Parkinson's Disease Rating Research Articles

Automatic labeling of Parkinson's Disease gait videos with weak supervision.

Motor dysfunction in Parkinson's Disease (PD) patients is typically assessed by clinicians employing the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Such comprehensive clinical assessments are time-consuming, expensive, semi-subjective, and may potentially result in conflicting labels across different raters. To address this problem, we propose an automatic, objective, and weakly-supervised method for labeling PD patients' gait videos. The proposed method accepts videos of patients and classifies their gait scores as normal (Gait score in MDS-UPDRS = 0) or PD (MDS-UPDRS ≥ 1). Unlike previous work, the proposed method does not require a priori MDS-UPDRS ratings for training, utilizing only domain-specific knowledge obtained from neurologists. We propose several labeling functions that classify patients' gait and use a generative model to learn the accuracy of each labeling function in a self-supervised manner. Since results depended upon the estimated values of the patients' 3D poses, and existing pre-trained 3D pose estimators did not yield accurate results, we propose a weakly-supervised 3D human pose estimation method for fine-tuning pre-trained models in a clinical setting. Using leave-one-out evaluations, the proposed method obtains an accuracy of 89% on a dataset of 29 PD subjects - a significant improvement compared to previous work by 7%-10% depending upon the dataset. The method obtained state-of-the-art results on the Human3.6M dataset. Our results suggest that the use of labeling functions may provide a robust means to interpret and classify patient-oriented videos involving motor tasks.

Video-Based Activity Recognition for Automated Motor Assessment of Parkinson's Disease.

Over the last decade, video-enabled mobile devices have become ubiquitous, while advances in markerless pose estimation allow an individual's body position to be tracked accurately and efficiently across the frames of a video. Previous work by this and other groups has shown that pose-extracted kinematic features can be used to reliably measure motor impairment in Parkinson's disease (PD). This presents the prospect of developing an asynchronous and scalable, video-based assessment of motor dysfunction. Crucial to this endeavour is the ability to automatically recognise the class of an action being performed, without which manual labelling is required. Representing the evolution of body joint locations as a spatio-temporal graph, we implement a deep-learning model for video and frame-level classification of activities performed according to part 3 of the Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS). We train and validate this system using a dataset of n = 7310 video clips, recorded at 5 independent sites. This approach reaches human-level performance in detecting and classifying periods of activity within monocular video clips. Our framework could support clinical workflows and patient care at scale through applications such as quality monitoring of clinical data collection, automated labelling of video streams, or a module within a remote self-assessment system.

How sleep quality affects activities of daily living in Parkinson's disease: the mediating role of disease severity and the moderating role of cognition.

The aim of this study was to explore the influential mechanism of the relationship between sleep quality and activities of daily living (ADL) in patients with Parkinson's disease (PD), we hypothesized disease severity as a mediator and assumed the mediating process was regulated by cognition. 194 individuals with PD (95 women and 99 men) were enrolled in study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality of PD patients. Patients' ADL, disease severity and cognition were measured by the Unified Parkinson's Disease Rating Scale-II (UPDRSII), Hoehn-Yahr (H-Y) Scale, and Mini-Mental State Examination (MMSE). We investigated the mediating role of disease severity and the moderating effect of cognition on the association between sleep quality and ADL in PD patients. The score of UPDRSII was positively correlated with the score of PSQI and H-Y stage, while the score of MMSE was negatively correlated with the score of H-Y stage and UPDRSII. Sleep quality predicts disease severity, and disease severity predicts ADL. Disease severity mediated the relationship between sleep quality and ADL, and the mediating effect was 0.179. Cognition alone did not affect ADL, but the interaction between disease severity and cognition was significantly affected ADL, confirming the moderating effect of cognition in PD patients. Disease severity mediated the association between sleep quality and ADL, good cognition significantly reduced disease severity's mediating influence on the relationship between sleep quality and ADL. Our study indicated a close relationship between ADL and sleep and cognition in PD, and also provided new insights into the overall management of PD and a better quality of life of PD patients.

Parkinson's Disease Tremor Differentially Responds to Levodopa and Subthalamic Stimulation.

Tremor in Parkinson's disease (PD) has an inconsistent response to levodopa and subthalamic deep brain stimulation (STN-DBS). To identify predictive factors of PD tremor responsiveness to levodopa and STN-DBS. PD patients with upper limb tremor who underwent STN-DBS were included. The levodopa responsiveness of tremor (overall, postural, and rest sub-components), was assessed using the relevant Unified Parkinson's Disease Rating Scale-III items performed during the preoperative assessment. Post-surgical outcomes were similarly assessed ON and OFF stimulation. A score for the rest/postural tremor ratio was used to determine the influence of rest and postural tremor severity on STN-DBS outcome. Factors predictive of tremor responsiveness were determined using multiple linear regression modeling. Volume of tissue activated measurement coupled to voxel-based analysis was performed to identify anatomical clusters associated with motor symptoms improvement. One hundred and sixty five patients were included in this study. Male gender was negatively correlated with tremor responsiveness to levodopa, whereas the ratio of rest/postural tremor was positively correlated with both levodopa responsiveness and STN-DBS tremor outcome. Clusters corresponding to improvement of tremor were in the subthalamic nucleus, the zona incerta and the thalamus, whereas clusters corresponding to improvement for akinesia and rigidity were located within the subthalamic nucleus. More severe postural tremor and less severe rest tremor were associated with both poorer levodopa and STN-DBS response. The different locations of clusters associated with best correction of tremor and other parkinsonian features suggest that STN-DBS effect on PD symptoms is underpinned by the modulation of different networks.

Correlation of glymphatic system abnormalities with Parkinson's disease progression: a clinical study based on non-invasive fMRI.

The glymphatic system is reportedly involved in Parkinson's disease (PD). Based on previous studies, we aimed to confirm the correlation between the glymphatic system and PD progression by combining two imaging parameters, diffusion tensor image analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). Fifty-one PD patients and fifty healthy control (HC) were included. Based on the Hoehn-Yahr scale, the PD group was divided into early-stage and medium-to late-stage. All PD patients were scored using the Unified PD Rating Scale (UPDRS). We assessed the DTI-ALPS indices in the bilateral hemispheres and EPVS numbers in bilateral centrum semiovale (CSO), basal ganglia (BG), and midbrain. The DTI-ALPS indices were significantly lower bilaterally in PD patients than in the HC group, and EPVS numbers in any of the bilateral CSO, BG, and midbrain were significantly higher, especially for the medium- to late-stage group and the BG region. In PD patients, the DTI-ALPS index was significantly negatively correlated with age, while the BG-EPVS numbers were significantly positively correlated with age. Furthermore, the DTI-ALPS index was negatively correlated with UPDRS II and III scores, while the BG-EPVS numbers were positively correlated with UPDRS II and III scores. Similarly, the correlation was more pronounced in the medium- to late-stage group. The DTI-ALPS index and EPVS numbers (especially in the BG region) are closely related to age and PD progression and can serve as non-invasive assessments for glymphatic dysfunction and its interventions in clinical studies.

Retinal Thinning as a Marker of Disease Severity in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.

Theory of mind deficits in Parkinson's disease are not modulated by dopaminergic medication.

Patients with Parkinson's disease (PD) exhibit deficits in social cognition, particularly with respect to Theory of Mind (ToM) capacities. It is unclear whether they are associated with PD-related dopamine deficiency and modulated by levodopa replacement therapy. A total of 15 persons with PD and 13 healthy controls (HC) participated in the study. They performed different neuropsychological tasks, including the Faux Pas Recognition Test (FPRT), assessing different dimensions of cognitive ToM (e.g., detection, inappropriateness, intentions), and the Reading the Mind in the Eyes Test (RMET) as an index of affective ToM. Persons with PD were tested twice, once under their regular treatment and another time after at least 18 h of levodopa withdrawal (MED-ON and MED-OFF, respectively). On either occasion, serum drug levels and motor symptom severity [Unified Parkinson's Disease Rating Scale (UPDRS)] were measured. MED-ON and MED-OFF conditions in patients with PD were confirmed by higher serum drug levels in the former than in the latter state and a corresponding amelioration of the motor deficit. In so doing, no performance difference in any ToM-related task was identified as a function of the levodopa therapy. Generally, patients performed worse than controls in both affective and cognitive ToM tests. Patients with PD have deficits in cognitive and affective ToM. Dopamine replacement, effective for improving the motor condition, does not appear to counteract these dysfunctions.

Cholinergic innervation topography in GBA-associated de novo Parkinson's disease patients.

The most common genetic risk factors for Parkinson's disease are GBA1 mutations, encoding the lysosomal enzyme glucocerebrosidase. Patients with GBA1 mutations (GBA-PD) exhibit earlier age of onset and faster disease progression with more severe cognitive impairments, postural instability and gait problems. These GBA-PD features suggest more severe cholinergic system pathologies. PET imaging with the vesicular acetylcholine transporter ligand 18F-F-fluoroethoxybenzovesamicol (18F-FEOBV PET) provides the opportunity to investigate cholinergic changes and their relationship to clinical features in GBA-PD. The study investigated 123 newly diagnosed, treatment-naïve Parkinson's disease subjects-with confirmed presynaptic dopaminergic deficits on PET imaging. Whole-gene GBA1 sequencing of saliva samples was performed to evaluate GBA1 variants. Patients underwent extensive neuropsychological assessment of all cognitive domains, motor evaluation with the Unified Parkinson's Disease Rating Scale, brain MRI, dopaminergic PET to measure striatal-to-occipital ratios of the putamen and 18F-FEOBV PET. We investigated differences in regional cholinergic innervation between GBA-PD carriers and non-GBA1 mutation carriers (non-GBA-PD), using voxel-wise and volume of interest-based approaches. The degree of overlap between t-maps from two-sample t-test models was quantified using the Dice similarity coefficient. Seventeen (13.8%) subjects had a GBA1 mutation. No significant differences were found in clinical features and dopaminergic ratios between GBA-PD and non-GBA-PD at diagnosis. Lower 18F-FEOBV binding was found in both the GBA-PD and non-GBA-PD groups compared to controls. Dice (P < 0.05, cluster size 100) showed good overlap (0.7326) between the GBA-PD and non-GBA-PD maps. GBA-PD patients showed more widespread reduction in 18F-FEOBV binding than non-GBA-PD when compared to controls in occipital, parietal, temporal and frontal cortices (P < 0.05, FDR-corrected). In volume of interest analyses (Bonferroni corrected), the left parahippocampal gyrus was more affected in GBA-PD. De novo GBA-PD show a distinct topography of regional cholinergic terminal ligand binding. Although the Parkinson's disease groups were not distinguishable clinically, in comparison to healthy controls, GBA-PD showed more extensive cholinergic denervation compared to non-GBA-PD. A larger group is needed to validate these findings. Our results suggest that de novo GBA-PD and non-GBA-PD show differential patterns of cholinergic system changes before clinical phenotypic differences between carriers versus non-carrier groups are observable.

Exploring Potential Predictors of Treadmill Training Effects in People With Parkinson Disease

ObjectiveTo explore the potential predictors of people with Parkinson disease (PD) who would benefit the most from treadmill training. DesignA cohort study. SettingMedical university rehabilitation settings. ParticipantsSeventy participants diagnosed of idiopathic PD. InterventionsTwelve sessions of treadmill training. Main Outcome MeasuresHierarchical logistic regression models were used to explore significant predictors of the treadmill training effect with respect to 3 health domains: Unified Parkinson's Disease Rating Scales part III (UPDRS III); gait speed; Parkinson's Disease Questionnaire-39 (PDQ-39). A receiver operating characteristic (ROC) curve analysis was conducted to identify proper cut-off points for clinical use. ResultsMale sex (adjusted odds ratio [OR]: 3.73, P=.036) significantly predicted the improvement of UPDRS III. Individuals with a slower baseline gait speed (cut-off: 0.92 m/s, adjusted OR: 14.06, P<.001) and higher baseline balance confidence measured by the Activity-specific Balance Confidence scale (cut-off: 84.5 points, adjusted OR: 4.66, P=.022) have greater potential to achieve clinically relevant improvements in gait speed. A poorer baseline PDQ-39 score (cut-off: 23.1, adjusted OR: 7.47, P<.001) predicted a greater quality of life improvement after treadmill training. ConclusionsThese findings provide a guideline for clinicians to easily identify suitable candidates for treadmill training. Generalization to more advanced patients with PD warrants further investigation.

Brain olfactory-related atrophy in isolated rapid eye movement sleep behavior disorder.

To investigate structural and functional connectivity changes in brain olfactory-related structures in a longitudinal prospective cohort of isolated REM sleep behavior disorder (iRBD) and their clinical correlations, longitudinal evolution, and predictive values for phenoconversion to overt synucleinopathies, especially Lewy body diseases. The cohort included polysomnography-confirmed iRBD patients and controls. Participants underwent baseline assessments including olfactory tests, neuropsychological evaluations, the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, 3T brain MRI, and 18 F-FP-CIT PET scans. Voxel-based morphometry (VBM) was performed to identify regions of atrophy in iRBD, and volumes of relevant olfactory-related regions of interest (ROI) were estimated. Subgroups of patients underwent repeated volumetric MRI and resting-state functional MRI (fMRI) scans after four years. A total of 51 iRBD patients were included, with 20 of them converting to synucleinopathy (mean time to conversion 3.08 years). Baseline VBM analysis revealed atrophy in the right olfactory cortex and gyrus rectus in iRBD. Subsequent ROI comparisons with controls showed atrophy in the amygdala. These olfactory-related atrophies tended to be associated with worse depression, anxiety, and urinary problems in iRBD. Amygdala 18 F-FP-CIT uptake tended to be reduced in iRBD patients with hyposmia (nonsignificant after multiple comparison correction) and correlated with urinary problems. Resting-state fMRI of 23 patients and 32 controls revealed multiple clusters with aberrant olfactory-related functional connectivity. Hypoconnectivity between the putamen and olfactory cortex was associated with mild parkinsonian signs in iRBD. Longitudinal analysis of volumetric volumetric MRI in 22 iRBD patients demonstrated four-year progression of olfactory-related atrophy. Cox regression analysis revealed that this atrophy significantly predicted phenoconversion. Progressive atrophy of central olfactory structures may be a potential indicator of Lewy body disease progression in iRBD.

Chronic cadmium exposure induces Parkinson-like syndrome by eliciting sphingolipid disturbance and neuroinflammation in the midbrain of C57BL/6J mice

Cadmium (Cd) is known as a widespread environmental neurotoxic pollutant. Cd exposure is recently recognized as an etiological factor of Parkinson's disease (PD) in humans. However, the mechanism underlying Cd neurotoxicity in relation to Parkinsonism pathogenesis is unclear. In our present study, C57BL/6 J mice were exposed to 100 mg/L CdCl2 in drinking water for 8 weeks. It was found Cd exposure caused motor deficits, decreased DA neurons and induced neuropathological changes in the midbrain. Non-targeted lipidomic analysis uncovered that Cd exposure altered lipid profile, increased the content of proinflammatory sphingolipid ceramides (Cer), sphingomyelin (SM) and ganglioside (GM3) in the midbrain. In consistency with increased proinflammatory lipids, the mRNA levels of genes encoding sphingolipids biosynthesis in the midbrain were dysregulated by Cd exposure. Neuroinflammation in the midbrain was evinced by the up-regulation of proinflammatory cytokines at mRNA and protein levels. Blood Cd contents and lipid metabolites in Parkinsonism patients by ICP-MS and LC-MS/MS analyses demonstrated that elevated blood Cd concentration and proinflammatory lipid metabolites were positively associated with the score of Unified Parkinson's Disease Rating Scale (UPDRS). 3 ceramide metabolites in the blood showed good specificity as the candidate biomarkers to predict and monitor Parkinsonism and Cd neurotoxicity (AUC>0.7, p < 0.01). In summary, our present study uncovered that perturbed sphingomyelin lipid metabolism is related to the Parkinsonism pathogenesis and Cd neurotoxicity, partially compensated for the deficiency in particular metabolic biomarkers for Parkinsonism in relation to Cd exposure, and emphasized the necessity of reducing Cd exposure at population level.

Identifying prodromal symptoms at high specificity for Parkinson's disease.

To test drugs with the potential to prevent the onset of Parkinson's disease (PD), it is key to identify individuals in the general population at high risk of developing PD. This is often difficult because most of the clinical markers are non-specific, common in PD but also common in older adults (e.g., sleep problems). We aimed to identify the clinical markers at high specificity for developing PD by comparing individuals with PD or prodromal PD to healthy controls. We investigated motor and non-motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale Part 1 and 2 items) in 64 prodromal PD and 422 PD individuals calculating the odds ratios, adjusting for age and gender, for PD and prodromal PD versus 195 healthy controls. Symptoms at high specificity were defined as having an adjusted odds ratio ≥ 6. Constipation had an adjusted odds ratio, 6.14 [95% CI: 2.94-12.80] showing high specificity for prodromal PD, and speech difficulties had an adjusted odds ratio, 9.61 [95% CI: 7.88-48.81] showing high specificity for PD. The proportion of participants showing these specific markers was moderate (e.g., prevalence of constipation was 43.75% in prodromal PD, and speech difficulties was 33.89% in PD), suggesting these symptoms may make robust predictors of prodromal PD and PD, respectively. Clinical markers at high specificity for developing PD could be used as tools in the screening of general populations to identify individuals at higher risk of developing PD.

Parkinson Hastalığının İlerlemesini Tahmin Etmek: Ses Girişlerinden Yararlanan İnvazif Olmayan Bir Yöntem

Parkinson's Disease (PD) is a complex neurodegenerative condition with a global impact, demanding precise disease progression prediction to facilitate effective treatment strategies. To assess PD symptoms, the Unified Parkinson's Disease Rating Scale (UPDRS) is widely adopted, encompassing both motor and non-motor assessments. This research delves into voice inputs as a non-intrusive method to predict total UPDRS and motor UPDRS scores, offering new possibilities for Parkinson's assessment. Feature engineering and data augmentation techniques address challenges related to class imbalance and diverse demographics, including an original imbalanced dataset with more females than males. Additionally, three new datasets are created: oversampled balanced, only-female, and only-male datasets. Ensemble-based stacking model, including random forest and extreme gradient boosting as base models and the gradient boosting regressor as the meta-regressor, demonstrate promising performance and robustness in predicting UPDRS scores, showcasing the efficacy of voice inputs for PD assessment. Furthermore, the feature importance analysis provides insights into crucial contributors influencing predictions. Various performance metrics, such as accuracy, mean squared error (MSE), root mean squared error (RMSE), mean absolute error (MAE), and R-squared (R2), are used to evaluate the model’s performance. Additionally, by incorporating telemonitoring capabilities, the voice-based approach offers the possibility of remote and continuous PD assessment, allowing for real-time monitoring and early detection. This advancement could significantly improve the quality of life for PD patients and facilitate more personalized and effective treatment plans.

Effect of Zishen pingchan granules combined with pramipexole on serum BDNF, IL-1β, IL-6, CRP, TNF-α levels in depressed patients with Parkinson's disease: Results of a randomized, double-blind, controlled study

IntroductionDepression is a common comorbidity in Parkinson's Disease (PD) and treatment of depression can significantly support PD management. Zishen pingchan granules (ZPG), a traditional Chinese herbal formula, may help ameliorate depressive symptoms in PD patients. However, the molecular mechanisms underlying the effects of ZPG remain unclear. This study aimed to investigate the impact of ZPG on serum levels of brain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in PD patients with depression. MethodsEighty PD patients treated with pramipexole but still experiencing mild to moderate depression symptoms were randomly allocated to a group receiving 12-week ZPG treatment (n = 40) or placebo (n = 40). The Hamilton Depression Scale 17 items (HAM-D-17) was utilized to evaluate changes in depressive symptoms from baseline over 12 weeks, while the Unified Parkinson's Disease Rating Scales (UPDRS) part 3 was employed to assess changes in motor symptoms over the same duration. Serum levels of BDNF, IL-1β, IL-6, CRP, and TNF-α were measured at baseline and post-treatment. ResultsSeventy-one participants completed the study. Following treatment, both groups showed significantly reduced HAMD scores. The placebo group demonstrated a decrease in BDNF levels, while the ZPG group showed an increase in IL-6 levels post-treatment. In the examination of the group-time interaction, the ZPG group exhibited a greater decrease in HAMD scores and increase in IL-6 levels compared to the placebo group. Conversely, the placebo group showed a greater decrease in BDNF levels compared to the ZPG group. However, no significant group differences were observed in UPDRS part 3 change scores or serum levels of IL-1β, CRP, or TNF-α change from baseline. ConclusionZPG may potentially ameliorate depressive symptoms in PD patients, with the potential mechanism involving mitigation of reductions in serum BDNF level and an increase in IL-6 level.

Unilateral anterior capsulotomy combined with deep brain stimulation for Parkinson's disease psychosis and motor dysfunctions

Psychosis is a frequent and debilitating non-motor symptom of Parkinson's disease (PD). This study aimed to evaluate the availability of unilateral anterior capsulotomy combined with subthalamic nucleus deep brain stimulation (STN-DBS) in managing advanced PD patients comorbid with psychosis. Five advanced PD patients with psychosis who had been treated with unilateral anterior capsulotomy combined with bilateral STN-DBS were assessed. The positive subscore of the Positive and Negative Syndrome Scale (PANSS) and the Unified Parkinson's Disease Rating Scale III (UPDRS-III) were used to assess the efficacy parameter of psychosis and the improved motor symptoms, respectively. The quality of life (QoL) was accessed by an 8-item Parkinson's disease Questionnaire (PDQ-8). Clinical outcome assessments were performed at baseline and follow-ups after one or two years. Significant improvement was observed in PD patients during follow-up after the combined treatment. The positive subscore of PANSS improved by 13.4 (5.7) (mean (SD), p = 0.006). Item P1 (delusions) and Item P3 (hallucinations) of the PANSS improved by 5.0 (0.71) (p < 0.0001) and 3.6 (0.89) (p = 0.0008), respectively. Furthermore, the motor symptoms improved by 32.4 (5.7) (UPDRS-III, p = 0.0002), and the QoL improved by 6.4 (3.8) (PDQ-8, p = 0.021). No significant side effects or complications occurred during the study. For advanced PD patients with refractory psychosis, unilateral anterior capsulotomy combined with bilateral STN-DBS improved PD psychosis and motor dysfunction, providing an effective therapeutic option for such patients.

The correlation between nutritional status, body composition, and symptoms in Parkinson's disease patients

Objective: To investigate the relationship between nutritional status, body composition and symptoms of Parkinson's disease (PD). Methods: The study was conducted among 102 PD patients between November 2020 to April 2021 in the outpatient and inpatient of Neurology department of the Second Affiliated Hospital of Suzhou University. Basic data, such as age, gender, course of disease and Hoehn-Yahr (H-Y) stage of the patients, were collected. In the "open" state, the Unified Parkinson's Disease Rating Scale (UPDRS) and other scales were used to evaluate the clinical symptoms of PD patients. The nutritional status of PD patients was evaluated by the micro-nutrition rating Scale (MNA), and the body composition data of PD patients was measured by the body composition analyzer.The patients were divided into three groups according to the MNA: well-nourished group(45 cases), malnutrition-risk group (43 cases)and malnutrition group(14 cases). Body composition, laboratory tests, bone density, and symptoms of PD were compared among the three groups. Results: Among 102 PD patients, 48 were males (47.1%) and 54 were females (52.9%), aged 42-86 (66±9) years old. Compared with the malnutrition-risk group, lymphocytes in the malnutrition group [(1.45±0.48) × 109/L vs (1.76±0.43)×109/L], uric acid [(227±54) μmol/L vs (282±63) μmol/L] were all low, and the difference was statistically significant (all P<0.05). Compared with the well-nourished group, hemoglobin [(125±17) g/L vs (136±14) g/L], prealbumin [(0.23±0.05) g/L vs (0.27±0.06) g/L], and uric acid [(227±54) μmol/L vs (312±76) μmol/L] and Retinol binding protein [(33±7) mg/L were lower than (39±10) mg/L] in the malnutrition group, the difference was statistically significant (P<0.05). Except for the visceral fat area and body fat percentages, there was no significant difference in body composition indexes and bone mineral density T-value between the malnutrition-risk and malnutrition groups (P<0.05). Compared with the well-nourished group, the body fat [(16±6) kg vs (20±6) kg], the percentage of body fat [(26±9)% vs (29±7)%], the waist-hip ratio [(0.86±0.05) vs (0.89±0.05)], and the upper arm circumference [(29.00±2.59) cm vs (30.74±2.75) cm] in the malnutrition risk group were lower, and the difference was statistically significant (P<0.05). There were statistically significant differences in all body composition indicators and T-values of bone density between the malnourished and well nourished groups (all P<0.05). The MNA score of PD patients was negatively correlated with UPDRS Ⅰ, UPDRS Ⅱ, and UPDRS Ⅳ scores (r=-0.347, -0.364, -0.303, all P<0.05); Body composition indicators: total body water and inorganic salts were negatively correlated with UPDRS-I (r=-0.206, -0.223, all P<0.05), and body fat was negatively correlated with levodopa Equivalent dose (LED) (r=-0.209, P<0.05) Conclusions: The malnutrition risk and incidence of malnutrition in PD patients are high; lymphocyte, uric acid, hemoglobin, Retinol binding protein, body composition and bone mineral density were low in malnutrition group. MNA score of PD patients was negatively correlated with Parkinson's disease symptoms.

Diagnostic value of plasma SIRT1 levels and whole-brain gray matter volume in Parkinson's disease patients with cognitive impairment.

This study was designed to investigate the diagnostic value of plasma SIRT1 levels and whole-brain gray matter (GM) volume in Parkinson's disease (PD) patients with cognitive impairment. Automated enzymatic analysis was performed to measure plasma SIRT1 levels in 80 healthy controls and 77 PD patients. Motor symptoms and nonmotor symptoms in PD patients were assessed using the corresponding scales. A Siemens MAGNETOM Prisma 3T MRI scanner was used to acquire images in 35 of 77 PD patients. Plasma SIRT1 levels in PD patients were lower than those in healthy controls. Plasma SIRT1 levels were negatively correlated with the age, Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores, anxiety, depression, excessive daytime sleepiness (EDS), quality of life, and especially cognitive impairment. Thus, it showed that plasma SIRT1 levels were relevant to visuospatial/executive function, memory, and language. Receiver-operating characteristic (ROC) analysis confirmed that plasma SIRT1 levels had good diagnostic accuracy for PD with anxiety and EDS. Furthermore, plasma SIRT1 levels had a significant positive correlation with GM volume in the whole brain, and ROC analysis confirmed that plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment. This study showed that plasma SIRT1 levels were correlated with the nonmotor symptoms of anxiety, depression, EDS, and especially cognitive impairment as well as the total GM volume. Furthermore, the combination of plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment.

Association between metabolic syndrome and progression in Parkinson's disease

BackgroundParkinson's disease (PD) and metabolic syndrome are separate entities that share common underlying pathophysiology. Management strategy for metabolic syndrome is clinically better characterized and finding a positive clinical correlation between the two could lead to a better understanding of Parkinson's disease progression and prognosis. PurposeTo explore the relationship between progression in PD and metabolic syndrome to characterize the underlying pathophysiology, which could then impact the clinical management of PD. MethodsUsing modified NCEP (National Cholesterol Education Program) ATP III (Adult Treatment Plan) criteria, patients enrolled in STEADY-PD III (Safety, Tolerability, and Efficacy Assessment of Isradipine) were classified into one of three categories of metabolic syndrome and compared on PD progression over a period of 3 years. ResultsParticipants with metabolic syndrome showed a trend for more progression in terms of PD, as measured by the total Unified Parkinson's Disease Rating Scale (UPDRS), the motor EDL (Experiences of daily living) scores of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and the Montreal Cognitive Assessment (MoCA). A significant trend for decline in MoCA was found in the group with metabolic syndrome (−0.78), compared with those without metabolic syndrome (0.14). Greater decline in MoCA signifies worse outcomes. ConclusionThe results demonstrate a trend in more clinical progression in PD in subjects with metabolic syndrome. However, results are limited by the sample size and the limited laboratory measurements available. We hope this study will encourage larger sample studies to explore this relationship further.

Sex, myelin, and clinical characteristics of Parkinson's disease.

To determine if there are sex differences in myelin in Parkinson's disease, and whether these explain some of the previously-described sex differences in clinical presentation. Thirty-three subjects (23 males, 10 females) with Parkinson's disease underwent myelin water fraction (MWF) imaging, an MRI scanning technique of in vivo myelin content. MWF of 20 white matter regions of interest (ROIs) were assessed. Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Principal component analysis, logistic and multiple linear regressions, and t-tests were used to determine which white matter ROIs differed between sexes, the clinical features associated with these myelin changes, and if overall MWF and MWF laterality differed between males and females. Consistent with prior reports, tremor and bradykinesia were more likely seen in females, whereas rigidity and axial symptoms were more likely seen in males in our cohort. MWF of the thalamic radiation, cingulum, cingulum hippocampus, inferior fronto-occipital fasciculi, inferior longitudinal fasciculi, and uncinate were significant in predicting sex. Overall MWF and asymmetry of MWF was greater in males. MWF differences between sexes were associated with tremor symptomatology and asymmetry of motor performance. Sex differences in myelin are associated with tremor and asymmetry of motor presentation. While preliminary, our results suggest that further investigation of the role of biological sex in myelin pathology and clinical presentation in Parkinson's disease is warranted.

Treadmill Training Plus Semi-Immersive Virtual Reality in Parkinson's Disease: Results from a Pilot Study.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders that causes postural instability and gait alterations, such as reduced walking speed, shorter step length, and gait asymmetry, exposing patients to a higher risk of falling. Recently, virtual reality (VR) was added to a treadmill, in order to promote motor functional recovery and neuroplastic processes. Twenty PD patients were enrolled and randomly assigned to two groups: the experimental group (EG) and the control group (CG). In particular, patients in the EG were trained with the C-Mill, an innovative type of treadmill, which is equipped with semi-immersive VR, whereas the CG performed conventional physiotherapy. Patients in both groups were evaluated through a specific motor assessment battery at baseline (T0) and after the training (T1). Comparing pre-(T0) and post-(T1) treatment scores, in the EG, we found statistical significances in the following outcome measures: 6 Minutes Walking Test (6MWT) (p < 0.0005), Timed up and go (TUG right) (p < 0.03), Berg Balance Scale (BBS) (p < 0.006), Tinetti Scale (TS) (p < 0.002), Falls Efficacy Scale- International (FES-I), (p < 0.03) Unified PD Rating Scale-III (UPDRS) (p < 0.002), and Functional Independence Measure (FIM) (p < 0.004). Also, the CG showed statistical significances after the training. Between-group (EG and CG) analysis showed significative statistical differences in 6MWT (p < 0.006), BBS (p < 0.006), TS (p < 0.008), FES-I (p < 0.01), and FIM (p < 0.009). From our results it emerges that both groups (EG and CG) achieved better outcome scores after the treatment, suggesting that both physiotherapy interventions were effective. However, the EG training using VR seemed to have induced more improvements, especially in gait and balance skills. Then, C-Mill could be a valid adjunctive treatment in the context of gait and balance disturbances, which are very common in the PD population.