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• Measurement of underlying movement-related electro-cortical activity during sinusoidal GVS. • GVS-related alterations to the Bereitschaftspotential and mu-rhythm. • Potential for GVS to improve functional limb movement in Parkinson's disease. We recently showed that vestibular stimulation can produce a long-lasting alleviation of motor features in Parkinson's disease. Here we investigated whether components of the motor related cortical response that are commonly compromised in Parkinson's – the Bereitschaftspotential and mu-rhythm event-related desynchronization – are modulated by concurrent, low frequency galvanic vestibular stimulation (GVS) during repetitive limb movement amongst 17 individuals with idiopathic Parkinson's disease. Relative to sham, GVS was favourably associated with higher amplitudes during the late and movement phases of the Bereitschaftspotential and with a more pronounced decrease in spectral power within the mu-rhythm range during finger-tapping. These data increase understanding of how GVS interacts with the preparation and execution of voluntary movement and give added impetus to explore its therapeutic effects on Parkinsonian motor features. [ABSTRACT FROM AUTHOR]

Background Speech impairments are common with Parkinson’s disease (reported prevalence 68%), increasing conversational demands, reliance on family and social withdrawal. Objective(s) The PD COMM trial compared the clinical and cost-effectiveness of two speech and language therapy approaches: Lee Silverman Voice Treatment LOUD and National Health Service speech and language therapy for the treatment of speech or voice problems in people with Parkinson’s disease to no speech and language therapy (control) and against each other. Design PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Participants were randomised in a 1 : 1 : 1 ratio to control, National Health Service speech and language therapy or Lee Silverman Voice Treatment LOUD via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Mixed-methods process and health economic evaluations were conducted. Setting United Kingdom outpatient and home settings. Participants People with idiopathic Parkinson’s disease, with self-reported or carer-reported speech or voice problems. We excluded people with dementia, laryngeal pathology and those within 24 months of previous speech and language therapy. Interventions The Lee Silverman Voice Treatment LOUD intervention included maximum effort drills and high-effort speech production tasks delivered over four 50-minute therapist-led personalised sessions per week, for 4 weeks with prescribed daily home practice. National Health Service speech and language therapy content and dosage reflected local non-Lee Silverman Voice Treatment speech and language therapy practices, usually 1 hour, once weekly, for 6 weeks. Trained, experienced speech and language therapists or assistants provided interventions. The control was no speech and language therapy until the trial was completed. Main outcome measures Primary outcome: Voice Handicap Index total score at 3 months. Secondary outcomes: Voice Handicap Index subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5L; ICEpop Capabilities Measure for Older Adults; Parkinson’s Disease Questionnaire – Carers; resource utilisation; and adverse events. Assessments were completed pre-randomisation and at 3, 6 and 12 months post randomisation. Results Three hundred and eighty-eight participants were randomised to Lee Silverman Voice Treatment LOUD (n = 130), National Health Service speech and language therapy (n = 129) and control (n = 129). The impact of voice problems at 3 months after randomisation was lower for Lee Silverman Voice Treatment LOUD participants than control [−8.0 (99% confidence interval: −13.3, −2.6); p = 0.001]. There was no evidence of improvement for those with access to National Health Service speech and language therapy when compared to control [1.7 (99% confidence interval: −3.8, 7.1); p = 0.4]. Participants randomised to Lee Silverman Voice Treatment LOUD reported a lower impact of their voice problems than participants randomised to National Health Service speech and language therapy [99% confidence interval: −9.6 (−14.9, −4.4); p 70 years); disease severity measured using the Hoehn and Yahr staging (1.0–2.5, 3.0–5.0) and severity of speech measured using the Voice Handicap Index (VHI) total score (≤ 33, mild 34–44, moderate 45–61, severe > 61). To avoid any possibility of the treatment allocation becoming predictable, a random element was included within the randomisation process. Once the participant was randomised into the trial, they were given a unique trial identifier and the treatment allocation was confirmed by e-mail to the site. The primary outcome measure for the trial was patient-reported VHI total score at 3 months. The VHI measures the psychosocial consequences of voice disorders and provides an overall perception of effectiveness of voice-related communication. The VHI comprises of 30 questions (0–120 negatively scored) divided into emotional, functional and physical subscales (0–40 subscale score). Secondary outcomes were: the VHI subscales; the Parkinson’s Disease Questionnaire-39, a validated, health-related quality-of-life measure specific to PD; the Questionnaire on Acquired Speech Disorders, self-reported participation restriction related to speech and communication; the participant-rated EuroQol5D (5-level version) which provides a simple descriptive profile and a single index value for health status; the ICEpop Capabilities Measure for Older Adults (ICECAP-O), a measure of capability in older people for use in economic evaluations; a disease-specific participant resource usage questionnaire; carer quality of life, measured using the PD Questionnaire – carer; and adverse events. For participants in either SLT arm, any vocal strain or abuse believed to be associated with treatment was identified by the therapists at the participants’ SLT session and was reported in the adverse event log. All participant-reported resource usage forms completed for the trial were checked to ensure that no vocal strain or abuse had occurred in outpatient appointments with ENT specialists. At the 12-month clinical visit, the medical professional also checked whether any adverse events had occurred since entering the trial. There were two nested studies within this trial: a process evaluation and an economic evaluation. A process evaluation of the content of the interventions examined participants’ and therapists’ reported content of a subset of the two SLT interventions. Individual participant therapy data recorded by participants and therapists during the PD COMM trial were extracted from treatment record forms and therapy notes. Extraction category headings were piloted and reflected the Template for Intervention Description and Replication intervention reporting guidelines, with ongoing refinement as extraction progressed and components of the interventions were identified which were inadequately accounted for in the initial framework. The process evaluation of the implementation of the interventions used normalisation process theory which is highly attuned to the challenges of complex interventions as it encourages looking at systems as a whole. We considered that its conceptual framework would assist the interpretation and synthesis of data and analysis to explain what implementation processes took place and the interactions and gaps between the PD COMM interventions, the changing context, speech and language therapists and their practice. A within-trial economic evaluation in the form of cost–utility analysis was conducted from the perspective of the NHS. The primary results were expressed in terms of cost per quality-adjusted life-year (QALY) gained at 12 months for the three trial comparisons. Additional secondary analyses were performed from the NHS, personal social services perspective, broader societal perspective and using the capability approach, which uses broader measures of capability well-being. Results The mean age of participants in PD COMM was approximately 70 years old, and 74% were male (286/388). The mean duration of PD was between 5 and 6 years, with a broad range from newly diagnosed to over 30 years, and the majority (61%) were in Hoehn and Yahr stage of 2 or less (

Abstract Objectives This study aims to investigate the potential of radiomics with multiple parameters from conventional T1 weighted imaging (T1WI) and susceptibility weighted imaging (SWI) in distinguishing between idiopathic Parkinson’s disease (PD) and multiple system atrophy (MSA). Methods A total of 201 participants, including 57 patients with PD, 74 with MSA, and 70 healthy control (HCs) individuals, underwent T1WI and SWI scans. From the 12 subcortical nuclei (e.g. red nucleus, substantia nigra, subthalamic nucleus, putamen, globus pallidus, and caudate nucleus), 2640 radiomic features were extracted from both T1WI and SWI scans. Three classification models - logistic regression (LR), support vector machine (SVM), and light gradient boosting machine (LGBM) - were used to distinguish between MSA and PD, as well as among MSA, PD, and HC. These classifications were based on features extracted from T1WI, SWI, and a combination of T1WI and SWI. Five-fold cross-validation was used to evaluate the performance of the models with metrics such as sensitivity, specificity, accuracy, and area under the receiver operating curve (AUC). During each fold, the ANOVA and least absolute shrinkage and selection operator (LASSO) methods were used to identify the most relevant subset of features for the model training process. Results The LGBM model trained by the features combination of T1WI and SWI exhibited the most outstanding differential performance in both the three-class classification task of MSA vs. PD vs. HC and the binary classification task of MSA vs. PD, with an accuracy of 0.814 and 0.854, and an AUC of 0.904 and 0.881, respectively. The texture-based differences (GLCM) of the SN and the shape-based differences of the GP were highly effective in discriminating between the three classes and two classes, respectively. Conclusions Radiomic features combining T1WI and SWI can achieve a satisfactory differential diagnosis for PD, MSA, and HC groups, as well as for PD and MSA groups, thus providing a useful tool for clinical decision-making based on routine MRI sequences.

Abstract Background Freezing of gait (FOG) is one of the most debilitating symptoms in patients with idiopathic Parkinson’s disease (IPD). Visual cues can relieve FOG symptoms. However, there is no consensus on patient characteristics that can benefit from visual cues. Therefore, we examined the differences in IPD patient characteristics according to the effectiveness of visual cueing. Methods Through gait experiments, we investigated the number of FOG occurrences, average FOG period per episode, proportion of FOG duration in the total gait cycles, and FOG-free period gait spatiotemporal parameters in ten participants diagnosed with FOG due to IPD. Subsequently, the differences between their clinical characteristics and striatal dopamine active transporter availability from six subregions of the striatum were compared by dividing them into two groups based on the three reduction rates: occurrence numbers, mean durations per episode, and proportion of FOG duration in the total gait cycles improved by visual cueing using laser shoes. The relationships among these three reduction rates and other FOG-related parameters were also investigated using Spearman correlation analyses. Results According to the three FOG-related reduction rates, the group assignments were the same, which was also related to the baseline self-reported FOG severity score (New Freezing of Gait Questionnaire): the more severe the FOG, the poorer the response to the visual cueing. By visual cueing, the better response group demonstrated the characteristics of lower new FOG questionnaire total scores, higher dopamine active transporter availability of the anterior and posterior putamen, and shorter mean duration of FOG per episode in the absence of cueing. These results were replicated using Spearman correlation analyses. Conclusions For FOG symptoms following IPD, gait assistance by visual cueing may be more effective when the total NFOGQ score is lower and the DAT of putamen is higher. Through this study, we demonstrated clinical and striatal dopaminergic conditions to select patients who may be more likely to benefit from visual cueing with laser shoes, and these findings lead to the need for early diagnosis of FOG in patients with IPD. Trial registration ClinicalTrials.gov identifier: NCT05080413. Registered on September 14, 2021.

Objectives: This study aims to investigate the potential of radiomics with multiple parameters from conventional T1 weighted imaging (T1WI) and susceptibility weighted imaging (SWI) in distinguishing between idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA). Methods: A total of 201 participants, including 57 patients with PD, 74 with MSA, and 70 healthy control (HCs) individuals, underwent T1WI and SWI scans. From the 12 subcortical nuclei (e.g. red nucleus, substantia nigra, subthalamic nucleus, putamen, globus pallidus, and caudate nucleus), 2640 radiomic features were extracted from both T1WI and SWI scans. Three classification models - logistic regression (LR), support vector machine (SVM), and light gradient boosting machine (LGBM) - were used to distinguish between MSA and PD, as well as among MSA, PD, and HC. These classifications were based on features extracted from T1WI, SWI, and a combination of T1WI and SWI. Five-fold cross-validation was used to evaluate the performance of the models with metrics such as sensitivity, specificity, accuracy, and area under the receiver operating curve (AUC). During each fold, the ANOVA and least absolute shrinkage and selection operator (LASSO) methods were used to identify the most relevant subset of features for the model training process. Results: The LGBM model trained by the features combination of T1WI and SWI exhibited the most outstanding differential performance in both the three-class classification task of MSA vs. PD vs. HC and the binary classification task of MSA vs. PD, with an accuracy of 0.814 and 0.854, and an AUC of 0.904 and 0.881, respectively. The texture-based differences (GLCM) of the SN and the shape-based differences of the GP were highly effective in discriminating between the three classes and two classes, respectively. Conclusions: Radiomic features combining T1WI and SWI can achieve a satisfactory differential diagnosis for PD, MSA, and HC groups, as well as for PD and MSA groups, thus providing a useful tool for clinical decision-making based on routine MRI sequences. [ABSTRACT FROM AUTHOR]

Background and purpose: Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder that is strongly associated with age. The aim of the present study was to describe current sex‐ and age‐specific trends and regional differences in the incidence of IPD diagnosed in older people in Germany. Methods: This study was based on nationwide outpatient claims and drug prescription data from the German Statutory Health Insurance, covering approximately 87% of the general population. We conducted a cohort study in patients aged 50 years or older with observation time of at least 4 years. To assess the robustness of nationwide annual IPD incidence trends from 2013 to 2019, three case definitions with varying levels of stringency regarding coded outpatient diagnoses and drug prescriptions were applied. Results: In 2019, the population at risk comprised 30,575,726 persons. Using the primary and most specific case definition, annual age‐ and sex‐standardized cumulative IPD incidence decreased stepwise from 137 (2013) to 106 (2019) new cases per 100,000 persons. The decline in incidence was seen in both sexes, in all age groups and in the majority of German regions. The relative decrease (2013–2019) in the annual age‐ and sex‐standardized IPD incidence varied from 23% to 28% among case definitions. Conclusion: Our findings indicate a nationwide decline in the age‐ and sex‐standardized incidence of IPD from 2013 to 2019 in Germany. This trend was consistent using different case definitions. Further research is needed to elucidate the factors underlying this trend. [ABSTRACT FROM AUTHOR]

Abstract Background Quantitative assessments of neuromelanin (NM) of the substantia nigra pars compacta (SNpc) in neuromelanin-sensitive MRI (NM-MRI) to determine its abnormality have been conducted by measuring either the volume or contrast ratio (CR) of the SNpc. A recent study determined the regions in the SNpc that are significantly different between early-stage idiopathic Parkinson’s disease (IPD) patients and healthy controls (HCs) using a high spatial-resolution NM-MRI template, which enables a template-based voxelwise analysis to overcome the susceptibility of CR measurement to inter-rater discrepancy. We aimed to assess the diagnostic performance, which has not been reported, of the CRs between early-stage IPD patients and HCs using a NM-MRI template. Methods We retrospectively enrolled early-stage IPD patients (n = 50) and HCs (n = 50) who underwent 0.8-mm isovoxel NM-MRI and dopamine-transporter PET as the standard of reference. A template-based voxelwise analysis revealed two regions in nigrosomes 1 and 2 (N1 and N2, respectively), with significant differences in each substantia nigra (SNpc) between IPD and HCs. The mean CR values of N1, N2, volume-weighted mean of N1 and N2 (N1 + N2), and whole SNpc on each side were compared between IPD and HC using the independent t-test or the Mann-Whitney U test. The diagnostic performance was compared in each region using receiver operating characteristic curves. Results The mean CR values in the right N1 (0.149459 vs. 0.194505), left N1 (0.133328 vs. 0.169160), right N2 (0.230245 vs. 0.278181), left N2 (0.235784 vs. 0.314169), right N1 + N2 (0.155322 vs. 0.278143), left N1 + N2 (0.140991 vs. 0.276755), right whole SNpc (0.131397 vs. 0.141422), and left whole SNpc (0.127099 vs. 0.137873) significantly differed between IPD patients and HCs (all p

Background: Freezing of gait (FOG) is one of the most debilitating symptoms in patients with idiopathic Parkinson's disease (IPD). Visual cues can relieve FOG symptoms. However, there is no consensus on patient characteristics that can benefit from visual cues. Therefore, we examined the differences in IPD patient characteristics according to the effectiveness of visual cueing. Methods: Through gait experiments, we investigated the number of FOG occurrences, average FOG period per episode, proportion of FOG duration in the total gait cycles, and FOG-free period gait spatiotemporal parameters in ten participants diagnosed with FOG due to IPD. Subsequently, the differences between their clinical characteristics and striatal dopamine active transporter availability from six subregions of the striatum were compared by dividing them into two groups based on the three reduction rates: occurrence numbers, mean durations per episode, and proportion of FOG duration in the total gait cycles improved by visual cueing using laser shoes. The relationships among these three reduction rates and other FOG-related parameters were also investigated using Spearman correlation analyses. Results: According to the three FOG-related reduction rates, the group assignments were the same, which was also related to the baseline self-reported FOG severity score (New Freezing of Gait Questionnaire): the more severe the FOG, the poorer the response to the visual cueing. By visual cueing, the better response group demonstrated the characteristics of lower new FOG questionnaire total scores, higher dopamine active transporter availability of the anterior and posterior putamen, and shorter mean duration of FOG per episode in the absence of cueing. These results were replicated using Spearman correlation analyses. Conclusions: For FOG symptoms following IPD, gait assistance by visual cueing may be more effective when the total NFOGQ score is lower and the DAT of putamen is higher. Through this study, we demonstrated clinical and striatal dopaminergic conditions to select patients who may be more likely to benefit from visual cueing with laser shoes, and these findings lead to the need for early diagnosis of FOG in patients with IPD. Trial registration: ClinicalTrials.gov identifier: NCT05080413. Registered on September 14, 2021. [ABSTRACT FROM AUTHOR]

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson's disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed. [ABSTRACT FROM AUTHOR]

Background: Transcranial sonography (TCS) is a noninvasive imaging method that practices ultrasound waves to examine the brain structure changes in many neurological pathologies, including Parkinson's disease (PD) and parkinsonism. It allows for the visualization of the substantia nigra (SN), which is affected in these conditions and other brain parts. This technique has shown promise in aiding the diagnosis, follow-up, and progress of PD, in addition to differentiating it from other movement disorders. Our research explores the reliability of TCS in the diagnosis of PD and its impact on the differential diagnosis of atypical parkinsonism syndromes. Subjects and Methods: This study involved 52 PD patients, nine with other parkinsonism, and 54 healthy people. The same neurosonologist, blind to the patient's diagnosis, assessed each individual's SN, and the hyperechogenic area measurement was obtained. These measurements were compared between PD patients, with other forms of PD, and healthy people. In addition, hyperechogenic regions were compared based on the PD subtypes, dominant disease side, severity, and duration of the disease. Results: PD patients were presented with the highest value of SN hyperechogenic regions. TCS had an 87.5% specificity and a 73.3% sensitivity rate for the diagnosis of PD. The akinetic-rigid subtype of PD showed higher hyperechogenicity. In PD patients, there was no correlation between the disease side, length of the disease, Hoehn and Yahr stage, and SN hyperechogenicity. Conclusion: The results of this research demonstrate that the visualizing of SN hyperechogenicity with TCS in PD has diagnostic significance and may be valuable in the differential diagnosis of atypical parkinsonism disorders. However, the evaluation of only the SN may not be sufficient to advantage from TCS in the diagnosis of other parkinsonisms, and it may be essential to investigate the mesencephalon, other basal ganglia, and the third ventricle.

Background: Quantitative assessments of neuromelanin (NM) of the substantia nigra pars compacta (SNpc) in neuromelanin-sensitive MRI (NM-MRI) to determine its abnormality have been conducted by measuring either the volume or contrast ratio (CR) of the SNpc. A recent study determined the regions in the SNpc that are significantly different between early-stage idiopathic Parkinson's disease (IPD) patients and healthy controls (HCs) using a high spatial-resolution NM-MRI template, which enables a template-based voxelwise analysis to overcome the susceptibility of CR measurement to inter-rater discrepancy. We aimed to assess the diagnostic performance, which has not been reported, of the CRs between early-stage IPD patients and HCs using a NM-MRI template. Methods: We retrospectively enrolled early-stage IPD patients (n = 50) and HCs (n = 50) who underwent 0.8-mm isovoxel NM-MRI and dopamine-transporter PET as the standard of reference. A template-based voxelwise analysis revealed two regions in nigrosomes 1 and 2 (N1 and N2, respectively), with significant differences in each substantia nigra (SNpc) between IPD and HCs. The mean CR values of N1, N2, volume-weighted mean of N1 and N2 (N1 + N2), and whole SNpc on each side were compared between IPD and HC using the independent t-test or the Mann-Whitney U test. The diagnostic performance was compared in each region using receiver operating characteristic curves. Results: The mean CR values in the right N1 (0.149459 vs. 0.194505), left N1 (0.133328 vs. 0.169160), right N2 (0.230245 vs. 0.278181), left N2 (0.235784 vs. 0.314169), right N1 + N2 (0.155322 vs. 0.278143), left N1 + N2 (0.140991 vs. 0.276755), right whole SNpc (0.131397 vs. 0.141422), and left whole SNpc (0.127099 vs. 0.137873) significantly differed between IPD patients and HCs (all p < 0.001). The areas under the curve of the left N1 + N2, right N1 + N2, left N1, right N1, left N2, right N2, left whole SNpc, and right whole SNpc were 0.994 (sensitivity, 98.0%; specificity, 94.0%), 0.985, 0.804, 0.802, 0.777, 0.766, 0.632, and 0.606, respectively. Conclusion: Our NM-MRI template-based CR measurements revealed significant differences between early-stage IPD patients and HCs. The CR values of the left N1 + N2 demonstrated the highest diagnostic performance. [ABSTRACT FROM AUTHOR]

Background: There are currently no specific tests for either idiopathic Parkinson’s disease or Parkinson-plus syndromes. The study aimed to investigate the diagnostic performance of features extracted from the whole brain using diffusion tensor imaging concerning parkinsonian disorders. Methods: The retrospective data yielded 625 participants (average age: 61.4 ± 8.2, men/women: 313/312; healthy controls/idiopathic Parkinson’s disease/multiple system atrophy/progressive supranuclear palsy: 219/286/51/69) between 2008 and 2017. Diffusion-weighted images were obtained using a 3T MR scanner. The 90th, 50th, and 10th percentiles of fractional anisotropy and mean/axial/radial diffusivity from each parcellated brain area were recorded. Statistical analysis was evaluated based on the features extracted from the whole brain, as determined using discriminant function analysis and support vector machine. 20% of the participants were used as an independent blind dataset with 5 times cross-verification. Diagnostic performance was evaluated by the sensitivity and the F1 score. Results: Diagnoses were accurate for distinguishing idiopathic Parkinson’s disease from healthy control and Parkinson-plus syndromes (87.4 ± 2.1% and 82.5 ± 3.9%, respectively). Diagnostic F1 scores varied for Parkinson-plus syndromes with 67.2 ± 3.8% for multiple system atrophy and 71.6 ± 3.5% for progressive supranuclear palsy. For early and late detection of idiopathic Parkinson’s disease, the diagnostic performance was 79.2 ± 7.4% and 84.4 ± 6.9%, respectively. The diagnostic performance was 68.8 ± 11.0% and 52.5 ± 8.9% in early and late detection to distinguish different Parkinson-plus syndromes. Conclusions: Features extracted from diffusion tensor imaging of the whole brain can provide objective evidence for the diagnosis of healthy control, idiopathic Parkinson’s disease, and Parkinson-plus syndromes with fair to very good diagnostic performance.

There is much controversy about the link between motor symptom progression and the plethora of reported brain atrophy patterns in idiopathic Parkinson's disease (PD). The main goal of this study is to provide empirical evidence for unique and common contributions of clinical phenotype characteristics on the dynamic changes of brain structure over time. We analyzed the behavioral and magnetic resonance imaging (MRI) data of PD patients (n = 22) and healthy individuals (n = 21) acquired two years apart through the computational anatomy framework of longitudinal voxel-based morphometry (VBM). This analysis revealed a symmetrical bi-hemispheric pattern of accelerated grey matter decrease in PD extending through the insula, parahippocampal gyrus, medial temporal lobes and the precuneus. We observed a hemisphere-specific correlation between the established scores for motor symptoms severity and the rate of atrophy within motor regions, which was further differentiated by the clinical phenotype characteristics of PD patients. Baseline cerebellum anatomy differences between the tremor-dominant and akineto-rigid PD remained stable over time and can be regarded as trait rather than state-associated features. We interpret the observed pattern of progressive brain anatomy changes as mainly linked to insular areas that determine together with basal ganglia the motor and non-motor phenotype in PD. Our findings provide empirical evidence for the sensitivity of computational anatomy to dynamic changes in PD, offering additional opportunities to establish reliable models of disease progression. [ABSTRACT FROM AUTHOR]

Background: Uncertainty prevails regarding the patterns of autonomic dysfunction in patients with idiopathic Parkinson's disease (IPD). This study was undertaken with the aim of assessing the complete spectrum of cardiovascular autonomic function tests (CAFTs) and blood pressure variability patterns in IPD patients while comparing the same with age-matched controls. Methods: Patients with IPD presenting to the Christian Medical College and Hospital from December 2016 to November 2018 along with age-matched controls were prospectively evaluated using CAFTs. The IPD patients also underwent ambulatory blood pressure (BP) monitoring (ABPM), and the diurnal systolic BP differences were used to classify into dippers (10-20%), non-dippers (0–10%), reverse dippers (20%). Results: Autonomic dysfunction (AD) was prevalent in 41 (68.3%) IPD patients even in early disease (median (inter-quartile range) symptom duration 2 (1–4) years, mean Hoehn and Yahr (H&Y) stage 2 (1.5–2.8). Both sympathetic and parasympathetic parameters were impaired among IPD patients when compared to healthy controls. (E: I ratio 1.17 ± 0.12 vs 1.26 ± 0.14 (P < 0.001), Valsalva ratio (VR) 1.33 ± 0.27 vs 1.55 ± 0.25 (P < 0.001), PRT100 9.6 ± 8.0 vs 3.1 ± 1.8 (P < 0.001), tilt-up SBPAvg change 8.8 (4.2–13.8) vs 1.8 (−2.9–6.1) (P < 0.001), tilt-up HRAvg change 4.8 (2.2–8.2) vs 1.9 (−0.7–5.1) (P < 0.001). BP variability was demonstrated in 47 (79.7%) of IPD patients, with reverse dipping pattern in 28 (47.5%) seen more frequently in this cohort. Conclusions: Timely detection of AD may be helpful not only in recognizing IPD in its pre-motor stages but also in optimizing management for this population of patients. BP variability and abnormal dipping patterns on ABPM can be a potential marker of dysautonomia.

Background: The Radboud Oral Motor Inventory for Parkinson's disease (ROMP) is a patient-rated assessment measuring patients' perceptions of speech, swallowing, and saliva control among patients with idiopathic Parkinson's disease (IPD). Objective: The present study was carried out to adapt and validate the Sinhala version of the ROMP questionnaire in a Sinhala-speaking patient cohort diagnosed with IPD. Materials and Methods: The study population consisted of patients diagnosed with IPD attending a tertiary care neurology clinic at the National Hospital of Sri Lanka. ROMP was translated from English to Sinhala, and an expert committee verified its content. Construct validity was assessed by correlating the Sinhala ROMP scores with the subscales in speech, salivation, and swallowing of the Unified Parkinson's Disease Rating Scale and with five-point Likert-type scale to assess dysarthria, dysphagia, and drooling by a speech and language therapist. Test–retest reproducibility was assessed by repeating the questionnaire in 2 weeks. Results: A cohort of 21 patients was evaluated (male to female ratio = 2.5:1, mean age was 58.8 [±8.3] years). The Spearman's correlations between ROMP and the Likert-type scale assessment, that is, speech r = 0.85 (P < 0.01), swallowing r = 0.86 (P < 0.01), and drooling r = 0.88 (P < 0.01), and subscales of the UPDRS were statistically significant, that is, speech r = 0.75 (P < 0.01), swallowing r = 0.96 (P < 0.01), and salivation r = 0.94 (P < 0.01). Reproducibility of the three domains and total intraclass correlation coefficients indicated a high level of agreement in test–retest reproducibility (range: 0.98–0.99). The three subdomains of the instrument also had excellent internal consistency (total Cronbach's α = 0.99). Conclusion: The Sinhala version of ROMP has proved to be a good assessment tool for dysphagia, dysarthria, and drooling in the early stage of IPD patients.

Background: The hypothesis of body-first vs. brain-first subtype of PD has been proposed with REM-Sleep behavior disorder (RBD) defining the former. The body-first PD presumes an involvement of the brainstem in the pathogenic process with higher burden of autonomic dysfunction. Objective: To identify distinctive clinical subtypes of idiopathic Parkinson's disease (iPD) in line with the formerly proposed concept of body-first vs. brain-first subtypes in PD, we analyzed the presence of probable RBD (pRBD), sex, and the APOEɛ4 carrier status as potential sub-group stratifiers. Methods: A total of 400 iPD patients were included in the cross-sectional analysis from the baseline dataset with a completed RBD Screening Questionnaire (RBDSQ) for classifying as pRBD by using the cut-off RBDSQ≥6. Multiple regression models were applied to explore (i) the effect of pRBD on clinical outcomes adjusted for disease duration and age, (ii) the effect of sex on pRBD, and (iii) the association of APOEɛ4 and pRBD. Results: iPD-pRBD was significantly associated with autonomic dysfunction (SCOPA-AUT), level of depressive symptoms (BDI-I), MDS-UPDRS I, hallucinations, and constipation, whereas significantly negatively associated with quality of life (PDQ-39) and sleep (PDSS). No significant association between sex and pRBD or APOE ɛ4 and pRBD in iPD was found nor did we determine a significant effect of APOE ɛ4 on the PD phenotype. Conclusion: We identified an RBD-specific PD endophenotype, characterized by predominant autonomic dysfunction, hallucinations, and depression, corroborating the concept of a distinctive body-first subtype of PD. We did not observe a significant association between APOE ɛ4 and pRBD suggesting both factors having an independent effect on cognitive decline in iPD. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is frequent in Parkinson's disease (PD) and several neurotransmitter changes have been reported since the time of diagnosis, although seldom investigated altogether in the same patient cohort. Objective: Our aim was to evaluate the association between neurotransmitter impairment, brain metabolism, and cognition in a cohort of de novo, drug-naïve PD patients. Methods: We retrospectively selected 95 consecutive drug-naïve PD patients (mean age 71.89±7.53) undergoing at the time of diagnosis a brain [18F]FDG-PET as a marker of brain glucose metabolism and proxy measure of neurodegeneration, [123I]FP-CIT-SPECT as a marker and dopaminergic deafferentation in the striatum and frontal cortex, as well as a marker of serotonergic deafferentation in the thalamus, and quantitative electroencephalography (qEEG) as an indirect measure of cholinergic deafferentation. Patients also underwent a complete neuropsychological battery. Results: Positive correlations were observed between (i) executive functions and left cerebellar cortex metabolism, (ii) prefrontal dopaminergic tone and working memory (r = 0.304, p = 0.003), (iii) qEEG slowing in the posterior leads and both memory (r = 0.299, p = 0.004) and visuo-spatial functions (r = 0.357, p < 0.001). Conclusions: In subjects with PD, the impact of regional metabolism and diffuse projection systems degeneration differs across cognitive domains. These findings suggest possible tailored approaches to the treatment of cognitive deficits in PD. [ABSTRACT FROM AUTHOR]

Aims: To develop an automatic method of classification for parkinsonian variant of multiple system atrophy (MSA‐P) and Idiopathic Parkinson's disease (IPD) in early to moderately advanced stages based on multimodal striatal alterations and identify the striatal neuromarkers for distinction. Methods: 77 IPD and 75 MSA‐P patients underwent 3.0 T multimodal MRI comprising susceptibility‐weighted imaging, resting‐state functional magnetic resonance imaging, T1‐weighted imaging, and diffusion tensor imaging. Iron‐radiomic features, volumes, functional and diffusion scalars of bilateral 10 striatal subregions were calculated and provided to the support vector machine for classification Results: A combination of iron‐radiomic features, function, diffusion, and volumetric measures optimally distinguished IPD and MSA‐P in the testing dataset (accuracy 0.911 and area under the receiver operating characteristic curves [AUC] 0.927). The diagnostic performance further improved when incorporating clinical variables into the multimodal model (accuracy 0.934 and AUC 0.953). The most crucial factor for classification was the functional activity of the left dorsolateral putamen. Conclusion: The machine learning algorithm applied to multimodal striatal dysfunction depicted dorsal striatum and supervening prefrontal lobe and cerebellar dysfunction through the frontostriatal and cerebello‐striatal connections and facilitated accurate classification between IPD and MSA‐P. The dorsolateral putamen was the most valuable neuromarker for the classification. [ABSTRACT FROM AUTHOR]

Background: One of the non-motor features of idiopathic Parkinson's disease (IPD) is sexual dysfunction (SD) which is under-recognized and, consequently, undertreated. This study aimed to evaluate SD in patients with IPD. Patients and methods: The study was conducted on 67 IPD patients; 30 healthy subjects with age and gender matching with the patients served as the control group. All participants were subjected to sexual function assessment using the Arabic version of Arizona Sexual Experience Scale (ASEX), Mini-Mental State Examination (MMSE), and Beck Depression Inventory (BDI), while the severity of IPD was assessed using the modified Hoehn and Yahr scoring scale and MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: There were no statistically significant differences between patients with IPD and the control group regarding MMSE, hypertension, diabetes mellitus, or dyslipidemia. However, BDI scores were significantly higher in patients with IPD. The rate of SD among our patients was 64% compared to 30% in the control group. The total score and subscales of ASEX were significantly higher in IPD patients than in controls. SD showed a significant correlation with the severity of the IPD irrespective of other variables, including patient age, sex, disease duration, hypertension, diabetes, dyslipidemia, smoking, and dose of L-dopa. Conclusion: SD is a commonly underrated feature in patients with IPD; it should be investigated carefully as it is an important non-motor symptom that correlates with disease severity. [ABSTRACT FROM AUTHOR]

Background: In addition to motor findings, non-motor findings including alterations in visual acuity, decrease in blink reflex, and pupil reactivity cause the impaired quality of life in idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA). Our study aimed to examine possible latency and amplitude changes in pattern visual evoked potentials (pVEP) along with retinal and macular changes in optical coherence tomography (OCT) in PD and MSA groups. We also intended to investigate whether any OCT parameters could be a biomarker for Parkinson's or MSA. Methods: Our study included 50 patients with PD, 15 with MSA, and 50 healthy control subjects. All patients in the study underwent neurological and ophthalmological examination and investigations of OCT to measure the retinal and macular thickness and pVEP to assess visual pathways. Results: When PD, MSA, and control groups were compared, a significant difference was found in all retinal thickness values in average, nasal, and superior retinal nerve fiber thickness (pRNFL), and in all macular thickness values except nasal outer and inferior outer quadrants and in ganglion cell complex (GCC) thicknesses (p < 0.05). Moreover, a significant difference was found in N75, P100, and N145 latencies and N75-P100 amplitude (p < 0.05). The thickness of both pRNFL, inner and outer macular quadrants, was thinner in the MSA group than in PD but GCC thickness was thinner in PD group. Conclusions: The present study compared pVEP and OCT parameters in PD and MSA groups. It was concluded that pVEP and OCT examinations were of importance in that they were easily accessible, affordable, noninvasive biomarkers that might be used in early periods and progression of the disease and in follow-up. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbances are one of the most common non-motor symptoms in Idiopathic Parkinson's Disease (IPD) patients. However, the effect of melatonin on sleep problems in Parkinson's disease patients is unclear., Aims and Objectives: To study the effect of melatonin on sleep in IPD patients through subjective and objective assessment., Methods: Between August 2023 to February 2024, we conducted a randomized, double-blind, placebo-controlled trial on IPD patients. We randomized eligible subjects to melatonin (3 mg) (n = 43) or placebo (n = 43) for 8 weeks. The primary endpoint was sleep quality assessed through the Pittsburgh sleep quality index and daytime sleepiness using Epworth sleepiness scale. Secondary endpoints were polysomnographic sleep parameters, quality of life, motor and non-motor symptoms. Assessments were done at baseline and at the end of 8 weeks., Results: We screened 107 IPD patients and 86 patients were included in the study. Seventy three patients (melatonin, 35 and placebo, 38) completed the study. The mean change in Pittsburgh Sleep Quality Index (PSQI) score between the two groups was 1.87 (95 % CI: 1.5-2.1; p = 0.001) and Epworth Sleepiness Scale (ESS) score was 1.25 (95 % CI: 0.80-1.71; p = 0.001) favoring melatonin. The mean difference between the two groups for Non-Motor Symptoms Scale (NMSS) was 6.11 (95 % CI 5.27-6.92; p = 0.001), Parkinson's Disease Questionnaire (PDQ 39) 8.12 (95 % CI 6.97-9.50; p = 0.001) & Polysomnography (PSG) parameters [sleep latency 8.36 (95 % CI 4.38-12.34; p = 0.001) and total sleep time 14.51 (95 % CI 5.00-24.41; p = 0.005)] favoring melatonin. Side effects attributable to melatonin were minimal., Conclusion: Melatonin is an effective and safe treatment option for sleep problems in PD patients, and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life. We need to emphasize the fact that though we had statistically significant changes in our outcomes, it is not clear whether such changes would have real-life impact (meaningfulness) that would be relevant to licensing authorities or management as patients in our study are young, have short disease duration, have high use of anticholinergics and on modest levodopa equivalent dose. So, we are doubtful if this could be generalized to the typical PD population who are older, have longer disease duration and are on potentially sedating medications or not., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Speech impairments are common with Parkinson's disease (reported prevalence 68%), increasing conversational demands, reliance on family and social withdrawal., Objective(s): The PD COMM trial compared the clinical and cost-effectiveness of two speech and language therapy approaches: Lee Silverman Voice Treatment LOUD and National Health Service speech and language therapy for the treatment of speech or voice problems in people with Parkinson's disease to no speech and language therapy (control) and against each other., Design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Participants were randomised in a 1 : 1 : 1 ratio to control, National Health Service speech and language therapy or Lee Silverman Voice Treatment LOUD via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Mixed-methods process and health economic evaluations were conducted., Setting: United Kingdom outpatient and home settings., Participants: People with idiopathic Parkinson's disease, with self-reported or carer-reported speech or voice problems. We excluded people with dementia, laryngeal pathology and those within 24 months of previous speech and language therapy., Interventions: The Lee Silverman Voice Treatment LOUD intervention included maximum effort drills and high-effort speech production tasks delivered over four 50-minute therapist-led personalised sessions per week, for 4 weeks with prescribed daily home practice. National Health Service speech and language therapy content and dosage reflected local non-Lee Silverman Voice Treatment speech and language therapy practices, usually 1 hour, once weekly, for 6 weeks. Trained, experienced speech and language therapists or assistants provided interventions. The control was no speech and language therapy until the trial was completed., Main Outcome Measures: Primary outcome: Voice Handicap Index total score at 3 months. Secondary outcomes: Voice Handicap Index subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5L; ICEpop Capabilities Measure for Older Adults; Parkinson's Disease Questionnaire - Carers; resource utilisation; and adverse events. Assessments were completed pre-randomisation and at 3, 6 and 12 months post randomisation., Results: Three hundred and eighty-eight participants were randomised to Lee Silverman Voice Treatment LOUD ( n  = 130), National Health Service speech and language therapy ( n  = 129) and control ( n  = 129). The impact of voice problems at 3 months after randomisation was lower for Lee Silverman Voice Treatment LOUD participants than control [-8.0 (99% confidence interval: -13.3, -2.6); p  = 0.001]. There was no evidence of improvement for those with access to National Health Service speech and language therapy when compared to control [1.7 (99% confidence interval: -3.8, 7.1); p  = 0.4]. Participants randomised to Lee Silverman Voice Treatment LOUD reported a lower impact of their voice problems than participants randomised to National Health Service speech and language therapy [99% confidence interval: -9.6 (-14.9, -4.4); p  < 0.0001]. There were no reports of serious adverse events. Staff were confident with the trial interventions; a range of patient and therapist enablers of implementing Lee Silverman Voice Treatment LOUD were identified. The economic evaluation results suggested Lee Silverman Voice Treatment LOUD was more expensive and more effective than control or National Health Service speech and language therapy but was not cost-effective with incremental cost-effectiveness ratios of £197,772 per quality-adjusted life-year gained and £77,017 per quality-adjusted life-year gained, respectively., Limitations: The number of participants recruited to the trial did not meet the pre-specified power., Conclusions: People that had access to Lee Silverman Voice Treatment LOUD described a significantly greater reduction in the impact of their Parkinson's disease-related speech problems 3 months after randomisation compared to people that had no speech and language therapy. There was no evidence of a difference between National Health Service speech and language therapy and those that received no speech and language therapy. Lee Silverman Voice Treatment LOUD resulted in a significantly lower impact of voice problems compared to National Health Service speech and language therapy 3 months after randomisation which was still present after 12 months; however, Lee Silverman Voice Treatment LOUD was not found to be cost-effective., Future Work: Implementing Lee Silverman Voice Treatment LOUD in the National Health Service and identifying alternatives to Lee Silverman Voice Treatment LOUD for those who cannot tolerate it. Investigation of less costly alternative options for Lee Silverman Voice Treatment delivery require investigation, with economic evaluation using a preference-based outcome measure that captures improvement in communication., Study Registration: This study is registered as ISRCTN12421382., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 10/135/02) and is published in full in Health Technology Assessment ; Vol. 28, No. 58. See the NIHR Funding and Awards website for further award information.

Introduction: The study aims to evaluate the motor, non-motor, cognitive and psychiatric conditions of our patients diagnosed with Idiopathic Parkinson's Disease (IPD) before and after the COVID-19 pandemic and to investigate the effect of the pandemic on male and female genders. Methods: Ninety patients were included in the study. Demographic data such as age, gender, and duration of disease, type of disease of the patients were recorded. Patients were then divided into 2 groups: male and female. Movement disorders of both groups before the pandemic, disease stage determined by H&Y and UPDRS at the admission and after the pandemic, Levodopa equivalent dose used were recorded and all patients were surveyed to evaluate their motor, non-motor, cognitive, and psychiatric conditions during the COVID-19 pandemic. The effects of the COVID-19 pandemic on male and female genders were investigated. Results: Of the patients, 40 were male and 50 were female. Daytime drowsiness, weakness, impaired walking, constipation, sleep disorders, and inability to turn in the bed worsened compared to the period before the pandemic. Yet, of the psychiatric symptoms, boredom, unhappiness, anhedonia, irritability, and tension were found to increase during the pandemic. There was a statistically significant difference in UPDRS, H&Y and disease stages before and after the COVID-19 pandemic in both groups, especially in the female group (p<0.05). Conclusion: Although it was more pronounced in female patients with IPD diagnosis, both motor and non-motor symptoms were found to worsen during the COVID-19 pandemic in both groups. [ABSTRACT FROM AUTHOR]

Background: Uncertainty prevails regarding the patterns of autonomic dysfunction in patients with idiopathic Parkinson's disease (IPD). This study was undertaken with the aim of assessing the complete spectrum of cardiovascular autonomic function tests (CAFTs) and blood pressure variability patterns in IPD patients while comparing the same with age-matched controls. Methods: Patients with IPD presenting to the Christian Medical College and Hospital from December 2016 to November 2018 along with age-matched controls were prospectively evaluated using CAFTs. The IPD patients also underwent ambulatory blood pressure (BP) monitoring (ABPM), and the diurnal systolic BP differences were used to classify into dippers (10-20%), non-dippers (0–10%), reverse dippers (<0%), and extreme dippers (>20%). Results: Autonomic dysfunction (AD) was prevalent in 41 (68.3%) IPD patients even in early disease (median (inter-quartile range) symptom duration 2 (1–4) years, mean Hoehn and Yahr (H&Y) stage 2 (1.5–2.8). Both sympathetic and parasympathetic parameters were impaired among IPD patients when compared to healthy controls. (E: I ratio 1.17 ± 0.12 vs 1.26 ± 0.14 (P < 0.001), Valsalva ratio (VR) 1.33 ± 0.27 vs 1.55 ± 0.25 (P < 0.001), PRT100 9.6 ± 8.0 vs 3.1 ± 1.8 (P < 0.001), tilt-up SBPAvg change 8.8 (4.2–13.8) vs 1.8 (−2.9–6.1) (P < 0.001), tilt-up HRAvg change 4.8 (2.2–8.2) vs 1.9 (−0.7–5.1) (P < 0.001). BP variability was demonstrated in 47 (79.7%) of IPD patients, with reverse dipping pattern in 28 (47.5%) seen more frequently in this cohort. Conclusions: Timely detection of AD may be helpful not only in recognizing IPD in its pre-motor stages but also in optimizing management for this population of patients. BP variability and abnormal dipping patterns on ABPM can be a potential marker of dysautonomia. [ABSTRACT FROM AUTHOR]

The diagnostic performance of a combined architecture on Parkinson's disease using diffusion tensor imaging was evaluated. A convolutional neural network was trained from multiple parcellated brain regions. A greedy algorithm was proposed to combine the models from individual regions into a complex one. Total 305 Parkinson's disease patients (aged 59.9±9.7 years old) and 227 healthy control subjects (aged 61.0±7.4 years old) were enrolled from 3 retrospective studies. The participants were divided into training with ten-fold cross-validation (N = 432) and an independent blind dataset (N = 100). Diffusion-weighted images were acquired from a 3T scanner. Fractional anisotropy and mean diffusivity were calculated and was subsequently parcellated into 90 cerebral regions of interest based on the Automatic Anatomic Labeling template. A convolutional neural network was implemented which contained three convolutional blocks and a fully connected layer. Each convolutional block consisted of a convolutional layer, activation layer, and pooling layer. This model was trained for each individual region. A greedy algorithm was implemented to combine multiple regions as the final prediction. The greedy algorithm predicted the area under curve of 94.1±3.2% from the combination of fractional anisotropy from 22 regions. The model performance analysis showed that the combination of 9 regions is equivalent. The best area under curve was 74.7±5.4% from the right postcentral gyrus. The current study proposed an architecture of convolutional neural network and a greedy algorithm to combine from multiple regions. With diffusion tensor imaging, the algorithm showed the potential to distinguish patients with Parkinson's disease from normal control with satisfactory performance. [ABSTRACT FROM AUTHOR]

Background: The Radboud Oral Motor Inventory for Parkinson's disease (ROMP) is a patient-rated assessment measuring patients' perceptions of speech, swallowing, and saliva control among patients with idiopathic Parkinson's disease (IPD). Objective: The present study was carried out to adapt and validate the Sinhala version of the ROMP questionnaire in a Sinhala-speaking patient cohort diagnosed with IPD. Materials and Methods: The study population consisted of patients diagnosed with IPD attending a tertiary care neurology clinic at the National Hospital of Sri Lanka. ROMP was translated from English to Sinhala, and an expert committee verified its content. Construct validity was assessed by correlating the Sinhala ROMP scores with the subscales in speech, salivation, and swallowing of the Unified Parkinson's Disease Rating Scale and with five-point Likert-type scale to assess dysarthria, dysphagia, and drooling by a speech and language therapist. Test–retest reproducibility was assessed by repeating the questionnaire in 2 weeks. Results: A cohort of 21 patients was evaluated (male to female ratio = 2.5:1, mean age was 58.8 [±8.3] years). The Spearman's correlations between ROMP and the Likert-type scale assessment, that is, speech r = 0.85 (P < 0.01), swallowing r = 0.86 (P < 0.01), and drooling r = 0.88 (P < 0.01), and subscales of the UPDRS were statistically significant, that is, speech r = 0.75 (P < 0.01), swallowing r = 0.96 (P < 0.01), and salivation r = 0.94 (P < 0.01). Reproducibility of the three domains and total intraclass correlation coefficients indicated a high level of agreement in test–retest reproducibility (range: 0.98–0.99). The three subdomains of the instrument also had excellent internal consistency (total Cronbach's α = 0.99). Conclusion: The Sinhala version of ROMP has proved to be a good assessment tool for dysphagia, dysarthria, and drooling in the early stage of IPD patients. [ABSTRACT FROM AUTHOR]

Background: The need for imaging-guided optimization of Deep Brain Stimulation (DBS) parameters is increasing with recent developments of sophisticated lead designs offering highly individualized, but time-consuming and complex programming. Objective: The objective of this study was to compare changes in motor symptoms of Parkinson's Disease (PD) and the corresponding volume of the electrostatic field (VEsF) achieved by DBS programming using GUIDE XT™, a commercially available software for visualization of DBS leads within the patient-specific anatomy from fusions of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans, versus standard-of-care clinical programming. Methods: Clinical evaluation was performed to identify the optimal set of parameters based on clinical effects in 29 patients with PD and bilateral directional leads for Subthalamic Nucleus (STN) DBS. A second DBS program was generated in GUIDE XT™ based on a VEsF optimally located within the dorsolateral STN. Reduction of motor symptoms (Movement Disorders Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS) and the overlap of the corresponding VEsF of both programs were compared. Results: Clinical and imaging-guided programming resulted in a significant reduction in the MDS-UPDRS scores compared to off-state. Motor symptom control with GUIDE XT™-derived DBS program was non-inferior to standard clinical programming. The overlap of the two VEsF did not correlate with the difference in motor symptom reduction by the programs. Conclusions: Imaging-guided programming of directional DBS leads using GUIDE XT™ is possible without computational background and leads to non-inferior motor symptom control compared with clinical programming. DBS programs based on patient-specific imaging data may thus serve as starting point for clinical testing and may promote more efficient DBS programming.

Objective: To determine homocysteine, vitamin B12, and folate levels in patients with Parkinson’s disease and to investigate the effect of entacapone use on homocysteine levels. Materials and Methods: The records of patients who were followed up in our outpatient clinic between 2009 and 2010 were reviewed retrospectively. The demographic, clinical characteristics, and laboratory findings of the patients were recorded. The control group consisted of healthy subjects with similar demographic characteristics. The patients were divided into two groups according to the treatment they received. Results: The control group consisted of 22 healthy subjects (group 1), group 2 comprised 22 patients [entacapone (+)], and group 3 constitued 50 patients [entacapone (-)]. The homocysteine levels of the control group were significantly lower than the entacapone (-) and entacapone (+) groups. The vitamin B12 level of the control group was significantly higher than in the entacapone (-) group. The folate levels of the control group were significantly higher than those of the entacapone (-) group. There was no significant difference between the entacapone (-) and entacapone (+) groups in terms of homocysteine, vitamin B12, and folate levels. Conclusion: Levodopa treatment affects homocysteine levels in patients with Parkinson’s disease. The effect of levodopa + entacapone on plasma homocysteine levels should be evaluated together with basal vitamin B12 and folate levels and genetic features.

Background: Regular physical activity is of great relevance in Parkinson's disease. As part of the project "Individualized training program for Parkinson's disease patients" (ParkProTrain), a tablet-based program was developed to support individual self-training. It has been tested over a period of 9 months in domestic settings. Patients were asked about the feasibility of use and satisfaction. Methods: Patients who used the program at home following inpatient Parkinson's complex treatment (PCT) were interviewed twice (9 and 36 weeks after PCT). Results: The program helped patients to stay motivated throughout the interventional period. It provided them with both structure and flexibility to develop their own training routine. The following were named as positive aspects (success factors), including: the introductory seminars in the clinic, the close supervision during the interventional period, the soundness and Parkinson's specificity, the feasibility and manageability of the program and the individualized training plans; however, patients also provided information on how the program could still be optimized (barriers). Discussion: The program has already successfully implemented a number of aspects that promote activity. Further recommendations were derived for future use, to which more attention should be paid: Parkinson's specificity and individualization of the program, flexible training in terms of location and time, close and personal support throughout the study period and the technique should be designed to be easy to learn and manage. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine the prevalence and risk factors of idiopathic Parkinson's disease (IPD) in Western Turkey, which encompasses Edirne and its surrounding districts. Methods: In this study, 9887 individuals, able to communicate and agreed to participate in the study, were evaluated. The data was obtained by answering a face-to-face questionnaire consisting of 53 questions from volunteers living at 30 randomly selected family health centers in Edirne and its counties. The questionnaire included demographic information, questions to evaluate potential concomitant conditions, and questions regarding the symptomatology used in IPD diagnosis. Following the questionnaire, it was planned to determine the degree of IPD with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale (HY) clinical rating scale in patients diagnosed with IPD to assess disease severity in patients diagnosed with IPD Results: Of the 9887 individuals, 118 were diagnosed with IPD according to the questionnaire results from Edirne and its districts, and the prevalence of IPD was 1.2%. Approximately, 58.4% of the patients with IPD were male and 41.6% were female, which was not significantly different (p=0.214). Non-motor symptoms such as difficulty urinating, anxiety, depression, fatigue, REM sleep behavior disorder, and difficulty falling asleep or staying asleep were also examined in patients diagnosed with IPD. Depression was identified in 45.7% of the cases, while the control group was 4.3% (p=0.001). Fatigue was identified in 46.8% of the cases and control group was 3.5% (p=0.002). Conclusions: IPD prevalence studies will increase the awareness in the community and provide early diagnosis and treatment as well as serve as a basis to increased life expectancy, reduce morbidity, and improve life quality. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to compare the balance, gait, and quality of life of patients with idiopathic Parkinson's disease (PD), progressive supranuclear palsy (PSP), and healthy controls (HCs). Materials and Methods: The present study included 26 patients with PD, 14 patients with PSP, and 22 HCs. The Berg Balance Scale (BBS), Dynamic Gait Index (DGI), and the Turkish version of Mini-Mental State Examination (MMSE) were administered to all participants. The Parkinson 's disease questionnaire (PDQ-39) and Unified PD Rating Scale were evaluated only among patients with PD and PSP. Results: There was a significant difference between PD and PSP in terms of BBS, DGI, and all variables of PDQ-39 except “social support” (P < 0.05). Although a significant difference was found between patients with PSP and HCs in the BBS and DGI, there was no significant difference between patients with PD and HCs in the DGI and BBS. Further, the BBS and DGI were strongly correlated regarding the “mobility” and “activities of daily living” variables of the PDQ-39 and moderately correlated in terms of “total scores of PDQ-39,” “stigma,” and “communication” subscores. The MMSE was moderately associated with “total scores of PDQ-39” and the “mobility” subscore. Conclusion: This study demonstrated a significant deterioration in balance, gait, and the quality of life in patients with PSP compared with PD and HCs. However, there was no difference between patients with PD and HCs.

Aim:It has been proposed that elevated levels of uric acid (UA) has a protective effect against the development of Idiopathic Parkinson’s Disease (IPD), however, since IPD has been found to be more common in gout patients, their relationship became controversial. Our aim was to investigate the relationship of UA level and UA-to-creatinine ratio (UCR) with IPD stages and their effects on disease severity.Methods:Patients were grouped as early stage (ES) (Hoehn-Yahr (HY); 1-2), middle stage (MS) (HY; 2.5-3) and advanced stage (AS) (HY; 4-5). UA levels and UCR were compared between the groups. After age and L-dopa dose were corrected, differences between the groups were recalculated.Results:There were 39 ES, 33 MS, 28 AS patients. The mean UA level was 4.9±1.26 in ES, 5.02±1.22 in MS and 5.1±1.64 in AS (p=0.85). The mean UCR was 5.91±1.78 in ES, 6.03±1.66 in MS and 5.72±1.73 in AS (p=0.79). When corrected age was 67.42, there was no difference in UA (p=0.93), creatinine (p=0.92) and UCR (p=0.91). When corrected L-Dopa dose was 561.18, there was no difference in UA (p=0.99), creatinine (p=0.51) and UCR (p=0.21). When age and L-Dopa were corrected, there was no difference in UA (p=0.96), creatinine (p=0.82) and UCR (p=0.21).Conclusion:Despite corrected age and L-Dopa dose, UA and UCR did not differ between the stages. UA and UCR used as biomarkers of disease severity may not always yield accurate results.

INTRODUCTION[|]The present study aims to evaluate the efficacy and safety of botulinum toxin A (BONT-A) injection therapy on a group of patients with Idiopathic Parkinson's disease (IPD)-associated sialorrhea.[¤]METHODS[|]A retrospective analysis of 21 patients with sialorrhea and IPD treated with BoNT-A at our neurology outpatient clinic was conducted between June 2017- December 2018. BoNT-A was injected into the parotid glands without ultrasound guidance. Pre-treatment sialorrhea severity was quantified according to the Drooling Frequency and Severity Scale (DFSS) and Unified Parkinson's Disease Rating Scale (UPDRS) part 2 item 6 Demographic characteristics of all the patients were recorded. Patients were summoned before the injection, one week after the injection, one month after the injection and three months after the injection and adverse effects on patients associated with the medical treatment were evaluated.[¤]RESULTS[|]A significant decrease in the UPDRS and DSFS scores was observed when the 1st week, 1st month and 3rd months after the procedure are evaluated. However, the DSFS and UPDRS scores were significantly lower in the 1st month after the injection with regards to the 3rd month after the injection. No serious side effects were observed in the patients.[¤]DISCUSSION AND CONCLUSION[|]In this study, it is demonstrated that BoNT-A injection is simple, safe, tolerable and effective in sialorrhea treatment of patients with IPD. However, further clinical studies involving longer-term follow-up and a larger number of patients are required to confirm and extend our results.[¤]

Abstract Background Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382 . Registered on 18 April 2016.

There is much controversy about the link between motor symptom progression and the plethora of reported brain atrophy patterns in idiopathic Parkinson’s disease (PD). The main goal of this study is to provide empirical evidence for unique and common contributions of clinical phenotype characteristics on the dynamic changes of brain structure over time. We analyzed the behavioral and magnetic resonance imaging (MRI) data of PD patients (n = 22) and healthy individuals (n = 21) acquired two years apart through the computational anatomy framework of longitudinal voxel-based morphometry (VBM). This analysis revealed a symmetrical bi-hemispheric pattern of accelerated grey matter decrease in PD extending through the insula, parahippocampal gyrus, medial temporal lobes and the precuneus. We observed a hemisphere-specific correlation between the established scores for motor symptoms severity and the rate of atrophy within motor regions, which was further differentiated by the clinical phenotype characteristics of PD patients. Baseline cerebellum anatomy differences between the tremor-dominant and akineto-rigid PD remained stable over time and can be regarded as trait rather than state-associated features. We interpret the observed pattern of progressive brain anatomy changes as mainly linked to insular areas that determine together with basal ganglia the motor and non-motor phenotype in PD. Our findings provide empirical evidence for the sensitivity of computational anatomy to dynamic changes in PD, offering additional opportunities to establish reliable models of disease progression.

Purpose: Cardiac autonomic dysfunction in idiopathic Parkinson's disease (PD) manifests as reduced heart rate variability (HRV). In the present study, we explored the deceleration capacity of heart rate (DC) in patients with idiopathic PD, an advanced HRV marker that has proven clinical utility. Methods: Standard and advanced HRV measures derived from 7-min electrocardiograms in 20 idiopathic PD patients and 27 healthy controls were analyzed. HRV measures were compared using regression analysis, controlling for age, sex, and mean heart rate. Results: Significantly reduced HRV was found only in the subcohort of PD patients older than 60 years. Low- frequency power and global HRV measures were lower in patients than in controls, but standard beat-to-beat HRV markers (i.e., rMSSD and high-frequency power) were not significantly different between groups. DC was significantly reduced in the subcohort of PD patients older than 60 years compared to controls. Conclusions: Deceleration-related oscillations of HRV were significantly reduced in the older PD patients compared to healthy controls, suggesting that short-term DC may be a sensitive marker of cardiac autonomic dysfunction in PD. DC may be complementary to traditional markers of short-term HRV for the evaluation of autonomic modulation in PD. Further study to examine the association between DC and cardiac adverse events in PD is needed to clarify the clinical relevance of DC in this population. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is characterized by motor deficits and brain alterations having a detrimental impact on balance, gait, and cognition. Intensive physical exercise can induce changes in the neural system, potentially counteracting neurodegeneration in PD and improving clinical symptoms. Objective: This randomized controlled trial investigated effects of a highly challenging, cognitively demanding, balance and gait training (HiBalance) program in participants with PD on brain structure. Methods: 95 participants were assigned to either the HiBalance or an active control speech training program. The group-based interventions were performed in 1-hour sessions, twice per week over a 10-week period. Participants underwent balance, gait, cognitive function, and structural magnetic resonance imaging assessments before and after the interventions. Voxel-based morphometry was analyzed in 34 HiBalance and 31 active controls. Additionally, structural covariance networks were assessed. Results: There was no significant time by group interaction between the HiBalance and control training in balance, gait, or brain volume. Within-HiBalance-group analyses showed higher left putamen volumes post-training. In repeated measures correlation a positive linear, non-significant relationship between gait speed and putamen volume was revealed. In the HiBalance group we found community structure changes and stronger thalamic-cerebellar connectivity in structural covariance networks. Neither brain volume changes nor topology changes were found for the active controls after the training. Conclusion: Thus, subtle structural brain changes occur after balance and gait training. Future studies need to determine whether training modifications or other assessment methods lead to stronger effects. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is a neurodegenerative disease with unknown cause in the majority of patients, who are therefore considered “idiopathic” (IPD). PD predominantly affects dopaminergic neurons in the substantia nigra pars compacta (SNpc), yet the pathology is not limited to this cell type. Advancing age is considered the main risk factor for the development of IPD and greatly influences the function of microglia, the immune cells of the brain. With increasing age, microglia become dysfunctional and release pro-inflammatory factors into the extracellular space, which promote neuronal cell death. Accordingly, neuroinflammation has also been described as a feature of PD. So far, studies exploring inflammatory pathways in IPD patient samples have primarily focused on blood-derived immune cells or brain sections, but rarely investigated patient microglia in vitro. Accordingly, we decided to explore the contribution of microglia to IPD in a comparative manner using, both, iPSC-derived cultures and postmortem tissue. Our meta-analysis of published RNAseq datasets indicated an upregulation of IL10 and IL1B in nigral tissue from IPD patients. We observed increased expression levels of these cytokines in microglia compared to neurons using our single-cell midbrain atlas. Moreover, IL10 and IL1B were upregulated in IPD compared to control microglia. Next, to validate these findings in vitro, we generated IPD patient microglia from iPSCs using an established differentiation protocol. IPD microglia were more readily primed as indicated by elevated IL1B and IL10 gene expression and higher mRNA and protein levels of NLRP3 after LPS treatment. In addition, IPD microglia had higher phagocytic capacity under basal conditions—a phenotype that was further exacerbated upon stimulation with LPS, suggesting an aberrant microglial function. Our results demonstrate the significance of microglia as the key player in the neuroinflammation process in IPD. While our study highlights the importance of microglia-mediated inflammatory signaling in IPD, further investigations will be needed to explore particular disease mechanisms in these cells.

Introduction: Aim of this study was identify the prevalence of frailty in patients with idiopathic Parkinson's disease (PD), to describe the relationship between severity of the disease and frailty, and to evaluate if timed up and go (TUG) is an eligible test for determination of frailty in idiopathic PD patients. Methods: We conducted a cross-sectional study which included 66 patients, aged 60 and over in a tertiary hospital. Frailty was assessed by the Fried Frailty Index (FFI). Severity of the idiopathic PD was detected by the Hoehn and Yahr (H&Y) scale. Mobility was measured by the TUG test. Demographic characteristics and comprehensive geriatric assessments were evaluated. Descriptive statistics and logistic regression were used in analyses. Receiver operating characteristic (ROC) curves were used to identify the discriminative effect of TUG test on frailty. Results: The numbers of frail, prefrail, and robust subjects were 34 (51.5%), 24 (36.4%), and 8 (12.1%), respectively. Dependency in instrumental activities of daily living (IADL) was significantly associated with frailty (Odds ratio (OR): 36.00, Confidence interval (CI): 8.43-153.80). Multivariate logistic regression analysis results yielded, depression (OR: 10.37, CI: 2.82-38.12) and higher levodopa doses (OR: 6.28, CI: 1.77-22.24) were independently associated with frailty. TUG test performance was strongly associated with frailty with high sensitivity (0.806) and specificity (0.826) (Area under the curve (AUC): 0.831). Conclusions: Frailty is highly prevalent in idiopathic PD and is strongly associated with disabilities as well as specific risk factors of the disease. The TUG may be a reliable test for prediction of frailty in patients with idiopathic PD. [ABSTRACT FROM AUTHOR]

The need for imaging-guided optimization of Deep Brain Stimulation (DBS) parameters is increasing with recent developments of sophisticated lead designs offering highly individualized, but time-consuming and complex programming. The objective of this study was to compare changes in motor symptoms of Parkinson's Disease (PD) and the corresponding volume of the electrostatic field (VEsF) achieved by DBS programming using GUIDE XT™, a commercially available software for visualization of DBS leads within the patient-specific anatomy from fusions of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans, versus standard-of-care clinical programming. Clinical evaluation was performed to identify the optimal set of parameters based on clinical effects in 29 patients with PD and bilateral directional leads for Subthalamic Nucleus (STN) DBS. A second DBS program was generated in GUIDE XT™ based on a VEsF optimally located within the dorsolateral STN. Reduction of motor symptoms (Movement Disorders Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS) and the overlap of the corresponding VEsF of both programs were compared. Clinical and imaging-guided programming resulted in a significant reduction in the MDS-UPDRS scores compared to off-state. Motor symptom control with GUIDE XT™-derived DBS program was non-inferior to standard clinical programming. The overlap of the two VEsF did not correlate with the difference in motor symptom reduction by the programs. Imaging-guided programming of directional DBS leads using GUIDE XT™ is possible without computational background and leads to non-inferior motor symptom control compared with clinical programming. DBS programs based on patient-specific imaging data may thus serve as starting point for clinical testing and may promote more efficient DBS programming. • Double-blinded study assessing a commercially available software for visualization of DBS leads. • Reliable visualization of DBS leads, including rotation angles was achieved. • Motor symptom control with the GUIDE XT™-derived DBS program was non-inferior to standard clinical programming. • The difference in motor symptom reduction did not correlate with overlap of the volumes of the electrostatic field. • DBS programs based on patient-specific imaging data may promote more efficient DBS programming. [ABSTRACT FROM AUTHOR]

Aim: Idiopathic Parkinson's disease (IPD) is the second most common progressive neurodegenerative disorder and well known with typical motor impairment. Besides motor symptoms, non-motor symptoms (NMS) occur very frequently among patients with IPD. This study aims to assess the presence of non-motor symptoms with the severity of motor symptoms. Materials and Methods: Alaaddin Keykubat University Training and Research Hospital's database has been screened for identifying patients with IPD from 2015-2019. The patients' motor symptom, NMS, and Hoehn & Yahr stage (H&Y stage) were assessed with the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: A total of 50 IPD patients were analyzed. Analysis by NMS part of MDS-UPDRS (Part I) showed that NMS was present in 99.7% of patients. NMS part score was positively correlated with H&Y stages and total motor scores of MDS-UPDRS (part II-III). The most common symptoms were pain (84%), daytime sleepiness (78%), and urinary problems (76%). Significantly, there was an association between motor impairment, H&Y, and the following NMS items; hallucinations/psychosis, depressed mood, daytime sleepiness, urinary problems, constipation, light-headedness on standing, and fatigue (p<0.05, Spearman's rho). Conclusions: Considering our data suggested that almost all patients with PD experience NMS. NMS are mostly worsened with exacerbation of MS (motor symptoms) and H&Y in cases. These findings will help understand the clinical aspect of PD and may improve personalized medicine and research in PD. [ABSTRACT FROM AUTHOR]

Objective: Identification of serum C-reactive protein (CRP)/albumin ratio according to disease stage in idiopathic Parkinson’s disease (IPD) with the aim of collecting data about the role of inflammation and oxidative stress in etiopathogenesis and about CRP/albumin ratio’s possible effects on disease progression. Materials and Methods: The study was completed with 151 patients being staged according to the Modified Hoehn and Yahr (H&Y) criteria and 150 healthy volunteers in the same age interval with patients. In our retrospective study, the Unified Parkinson disease rating scale (UPDRS) and H&Y scales were applied to the patients with IPD diagnosed according to the diagnostic criteria of the “United Kingdom Parkinson Disease Society Brain Bank”. Patient and control groups had venous blood samples taken for biochemical study after 12-14 hours of fasting. Results: The serum albumin levels were lower, while serum CRP levels and CRP/albumin ratios were higher in the IPD group (p

In the past two decades, mutations in multiple genes have been linked to autosomal dominant or recessive forms of monogenic Parkinson’s disease (PD). Collectively, these monogenic (often familial) cases account for less than 5% of all PD, the majority being apparently sporadic cases. More recently, large-scale genome-wide association studies have identified over 40 loci that increase risk of PD. Importantly, there is overlap between monogenic and sporadic PD genes, particularly for the loci that contain the genes SNCA and LRRK2, which are mutated in monogenic dominant PD. There have also been reports of idiopathic PD cases with heterozygous variants in autosomal recessive genes suggesting that these mutations may increase risk of PD. These observations suggest that monogenic and idiopathic PD may have shared pathogenic mechanisms. Here, we focus mainly on the role of monogenic PD genes that represent pleomorphic risk loci for idiopathic PD. We also discuss the functional mechanisms that may play a role in increasing risk of disease in both monogenic and idiopathic forms.

AIM: Premotor phase in Parkinson’s disease (PD) begins many years before the onset of motor symptoms. Despite advancement in the understanding of this common neurodegenerative disease, clinical diagnosis is still the gold standard. Various fluid- and tissue-based biomarkers have been postulated to play a role in the pathogenesis of PD. We aimed to study the role of serum DJ-1 and apolipoprotein A1 (Apo A1) in PD. SETTINGS AND DESIGN: A cross-sectional observational study was conducted in the Department of Neurology, in collaboration with the Department of Pharmacology. Cases of PD and healthy controls were recruited over 1 year with written informed consent from all the participants. The study was approved by the institutional ethics committee. SUBJECTS AND METHODS: All cases underwent detailed neurological examination, Hoehn and Yahr staging, and MDS-UPDRS (MDS-UPDRS (Movement Disorders Society–Unified Parkinson Disease Rating Scale) scoring. Serum of all the cases and controls were collected for the estimation of DJ-1 and Apo A1 by enzyme-linked immunosorbent assay. STATISTICAL ANALYSIS: Serum DJ-1 and Apo A1 levels were compared between cases and controls using Mann–Whitney test. Correlation of characteristics was carried out using Spearman correlation coefficient. RESULTS: The study cohort included 77 cases of PD and 69 healthy controls. Serum DJ-1 and Apo A1 levels were found to be significantly lower in cases compared to controls (P < 0.001). However, no correlation was found with age of onset, duration of disease, and severity of illness. A negative correlation was observed between DJ-1 levels and cognitive impairment and bladder dysfunction. CONCLUSION: Low levels of DJ-1 and Apo A1 are found in patients with PD of Indian origin. However, correlation of these biomarkers with progression and severity is needed to be explored in future randomized controlled trials with a large sample size.

Objective: To determine homocysteine, vitamin B12, and folate levels in patients with Parkinson's disease and to investigate the effect of entacapone use on homocysteine levels. Materials and Methods: The records of patients who were followed up in our outpatient clinic between 2009 and 2010 were reviewed retrospectively. The demographic, clinical characteristics, and laboratory findings of the patients were recorded. The control group consisted of healthy subjects with similar demographic characteristics. The patients were divided into two groups according to the treatment they received. Results: The control group consisted of 22 healthy subjects (group 1), group 2 comprised 22 patients [entacapone (+)], and group 3 constitued 50 patients [entacapone (-)]. The homocysteine levels of the control group were significantly lower than the entacapone (-) and entacapone (+) groups. The vitamin B12 level of the control group was significantly higher than in the entacapone (-) group. The folate levels of the control group were significantly higher than those of the entacapone (-) group. There was no significant difference between the entacapone (-) and entacapone (+) groups in terms of homocysteine, vitamin B12, and folate levels. Conclusion: Levodopa treatment affects homocysteine levels in patients with Parkinson's disease. The effect of levodopa + entacapone on plasma homocysteine levels should be evaluated together with basal vitamin B12 and folate levels and genetic features. [ABSTRACT FROM AUTHOR]