 in saffron and 27 in placebo groups) were included. Our results demonstrated that saffron could not improve motor symptoms of PD patients (F=0.53, df=1, p=0.424). However, repeated-measures analysis showed a significant effect of time × treatment (F=8.24, df=1, p=0.006) on HAMD scores, indicating a greater improvement of depressive symptoms in saffron compared to placebo groups. Our study showed nonsignificant findings regarding the secondary outcome measures (GDS-30, item 3 of MDS-UPDRS part 1, and H and Y scale). We showed that treatment with saffron is safe in PD. ConclusionWe substantiated that add-on treatment with saffron significantly improved depression, but not motor symptoms, in PD. Further trials with larger sample sizes and longer follow-ups are needed to confirm our findings.

Clinical significance of MRI-measured olfactory bulb height as an imaging biomarker of idiopathic Parkinson's disease.

This study aimed to determine whether the olfactory bulb height (OBH) measured using magnetic resonance imaging (MRI) has clinical utility as an imaging biomarker in the evaluation of patients with idiopathic Parkinson's disease (iPD) through its correlation with movement impairment. This retrospective study included cognitively intact patients with suspected parkinsonism. All participants underwent T2-weighted imaging to measure OBH. Logistic regression was used to determine whether OBH was an independent risk factor for distinguishing iPD patients from disease controls, and its relation with clinical parameters related to motor impairment, including clinical laterality, modified Hoehn and Yahr (HY) stage, and Unified Parkinson's Disease Rating Scale (UPDRS) III score, was investigated. Based on the final clinical diagnosis, 79 patients with iPD and 16 disease controls were included. The mean OBH was significantly smaller in iPD than in disease controls (p < 0.0001). OBH was a significant independent predictor of iPD, with a cutoff of 1.52 mm. In the comparison among the ipsilateral, contralateral side of iPD with clinical laterality, and disease control group, the OBH of the disease control group was significantly larger than both the ipsilateral and contralateral sides (P < 0.05). However, there was no significant difference in OBH between the ipsilateral and contralateral sides (p > 0.05). OBH according to HY stage was significantly smaller in HY stage 2-3 groups than in the disease control group (p < 0.001). The correlation analysis between UPDRS III and OBH showed a mild negative correlation (r = -0.32, p = 0.013). MRI-measured OBH is decreased in iPD regardless of age and sex and may be correlated with the progression of motor symptoms in the iPD.

Changes in serum uric acid, glutathione, and amyloid-β1-42 levels in Parkinson’s disease patients and their association with disease progression and cognitive decline

Objective This study aims to evaluate the diagnostic significance of serum uric acid (UA), glutathione (GSH), and amyloid-β1-42 (Aβ1-42) levels in relation to disease progression and cognitive impairment in patients with Parkinson’s disease (PD). Methods A total of 209 PD patients with disease duration ranging from 4.0 to 6.8 years were enrolled. Based on the Hoehn-Yahr staging system, patients were classified into Early (n = 67), Medium-term (n = 70), and Advanced (n = 72) stages. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), dividing the cohort into CD (cognitive dysfunction, n = 94) and NO-CD (no cognitive dysfunction, n = 115) groups. Serum UA, GSH, and Aβ1-42 levels were analyzed for correlations with clinical data. Independent risk factors and diagnostic value were determined through multivariable logistic regression models and receiver operating characteristic curve analysis. Results Serum UA and GSH levels progressively declined with advancing disease stage, while Aβ1-42 increased. Compared to the NO-CD group, the CD group showed lower serum UA and GSH levels, and higher Aβ1-42 levels. Serum UA and GSH were inversely correlated with disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale scores, while Aβ1-42 showed positive correlations. UA (p = 0.006), GSH (p < 0.001), and Aβ1-42 (p = 0.040) were independent predictors of disease stage. Similarly, UA (p = 0.003), GSH (p < 0.001), and Aβ1-42 (p < 0.001) were independent predictors of cognitive dysfunction. The combined assessment of these markers demonstrated a higher area under the curve (AUC) than individual markers for disease and cognitive decline identification. Conclusions Serum UA, GSH, and Aβ1-42 are independent predictors of disease progression and cognitive decline in PD patients. Their combined use offers enhanced diagnostic accuracy for disease staging and cognitive impairment in PD.

Biomarker Assessment in Parkinson's Disease Dementia and Dementia with Lewy Bodies by the Immunomagnetic Reduction Assay and Clinical Measures.

Plasma biomarker assays provide an opportunity to reassess whether Alzheimer's disease, Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB) plasma biomarkers are diagnostically useful. We hypothesized that immunomagnetic reduction (IMR) of plasma biomarkers could differentiate between patients with PDD and DLB and healthy patients when combined with established clinical testing measures. Plasma samples from 61 participants (12 PDD, 12 DLB, 37 controls) were analyzed using IMR to quantify amyloid-β 42 (Aβ42), total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and α-synuclein (α-syn). Receiver operating characteristic curve (ROC) analysis was used to obtain sensitivity, specificity, and area under the ROC curve. Biomarker results were combined with clinical measures from the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Hoehn-Yahr stage to optimize diagnostic test performance. Participants with PDD had higher α-syn than those with DLB and healthy participants and were distinguishable by their biomarker products Aβ42×p-tau181 and Aβ42×α-syn. Patients with DLB had higher p-tau181 than those with PDD and healthy participants and were distinguishable by their concentrations of α-syn×p-tau181. Plasma α-syn plus UPDRS versus either test alone increased sensitivity, specificity, and AUC when healthy patients were compared with those with PDD and DLB. Combined clinical examination scores and plasma biomarker products demonstrated utility in differentiating PDD from DLB when p-tau181 was combined with UPDRS, α-syn was combined with UPDRS, and α-syn×p-tau181 was combined with UPDRS. In this pilot study, IMR plasma p-tau181 and α-syn may discriminate between PDD and DLB when used in conjunction with clinical testing.

Immediate modulatory effects of transcutaneous vagus nerve stimulation on patients with Parkinson's disease: a crossover self-controlled fMRI study.

Previous studies have evaluated the safety and efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of Parkinson's disease (PD). However, the mechanism underlying the effect of taVNS on PD remains to be elucidated. This study aimed to investigate the immediate effects of taVNS in PD patients. This crossover self-controlled study included 50 PD patients. Each patient underwent three sessions of resting-state functional magnetic resonance imaging (rs-fMRI) under three conditions: real taVNS, sham taVNS, and no taVNS intervention. We analyzed whole-brain amplitude of low-frequency fluctuations (ALFF) from preprocessed fMRI data across different intervention conditions. ALFF values in altered brain regions were correlated with clinical symptoms in PD patients. Forty-seven participants completed the study and were included in the final analysis. Real taVNS was associated with a widespread decrease in ALFF in the right hemisphere, including the superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus (voxel p < 0.001, GRF corrected). The ALFF value in the right superior parietal lobule during real taVNS was negatively correlated with the Unified Parkinson's Disease Rating Scale Part III (r = -0.417, p = 0.004, Bonferroni corrected). TaVNS could immediately modulate the functional activity of brain regions involved in superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus. These findings offer preliminary insights into the mechanism of taVNS in treating PD and bolster confidence in its long-term therapeutic potential. TaVNS appears to reduce ALFF values in specific brain regions, suggesting a potential modulation mechanism for treating PD.

Impaired Gait, Postural Instability, and Rigidity in Relation to CB1 Receptor Availability in Parkinson's Disease.

In Parkinson's disease (PD), postural instability and gait disorder (PIGD) symptoms are associated with a worse prognosis for an unknown reason. The objective was to explore the relationship between cannabinoid receptor type 1 (CB1R) availability and motor symptoms in PD with [18F]FMPEP-d2 positron emission tomography (PET). Fifteen individuals with PD underwent [18F]FMPEP-d2 PET to measure cerebral CB1R availability. The Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) was used to evaluate the motor symptoms. A negative correlation was observed between [18F]FMPEP-d2 VT and PIGD score (P = 0.002) as well as rigidity subscore (P < 0.001). Both clusters covered widespread areas of both hemispheres. In contrast, tremor or bradykinesia did not correlate to [18F]FMPEP-d2 VT. Gait, postural instability, and rigidity in PD are associated with decreased CB1R availability, unlike tremor or bradykinesia, suggesting that the endocannabinoid system has a role in the pathophysiology of different motor symptoms in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prospective Connectomic-Based Deep Brain Stimulation Programming for Parkinson's Disease.

Efficacy of deep brain stimulation (DBS) relies on accurate lead placement as well as optimization of the stimulation parameters. Although clinical software tools are now available, programming still largely relies on a monopolar review, a tedious process for both patients and programmers. This study investigates the safety and feasibility of prospective automated connectomic DBS programming (automated connectomic programming [ACP]), focusing on the recruitment of specific white matter pathways. After DBS implantation, a detailed connectomic DBS model in patient-specific space was developed for each study participant. A driving-force model was used to quantify pathway recruitment across 2400 different DBS settings. Optimization algorithms maximized recruitment of therapeutic pathways while minimizing recruitment of side-effect pathways. Thirteen subjects were enrolled in two study phases that compared DBS settings derived from ACP to standard clinical DBS settings. Nine patients underwent reprogramming with ACP (5 globus pallidus interna [GPi], 4 subthalamic nucleus [STN]). Four patients underwent initial programming with ACP (3 GPi, 1 STN). All patients tolerated ACP without persistent side effects. In the reprogramming cohort, 3 patients preferred their ACP program, and 1 patient felt it was comparable to their clinical program. Unified Parkinson's Disease Rating Scale, Part III, scores for the initial ACP cohort (3 GPi, 1 STN) improved by an average of 43.5% (40.4-52.6 ± 5.6%). ACP appeared clinically safe and feasible. It provided reasonable motor improvement, which can be further optimized with subsequent clinical adjustment. Additional investigation is required to refine the optimization algorithm and to quantify the clinical benefit of ACP in a larger cohort. © 2024 International Parkinson and Movement Disorder Society.

A prediction model for the walking and balance milestone in Parkinson's disease

BackgroundWalking and balance impairments, represented by freezing of gait and falls, are significant contributors to disability in advanced Parkinson's disease (PD) patients. However, the composite measure of the Walking and Balance Milestone (WBMS) has not been thoroughly investigated. MethodsThis study included 606 early-stage PD patients from the Parkinson's Progression Markers Initiative (PPMI) database, with a disease duration of less than 2 years and no WBMS at baseline. Patients were divided into a model development cohort (70 %) and a validation cohort (30 %) according to the enrollment site. Longitudinal follow-up data over a period of 12 years were analyzed. ResultsAmong all 606 patients, the estimated probability of being WBMS-free at the 5th and 10th year was 88 % and 60 %, respectively. Five clinical variables (Age, Symbol Digit Modalities Test (SDMT), postural instability and gait difficulty (PIGD) score, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part I (MDS-UPDRS-I) score, and REM Sleep Behavior Disorder (RBD) were used to construct the Cox predictive model. The C-index of the model was 0.75 in the development cohort and 0.76 in the validation cohort. By optimizing the PIGD and MDS-UPDRS-I variables, an easy-to-use model was achieved with comparable predictive performance. ConclusionA predictive model based on five baseline clinical measures (Age, SDMT, PIGD score, MDS-UPDRS-I score, RBD) could effectively estimate the risk of the WBMS in early PD patients. This model is valuable for prognostic counseling and clinical intervention trials for gait and balance impairment.

Correlation between voice intensity and swallowing function in subjects with Parkinson's disease.

People with Parkinson's Disease (PD) experience reduced voice intensity and dysphagia. Organs related to voice production and swallowing are structurally and neurologically intertwined. Thus, instrumental voice assessment may be useful in identifying voice impairments that can show swallowing disorders. Timely assessment of swallowing disorders may prevent the occurrence of malnutrition, dehydration, pneumonia, and death. The aim of this study was to investigate the relationship between voice intensity and swallowing function in PD. 30 participants with PD were recruited. Motor disability was evaluated by the Unified Parkinson's Disease Rating Scale part III; voice intensity was assessed by PRAAT software during sustained /a/ and 1min of monologue. The Penetration Aspiration Scale, the Dysphagia Outcome Severity Scale, and the Videofluoroscopic Dysphagia Scale were used to assess swallowing during videofluoroscopy. Spearman correlation coefficients, logistic, and linear models were used to analyze data. Voice intensity correlated with swallowing: as voice intensity decreased, swallowing function deteriorated (Spearman coefficients from -0.42 to -0.72 across scales), and this holds even when adjusted for MDS-UPDRS motor scores. Swallowing impairment is 56 times more likely (p<0.01) when the voice intensity is below the normal cut-off score (60 dB) with a positive predictive value of 93%. Reduction in voice intensity is indicative of a higher risk of swallowing dysfunction. Thus, an instrumental voice analysis seems to be a non-invasive, lowcost, easy-to-use tool to identify people with PD in need of an assessment to allow for timely swallowing management and reduction of complications caused by dysphagia.

Sustained effect of prasinezumab on Parkinson's disease motor progression in the open-label extension of the PASADENA trial.

The Phase II trial of Anti-alpha-Synuclein Antibody in Early Parkinson's Disease (PASADENA) is an ongoing double-blind, placebo-controlled trial evaluating the safety and efficacy of prasinezumab in early-stage Parkinson's disease (PD). During the double-blind period, prasinezumab-treated individuals showed less progression of motor signs (Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III) than placebo-treated individuals. We evaluated whether the effect of prasinezumab on motor progression, assessed as a change in MDS-UPDRS Part III score in the OFF and ON states, and MDS-UPDRS Part II score, was sustained for 4 years from the start of the trial. We compared participants enrolled in the PASADENA open-label extension study with those enrolled in an external comparator arm derived from the Parkinson's Progression Markers Initiative observational study. The PASADENA delayed-start (n = 94) and early-start (n = 177) groups showed a slower decline (a smaller increase in score) in MDS-UPDRS Part III scores in the OFF state (delayed start, -51%; early start, -65%), ON state (delayed start, -94%; early start, -118%) and MDS-UPDRS Part II (delayed start, -48%; early start, -40%) than did the Parkinson's Progression Markers Initiative external comparator (n = 303). This exploratory analysis, which requires confirmation in future studies, suggested that the effect of prasinezumab in slowing motor progression in PD may be sustained long term. PASADENA ClinicalTrials.gov no. NCT03100149 .

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 &lt; 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.

Clinical efficacy of low-intensity pulsed ultrasound in Parkinson's disease with cognitive impairment.

Low-intensity pulsed ultrasound (LIPUS), is a new technique for invasive brain stimulation and modulation that has emerged recently, but the effects in Parkinson's disease with cognitive impairment (PD-CI) have been less observed. In this study, we collected 56 patients with PD-CI who were continuously treated with LIPUS for 8 weeks, and observed the clinical efficacy of LIPUS on PD-CI patients by comparing with the Sham stimulation continuous treatment. Fifty-six PD-CI patients were divided into the Sham group (given Sham stimulation on top of conventional medication, n = 28) and the LIPUS group (given LIPUS stimulation on top of conventional medication, n = 28), and both groups continued treatment for 8 weeks. Post-treatment efficacy and pre- and post-treatment cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA)], emotional state [Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI)], quality of life [Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39)], and serologic indices [5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA)] were compared. The total effective rate of the LIPUS group was higher versus that of the Sham group. In both groups, MMSE and MoCA scores increased; BDI and BAI scores decreased; UPDRS and PDQ-39 scores were reduced; the levels of 5-HT, NE, and DA were elevated. The above changes were more pronounced in the LIPUS group (all P < 0.05). The application of LIPUS on PD-CI could ameliorate patients' cognitive function, emotional state and quality of life, and regulate and optimize neurotransmitter expression levels.

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.

Correlations of gray matter volume with peripheral cytokines in Parkinson's disease

IntroductionPeripheral cytokine levels may affect specific brain volumes. Few studies have examined this possible relationship. ObjectiveIn a case–control study, we used magnetic resonance imaging (MRI) voxel-based morphological analysis techniques to examine the relationship between gray matter volume changes and cognitive, motor and emotional dysfunction as well as between gray matter volume changes and peripheral blood cytokine levels. MethodA total of 134 subjects, comprising 66 PD patients and 68 healthy controls, were recruited. Peripheral venous blood was collected to measure the concentrations of 12 cytokines, including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-α, IFN-γ, and TNF-α. All the subjects also underwent MRI, where 3D-T1-weighted MR images were used for the analysis. In addition, the Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSE), Unified Parkinson's disease Rating Scale (UPDRS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were assessed in PD patients. Statistical parameter mapping 12 software was used for the statistical analysis of the images. ResultCompared with control patients, PD patients presented decreased gray matter volume (GMV) in the bilateral frontal lobe, temporal lobe, parietal lobe, occipital lobe, insula, and right cerebellar lobule VIII. Regional GMV in the temporal lobe, parietal lobe, and cerebellum was correlated with MoCA, MMSE, UPDRS, HAMA, and HAMD scores in PDs. In addition, the regional GMV in PDs was correlated with the concentrations of cytokines, including IL-4, IL-6, IFN-γ, and TNF-α. The IL-6 concentration was negatively correlated with the UPDRS-IV score. ConclusionPD patients exhibit gray matter atrophy in a wide range of brain regions, which are symmetrically distributed and mainly concentrated in the frontal and temporal lobes, and these changes may be linked to motor disorders and neuropsychiatric manifestations. Cytokine concentrations in peripheral blood are correlated with regional gray matter volume in PDs, and the IL-6 level affects gray matter volume in the left precentral gyrus and the manifestation of motor complications.

Test-retest and inter-rater reliability and construct validity of the 2-minute step test in individuals with Parkinson's disease

ObjectiveTo evaluate the test-retest and inter-rater reliability and construct validity of the 2-minute step test (2MST) in individuals with Parkinson's disease (PD). MethodsTwo previously trained examiners applied the 2MST in two moments. Clinical measurements of PD were obtained using the following instruments: Berg Balance Scale (BBS), Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr Scale (H&Y), gait speed and cadence, 5-time Sit-to-Stand Test (5TSST) and Timed Up and Go (TUG). For reliability, the intraclass correlation coefficient (ICC), standard error of measurement (SEM) and minimal detectable change (MDC) were calculated. For construct validity, Pearson's and Spearman's correlation coefficient were used. The agreement between the measurement in person and via recorded video was assessed by means of Bland-Altman plots. ResultsThe 2MST showed adequate test-retest reliability (ICC = 0.80, SEM = 10.59, MDC = 29.35) and excellent inter-rater reliability (ICC = 0.93, SEM = 4.49, MDC = 12.46). There was acceptable agreement between assessments made with in person and via video. A correlation magnitude above 0.50 was found between 2MST and gait speed, and a correlation magnitude between 0.30 and 0.50 with BBS, gait cadence, UPDRS and TUG. ConclusionThe 2MST presents adequate test-retest and inter-rater reliability and a valid construct to evaluate the aerobic endurance of individuals with PD.