Unified Parkinson's Disease Rating Scale Part Research Articles

Fatigue and long duration of infection are associated with worsen motor and non‐motor symptoms in Parkinson's disease following Omicron COVID‐19 pandemic

AbstractBackgroundCoronavirus disease 2019 (COVID‐19) may influence the clinical course and symptoms of chronic neurological diseases, such as Parkinson's disease (PD), which can persist even after recovery from the infection. This longitudinal study aimed at exploring the impact of the COVID‐19 on motor and non‐motor symptoms and the related risk factors for exacerbation of PD symptoms.MethodsOne hundred and two PD patients underwent a first assessment between September 2022 and November 2022 (T0) before Omicron COVID‐19 pandemic. They were then contacted again and asked to complete the second assessment between December 2022 and February 2023 (T1) following Omicron infection. Movement Disorders Society Unified PD Rating Scale Part III, Non‐Motor Symptoms Scale, Fatigue Severity Scale (FSS), and quality of life were investigated.ResultsNinety‐five PD patients (93.1%) with COVID‐19 for the first time were mild cases. However, 55 patients (55.9%) experienced worsening motor symptoms of PD after recovering from the infectious symptoms. Preinfection FSS score (odds ratios [OR] 2.062, 95% confidence interval [CI] 1.081–3.933, p = .028) and duration of infection (OR 1.232, 95% CI 1.024–1.481, p = .027) were independent risk factors for the worsening of motor symptoms. PD patients with post‐COVID‐19 fatigue were more likely to experience worsened non‐motor symptoms, resulting in an impaired quality of life.ConclusionThis study confirms the impact of the Omicron COVID‐19 pandemic on the motor and non‐motor symptoms of PD, suggesting that management of related factors, including fatigue and duration of infection, may be beneficial in preventing or dealing with the exacerbation of PD symptoms after infection.

Freezing of gait in Parkinson’s disease with glucocerebrosidase mutations: prevalence, clinical correlates and effect on quality of life

ObjectivesMutations in glucocerebrosidase (GBA1) can change the clinical phenotype of Parkinson’s disease (PD). This study aimed to explore the clinical characteristics of freezing of gait (FOG) in PD patients with GBA1 mutations.MethodsA whole-exome sequencing analysis was used to identify the GBA1 mutations (pathogenic or likely pathogenic) and exclude other PD-related gene mutations. A forward binary logistic regression model was conducted to identify the associated factors of FOG. The stepwise multiple linear regression analysis models were used to explore the effect of FOG on quality of life.ResultsThe prevalence of FOG in patients with GBA1 mutations (30/95, 31.6%) was significantly higher than those in patients without GBA1 mutations (152/760, 20%) (p = 0.009). A higher (i.e., worse) Unified PD Rating Scale part III score (OR = 1.126, 95%CI = 1.061–1.194, p < 0.001) and a lower (i.e., worse) Montreal Cognitive Assessment score (OR = 0.830, 95%CI = 0.713–0.967, p = 0.017) were significantly associated with FOG in PD patients with GBA1 mutations. The presence of FOG was significantly associated with the decreased (i.e., worse) score of PD Questionnaire 39 after adjustment for sex, age, disease duration, motor score, and non-motor score (B = 14.981, p = 0.001).ConclusionFOG is a relatively common disabling symptom in PD patients with GBA1 mutations, which is affected by motor disability and cognitive decline. Quality of life is reduced in patients with FOG and GBA1 mutations.

2 A Randomized, Double-blinded, Placebo-controlled Trial of Liraglutide in Patients with Parkinson’s Disease: Neuropsychological Outcomes

Objective:Parkinson’s disease (PD) is associated with metabolic disorders such as insulin resistance. Pharmacological intervention used to treat insulin resistance, like GLP-1 agonists, may have auspicious results in the treatment for PD. The objective of this clinical trial was to assess the therapeutic effect of liraglutide on non-motor symptoms, such as, but not limited to, cognitive function and emotional well-being, and quality of life for individuals with PD.Participants and Methods:In a single-center, randomized, double-blind, placebo-controlled trial, PD patients self-administered liraglutide injections once-daily (1.2 or 1.8 mg, as tolerated) or placebo in a 2:1 study design for 52 weeks after titration. Primary outcomes included adjusted difference in the OFF-state Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) part III, non-motor symptom scale (NMSS) and Mattis Dementia Rating Scale (MDRS-2). Secondary outcomes included quality of life scores (Parkinson Disease Questionnaire, PDQ-39) and other neuropsychological tests, including Delis-Kaplan Executive Function System (DKEFS), Geriatric Depression Scale (GDS), and Parkinson’s Anxiety Scale (PAS) scores.Results:Sixty-three subjects were enrolled and randomized to liraglutide (n=42) or placebo (n=21). Mean age in years was 63.5 (9.8) and 64.2 (6.4) for liraglutide and placebo cohorts, respectively (p=0.78), and mean age at symptom onset was 58.9 (10.5) and 59.3 (7.5) for liraglutide and placebo cohorts, respectively (p=0.86). At 54 weeks, NMSS scores had improved by 6.6 points in the liraglutide group and worsened by 6.5 points in the placebo group, a 13.1 point adjusted mean difference (p<0.05). Further analysis showed all nine NMSS sub-domain changes favoring the liraglutide group, with one (attention/memory) reaching statistical significance (p<0.05). Secondary outcome analyses revealed a significant improvement of PDQ-39 (p<0.001) and Parkinson’s Anxiety Scale - Avoidance Behavior scores (p<0.05) in the treatment group. MDRS-2 sub-scores did not further differentiate study groups, while DKEFS letter fluency scores favored placebo group (p<0.05).Conclusions:Treatment with liraglutide improved self-reported non-motor symptoms of PD, activities of daily living, and quality of life. These results validate similar outcomes reported with other GLP-1 agonists implicating consideration for novel treatment opportunities for individuals with PD. Notably, the absence of significant performance-based cognitive changes over the duration of the trial for the participants in this study has several plausible explanations given participant-related baseline demographic and clinical factors. Implications for neuropsychologists will be discussed.

A 12-month prospective real-life study of opicapone efficacy and tolerability in Emirati and non-White subjects with Parkinson’s disease based in United Arab Emirates

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and the condition is complicated by the emergence of wearing off/motor fluctuations with levodopa treatment after a variable period. COMT inhibitors when used as adjunct therapy to levodopa tend to smoothen out these wearing off fluctuations by enhancing delivery of levodopa and increasing its bioavailability to the brain. The study was conducted to investigate the motor and nonmotor effect, safety and tolerability of the third generation once-daily COMT inhibitor (opicapone), as add-on, adjuvant therapy to levodopa and at 6 and 12 months follow-up in a real-life cohort of consecutive Emirati and non-White PD patients. A real-life observational analysis using tolerability parameters as used previously by Rizos et al. and Shulman et al. based on clinical database of cases rat Kings College Hospital Dubai Parkinson care database. This was a prospective, single-arm follow-up clinical evaluation study that evaluated the effectiveness of opicapone 50 mg once-daily regime in 50 patients diagnosed with idiopathic neurodegenerative disorder. All patients were assessed with scales used in clinical pathway and include motor Unified Parkinson’s Disease Rating Scale (UPDRS), nonmotor symptom scale (NMSS), quality of life (PDQ8) Parkinson’s fatigue scale (PFS16) and King’s Parkinson’s Pain Scale (KIPS). Out of 50 patients treated with opicapone (72% male, mean age 66.9 years (SD 9.9, range 41–82 years) and mean duration of disease 5.7 years (SD 2.5 range (2–11), there was significant statistical improvements shown in motor function-UPDRS part 3: baseline 40.64 ± 2.7, at 6 months 32.12 ± 3.14 and after 12 months 33.72 ± 3.76. Nonmotor burden NMSS: 107.00 ± 21.86, at 6 months 100.78 ± 17.28 and 12 months 96.88 ± 16.11. Reduction in dyskinesias (UPDRS part 4): baseline 8.78 ± 1.07, at 6 months 7.4 ± 0.81 and 12 months 6.82 ± 0.75. Opicapone provides beneficial motor and nonmotor effects in Emirati and other non-White Parkinson’s patients, resident in UAE, proving its efficacy across different racial groups as COMT activity may vary between races.

Dorsal subthalamic deep brain stimulation improves pain in Parkinson's disease.

Inconsistent effects of subthalamic deep brain stimulation (STN DBS) on pain, a common non-motor symptom of Parkinson's disease (PD), may be due to variations in active contact location relative to some pain-reducing locus of stimulation. This study models and compares the loci of maximal effect for pain reduction and motor improvement in STN DBS. We measured Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part I pain score (item-9), and MDS-UPDRS Part III motor score, preoperatively and 6-12 months after STN DBS. An ordinary least-squares regression model was used to examine active contact location as a predictor of follow-up pain score while controlling for baseline pain, age, dopaminergic medication, and motor improvement. An atlas-independent isotropic electric field model was applied to distinguish sites of maximally effective stimulation for pain and motor improvement. In 74 PD patients, mean pain score significantly improved after STN DBS (p = 0.01). In a regression model, more dorsal active contact location was the only significant predictor of pain improvement (R2 = 0.17, p = 0.03). The stimulation locus for maximal pain improvement was lateral, anterior, and dorsal to that for maximal motor improvement. STN stimulation, dorsal to the site of optimal motor improvement, improves pain. This region contains the zona incerta, which is known to modulate pain in humans, and may explain this observation.

Association of choroid plexus volume with motor symptoms and dopaminergic degeneration in Parkinson’s disease

BackgroundThe choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain, as a part of the glymphatic system. This study aimed to investigate the association between...

Predictors of cognitive impairment in newly diagnosed Parkinson's disease with normal cognition at baseline: A 5-year cohort study.

Cognitive impairment (CI) is a substantial contributor to the disability associated with Parkinson's disease (PD). We aimed to assess the clinical features and explore the underlying biomarkers as predictors of CI in patients with newly diagnosed PD (NDPD; less than 2 years). We evaluated the cognitive function status using the Montreal Cognitive Assessment (MoCA) and a battery of neuropsychological tests at baseline and subsequent annual follow-up for 5 years from the Parkinson's Progression Markers Initiative (PPMI) database. We assessed the baseline clinical features, apolipoprotein (APO) E status, β-glucocerebrosidase (GBA) mutation status, cerebrospinal fluid findings, and dopamine transporter imaging results. Using a diagnosis of CI (combined mild cognitive impairment and dementia) developed during the 5-year follow-up as outcome measures, we assessed the predictive values of baseline clinical variables and biomarkers. We also constructed a predictive model for the diagnosis of CI using logistic regression analysis. A total of 409 patients with NDPD with 5-year follow-up were enrolled, 232 with normal cognitive function at baseline, and 94 patients developed CI during the 5-year follow-up. In multivariate analyses, age, current diagnosis of hypertension, baseline MoCA scores, Movement disorder society Unified PD Rating Scale part III (MDS-UPDRS III) scores, and APOE status were associated with the development of CI. Predictive accuracy of CI using age alone improved by the addition of clinical variables and biomarkers (current diagnosis of hypertension, baseline MoCA scores, and MDS-UPDRS III scores, APOE status; AUC 0.80 [95% CI 0.74-0.86] vs. 0.71 [0.64-0.77], p = 0.008). Cognitive domains that had higher frequencies of impairment were found in verbal memory (12.6 vs. 16.8%) and attention/processing speed (12.7 vs. 16.9%), however, no significant difference in the prevalence of CI at annual follow-up was found during the 5-year follow-up in NDPD patients. In NDPD, the development of CI during the 5-year follow-up can be predicted with good accuracy using a model combining age, current diagnosis of hypertension, baseline MoCA scores, MDS-UPDRS III scores, and APOE status. Our study underscores the need for the earlier identification of CI in NDPD patients in our clinical practice.

Relationship between motor dysfunction and chewing movement in patients with Parkinson's disease: A transversal study.

To assess the impact of chewing movement in patients with Parkinson's disease (PD), we examined the relation between chewing movement and motor dysfunction in association with PD progression. Thirty patients with PD (mean age, 68.9 ± 9.0 years; mean Hoehn and Yahr stage, 3.0 ± 0.7) were recruited. The PD condition was assessed in each patient by using the score of Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) part III score, body mass index (BMI), serum albumin (Alb), and tongue pressure, number of chews, mealtime, and chewing speed were collected. The patients were divided into two groups (mild and moderate PD groups) based on an MDS-UPDRS part III cut-off value of 32. The chewing speed positively correlated with tongue pressure (rho = 0.69, p < 0.01) in the mild group, and with BMI (rho = 0.54, p = 0.03), serum Alb (rho = 0.63, p = 0.02), and number of chews (rho = 0.69, p < 0.01) in the moderate group. The MDS-UPDRS part III scores for all participants correlated negatively with chewing speed (rho = -0.48, p < 0.01), serum Alb (rho = -0.49, p < 0.01), and positively with mealtime (rho = 0.43, p = 0.01). Tongue pressure and serum Alb were identified to be as factors affecting the chewing speed (β= 0.560, p < 0.01; β= 0.457, p < 0.01, respectively). These results indicated that the progression of motor dysfunction in patients with PD is likely to affect chewing speed and the nutritional status decline may be linked to the impairment of chewing movement in these patients.

Patterns of striatal dopamine depletion and motor deficits in de novo Parkinson's disease.

The background of this study is to investigate whether striatal dopamine depletion patterns (selective involvement in the sensorimotor striatum or asymmetry) are associated with motor deficits in Parkinson's disease (PD). We enrolled 404 drug-naïve patients with early stage PD who underwent dopamine transporter (DAT) imaging. After quantifying DAT availability in each striatal sub-region, principal component (PC) analysis was conducted to yield PCs representing the spatial patterns of striatal dopamine depletion. Subsequently, multivariate linear regression analysis was conducted to investigate the relationship between striatal dopamine depletion patterns and motor deficits assessed using the Unified PD Rating Scale Part III (UPDRS-III). Mediation analyses were used to evaluate whether dopamine deficiency in the posterior putamen mediated the association between striatal dopamine depletion patterns and parkinsonian motor deficits. Three PCs indicated patterns of striatal dopamine depletion: PC1 (overall striatal dopamine deficiency), PC2 (selective dopamine loss in the sensorimotor striatum), and PC3 (symmetric dopamine loss in the striatum). Multivariate linear regression analysis revealed that PC1 (β = -1.605, p < 0.001) and PC2 (β = 3.201, p < 0.001) were associated with motor deficits (i.e., higher UPDRS-III scores in subjects with severe dopamine depletion throughout the whole striatum or more selective dopamine loss in the sensorimotor striatum), whereas PC3 was not (β = -0.016, p = 0.992). Mediation analyses demonstrated that the effects of PC1 and PC2 on UPDRS-III scores were indirectly mediated by DAT availability in the posterior putamen, with a non-significant direct effect. Dopamine deficiency in the posterior putamen was most relevant to the severity of motor deficits in patients with PD, while the spatial patterns of striatal dopamine depletion were not a key determinant.

Motor progression marker for newly diagnosed drug-naïve patients with Parkinson's disease: A resting-state functional MRI study.

The effective early prediction of clinical outcomes of Parkinson's disease (PD) is of great significance in the implementation of appropriate interventions. We aimed to propose a method based on the use of baseline resting-state functional characteristics (i.e., fractional amplitude of low-frequency fluctuations, fALFF) to predict motor progression in PD patients. Resting-state functional magnetic resonance imaging was performed on 48 newly-diagnosed drug-naïve PD patients and 27 age- and sex- matched healthy controls (HCs). Two PD subgroups were defined with different annual increase of Unified PD Rating Scale Part III motor scores. Least absolute shrinkage and selection operator regression analysis was performed to explore the baseline region-functional indicators for PD discrimination as well as the predictors for future motor deficits. Two significant models composed of baseline fALFF values from cerebral subregions were proposed. The classification model that distinguished PD patients from HCs (area under the curve [AUC]=0.897) showed the most significant imaging characteristics in the putamen and precentral gyrus. The other prediction model that evaluated the degree of future deterioration of motor symptoms in PD patients (AUC=0.916) showed the most significant imaging characteristics in the superior occipital gyrus and caudate nucleus. Furthermore, the increased regional function in bilateral caudate nuclei was correlated with the lower annual increase in motor deficits in all PD patients. The caudate nucleus might be the core region responsible for future motor deficits in newly-diagnosed PD patients, which may aid the development of disease progression preventive strategies in clinical practice.

Efficacy of rasagiline monotherapy for early Parkinson disease: A systematic review and meta-analysis of randomized controlled trials.

Rasagiline monotherapy is approved in early Parkinson's disease (PD) for motor benefit. However, the efficacy and optimal rasagiline dosage in improving Unified Parkinson's Disease Rating Scale (UPDRS) subscale scores between Japanese and Caucasian individuals remain uncertain. To investigate the efficacy of rasagiline monotherapy and evaluate differences between early PD patients in Eastern and Western countries. The study design involved the meta-analysis of randomized controlled trials identified using electronic databases. The mean difference (MD) in total UPDRS scores indicated no significant difference between the 1 and 2 mg rasagiline (MD = -0.00, 95% confidence interval (CI) = -0.82 to 0.81). Compared with the placebo, the MD of UPDRS part I scores significantly improved in the 1 mg (MD = -0.33, 95% CI = -0.57 to -0.10) but not in the 2 mg. For UPDRS part II scores, the MD significantly improved in the 1 mg (MD = -0.87, 95% CI = -1.48 to -0.27) and 2 mg (MD = -0.98, 95% CI = -1.28 to -0.68). Regarding the UPDRS part III, the MD significantly improved in both (1 mg: MD = -2.41, 95% CI = -3.26 to -1.56; 2 mg: MD = -2.05, 95% CI = -2.64 to -1.46). The most commonly reported adverse events were headaches, back pain, and dizziness, with no statistical difference between the 1 mg rasagiline and placebo groups. Subgroup analysis revealed similar effects between Asian and Western participants. Rasagiline monotherapy at 1 mg per day is recommended for patients with early PD because of the benefits for motor, nonmotor functions, and safety.

Reduced cerebral blood flow of lingual gyrus associated with both cognitive impairment and gait disturbance in patients with idiopathic normal pressure hydrocephalus

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is primarily characterized by cognitive impairment and gait disturbance. Our objective was to evaluate the clinical characteristics of iNPH and the association between cerebral blood flow (CBF), measured using single-photon emission computed tomography (SPECT), and both cognitive and gait disturbances in iNPH patients. MethodsWe compared cognitive and motor functions and neuroimaging findings between 29 iNPH patients and 35 age-matched Parkinson's disease (PD) patients. We examined the associations between cognitive and motor dysfunctions and CBF in iNPH patients using 99mTc-ECD SPECT subtraction imaging data from a database of healthy control subjects. ResultsThe cognitive function of iNPH patients, as measured by the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB), was significantly poorer than that of PD patients; however motor function of the legs based on the Unified PD Rating Scale (UPDRS) part III was similar across groups. Impairment in cognitive function based on the MMSE and FAB was significantly correlated with motor dysfunction of the legs on the UPDRS part III and the 3-m Timed Up and Go test. Furthermore, 99mTc-ECD SPECT subtraction imaging revealed lower CBF in the bilateral lingual gyrus of iNPH patients with severely impaired cognitive and motor functions than healthy control subjects. ConclusionPatients with iNPH have severely impaired cognitive function; however, motor dysfunction of the legs is similar to PD patients. The cognitive and gait disturbances of iNPH are significantly interrelated, which may be associated with an impaired brain network that includes the bilateral lingual gyrus.

Safety and tolerability of aripiprazole in patients with psychosis associated with Parkinson's disease-Results of a multicenter open trial.

AimTo evaluate the effect of aripiprazole on psychosis and motor function in Japanese Parkinson's disease patients.MethodsPatients with Parkinson's disease and hallucinations and/or delusions were enrolled. They were administered aripiprazole 3 mg/day, with dosage increased or reduced as needed. Patients were evaluated using the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression‐Severity (CGI‐S) scale, and Clinical Global Impression‐Improvement scale for psychiatric response; Hoehn & Yahr staging and Unified Parkinson's Disease Rating Scale (UPDRS) part III for motor response; Mini‐Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) for cognitive response; and Schwab and England Activities of Daily Living scale for daily activities of patients, before and at 2, 4, and 12 weeks after initiation of open‐label aripiprazole administration. This study was registered at the University Hospital Medical Information Network Center (registration number: UMIN000007711).ResultsNine of the 24 enrolled patients discontinued the study. Among them, eight patients discontinued the trial on account of their worsening parkinsonian symptoms. There were no differences in age, disease duration, disease severity, and MMSE and FAB scores at baseline between patients who continued and discontinued the study. However, in patients who continued aripiprazole administration at 3 mg/day or less significantly improved BPRS, CGI‐S scale, and UPDRS parts I and III scores.ConclusionSignificant improvements in hallucinations and delusions can be expected, although aripiprazole may aggravate parkinsonism in Parkinson's disease patients. Low‐dose use of aripiprazole may be useful for managing Parkinson's disease patients with psychosis, but only with close observation of extrapyramidal symptoms.

Pingchan Granule for Motor Symptoms and Non-Motor Symptoms of Parkinson’s Disease: A Randomized, Double-Blind, Placebo-Controlled Study

Background: Pingchan granule (PCG) is a traditional Chinese medicine for treating Parkinson’s disease (PD). Objective: This study aimed at evaluating the efficacy and safety of PCG for motor and non-motor symptoms of PD. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 292 participants with mild-to-moderate PD were included and followed for 36 weeks (24 week treatment, 12-week follow-up after intervention), randomly assigned at a 1:1 ratio to receive PCG or placebo. The primary outcomes included the severity of motor symptoms assessed by the Unified Parkinson’s disease Rating Scale (UPDRS) part 3 (UPDRS-III) score and the rate of disease progression assessed by the total UPDRS score. Secondary outcomes included non-motor symptoms assessed using the Scale for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT), Parkinson’s disease Sleep Scale (PDSS), 24-item Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), UPDRS part 2 (UPDRS-II), and 39-item Parkinson’s Disease Questionnaire (PDQ-39) scores. Assessments were done at baseline (T0), 12 weeks (T1), 24 weeks (T2), and 36 weeks (T3). Results: Generalized estimating equation analyses revealed that the PCG group had significantly better improvement in UPDRS-III score at T1, T2, and T3 [time-by-group interaction, T1: β, −0.92 (95% CI, −1.59–−0.25; p = 0.01); T2: β, −2.08 (95% CI, −2.90–−1.27; p < 0.001); T3: β, −4.54 (95% CI, −5.37–−3.71; p < 0.001))]. The PCG group showed a greater decrease (rate of disease change) in the total UPDRS score between T0 and T2 [−2.23 (95% CI, −2.72–−1.73; p < 0.001) points per week vs. −0.21 (95% CI, −0.80–0.39; p = 0.50) points per week in the placebo group, p < 0.001]. Ameliorations of SCOPA-AUT, PDSS, HAM-D, HAM-A, UPDRS-II, and PDQ-39 scores were also observed. Conclusion: PCG had a long-lasting and extensive symptomatic efficacy for both motor and non-motor symptoms of PD with good tolerance. Trial registration: Chinese Clinical Trial Register, ChiCTR-INR-17011949.

Enriched Rehabilitation Improves Gait Disorder and Cognitive Function in Parkinson's Disease: A Randomized Clinical Trial.

Background: Studies on non-pharmacological strategies for improving gait performance and cognition in Parkinson’s disease (PD) are of great significance. We aimed to investigate the effect of and mechanism underlying enriched rehabilitation as a potentially effective strategy for improving gait performance and cognition in early-stage PD.Methods: Forty participants with early-stage PD were randomly assigned to receive 12 weeks (2 h/day, 6 days/week) of enriched rehabilitation (ER; n = 20; mean age, 66.14 ± 4.15 years; 45% men) or conventional rehabilitation (CR; n = 20; mean age 65.32 ± 4.23 years; 50% men). In addition, 20 age-matched healthy volunteers were enrolled as a control (HC) group. We assessed the general motor function using the Unified PD Rating Scale—Part III (UPDRS-III) and gait performance during single-task (ST) and dual-task (DT) conditions pre- and post-intervention. Cognitive function assessments included the Montreal Cognitive Assessment (MoCA), the Symbol Digit Modalities Test (SDMT), and the Trail Making Test (TMT), which were conducted pre- and post-intervention. We also investigated alteration in positive resting-state functional connectivity (RSFC) of the left dorsolateral prefrontal cortex (DLPFC) in participants with PD, mediated by ER, using functional magnetic resonance imaging (fMRI).Results: Compared with the HC group, PD participants in both ER and CR groups performed consistently poorer on cognitive and motor assessments. Significant improvements were observed in general motor function as assessed by the UPDRS-III in both ER and CR groups post-intervention. However, only the ER group showed improvements in gait parameters under ST and DT conditions post-intervention. Moreover, ER had a significant effect on cognition, which was reflected in increased MoCA, SDMT, and TMT scores post-intervention. MoCA, SDMT, and TMT scores were significantly different between ER and CR groups post-intervention. The RSFC analysis showed strengthened positive functional connectivity between the left DLPFC and other brain areas including the left insula and left inferior frontal gyrus (LIFG) post-ER.Conclusion: Our findings indicated that ER could serve as a potentially effective therapy for early-stage PD for improving gait performance and cognitive function. The underlying mechanism based on fMRI involved strengthened RSFC between the left DLPFC and other brain areas (e.g., the left insula and LIFG).

Quantitative Gait Analysis Using a Pose-Estimation Algorithm with a Single 2D-Video of Parkinson’s Disease Patients

Clinician-based rating scales or questionnaires for gait in Parkinson's disease (PD) are subjective and sensor-based analysis is limited in accessibility. To develop an easily accessible and objective tool to evaluate gait in PD patients, we analyzed gait from a single 2-dimensional (2D) video. We prospectively recorded 2D videos of PD patients (n = 16) and healthy controls (n = 15) performing the timed up and go test (TUG). The gait was simultaneously evaluated with a pressure-sensor (GAITRite). We estimated the 3D position of toes and heels with a deep-learning based pose-estimation algorithm and calculated gait parameters including step length, step length variability, gait velocity and step cadence which was validated with the result from the GAITRite. We further calculated the time and steps required for turning. Then, we applied the algorithm to previously recorded and archived videos of PD patients (n = 32) performing the TUG. From the validation experiment, gait parameters derived from video tracking were in excellent agreement with the parameters obtained with the GAITRite. (Intraclass correlation coefficient > 0.9). From the analysis with the archived videos, step length, gait velocity, number of steps, and the time required for turning were significantly correlated (Absolute R > 0.4, p < 0.005) with the Freezing of gait questionnaire, Unified PD Rating scale part III total score, HY stage and postural instability. Furthermore, the video-based tracking objectively measured significant improvement of step length, gait velocity, steps and the time required for turning with antiparkinsonian medication. 2D video-based tracking could objectively evaluate gait in PD patients.

Impact of Progression of Parkinson's Disease on Swallowing Ability and Oral Environment.

This study investigated the impact of the severity and treatment of Parkinson's disease (PD) on the swallowing ability and oral environment of patients. Swallowing dysfunction increases the aspiration risk and may lead to poor oral health among patients with PD. We investigated the influences of PD progression and drug treatment on the swallowing ability and oral environment using simple noninvasive screening measurements. We recruited 87 patients with PD (mean age, 71.9 ± 8.0 years; mean Hoehn and Yahr score, 2.9 ± 0.9). The PD condition was assessed in each patient using the unified Parkinson's disease rating scale (UPDRS) part III, diet type and oropharyngeal function using the swallowing disturbances questionnaire (SDQ), maximum bite force (MBF), tongue pressure (TP), and oral bacterial count (OBC). Levodopa equivalent daily dose (LEDD) was also calculated for 56 participants. Based on an SDQ score of ≥11, 29.5% of patients were dysphagic, but almost all were still on a regular diet. The SDQ score was positively correlated with disease duration (rho = 0.228, p=0.047) and UPDRS part III score (rho = 0.307, p=0.007) but was negatively correlated with OBC (rho = −0.289, p=0.012). OBC was significantly higher among patients with an SDQ score of <11 (nondysphagic) (p=0.01), and the SDQ score was lower in patients with higher OBC requiring professional oral care (p=0.03). However, OBC was also negatively correlated with LEDD (rho = −0.411, p=0.004). These results indicated low self-awareness of dysphagia among the participants and an association between dysphagia and PD progression. Moreover, the oral environment could have deteriorated with swallowing dysfunction. Patients and clinicians should be aware that higher LEDD can increase xerostomia and associated deficits in oral health.

Factors Associated with Health-Related Quality of Life in Late-Stage Parkinson's Disease.

There is limited knowledge on health-related quality of life (HRQoL) in late-stage Parkinson's disease (PD). To assess factors associated with HRQoL in patients with late-stage PD, with a focus on health care provision. The Care of Late Stage Parkinsonism (CLaSP) project is the largest study on late-stage PD to date. The current study analyzed data of 401 patients from 6 European countries in whom HRQoL was assessed with the 8-item PD Questionnaire in patients without dementia. Factors potentially associated with HRQoL were assessed and examined in linear regression analyses. Better HRQoL was associated with living at home, greater independence in activities of daily living (Schwab and England Scale), less severe disease (Hoehn and Yahr stage), better motor function (Unified PD Rating Scale Part III), and lower non-motor symptoms burden (Non-Motor Symptoms Scale [NMSS]) across all NMSS domains. Having a PDspecialist as physician for PD, contact with a PDnurse, and no hospital admission during the past 3 months were associated with better HRQoL, but having seen a physiotherapist or occupational therapist was associated with worse HRQoL. The results emphasize the importance of optimizing treatment for motor and multiple non-motor symptoms to improve HRQoL in patients with late-stage PD. PD-specific health care resources, particularly PDnurses, are likely important in addressing issues to improve HRQoL in this population. Worse HRQoL in those who had recently seen a physiotherapist or occupational therapist may reflect referral based on factors not measured in this study.

Pingchan granule for depressive symptoms in parkinson’s disease: A randomized, double-blind, placebo-controlled trial

BackgroundDepression in Parkinson’s disease (dPD) is closely related to quality of life. Current studies have suggested that Pingchan Granule (PCG) might be effective for treating dPD. ObjectiveThis study determines the efficacy of PCG for depressive symptoms in Parkinson’s disease (PD). Design, setting, participants and interventionsThis was a randomized, double-blind, placebo-controlled trial, conducted in Longhua Hospital, Shanghai, China. Patients diagnosed with idiopathic PD and clinically significant depressive symptoms (defined by a 24-item Hamilton Rating Scale for Depression [HAM-D] score ≥ 8) were included in this study, randomly assigned to PCG or placebo group in a 1:1 ratio and followed for 24 weeks. Main outcome measuresThe primary outcome was the change from baseline to week 24 in HAM-D score among the set of patients who completed the study following the treatment protocol (per-protocol set). Secondary outcomes included changes in scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) part 2 (UPDRS-II), UPDRS part 3 (UPDRS-III), Parkinson’s Disease Sleep Scale (PDSS) and Hamilton Rating Scale for Anxiety (HAM-A), between baseline and week 24. ResultsEighty-six patients were enrolled, and 85 patients were included in the per-protocol set. HAM-D scores decreased by an adjusted mean of 11.77 (standard error [SE] 0.25) in the PCG group and 3.86 (SE 0.25) in the placebo group (between-group difference = 7.91, 95% confidence interval [7.22, 8.80], P < 0.001), in the multivariable linear regression. Improvements in scores on the UPDRS-II, UPDRS-III, PDSS, and HAM-A scales were also observed. ConclusionTreatment with PCG was well tolerated and improved depressive symptoms and motor and other non-motor symptoms in PD. Trial registrationChinese Clinical Trial Register: ChiCTR-INR-17011949.

The use of vortioxetine for depression in patients with Parkinson's disease in the early and advanced stages of the disease

Depression is one of the most common non-motor manifestations of Parkinson's disease (PD), which largely determines both the severity of the course of the disease and the life expectancy of patients, as well as the compliance of patients to and the efficiency of antiparkinsonian therapy. In this connection, the search for a safe and effective antidepressant for patients with PD is of particular relevance.Objective: to evaluate the efficacy and safety of vortioxetine in patients with PD complicated by mild to moderate depression.Patients and methods. Examinations were made in 150 patients with PD in its early and advanced stages (Hoehn-Yahr stages: 1.0 to 3.0). All the patients were treated with vortioxetine at a dose of 15 or 20 mg/day for 8 months. The investigators used clinical and psychopathological rating scales, such as the Hospital Depression Scale (HADS-D), the Hospital Anxiety Scale (HADS-A), the Beck Depression Inventory (BDI), and the Montgomery-Asberg Depression Rating Scale (MADRS). The severity of PD motor manifestations was assessed according to the Unified PD Rating Scale (UPDRS) Part III.Results and discussion. During the follow-up period corresponding to 12 weeks of vortioxetine use, all the patients showed a significant decrease in MARDS, HADS-A and HADS-D, and BDI scores for depression and anxiety (p &lt; 0.001). Vortioxetine demonstrated an optimal balance between tolerability and clinical efficacy in correcting affective disorders in this patient group. In addition, analysis of the dynamics of motor disorders yielded data on the improvement of movement functions while correcting depression as lower UPDRS Part III total scores (p &lt; 0.001).Conclusion. The findings suggest that vortioxetine has a significant effect on depression and anxiety in patients with PD in its early and advanced stages, good tolerability, and a rapid-onset effect.