Showing papers in "Parkinson's Disease in 2021"

Freezing of Gait in Parkinson's Disease: Risk Factors, Their Interactions, and Associated Nonmotor Symptoms.

Abstract: Background. Freezing of gait (FOG) is a debilitating and incompletely understood symptom in Parkinson’s disease (PD). Objective. To determine the principal clinical factors predisposing to FOG in PD, their interactions, and associated nonmotor symptoms. Methods. 164 PD subjects were assessed in a cross-sectional retrospective study, using the MDS-UPDRS scale, MMSE, and Clinical Dementia Rating Scale. Clinical factors associated with FOG were determined using univariate analysis and nominal logistic regression. Receiver operating characteristic curves were computed, to obtain measures of sensitivity and specificity of predictors of FOG. Subgroups of patients with FOG were compared with those without FOG, based on defining aspects of their clinical phenotype. Results. Relative to non-FOG patients, those with FOG had a longer disease duration, higher PIGD and balance-gait score, higher LED, and more motor complications ( ) and were more likely to exhibit urinary dysfunction ( ), cognitive impairment, hallucinations, and psychosis ( ). The balance-gait score and motor complications, at their optimum cutoff values, together predicted FOG with 86% accuracy. Interactions were noted between cognitive dysfunction and both the Bal-Gait score and motor complication status, cognitive impairment or dementia increasing the likelihood of FOG in subjects without motor complications ( ), but not in those with motor complications. Conclusions. Both disease and treatment-related factors, notably LED, influence the risk of FOG in PD, with a selective influence of cognitive dysfunction in patients with balance-gait disorder but not in those with motor fluctuations. These findings may help to inform clinical management and highlight distinct subgroups of patients with PD-FOG, which are likely to differ in their network pathophysiology.

Focus on Depression in Parkinson's Disease: A Delphi Consensus of Experts in Psychiatry, Neurology, and Geriatrics.

Abstract: Major and minor forms of depression are significant contributors to Parkinson's disease morbidity and caregiver burden, affecting up to 50% of these patients. Nonetheless, symptoms of depression are still underrecognized and undertreated in this context due to scarcity of evidence and, consequently, consistent clinical guideline recommendations. Here, we carried out a prospective, multicentre, 2-round modified Delphi survey with 49 questions about the aetiopathological mechanisms of depression in Parkinson's disease (10), clinical features and connections with motor and nonmotor symptoms (10), diagnostic criteria (5), and therapeutic options (24). Items were assessed by a panel of 37 experts (neurologists, psychiatrists, and a geriatrist), and consensus was achieved in 81.6% of them. Depressive symptoms, enhanced by multiple patient circumstances, were considered Parkinson's disease risk factors but not clinical indicators of motor symptom and disease progression. These patients should be systematically screened for depression while ruling out both anhedonia and apathy symptoms as they are not necessarily linked to it. Clinical scales (mainly the Geriatric Depression Scale GDS-15) can help establishing the diagnosis of depression, the symptoms of which will require treatment regardless of severity. Efficacious and well-tolerated pharmacological options for Parkinson's comorbid depression were selective serotonin reuptake inhibitors (especially sertraline), dual-action serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine, and duloxetine), multimodal (vortioxetine, bupropion, mirtazapine, and tianeptine), and anti-Parkinsonian dopamine agonists (pramipexole, ropinirole, and rotigotine). Tricyclic antidepressants and combining type B monoamine oxidase inhibitors with serotonergic drugs have serious side effects in these patients and therefore should not be prescribed. Electroconvulsive therapy was indicated for severe and drug-refractory cases. Cognitive behavioural therapy was recommended in cases of mild depression. Results presented here are useful diagnostic and patient management guidance for other physicians and important considerations to improve future drug trial design.

Progression of Nonmotor Symptoms in Parkinson's Disease by Sex and Motor Laterality.

Abstract: Nonmotor symptoms (NMS) in Parkinson's disease (PD) can start up to a decade before motor manifestations and strongly correlate with the quality of life. Understanding patterns of NMS can provide clues to the incipient site of PD pathology. Our goal was to systematically characterize the progression of NMS in PD (n = 489), compared to healthy controls, HC (n = 241), based on the sex of the subjects and laterality of motor symptom onset. Additionally, NMS experienced at the onset of PD were also compared to subjects with scans without dopaminergic deficit, SWEDD (n = 81). The Parkinson's Progression Markers Initiative (PPMI) database was utilized to analyze several NMS scales. NMS experienced by PD and SWEDD cohorts were significantly higher than HC and both sex and laterality influenced several NMS scales at the onset of motor symptoms. Sex Differences. PD males experienced significant worsening of sexual, urinary, sleep, and cognitive functions compared to PD females. PD females reported significantly increased thermoregulatory dysfunction and anxious mood over 7 years and significantly more constipation during the first 4 years after PD onset. Laterality Differences. At onset, PD subjects with right-sided motor predominance reported significantly higher autonomic dysfunction. Subjects with left-sided motor predominance experienced significantly more anxious mood at onset which continued as Parkinson's progressed. In conclusion, males experienced increased NMS burden in Parkinson's disease. Laterality of motor symptoms did not significantly influence NMS progression, except anxious mood. We analyzed NMS in a large cohort of PD patients, and these data are valuable to improve PD patients' quality of life by therapeutically alleviating nonmotor symptoms.

Action Imagery and Observation in Neurorehabilitation for Parkinson’s Disease (ACTION-PD): development of a user-informed home training intervention to improve functional hand movements

Abstract: Parkinson’s disease (PD) causes difficulties with hand movements, which few studies have 48 addressed therapeutically. Training with action observation (AO) and motor imagery (MI) improves performance in healthy individuals, particularly when the techniques are applied 50 simultaneously (AO+MI). Both AO and MI have shown promising effects in people with PD, but previous studies have only used these separately. Objective: This article describes the development and pilot testing of an intervention combining AO+MI and physical practice to improve functional manual actions in people with PD. Methods: The home-based intervention, delivered using a tablet computer app, was iteratively designed by an interdisciplinary team including people with PD, and further developed through focus groups and initial field testing. Preliminary data on feasibility was obtained via a six-week pilot randomised controlled trial (ISRCTN 11184024) of 10 participants with mild to moderate PD (6 intervention; 4 treatment as usual). Usage and adherence data were recorded during training, and semi-structured interviews were conducted with participants. Exploratory outcome measures including dexterity and timed action performance were tested. Results: Usage and qualitative data provided preliminary evidence of acceptability and usability. Exploratory outcomes also suggested that subjective and objective performance of manual actions should be tested in a larger trial. The importance of personalisation, choice, and motivation was highlighted, as well as the need to facilitate engagement in motor imagery. Conclusions: The results indicate that a larger RCT is warranted, and have broader relevance 69 for the feasibility and development of AO+MI interventions for people with PD and in other populations.

Perspectives on Care for Late-Stage Parkinson's Disease.

Abstract: In the late stage of Parkinson's disease (PD), there is an increasing disease burden not only for the patients but also for their informal caregivers and the health and social services systems. The aim of this study was to explore experiences of late-stage PD patients' and their informal caregivers' satisfaction with care and support, in order to better understand how they perceive the treatment and care they receive. This qualitative substudy was part of the longitudinal European multicentre Care of Late Stage Parkinsonism (CLaSP) project. Individual semistructured interviews were conducted with patients (n = 11) and informal caregivers (n = 9) in Sweden. Data were analysed through the content analysis technique. The final analyses generated one main category: "We are trying to get by both with and without the formal care"and five subcategories: "Availability of health care is important for managing symptoms and everyday life"; "Dependence on others and scheduled days form everyday life"; "There is a wish to get adequate help when it is needed"; "Mixed feelings on future housing and respite care"; and "Family responsibility and loyalty for a functioning everyday life". Having regular contact with PD-specialised health care was perceived as important. Greater access to physiotherapy was wished for. Maintaining autonomy was perceived as important by patients, in both home health care and a future residential care setting. Responsibility and loyalty between spouses and support from children enabled everyday life to carry on at home, indicating a vulnerability for those without an informal caregiver. The results suggest that regular access to PD-specialised health care is important and that a specialised and multidisciplinary approach to the management of PD symptomatology is likely necessary. Non-PD-specialised staff in home health care and residential care facilities should regularly be given opportunities to obtain PD-specific education and information.

Movement Disorders Associated with COVID-19.

Abstract: As neurological complications associated with COVID-19 keep unfolding, the number of cases with COVID-19-associated de novo movement disorders is rising. Although no clear pathomechanistic explanation is provided yet, the growing number of these cases is somewhat alarming. This review gathers information from 64 reports of de novo movement disorders developing after/during infection with SARS-CoV-2. Three new cases with myoclonus occurring shortly after a COVID-19 infection are also presented. Treatment resulted in partial to complete recovery in all three cases. Although the overall percentage of COVID-19 patients who develop movement disorders is marginal, explanations on a probable causal link have been suggested by numerous reports; most commonly involving immune-mediated and postinfectious and less frequently hypoxic-associated and ischemic-related pathways. The current body of evidence points myoclonus and ataxia out as the most frequent movement disorders occurring in COVID-19 patients. Some cases of tremor, chorea, and hypokinetic-rigid syndrome have also been observed in association with COVID-19. In particular, parkinsonism may be of dual concern in the setting of COVID-19; some have linked viral infections with Parkinson's disease (PD) based on results from cerebrospinal fluid analyses, and PD is speculated to impact the outcome of COVID-19 in patients negatively. In conclusion, the present paper reviewed the demographic, clinical, and treatment-associated information on de novo movement disorders in COVID-19 patients in detail; it also underlined the higher incidence of myoclonus and ataxia associated with COVID-19 than other movement disorders.

Use of a Smartphone to Gather Parkinson's Disease Neurological Vital Signs during the COVID-19 Pandemic

Abstract: Introduction To overcome travel restrictions during the COVID-19 pandemic, consumer-based technology was rapidly deployed to the smartphones of individuals with Parkinson's disease (PD) participating in a 12-month exercise trial The aim of the project was to determine the feasibility of utilizing a combined synchronous and asynchronous self-administered smartphone application to characterize PD symptoms Methods A synchronous video virtual visit was completed for the administration of virtual Movement Disorder Society-Unified Parkinson's Disease Rating Scale III (vMDS-UPDRS III) Participants asynchronously completed a mobile application consisting of a measure of upper extremity bradykinesia (Finger Tapping Test) and information processing Results Twenty-three individuals completed the assessments The mean vMDS-UPDRS III was 23 65 ± 8 56 points On average, the number of taps was significantly greater for the less affected limb, 97 96 ± 17 77 taps, compared to the more affected, 89 33 ± 18 66 taps (p = 0 025) with a significantly greater number of freezing episodes for the more affected limb (p < 0 05) Correlation analyses indicated the number of errors and the number of freezing episodes were significantly related to clinical ratings of vMDS-UPDRS III bradykinesia (Rho = 0 44, p < 0 01 ;R = 0 43, p < 0 01 , resp ) and finger tapping performance (Rho = 0 31, p = 0 03 ;Rho = 0 32, p = 0 03 , resp ) Discussion The objective characterization of bradykinesia, akinesia, and nonmotor function and their relationship with clinical disease metrics indicate smartphone technology provides a remote method of characterizing important aspects of PD performance While theoretical and position papers have been published on the potential of telemedicine to aid in the management of PD, this report translates the theory into a viable reality [ABSTRACT FROM AUTHOR] Copyright of Parkinson's Disease (20420080) is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

Abstract: Introduction. In a degenerative disorder such as Parkinson’s disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr’s motor stage (HY 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0–20; B: NMSS = 21–40; C: NMSS = 41–70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the SchwabE e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; ). Conclusion. The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

Dance Is an Accessible Physical Activity for People with Parkinson's Disease.

Abstract: Objective To evaluate the outcomes of face-to-face, digital, and virtual modes of dancing for people living with Parkinson's disease (PD). Design Systematic review informed by Cochrane and PRIMSA guidelines. Data Sources. Seven electronic databases were searched: AMED, Cochrane, PEDro, CINHAL, PsycINFO, EMBASE, and MEDLINE. Methods Eligible studies were randomised controlled trials (RCT) and other trials with quantitative data. The PEDro scale evaluated risk of bias for RCTs. Joanna Briggs Institute instruments were used to critically appraise non-RCTs. The primary outcome was the feasibility of dance interventions, and the secondary outcomes included gait, balance, quality of life, and disability. Results The search yielded 8,327 articles after duplicates were removed and 38 met the inclusion criteria. Seven were at high risk of bias, 20 had moderate risk of bias, and 11 had low risk of bias. There was moderately strong evidence that dance therapy was beneficial for balance, gait, quality of life, and disability. There was good adherence to digital delivery of dance interventions and, for people with PD, online dance was easy to access. Conclusion Dancing is an accessible form of exercise that can benefit mobility and quality of life in people with PD. The COVID-19 pandemic and this review have drawn attention to the benefits of access to digital modes of physical activity for people living with chronic neurological conditions.

α-Synuclein E46K Mutation and Involvement of Oxidative Stress in a Drosophila Model of Parkinson's Disease.

Abstract: Parkinson's disease (PD) is an age-associated neurodegenerative condition in which some genetic variants are known to increase disease susceptibility on interaction with environmental factors inducing oxidative stress. Different mutations in the SNCA gene are reported as the major genetic contributors to PD. E46K mutation pathogenicity has not been investigated as intensive as other SNCA gene mutations including A30P and A53T. In this study, based on the GAL4-UAS binary genetic tool, transgenic Drosophila melanogaster flies expressing wild-type and E46K-mutated copies of the human SNCA gene were constructed. Western blotting, immunohistochemical analysis, and light and confocal microscopy of flies' brains were undertaken along with the survival rate measurement, locomotor function assay, and ethanol and paraquat (PQ) tolerance to study α-synuclein neurotoxicity. Biochemical bioassays were carried out to investigate the activity of antioxidant enzymes and alterations in levels of oxidative markers following damages induced by human α-synuclein to the neurons of the transgenic flies. Overexpression of human α-synuclein in the central nervous system of these transgenic flies led to disorganized ommatidia structures and loss of dopaminergic neurons. E46K α-synuclein caused remarkable climbing defects, reduced survivorship, higher ethanol sensitivity, and increased PQ-mediated mortality. A noticeable decline in activity of catalase and superoxide dismutase enzymes besides considerable increase in the levels of lipid peroxidation and reactive oxygen species was observed in head capsule homogenates of α-synuclein-expressing flies, which indicates obvious involvement of oxidative stress as a causal factor in SNCA E46K neurotoxicity. In all the investigations, E46K copy of the SNCA gene was found to impose more severe defects when compared to wild-type SNCA. It can be concluded that the constructed Drosophila models developed PD-like symptoms that facilitate comparative studies of molecular and cellular pathways implicated in the pathogenicity of different α-synuclein mutations.

The Subjective Experience of Living with Parkinson's Disease: A Meta-Ethnography of Qualitative Literature

Abstract: BACKGROUND: A better understanding of the subjective experience of living with Parkinson's disease (PD) and the factors that influence this experience can be used to improve wellbeing of people with PD (PwP). OBJECTIVE: To gain more insight in the subjective experience of PD from the PwP's perspective, and the factors that contribute to this experience. METHODS: In this qualitative review, we performed a systematic search of qualitative studies discussing the subjective experience of PD and extracted reported themes (first order themes). Using a meta-ethnographic approach, we categorized the first order themes into second order themes, and created a third order construct: a holistic model of the subjective experience of living with PD. RESULTS: We included 20 studies with a total sample of 279 PwP. Data-extraction yielded 227 first order themes, which were categorized into the second order themes: 1) Awareness, 2) Disruption, 3) Adjustment, 4) The external environment, and 5) The changing self. With these themes, we developed the "model of dialectic change" which conceptualizes life with PD as a transformative journey, wherein PwP employ strategies to stabilize their changeable relationship with their external environment, while simultaneously redefining their self-concept. CONCLUSION: Our findings indicate that not only the symptoms of PD, but also the manner in which these cause disruptions in the PwP's interaction with their personal environment and self-concept, determine the subjective experience of PD andquality of life. Some PwP experience problems with adjusting, resulting in psychological distress. This calls for a holistic, multidisciplinary and participatory approach of PD.

Characterizing Advanced Parkinson’s Disease: Romanian Subanalysis from the OBSERVE-PD Study

Abstract: OBSERVE-PD was a cross-sectional, multicountry, observational study conducted in 128 Movement Disorders Centers (MDCs) in 18 countries. Overall, the study enrolled 2615 patients. The aim was to determine the proportion of patients with advanced Parkinson's disease (APD) versus non-APD from MDCs and to uncover the clinical burden of APD, as well as a correlation between overall assessment of APD and several indicators of APD. The advanced stage of the disease and severity were assessed by investigators using their clinical judgement. Data were collected during a single visit between February 2015 and January 2016. Agreement on physician judgement of APD diagnosis and fulfillment of at least one previously established APD indicator was calculated. Motor and nonmotor symptoms (NMSs), activities of daily living, treatment complications, quality of life (QoL), conventional treatments, and device-aided therapy (DAT) eligibility were assessed. Here, country-specific results of 161 Romanian patients with PD are presented. In total, 59.0% of patients were diagnosed with APD and 78.8% met at least one APD indicator. There was only moderate agreement between clinical judgement of APD and overall fulfillment of APD indicators. All scores related to motor symptoms, NMSs, and treatment complications, as well as to QoL, showed a higher disease burden for patients with APD versus non-APD. Physicians considered 73.7% of patients with APD eligible for DAT. The majority of patients eligible for DAT (54.3%) did not receive such treatment. Our results highlight the importance of earlier recognition of APD, by combining clinical judgement with more standardized clinical tools, such as generally recognized APD criteria. However, timely diagnosis of APD alone is not enough to improve patient outcomes. Other critical factors include patient acceptance and access to appropriate treatment.

Delirium after Deep Brain Stimulation in Parkinson's Disease.

Abstract: Deep brain stimulation is a primary treatment method that improves motor and motor complications in patients with advanced Parkinson's disease. Delirium is a common and serious complication following deep brain stimulation. However, the clinical attention toward this complication remains insufficient. Advanced age, cognitive decline, and the severity of the disease may all be risk factors for delirium. The presence of delirium may also affect cognitive function and disease prognosis. Neurotransmitters such as acetylcholine and dopamine may be involved in the occurrence of delirium. Furthermore, inflammation, the effects of microlesioning of local nuclei, and brain atrophy may also play roles in the onset of delirium. Nonpharmacological therapy appears to be the primary treatment for postoperative delirium in Parkinson's disease. The current article reviews the pathogenesis, epidemiology, prognosis, and treatment of delirium following deep brain stimulation in Parkinson's disease to help clinicians better understand this common complication and to prevent, identify, and treat it as soon as possible, as well as to provide more accurate treatment for patients.

Social Cognition in Patients with Early-Onset Parkinson's Disease.

Abstract: Social cognition (SC) deficits have been linked to Parkinson's disease (PD) but have been less well researched than general cognitive processes, especially in early-onset PD (EOPD), despite this population often having greater social and family demands. Most studies focus on recognition of facial emotion, theory of mind (ToM), and decision-making domains, with limited research reporting on social reasoning. The main objective of this work was to compare SC ability across four domains: emotional processing, social reasoning, ToM, and decision-making between patients with EOPD and healthy controls. Twenty-five nondemented patients with EOPD and 25 controls matched for sex, age, and educational level were enrolled. A battery that included six SC tests was administered to all study participants; a decision-making scale was completed by participants' partners. Statistically significant differences were found between patients with EOPD and controls in all subtests across the four SC domains studied. The EOPD group demonstrated worse performance on all tasks, with large effect sizes. Differences remained significant after adjusting for Montreal Cognitive Assessment (MoCA) test scores for all SC subtests except the decision-making scale and the Iowa gambling task. No significant correlations between SC and other clinical PD variables were found. Our study shows that patients with EOPD perform significantly below controls in multiple SC domains affecting recognition of facial emotion, social reasoning, ToM, and decision-making. Only decision-making seems to be mediated by overall cognitive ability. The confounding or contributing effect of other clinical PD variables should be studied further.

Pimavanserin Treatment for Parkinson's Disease Psychosis in Clinical Practice.

Abstract: Background Parkinson's disease psychosis (PDP) is a common, nonmotor symptom of Parkinson's disease (PD), which may affect up to 60% of patients and is associated with impaired quality of life, increased healthcare costs, and nursing home placement, among other adverse outcomes. Characteristic symptoms of PDP include illusions; visual, auditory, tactile, and olfactory hallucinations; and delusions. PDP symptoms typically progress over its course from being mild, infrequent, and often untroubling to complex, sometimes constant, and potentially highly disturbing. PDP has traditionally been treated with atypical antipsychotics (e.g., clozapine and quetiapine) although these are not approved for this indication and clozapine requires frequent white blood cell count monitoring due to the risk of agranulocytosis. Pimavanserin is a newer atypical antipsychotic with highly selective binding to serotonergic receptors, no evidence for worsening motor symptoms in PD, and no need for white blood cell count monitoring. It is currently the only approved medication indicated for PDP treatment. However, because it was approved relatively recently (2016), clinical experience with pimavanserin is limited. Case Presentations. A wide variety of representative clinical scenarios are presented, each with distinct variables and complications. Issues addressed include distinguishing PDP from similar symptoms caused by other disorders such as dementia, coordinating pimavanserin with other PD medications and with deep brain stimulation, adapting pimavanserin dosing for optimal benefit and tolerability, and recognizing variability of PDP symptoms due to patients' changing life circumstances. Conclusions These scenarios provide multiple insights regarding PDP management and the role of pimavanserin. Effective treatment of PDP may reduce disturbing symptoms of psychosis, thus improving patient function and quality of life. In addition, effective pharmacotherapy for PDP may also facilitate the use of other medications needed to treat neurological symptoms of PD (e.g., tremor, bradykinesia, and dyskinesia), although they may also have adverse effects that contribute to symptoms of PDP.

Abnormal Gray Matter Volume and Functional Connectivity in Parkinson’s Disease with Rapid Eye Movement Sleep Behavior Disorder

Abstract: Objective Rapid eye movement (REM) sleep behavior disorder (RBD) is a common symptom in Parkinson's disease (PD), and patients with PD-RBD tend to have an increased risk of cognitive decline and have the tendency to be akinetic/rigidity predominant. At the same time, the mechanisms of RBD in patients with PD remain unclear. Therefore, this study aimed to detect the structural and functional differences in patients with PD-RBD and PD without RBD (PD-nRBD). Methods Twenty-four polysomnography-confirmed patients with PD-RBD, 26 patients with PD-nRBD, and 26 healthy controls were enrolled. Structural and functional patterns were analyzed based on voxel-based morphometry and seed-based functional connectivity (FC). Correlations between altered gray matter volume (GMV)/FC values and cognitive scores and motor impairment scores in PD subgroups were assessed. Results Compared with patients with PD-nRBD, patients with PD-RBD showed relatively high GMV in the cerebellar vermis IV/V and low GMV in the right superior occipital gyrus (SOG). For the FC, patients with PD-RBD displayed lower FC between the right SOG and the posterior regions (left fusiform gyrus, left calcarine sulcus, and left superior parietal gyrus) compared with the patients with PD-nRBD. The GMV values in the right SOG were negatively correlated with the Unified PD Rating Scale-III scores in patients with PD-RBD but positively correlated with delayed memory scores. The GMV values in the cerebellar vermis IV/V were positively correlated with the tonic chin EMG density scores. There were positive correlations between the FC values in the right SOG-left superior parietal gyrus and MoCA and visuospatial skills/executive function scores and in the right SOG-left calcarine sulcus and delayed memory scores. Conclusion Higher GMV in the cerebellum may be linked with the abnormal motor behaviors during REM sleep in patients with PD-RBD, and lower GMV and FC in the posterior regions may indicate that PD-RBD correspond to more serious neurodegeneration, especially the visuospatial-executive function impairment and delayed memory impairment. These findings provided new insights to learn more about the complicated characteristics in patients with PD-RBD.

Identification of Potential Core Genes in Parkinson's Disease Using Bioinformatics Analysis.

Abstract: Purpose This study aimed to explore new core genes related to the occurrence of Parkinson's disease (PD) and core genes that can lead to the progression of PD. Methods The expression profile data of GSE42966, which contained six substantia nigra tissues isolated from normal individuals and nine substantia nigra tissues isolated from patients with PD, were obtained from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified, followed by functional enrichment analysis and protein-protein interaction (PPI) network construction. We then identified 10 hub genes and analyzed their expression in different Braak stages. Results A total of 773 DEGs were identified that were significantly enriched in metabolic pathways. Ten hub genes were identified through the PPI network, namely, GNG3, MAPK1, FPR1, ATP5B, GNG2, PRKACA, HRAS, HSPA8, PSAP, and GABBR2. The expression of HRAS was different in patients with PD with Braak stages 3 and 4. Conclusion These 10 hub genes and the metabolic pathways they are enriched in may be involved in the pathogenesis of PD. HRAS may have potential value in predicting the progression of PD.

Neuroprotective Effects of Estradiol plus Lithium Chloride via Anti-Apoptosis and Neurogenesis Pathway in In Vitro and In Vivo Parkinson's Disease Models

Abstract: Few pharmaceutical agents for slowing Parkinson's disease (PD) progression existed, especially for perimenopause females. The current general medications are mostly hormone replacement therapy and may have some side effects. Therefore, there is an urgent need for a novel treatment for PD. This study examined the possibility of estradiol plus lithium chloride (LiCl), one of the metal halides used as an alternative to salt. We showed that the combination of LiCl and estradiol could enhance neurogenesis proteins GAP-43 and N-myc in the human neuronal-like cells. We also further confirmed the neurogenesis activity in zebrafish. LiCl and LiCl plus estradiol could enhance 6-OHDA-induced upregulation of TGase-2b and Rho A mRNA expression. Besides, LiCl plus estradiol showed a synergic effect in anti-apoptotic activity. LiCl plus estradiol protected SH-SY5Y cells and zebrafish against 6-OHDA-induced damage on neurons than LiCl or estradiol alone groups via p-P38, p-Akt, Bcl-2, and caspase-3 cascade. The potential for developing this combination as a candidate treatment for PD is discussed.

Validation of the German Version of the New Freezing of Gait Questionnaire for People with Parkinson's Disease.

Abstract: Freezing of gait (FOG) in Parkinson's disease (PD) is a highly disabling symptom which impacts quality of life. The New FOG Questionnaire (NFOG-Q) is the most commonly used tool worldwide to characterize FOG severity in PD. This study aims to provide a German translation of the NFOG-Q and to assess its validity in people with PD. The questionnaire was translated using forward-backward translation. Validity was tested in 57 PD patients with FOG via Cronbach's alpha for internal consistency and Spearman correlations with several clinical measures to quantify disease severity, mobility, fall risk, and cognitive state for convergent and divergent validity. The German version of the NFOG-Q shows good internal consistency (Cα = 0.84). Furthermore, the NFOG-Q score was significantly correlated with the MDS-UPDRS III, H&Y stage, Timed Up and Go test, and the subjective fear of falling (FES-I). The lack of correlation with cognition (MoCA) points towards good divergent validity. This study provides a German version of the NFOG-Q which proved to be valid for the assessment of FOG severity in individuals with PD.

CUB and Sushi Multiple Domains (CSMD1) Gene Polymorphisms and Susceptibilities to Idiopathic Parkinson's Disease in Northern Chinese Han Population: A Case-Control Study.

Abstract: Evidence has shown that the CUB and Sushi Multiple Domains (CSMD1) gene is an inhibitor of the complement activation pathway and is also involved in central nervous system inflammation. Previous studies have revealed that the CSMD1 gene is related to familial Parkinson's disease. This study aimed to investigate the relationship between CSMD1 gene and susceptibility to Parkinson's disease in population of northern China. A case-control study was performed on 423 Parkinson's disease patients and 465 healthy controls matched for age and sex. DNA from enrolled subjects were extracted from the peripheral blood, and single nucleotide polymorphisms (SNPs) rs12681349 (C＞T), rs10503253 (C＞A), and rs1983474 (T＞G) within CSMD1 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequency of rs10503253 (CA versus CC : OR = 1.554, 95% CI = 1.169-2.066, p=0.002) and rs1983474 (GG versus TT : OR = 0.599, 95% CI = 0.401-0.895, p=0.012) was significantly different between PD cases and controls, but not for rs12681349. Comprehensive and subgroup analysis indicated that rs10503252 showed significant statistical differences in the dominant model (AA + CA versus CC : OR = 0.677, 95% CI = 0.517-0.886, p=0.004), late-onset cohort (CA versus CC : OR = 1.570, 95% CI = 1.159-2.126, p=0.004), and the female cohort (CA versus CC : OR = 0.687, 95% CI = 0.497-0.952, p=0.023), compared with the matched control group. The difference of recessive model of rs1983474 (GG versus TT + TG : OR = 1.837, 95% CI = 1.287-2.620, p=0.001) was significant in Parkinson's disease. According to the subgroup analysis, results indicated that late-onset cohort (GG versus TT : OR = 0.643, 95% CI = 0.420-0.985, p=0.042), male cohort (TG versus TT : OR = 2.160, 95% CI = 1.162-4.016, p=0.015), and female group (GG versus TT : OR = 0.418, 95% CI = 0.234-0.746, p=0.003) of rs1983474 were significantly associated with Parkinson's disease susceptibility. In both genotype and subgroup analysis, we failed to find any relationship between rs12681349 polymorphism and Parkinson's disease risk. Our results indicate that the rs10503253 and rs1983474 gene polymorphism may be associated with idiopathic Parkinson's disease susceptibility in Chinese population. Nevertheless, these conclusions need to be further verified by more studies.

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

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

Neuroprotective Effect of Intrastriatal Caffeic Acid Phenethyl Ester Treatment in 6-OH Dopamine Model of Parkinson's Disease in Rats.

Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and the main cause of PD is still not known. Until now, no cure for Parkinson’s disease is yet in sight. Caffeic acid phenethyl ester (CAPE) is a polyphenolic component of the propolis, which can be derived from honeybee hive propolis. We aimed to determine the effect of intrastriatal CAPE administration as a neuroprotective agent on 6-hydroxydopamine (6-OHDA)-induced PD model. Adult male Wistar rats weighing 280–320 g were used. The PD model was induced with unilateral intrastriatal 6-OHDA injection. Treatment groups received 20 μmol/5 μL/4 day and 80 μmol/5 μL/4 day CAPE 24 h after 6-OHDA injection. Eight days after 6-OHDA application, behavioral studies (adhesive tape removal test, open-field test, cylinder test, and apomorphine-induced asymmetric rotational behavior) were performed once more to compare the effects of CAPE on behavior tests. Striatal histological verifications, immunohistochemistry, and stereological quantitation were performed. Our results for the first time showed that, besides improving the motor performance, CAPE treatment also prevents 6-OHDA-induced loss of TH-positive neurons. From our results, CAPE may be a promising clinical agent in the treatment of PD.

Intraoperative Quantitative Measurements for Bradykinesia Evaluation during Deep Brain Stimulation Surgery Using Leap Motion Controller: A Pilot Study.

Abstract: Deep brain stimulation (DBS) has shown a remarkably high effectiveness for Parkinson's disease (PD). In many PD patients during DBS surgery, the therapeutic effects of the stimulation test are estimated by assessing changes in bradykinesia as the stimulation voltage is increased. In this study, we evaluated the potential of the leap motion controller (LMC) to quantify the motor component of bradykinesia in PD during DBS surgery, as this could make the intraoperative assessment of bradykinesia more accurate. Seven participants with idiopathic PD receiving chronic bilateral subthalamic nucleus deep brain stimulation (DBS) therapy were recruited. The motor tasks of finger tapping (FT), hand opening and closing (OC), and hand pronation and supination (PS) were selected pre- and intraoperatively in accordance with the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale. During the test, participants performed these tasks in sequence while being simultaneously monitored by the LMC and two professional clinicians. Key kinematic parameters differed between the preoperative and intraoperative conditions. We suggest that the average velocity ( ) and average amplitude ( ) of PS isolate the bradykinetic feature from that movement to provide a measure of the intraoperative state of the motor system. The LMC achieved promising results in evaluating PD patients’ hand and finger bradykinesia during DBS surgery.

Validation of the Parkinson's Disease Caregiver Burden Questionnaire in Progressive Supranuclear Palsy.

Abstract: Progressive supranuclear palsy (PSP) is an atypical Parkinson syndrome with axial akinetic-rigid symptoms, early postural instability, and ocular motor impairments. Patients experience a rapid loss of autonomy and care dependency; thus, caregivers must assist in the activities of daily living early in the course of the disease. Caregiver burden is an extremely important factor in disease management. However, there are no specific questionnaires for assessment of caregiver burden in PSP. This study aims to validate the Parkinson’s disease caregiver burden questionnaire (PDCB) as a specific measure of caregiver burden in PSP. PSP patients were assessed by the PSP rating scale, PSP quality-of-life questionnaire (PSP-QoL), Montreal cognitive assessment test (MoCA), and geriatric depression scale (GDS-15). Caregivers filled out the short form 36-health survey, GDS-15, PDCB, and the caregiver burden inventory (CBI). 22 patient caregiver pairs completed the study. PDCB showed a highly significant correlation with the CBI (r 0.911; ). Internal reliability of the PDCB measured by Cronbach’s alpha was favourable at 0.803. These data support the specificity of the PDCB in PSP caregivers. Future studies with larger sample sizes of PSP patients and caregivers and a multicentric longitudinal design should be performed to gain further insight of caregiver burden in PSP.

Quantitative Analysis of Postural Instability in Patients with Parkinson's Disease.

Abstract: Introduction. Postural instability is commonly observed in Parkinson’s disease, leading to an increasing risk of falling and worsening as the disease progresses. We found that limit of stability can be applied to reflect the dynamic evolution of postural instability in patients with Parkinson's disease. Methods. Forty-three patients (9 of Hoehn and Yahr stage I, 12 of stage II, 14 of stage III, and 8 of stage IV) met the criteria for the diagnosis of idiopathic Parkinson’s disease and could stand independently for at least 10 minutes. Twelve healthy controls with no sign of parkinsonism were also recruited. Postural instability was assessed by posturography in different directions (forward, backward, right, left, forward-right, forward-left, backward-right, and backward-left). This study trial was registered with the Chinese Clinical Trial Registry (no. ChiCTR1900022715 ). Results. All participants were able to complete the limit of stability tasks without any complications. Patients in stages II to IV exhibited smaller end point excursion and slower time to complete than controls, suggesting an impaired limit of stability. The patients in stage II exhibited a remarkable decline in most directions compared to controls, except for right and left, and forward and backward decline occurred the earliest. For patients in stage III, right was the only direction with no significant difference from controls. In stage IV patients, the limit of stability declined significantly in all directions ( ). Conclusions. The postural abnormalities of Parkinson’s disease can occur at early stages, and the pattern of decline is more severe in the forward-backward direction. This trial is registered with ChiCTR1900022715 .

Ultrasonographic Changes in Brain Hemodynamics in Patients with Parkinson's Disease and Risk Factors for Cerebrovascular Disease: A Pilot Study.

Abstract: Recent epidemiological studies have revealed a correlation between atypical features and worse functional outcomes in Parkinson's disease (PD) patients with cerebrovascular disease (CVD). We aimed to evaluate the brain hemodynamics of PD patients with risk factors for CVD using Doppler ultrasonography. In this prospective pilot study, we randomly included 27 outpatients diagnosed with PD. Transcranial color-coded sonography (TCCS) examinations were performed, obtaining measurements of middle cerebral artery mean flow velocities (Vm), the resistance index (RI), and the pulsatility index (PI). The breath-holding index (BHI) was used to assess cerebrovascular reactivity (cVR). Standardized functional scales (UPDRS III, Hoehn & Yahr scale, and MoCA) were administered. The patients were divided into two groups: those with two or more vascular risk factors (PDvasc) and those with fewer than two vascular risk factors (PDnvasc). Patients in the PDvasc group showed higher PI (1.00 vs. 0.85; p=0.020), RI (0.59 vs. 0.5; p=0.05), HY p=0.036), higher frequency of altered cVR (90.9% vs. 25.0%; p=0.001), and lower BHI (0.46 vs. 1.01; p=0.027). We also divided the patients in other two groups: one with patients with classical and another with akinetic-rigid PD clinical type. Patients with the akinetic-rigid type of PD had significantly higher RI (0.60 vs. 0.51; p=0.03), PI (0.99 vs. 0.77; p=0.03), higher frequency of altered cVR (80% vs. 35%; p=0.02), and lower BHI (0.48 vs. 0.96; p=0.05) than patients with classic-type PD. We concluded that TCCS displays impaired cerebrovascular reactivity and a more severe disease pattern in Parkinsonian patients with two or more risk factors for CVD and in the akinetic-rigid type. Doppler ultrasonography may be a useful tool in a clinical setting to investigate PD patients.

Time until Need for Levodopa among New Users of Dopamine Agonists or MAO-B Inhibitors.

Abstract: Objective To investigate the use of dopamine agonists and monoamine oxidase type B (MAO-B) inhibitors in the Norwegian population, between 1 July 2006 and 31 December 2016. Our primary endpoint was time until need for levodopa among new monotherapy users of dopamine agonists and MAO-B inhibitors. Methods A prospective cohort study including all patients, aged 50 years or above, who had at least one prescription for a dopamine agonist or a MAO-B inhibitor dispensed in the study period. We used data from the Norwegian Prescription Database (NorPD). As we wished to focus on new Parkinson patients, we excluded patients who had levodopa dispensed less than 180 days prior to their first dopamine agonist or MAO-B inhibitor redemption. We explored the demographics and the time until monotherapy was insufficient treatment (defined as need for levodopa prescription). Results We included 22958 new monotherapy users. Of these, 22108 used dopamine agonists and 850 used MAO-B inhibitors. The mean number of days until the first prescription of levodopa was dispensed was higher among the dopamine agonist users (621 days) compared to the MAO-B inhibitor users (352 days). The proportion of dopamine agonist users who started levodopa treatment during the study period was less than 7%, while the corresponding proportion of MAO-B inhibitor users was almost 59%. Conclusions We found that new dopamine agonist users had a much greater delay in the need for levodopa than new MAO-B inhibitor users. It seems to be beneficial to initiate treatment with dopamine agonists when starting pharmacological treatment for new Parkinson patients.

Central Pain in Parkinson's Disease: Behavioral and Cognitive Characteristics.

Abstract: Introduction Pain is a major nonmotor symptom of Parkinson's disease (PD), and central parkinsonian pain is the core feature of the putative Park pain subtype of PD. This study aimed to explore the cognitive and behavioral profile of PD patients with central parkinsonian pain. Material and Methods. A structured interview was used to identify and characterize pain in a cohort of 260 consecutive PD patients. The Ford classification of pain was applied. The Dementia Rating Scale-2 (DRS-2) and the Impulse Control Disorders in Parkinson's Disease Short Form (QUIP-S) were administered, and patients' smoking habits were recorded. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess motor and nonmotor symptoms in off and on conditions. Results One hundred and eighty-eight patients (68%) reported pain; and in 41 (22%) of them, the pain was classified as central parkinsonian pain. PD patients with central parkinsonian pain had better cognitive performance in DRS-2 Initiation/Perseveration and Conceptualization subscales but reported more other compulsive behaviors (e.g., hobbyism, punding, and walkabout) and had more current smoking habits than those without pain or with non-central parkinsonian pain. Multiple logistic regression analyses revealed that the DRS-2 Conceptualization subscale, other compulsive behaviors, and smoking habits remained statistically associated with central parkinsonian pain even when other significant covariates were considered. Only patients with pain, regardless of type, had a gambling disorder. Discussion. The study results provide further evidence that pain revealed that patients with central parkinsonian pain are more likely to present compulsive or addictive behaviors, despite having more preserved cognitive performance. Patients with central parkinsonian pain appear to have a distinct phenotype of PD.

Altered Regional Homogeneity and Functional Connectivity during Microlesion Period after Deep Brain Stimulation in Parkinson's Disease

Abstract: Background Patients with Parkinson's disease (PD) undergoing deep brain electrode implantation experience a temporary improvement in motor symptoms before the electrical stimulation begins. We usually call this the microlesion effect (MLE), but the mechanism behind it is not clear. Purpose This study aimed to assess the alterations in brain functions at the regional and whole-brain levels, using regional homogeneity (ReHo) and functional connectivity (FC), during the postoperative microlesion period after deep brain stimulation (DBS) in PD patients. Method Resting-state functional MRI data were collected from 27 PD patients before and after the first day of DBS and 12 healthy controls (HCs) in this study. The ReHo in combination with FC analysis was used to investigate the alterations of regional brain activity in all the subjects. Results There were increased ReHo in the basal ganglia-thalamocortical circuit (left supplementary motor area and bilateral paracentral lobule), whereas decreased ReHo in the default mode network (DMN) (left angular gyrus, bilateral precuneus), prefrontal cortex (bilateral middle frontal gyrus), and the cerebello-thalamocortical (CTC) circuit (Cerebellum_crus2/1_L) after DBS. In addition, we also found abnormal FC in the lingual gyrus, cerebellum, and DMN. Conclusion Microlesion of the thalamus caused by electrode implantation can alter the activity of the basal ganglia-thalamocortical circuit, prefrontal cortex, DMN, and CTC circuit and induce abnormal FC in the lingual gyrus, cerebellum, prefrontal cortex, and DMN among PD patients. The findings of this study contribute to the understanding of the mechanism of MLE.