Mild PD Research Articles

Association between Tumor Size at the Time of Disease Progression and Survival Outcomes.

This study evaluates the prognostic significance of tumor size at disease progression (PD) and depth of response (DOR) in cancer patients. We performed post hoc analysis using data from six prospective clinical trials conducted by the Korean Cancer Study Group. Patients with tumor size at PD was categorized into 'Mild PD' and 'Significant PD' based on the cutoff values of relative change from baseline using maximally selected rank statistics. The overall survival (OS) and progression-free survival (PFS) were compared between PD and DOR categories. Among the 194 evaluable patients, 130 experienced PD. A 35.48% decrease from baseline in tumor size at PD was chosen for the cutoff between mild and significant PD for OS (mild PD: tumor size from the baseline ≤ -35.48%; significant PD > -35.48%). The mild PD had superior OS compared to the significant PD (25.8 vs. 12.8 months; Hazard ratio [HR] 0.47, 95% CI 0.266-0.843, p=0.009). When using an exploratory cutoff based on whether the tumor size was below vs. exceeded from the baseline (mild PD: tumor size from the baseline ≤ 0%; significant PD > 0%), OS remained significantly longer in the mild PD (17.1 vs. 11.8 months; HR 0.60, 95% CI 0.392-0.932, p=0.021). The greatest DOR was associated with the longest OS and PFS (p<0.001 for both). Tumor size at PD and DOR were significant prognostic factors for progressive disease. Maintaining a sufficiently reduced tumor size even during PD was associated with better survival outcomes.

Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson’s disease

Parkinson’s disease (PD) is characterized by a progressive loss of dopaminergic neurons. Exercise has been reported to slow the clinical progression of PD. We evaluated the dopaminergic system of patients with mild and early PD before and after a six-month program of intense exercise. Using 18F-FE-PE2I PET imaging, we measured dopamine transporter (DAT) availability in the striatum and substantia nigra. Using NM-MRI, we evaluated the neuromelanin content in the substantia nigra. Exercise reversed the expected decrease in DAT availability into a significant increase in both the substantia nigra and putamen. Exercise also reversed the expected decrease in neuromelanin concentration in the substantia nigra into a significant increase. These findings suggest improved functionality in the remaining dopaminergic neurons after exercise. Further research is needed to validate our findings and to pinpoint the source of any true neuromodulatory and neuroprotective effects of exercise in PD in large clinical trials.

ITRAQ‐based proteomic analysis reveals myeloperoxidase (MPO) as a diagnostic and prognostic biomarker of cognitive decline in Parkinson’s disease

AbstractBackgroundParkinson’s disease (PD) is the second most common progressive neurodegenerative disorder and is characterized by loss of dopaminergic neurons, leading to debilitating motor, cognitive, and behavioral symptoms. At present, there are no biological markers for antemortem PD diagnosis.MethodsTo identify potential blood biomarkers of PD, Isobaric Tags for Relative and Absolute Quantitation (iTRAQ)‐based mass spectrometry (MS) was performed to characterize alterations of serum proteins amongst PD patients of varying disease severity according to their Hoehn and Yahr (HY) stages. Sera of mild PD (HY 1.5‐2.0, n = 10), severe PD (HY 3.0‐4.0, n = 10) patients and healthy controls (n = 10) were enriched and subjected to 2D LC‐MS/MS for proteomic analysis. Candidate protein biomarkers were identified based on the relative abundance of the identified tryptic peptides, and were validated using ELISA in a validation set consisting of 103 early PD and 48 healthy controls (HC). Association with clinical outcomes were analyzed at cross‐sectional and longitudinal timepoints.ResultsA total of 96 proteins in the mild PD group and 78 proteins in the severe PD group were found to differ significantly between PD patients and healthy controls. Thirteen proteins were common between the mild PD and severe PD groups and were chosen for further analysis. These dysregulated proteins represent a diversity of biological processes, including innate immune response, complement activation, cytoskeleton reorganization and response to oxidative stress. Of which, myeloperoxidase showed higher serum levels in mild and severe PD. In the validation PD cohort, higher MPO was significantly associated with worse executive function over 4 years.ConclusionUsing an unbiased proteomic approach, we identified serum MPO (a marker of oxidative stress) as a promising biomarker for PD. Our results suggest that MPO could also potentially be an early marker for cognitive decline in PD. Further studies with larger cohorts are needed to validate these findings.

A Three-dimensional Finger-tapping Framework for Recognition of Patients with Mild Parkinson's Disease.

Upper limb tremor is a prominent symptom of both Parkinson's disease and essential tremor. Its kinematic parameters overlap substantially for these two pathological conditions, thus leading to high rate of misdiagnosis, especially for community doctors. Several groups have proposed various methods for improving differential diagnosis. These prior studies have attempted to identify better kinematic parameters, however they have mainly focused on single limb features including tremor intensity, tremor frequency, and tremor variability. In this paper, we propose a wearable system for multi-segment assessment of upper limb tremor and differential diagnosis of Parkinson's disease versus essential tremor. The proposed system collected tremor data from both wrist and fingers simultaneously. From this data, we extracted multi-segment features in the form of phase relationships between limb segments. Using support vector machine classifiers, we then performed differential diagnosis from the extracted features. We evaluated the performance of the proposed system on 19 Parkinson's disease patients and 12 essential tremor patients. Moreover, we also assessed the performance cost associated with reducing task load and sensor array size. The proposed system reached perfect accuracy in leave-one-out cross validation. Task reduction and sensor array reduction were associated with penalties of 2% and 9-10% respectively. The results demonstrated that the proposed system could be simplified for clinical applications, and successfully applied to the differential diagnosis of Parkinson's disease versus essential tremor in real-world setting.

The prevention of falls in patients with Parkinson’s disease with in-home monitoring using a wearable system: a pilot study protocol

BackgroundParkinson's disease (PD) is a chronic, progressive neurodegenerative condition that gradually worsens motor function and leads to postural instability and, eventually, falls. Several factors may influence the frequency of future falls, such as slowness, freezing of gait, loss of balance, and mobility problems, cognitive impairments, and the number of previous falls. The TED bracelet is an advanced technological wearable device able to predict falls.AimsThis principal aim is to investigate the feasibility of a full-scale research project that uses the TED bracelet to identify whether individuals with PD are at risk of falling.MethodsThis study will involve a pilot prospective observational study design; the subjects will include 26 patients suffering from mild PD and 26 others with no PD and no gait problems. Data will be collected from the TED bracelet and then compared to a paper-based fall diary. The enrolled participants will have a scheduled outpatient evaluation to collect both clinical and instrumental data as well as biological samples.DiscussionThis pilot study could then be implemented in a larger form to further evaluate the effectiveness of the TED device. Finally, it will help further develop gait monitoring systems for people with Parkinson's disease and other neurodegenerative diseases that can affect physical function and mobility, such as dementia and Alzheimer's.ConclusionsPreventing falls and their complications could lead to major advancements in the quality of home care for patients with PD, which would significantly impact the quality of life of both these patients and their caregivers.

Traditional Chinese medicine syndrome differentiation and treatment by stages of Parkinson’s disease: study protocol for a multicentre, randomized, double-blind, placebo-controlled clinical trial

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disease common in aged populations. Classified by Hoehn & Yahr stages, patients are often divided into mild/early stage, moderate/middle stage, and advanced/late stage. With disease progression, PD shows high heterogeneity in each stage. Based on traditional Chinese medicine (TCM) syndrome differentiation theory and our previous works, we found that during the early stage, the main syndrome is Yin deficiency of the liver and kidney; during the moderate stage, the main syndromes are phlegm heat and wind stirring and blood stasis and wind stirring; and during the late stage, the dominant syndromes are deficiency of Yin and Yang and deficiency of Qi and blood. Hence, we proposed a new model of TCM treatment by the stage of PD. Based on Shudi Pingchan formula, an experimental formula of our team, we developed Ziyin Pingchan formula, Jiedu Pingchan formula, and Fuzheng Pingchan formula to treat each stage. This study is designed to evaluate the therapeutic effect of treating Parkinson’s disease by stages using traditional Chinese medicine and to provide an evidence base for forming a standardized scheme of diagnosis and treatment.MethodsThis study is designed as a multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients will be stratified into 3 subgroups according to Hoehn & Yahr stage; 172, 168, and 72 participants will be required to be in the mild PD, moderate PD, and advanced PD subgroups, respectively, and will be randomized into the treatment or control group at a 1:1 ratio. The mild PD subgroup will receive a 48-week intervention, and the other 2 groups will receive a 24-week intervention. All groups will have a follow-up visit 12 weeks after starting the intervention. The intervention group will receive the Ziyin Pingchan formula, Jiedu Pingchan formula, or Fuzheng Pingchan formula, and the control group will receive the corresponding placebo. The primary outcomes will be the first addition of levodopa for the mild PD subgroup, the duration of the “OFF” period for the moderate PD subgroup, and the Parkinson's Disease Questionnaire (PDQ-39) for the advanced PD subgroup. The secondary outcomes will also be verified by subgroups, including the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Sleep Scale-2 (PDSS-2), scales for Outcomes in Parkinson’s Disease—Autonomic (SCOPA-AUT), and the nonmotor symptom scale (NMSS).Expected outcomesTo our knowledge, this is the first trial to combine TCM syndrome differentiation with PD clinical stages and put it into clinical practice. The results of this trial will provide clinical evidence for the therapeutic effect of TCM formulas on PD patients of all stages and help build a new TCM treatment by stage model of PD.Trial registration: This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/). Registration number: ChiCTR2200056373, Date: 2022–02-04, version 1.

Prevalence and Risk Factors of Primary Dysmenorrhea in Students: A Meta-Analysis

ObjectivesPrimary dysmenorrhea (PD), as the most common complaint among students, is also one of the public problems worldwide. Prevalence and risk factors of PD were variant between studies; as the main population, no meta-analysis for PD has hitherto been conducted in students. MethodsWe searched the published literature in PubMed, Embase, the Cochrane Library, Web of Science, National Knowledge Infrastructure, WANFANG, and VIP database. After screening and assessing the quality of studies, data from eligible studies were extracted for meta-analysis via the R language. ResultsA total of 96 studies published from 1991 to 2021 with 78 068 students were included, the mean age of participants was 19.4, and 79.9% were university students. The pooled overall prevalence of PD was 66.1% (95% confidence interval [CI] 63.4-68.9), and 31.1% (CI 28.1-34.3), 25.7% (CI 23.4-28.0), and 8.3% of students (CI 7.4-9.3) reported mild, moderate, and severe PD, respectively. Besides, the prevalence of PD was estimated at 58.8% (CI 54.3-63.7) before 2010, but ascended to 68.5% (CI 65.5-71.6) after 2010 and rose to 71.5% (CI 65.8-76.6) in 2015 to 2021. About risk factors for PD, underweight, skipping breakfast, poor sleep quality, staying up late, lack of physical exercise, exposure to cold and eating cold or spicy foods during menstruation, dietary bias, prefer snacks, family history of dysmenorrhea, irregular menstrual cycle, heavy stress, negative emotion during menstruation, and anxiety were significantly related to PD. ConclusionsThe overall prevalence of PD among students was 66.1% and had a rising tendency in the last 10 years. Our findings helped understand the current prevalence and improve the administration of PD among students.

Neurofeedback-guided kinesthetic motor imagery training in Parkinson’s disease: Randomized trial

BackgroundParkinson’s disease (PD) causes difficulty with maintaining the speed, size, and vigor of movements, especially when they are internally generated. We previously proposed that the insula is important in motivating intentional movement via its connections with the dorsomedial frontal cortex (dmFC). We demonstrated that subjects with PD can increase the right insula-dmFC functional connectivity using fMRI-based neurofeedback (NF) combined with kinesthetic motor imagery (MI). The current study is a randomized clinical trial testing whether NF-guided kinesthetic MI training can improve motor performance and increase task-based and resting-state right insula-dmFC functional connectivity in subjects with PD. MethodsWe assigned nondemented subjects with mild PD (Hoehn & Yahr stage ≤ 3) to the experimental kinesthetic MI with NF (MI-NF, n = 22) and active control visual imagery (VI, n = 22) groups. Only the MI-NF group received NF-guided MI training (10–12 runs). The NF signal was based on the right insula-dmFC functional connectivity strength. All subjects also practiced their respective imagery tasks at home daily for 4 weeks. Post-training changes in 1) task-based and resting-state right insula-dmFC functional connectivity were the primary imaging outcomes, and 2) MDS-UPDRS motor exam and motor function scores were the primary and secondary clinical outcomes, respectively. ResultsThe MI-NF group was not significantly different from the VI group in any of the primary imaging or clinical outcome measures. The MI-NF group reported subjective improvement in kinesthetic body awareness. There was significant and comparable improvement only in motor function scores in both groups (secondary clinical outcome). This improvement correlated with NF regulation of the right insula-dmFC functional connectivity only in the MI-NF group. Both groups showed specific training effects in whole-brain functional connectivity with distinct neural circuits supporting kinesthetic motor and visual imagery (exploratory imaging outcome). ConclusionsThe functional connectivity-based NF regulation was unsuccessful, however, both kinesthetic MI and VI practice improved motor function in our cohort with mild PD.

Synthesis and properties of covalently linked di-p-benzihomoporphyrin-BODIPY conjugates

Two mono meso-functionalized [20]di-[Formula: see text]-benzihomoporphyrins containing [Formula: see text]-formylphenyl and [Formula: see text]-iodophenyl groups at meso-position respectively were synthesized by condensing one equivalent of appropriate tetrapyrrane with one equivalent of [Formula: see text]-formyl benzaldehyde/[Formula: see text]-iodo benzaldehyde in CH2Cl2 under mild acid catalyzed conditions. The meso-formylphenyl and meso-iodophenyl functionalized di-[Formula: see text]-benzihomoporphyrins were used to synthesize two covalently linked di-[Formula: see text]-benzihomoporphyrins-BODIPY conjugates. The meso-formylphenyl-functionalized di-[Formula: see text]-benzihomoporphyrin was converted to corresponding meso-dipyrrolyl substituted di-[Formula: see text]-benzihomoporphyrin by treating with excess pyrrole under acid catalyzed conditions. In the next step, the meso-dipyrrolyl di-[Formula: see text]-benzihomoporphyrin was subjected to oxidation followed by BF2 complexation to afford the directly linked di-[Formula: see text]-benzihomoporphyrin-BODIPY conjugate. The meso-iodophenyl functionalized di-[Formula: see text]-benzihomoporphyrin was coupled with ethynyl-functionalized BODIPY under mild Pd(0) coupling condition to synthesize diphenylethyne-bridged di-[Formula: see text]-benzihomoporphyrin-BODIPY conjugate. The two conjugates were characterized by HR-MS, NMR, absorption, electrochemical, fluorescence and DFT studies. The spectral and electrochemical studies indicated that the two constituents, di-[Formula: see text]-benzihomoporphyrin and BODIPY units in the conjugates interact weakly and retain their individual characteristic features. DFT studies indicated a possibility of charge transfer between di-[Formula: see text]-benzihomoporphyrin and BODIPY units in conjugates.

Contralateral Posterior Putaminal 18F-Fluorodopa Uptake in Mild Stage Parkinson's Disease: A PET/CT Study.

Previous studies revealed that 18F-FDOPA uptake was significantly decreased in the subregions of striatum contralateral to the side with predominant symptoms and was helpful for improving the early diagnostic accuracy of PD. However, in these studies, more than half of the PD patients already have bilateral motor symptoms (mH&Y stage≥2). This study was aimed to extend previous findings to a milder disease stage. Sixteen PD patients with only mild and unilateral motor symptoms (mH&Y stage=1 and disease duration≤2 years) and 22 healthy controls were involved. Striatal 18F-FDOPA uptake was analyzed using a ratio approach. The SORs in the subregions of the contralateral striatum, including caudate, anterior putamen and posterior putamen were significantly decreased in the mild stage PD patients. The SOR for the contralateral posterior putamen had the largest area under the receiver operating characteristic curve (0.963) and separated mild stage PD patients from healthy controls with a sensitivity of 93.75% and a specificity of 95.45% when the cut-off value of <2.160 was selected. These data indicate that contralateral posterior putaminal 18F-FDOPA uptake may represent a potential marker for early diagnosis of PD, especially in patients with only mild and unilateral motor symptoms.

The Frequency of Atypical and Extreme Values for Pharyngeal Phase Swallowing Measures in Mild Parkinson Disease Compared to Healthy Aging.

PurposeDysphagia is thought to be prevalent and a leading cause of morbidity and mortality in people with Parkinson disease (PwPD). The aim of this study was to compare the frequencies of atypical and extreme values for measures of swallowing physiology in PwPD and in an age- and sex-matched cohort of healthy adults. Atypical and extreme values were defined, respectively, as values falling in the 25% and 5% tails of the reference distribution for healthy adults under age 60 years.MethodA standard videofluoroscopy (VF) protocol was performed in 17 adults with mild PD and 17 age- and sex-matched healthy adults using 20% w/v liquid barium ranging from thin to extremely thick consistency. Blinded VF analysis was performed according to the Analysis of Swallowing Physiology: Events, Kinematics and Timing Method. Frequencies for atypical and extreme values were tabulated by cohort and compared using odds ratios.ResultsIncreased frequencies of atypical values (> 25%) were seen in the PwPD for prolonged swallow reaction time, prolonged time-to-laryngeal-vestibule-closure (LVC), and poor pharyngeal constriction. However, these findings were also observed in the healthy controls. The PwPD showed significantly higher odds of atypical values for narrow upper esophageal sphincter (UES) diameter on thin liquids, a short hyoid-burst-to-UES-opening interval on extremely thick liquids, and prolonged time-to-LVC, LVC duration, and UES opening duration on multiple consistencies. The frequencies of extreme values failed to show any significant cohort differences for any parameter.ConclusionsIn this study, a group of people with mild PD did not show clear evidence of swallowing impairments distinct from the changes seen in a healthy age-matched control group when odds ratios were used to compare the frequencies of atypical values between PwPD and the control group; only a few parameters showed significant differences. These were findings of significantly higher frequencies in PwPD of prolonged LVC and UES opening duration.Supplemental Material https://doi.org/10.23641/asha.15032241

People with mild PD have impaired force production in all lower limb muscle groups: A cross-sectional study.

Power is reduced in people with Parkinson's disease as a consequence of bradykinesia, but it is not clear whether reduced power is also due to a deficit in force production. The aim of this study was to quantify force production in all major lower limb muscle groups in people with PD during the "on" phase after medication, compared with aged-matched neurologically normal control participants. Design: A cross-sectional study was undertaken. Thirty ambulatory people with PD and 24 neurologically normal controls. Isometric force production of the hip flexors and extensors, hip adductors and abductors, hip internal rotators and external rotators, knee flexors and extensors, ankle dorsiflexors and plantarflexors, ankle invertors and evertors using hand-held dynamometry. There was a significant deficit in force production in participants with PD in all lower limb muscle groups tested, compared with control participants. On average, force production of participants with PD was 78% (range 67%-87%) of control participants, despite participants with PD regularly participating in exercise, being measured during their "on" phase after medication and having normal walking ability. The most severely affected muscle groups were the hip adductors (67%) and ankle plantarflexors (68%). People with PD have a significant loss of force production in all lower limb muscle groups compared with age-matched neurologically-normal controls. Clinicians should regularly assess the strength of all lower limb muscle groups, regardless of participation in physical activity, responsiveness to levodopa medication and walking ability.

Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson\u2019s disease

BackgroundCognitive impairment is an important and diverse symptom of Parkinson’s disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been comprehensively investigated.ObjectivesThis cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large PD cohort.MethodsCognitive function was evaluated using the Addenbrooke’s Cognitive Examination in 392 people with PD (PwP) from the Australian Parkinson’s Disease Registry. The influence of sex on domain-specific cognitive performance was investigated using covariate-corrected generalised linear models. In a repeated measures longitudinal subset of 127 PwP, linear mixed models were used to assess the impact of sex on cognition over time, while accounting for covariates.ResultsCross-sectional-corrected modelling revealed that sex was significantly predictive of cognitive performance, with males performing worse than females on global cognition, and memory and fluency domains. Longitudinally, sex was significantly predictive of cognitive decline, with males exhibiting a greater reduction in global cognition and language, whereas females showed a greater decline in attention/orientation, memory and visuospatial domains, despite starting with higher baseline scores. At follow-up, a significantly higher proportion of males than females fulfilled criteria for mild cognitive impairment or PD dementia.ConclusionsSex was revealed as a significant determinant of overall cognitive performance as well as specific cognitive domains, with a differential pattern of decline in male and female participants. Such sex-specific findings appear to explain some of the heterogeneity observed in PD, warranting further investigation of mechanisms underlying this sexual dimorphism.

1,2,3-Triazole framework: a strategic structure for C-H⋯X hydrogen bonding and practical design of an effective Pd-catalyst for carbonylation and carbon-carbon bond formation.

1,2,3-Triazole is an interesting N-heterocyclic framework which can act as both a hydrogen bond donor and metal chelator. In the present study, C–H hydrogen bonding of the 1,2,3-triazole ring was surveyed theoretically and the results showed a good agreement with the experimental observations. The click-modified magnetic nanocatalyst Pd@click-Fe3O4/chitosan was successfully prepared, in which the triazole moiety plays a dual role as both a strong linker and an excellent ligand and immobilizes the palladium species in the catalyst matrix. This nanostructure was well characterized and found to be an efficient catalyst for the CO gas-free formylation of aryl halides using formic acid (HCOOH) as the most convenient, inexpensive and environmentally friendly CO source. Here, the aryl halides are selectively converted to the corresponding aromatic aldehydes under mild reaction conditions and low Pd loading. The activity of this catalyst was also excellent in the Suzuki cross-coupling reaction of various aryl halides with phenylboronic acids in EtOH/H2O (1 : 1) at room temperature. In addition, this catalyst was stable in the reaction media and could be magnetically separated and recovered several times.

Combining a Cognitive Concurrent Task with a Motor or Motor-Cognitive Task: Which Is Better to Differentiate Levels of Affectation in Parkinson's Disease?

Introduction Cognitive decline usually coexists with motor impairment in PD. Multitask settings provide appropriate measures to evaluate the complex interaction between motor and cognitive impairments. The main objective was to analyze which concurrent task, i. e., motor or hybrid motor-cognitive, in combination with a cognitive task better differentiates between PD patients with mild and moderate levels of disease. Methods Thirty-seven individuals (19 male and 18 female) with idiopathic PD performed dual and triple tasks combining a cognitive task (phonemic fluency) with motor (pedaling) and/or cognitive-motor hybrid (tracking) tasks. Mild and moderate disability PD groups were specified considering the Hoehn and Yahr scale. Mixed ANOVA analyses for each of the concurrent task were carried out to test differences between the single and dual or triple condition performances comparing the low and high PD disability groups. Supplementary mixed ANCOVA analysis was performed considering the cognitive status as the covariate. Results The only significant differences between disability PD groups were found for performances in the cognitive-motor hybrid (tracking) task, both in dual and triple conditions. Our results showed a better performance for the mild rather than for the moderate disability group in the single condition task and a significant decline of the mild disability group in the dual and triple condition when compared to the levels of those shown by the moderate disability group. The group-condition interaction remained significant when the cognitive status was statistically controlled. Conclusion The hybrid of motor-cognitive task combining with a cognitive task (i. e., fluency) successfully differentiated between mild and moderate PD patients in the context of dual and triple multitask sets even when the cognitive status was statistically controlled. Our results highlight the importance of jointly measuring the complex interplay between motor and cognitive skills in PD.

Biometric handwriting analysis to support Parkinson\u2019s Disease assessment and grading

BackgroundHandwriting represents one of the major symptom in Parkinson’s Disease (PD) patients. The computer-aided analysis of the handwriting allows for the identification of promising patterns that might be useful in PD detection and rating. In this study, we propose an innovative set of features extracted by geometrical, dynamical and muscle activation signals acquired during handwriting tasks, and evaluate the contribution of such features in detecting and rating PD by means of artificial neural networks.MethodsEleven healthy subjects and twenty-one PD patients were enrolled in this study. Each involved subject was asked to write three different patterns on a graphic tablet while wearing the Myo Armband used to collect the muscle activation signals of the main forearm muscles. We have then extracted several features related to the written pattern, the movement of the pen and the pressure exerted with the pen and the muscle activations. The computed features have been used to classify healthy subjects versus PD patients and to discriminate mild PD patients from moderate PD patients by using an artificial neural network (ANN).ResultsAfter the training and evaluation of different ANN topologies, the obtained results showed that the proposed features have high relevance in PD detection and rating. In particular, we found that our approach both detect and rate (mild and moderate PD) with a classification accuracy higher than 90%.ConclusionsIn this paper we have investigated the representativeness of a set of proposed features related to handwriting tasks in PD detection and rating. In particular, we used an ANN to classify healthy subjects and PD patients (PD detection), and to classify mild and moderate PD patients (PD rating). The implemented and tested methods showed promising results proven by the high level of accuracy, sensitivity and specificity. Such results suggest the usability of the proposed setup in clinical settings to support the medical decision about Parkinson’s Disease.

A low-cost vision system based on the analysis of motor features for recognition and severity rating of Parkinson\u2019s Disease

BackgroundAssessment and rating of Parkinson’s Disease (PD) are commonly based on the medical observation of several clinical manifestations, including the analysis of motor activities. In particular, medical specialists refer to the MDS-UPDRS (Movement Disorder Society – sponsored revision of Unified Parkinson’s Disease Rating Scale) that is the most widely used clinical scale for PD rating. However, clinical scales rely on the observation of some subtle motor phenomena that are either difficult to capture with human eyes or could be misclassified. This limitation motivated several researchers to develop intelligent systems based on machine learning algorithms able to automatically recognize the PD. Nevertheless, most of the previous studies investigated the classification between healthy subjects and PD patients without considering the automatic rating of different levels of severity.MethodsIn this context, we implemented a simple and low-cost clinical tool that can extract postural and kinematic features with the Microsoft Kinect v2 sensor in order to classify and rate PD. Thirty participants were enrolled for the purpose of the present study: sixteen PD patients rated according to MDS-UPDRS and fourteen healthy paired subjects. In order to investigate the motor abilities of the upper and lower body, we acquired and analyzed three main motor tasks: (1) gait, (2) finger tapping, and (3) foot tapping. After preliminary feature selection, different classifiers based on Support Vector Machine (SVM) and Artificial Neural Networks (ANN) were trained and evaluated for the best solution.ResultsConcerning the gait analysis, results showed that the ANN classifier performed the best by reaching 89.4% of accuracy with only nine features in diagnosis PD and 95.0% of accuracy with only six features in rating PD severity. Regarding the finger and foot tapping analysis, results showed that an SVM using the extracted features was able to classify healthy subjects versus PD patients with great performances by reaching 87.1% of accuracy. The results of the classification between mild and moderate PD patients indicated that the foot tapping features were the most representative ones to discriminate (81.0% of accuracy).ConclusionsThe results of this study have shown how a low-cost vision-based system can automatically detect subtle phenomena featuring the PD. Our findings suggest that the proposed tool can support medical specialists in the assessment and rating of PD patients in a real clinical scenario.

Action observation and gait recovery in subject with Parkinson's disease. A new motor-cognitive combined approach. A preliminary report

Action observation (AO) has been recently described as an effective strategy in stroke rehabilitation, since it can shape neural circuit reorganization, promote neural plasticity and motor learning. Very few evidences are available for rehabilitation of patients with Parkinson disease trough AO. The specific aim of this paper is to evaluate the effectiveness of action observation as an adjunctive rehabilitative tool to improve balance, gait and to reduce falls and to investigate the changes in EEG pattern duo to the treatment's effects. Prospective quasi-experimental study, pre- and post-design. Five cognitively intact participants with mild Parkinson's disease and gait disturbance were enrolled in the study. The subjects underwent a rehabilitation programme of action observation for gait and balance recovery for 30 minutes, 3 times a week for 4 weeks. The assessments were performed at the beginning (T0) and at the end of the treatment (T1). The main outcome were: the Hoehn and Yahr scale; Unified Parkinson's Disease Rating Scale (UPDRS) motor section III, Mini Mental State Examination (MMSE), Freezing of gait Questionnaire (FOG-Q), Timed Up&Go Test (TUG), Ten meters walking test (steps and seconds) (10 MWT), Berg Balance Scale (BBS), the 39-items Parkinson's Disease Questionnaire (PDQ-39), Short-Form 12-items Healthy Survey (SF-12) and Functional Independence Measure (FIM). Action observation training was feasible, acceptable, safe, and the participants completed 100% of the prescribed training sessions. The statistical analysis performed by the t -test of the T1 vs. T0 showed statistically significant improvements for UPDRS motor section III P = 0.0082, SF12 MCS P = 0.0007, FOG Q P = 0.0030, PDQ39 P = 0.100 and for P300LD P = 0.0077. No statistically significant improvements for other scales were found. AO is a feasible and safe form of rehabilitative exercise for cognitively intact people with mild PD. Further investigation regarding the long-time effectiveness of robot training is warranted.

The clinical significance of 10-m walk test standardizations in Parkinson\u2019s disease

BackgroundThe 10-m walk test (10MWT) is a widely used measure of gait speed in Parkinson’s disease (PD). However, it is unclear if different standardizations of its conduct impact test results.Aim of the studyWe examined the clinical significance of two aspects of the standardization of the 10MWT in mild PD: static vs. dynamic start, and a single vs. repeated trials. Implications for fall prediction were also explored.Methods151 people with PD (mean age and PD duration, 68 and 4 years, respectively) completed the 10MWT in comfortable gait speed with static and dynamic start (two trials each), and gait speed (m/s) was recorded. Participants then registered all prospective falls for 6 months.ResultsAbsolute mean differences between outcomes from the various test conditions ranged between 0.016 and 0.040 m/s (effect sizes, 0.06–0.14) with high levels of agreement (intra-class correlation coefficients, 0.932–0.987) and small standard errors of measurement (0.032–0.076 m/s). Receiver operating characteristic curves showed similar discriminate abilities for prediction of future falls across conditions (areas under curves, 0.70–0.73). Cut-off points were estimated at 1.1–1.2 m/s.ConclusionsDifferent 10MWT standardizations yield very similar results, suggesting that there is no practical need for an acceleration distance or repeated trials when conducting this test in mild PD.

Abnormalities of age-related T cell senescence in Parkinson\u2019s disease

BackgroundA wealth of evidence implicates both central and peripheral immune changes as contributing to the pathogenesis of Parkinson’s disease (PD). It is critical to better understand this aspect of PD given that it is a tractable target for disease-modifying therapy. Age-related changes are known to occur in the immune system (immunosenescence) and might be of particular relevance in PD given that its prevalence rises with increasing age. We therefore sought to investigate this with respect to T cell replicative senescence, a key immune component of human ageing.MethodsPeripheral blood mononuclear cells were extracted from blood samples from 41 patients with mild PD (Hoehn and Yahr stages 1–2, mean (SD) disease duration 4.3 (1.2) years) and 41 age- and gender-matched controls. Immunophenotyping was performed with flow cytometry using markers of T lymphocyte activation and senescence (CD3, CD4, CD8, HLA-DR, CD38, CD28, CCR7, CD45RA, CD57, CD31). Cytomegalovirus (CMV) serology was measured given its proposed relevance in driving T cell senescence.ResultsMarkers of replicative senescence in the CD8+ population were strikingly reduced in PD cases versus controls (reduced CD57 expression (p = 0.005), reduced percentage of ‘late differentiated’ CD57loCD28hi cells (p = 0.007) and ‘TEMRA’ cells (p = 0.042)), whilst expression of activation markers (CD28) was increased (p = 0.005). This was not driven by differences in CMV seropositivity. No significant changes were observed in the CD4 population.ConclusionsThis study demonstrates for the first time that the peripheral immune profile in PD is distinctly atypical for an older population, with a lack of the CD8+ T cell replicative senescence which characterises normal ageing. This suggests that ‘abnormal’ immune ageing may contribute to the development of PD, and markers of T cell senescence warrant further investigation as potential biomarkers in this condition.