Plasma Exosomal Brain-Derived Neurotrophic Factor Correlated with the Postural Instability and Gait Disturbance–Related Motor Symptoms in Patients with Parkinson’s Disease

Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin, responsible for neuronal development, function, and survival. Assessments of peripheral blood BDNF in patients with Parkinson’s disease (PD) previously yielded inconsistent results. Plasma exosomes can carry BDNF, so this study investigated the role of plasma exosomal BDNF level as a biomarker of PD. A total of 114 patients with mild to moderate PD and 42 non-PD controls were recruited, and their clinical presentations were evaluated. Plasma exosomes were isolated with exoEasy Maxi Kits, and enzyme-linked immunosorbent assay was used to assess plasma exosomal BDNF levels. Statistical analysis was performed using SPSS version 19.0, and findings were considered significant at p < 0.05. The analysis revealed no significant differences in plasma exosomal BDNF levels between patients with PD and controls. Patients with PD with low plasma exosomal BDNF levels (in the lowest quartile) exhibited a significant association with daily activity dysfunction but not with cognition/mood or overall motor symptoms as assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Investigation of UPDRS part III subitems revealed that low plasma exosomal BDNF level was significantly associated with increased motor severity of postural instability and gait disturbance (PIGD)-associated symptoms (rising from a chair, gait, and postural stability) after adjustment for age and sex. In conclusion, although plasma exosomal BDNF level could not distinguish patients with PD from controls, the association with PIGD symptoms in patients with PD may indicate its potential role as a biomarker. Follow-up studies should investigate the association between plasma exosomal BDNF levels and changes in clinical symptoms.

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Evaluation of Knee Proprioception and Factors Related to Parkinson’s Disease

Neuroscience Journal ◽

10.1155/2016/6746010 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Nathalie Ribeiro Artigas ◽

Giovana Duarte Eltz ◽

Alexandre Severo do Pinho ◽

Vanessa Bielefeldt Leotti Torman ◽

Arlete Hilbig ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Ability ◽

Rating Scale ◽

Center Of Pressure ◽

Postural Instability ◽

Lower Limbs ◽

Controlled Study ◽

Motor Symptoms ◽

Cross Sectional

Background. Changes in proprioception may contribute to postural instability in individuals with neurological disorders. Objectives. Evaluate proprioception in the lower limbs of patients with Parkinson’s disease (PD) and the association between proprioception and cognitive ability, motor symptoms, postural instability, and disease severity. Methods. This is a cross-sectional, controlled study that evaluated proprioception in PD patients and healthy age- and sex-matched individuals. Kinetic postural proprioception of the knee was evaluated using an isokinetic dynamometer (Biodex® Multi-Joint System 4 Pro). Participants were evaluated using the Montreal Cognitive Assessment (MoCA), the Hoehn and Yahr rating scale and postural instability (pull test and stabilometric analysis), and motor function (UPDRS-III) tests. Results. A total of 40 individuals were enrolled in the study: 20 PD patients and 20 healthy controls (CG). The PD patients had higher angular errors on the proprioceptive ratings than the CG participants (p=0.002). Oscillations of the center of pressure (p=0.002) were higher in individuals with PD than in the controls. Proprioceptive errors in the PD patients were associated with the presence of tremors as the dominant symptom and more impaired motor performance. Conclusion. These findings show that individuals with PD have proprioceptive deficits, which are related to decreased cognitive ability and impaired motor symptoms.

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Serum concentration and clinical significance of brain-derived neurotrophic factor in patients with Parkinson’s disease or essential tremor

Journal of International Medical Research ◽

10.1177/0300060517748843 ◽

2018 ◽

Vol 46 (4) ◽

pp. 1477-1485 ◽

Cited By ~ 11

Author(s):

Yixian Huang ◽

Wenwei Yun ◽

Min Zhang ◽

Weifeng Luo ◽

Xianju Zhou

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Serum Concentration ◽

Essential Tremor ◽

Neurotrophic Factor ◽

Rating Scale ◽

Brain Derived Neurotrophic Factor ◽

Significant Difference ◽

Advanced Stages ◽

Serum Bdnf

Objectives The serum concentration of brain-derived neurotrophic factor (BDNF) was compared among patients with Parkinson’s disease (PD), patients with essential tremor (ET), and healthy participants, and its association with clinical features of PD and ET was assessed. Methods Demographic and clinical data were collected from 60 patients with PD at different clinical stages, 60 patients with ET, and 60 controls. All participants’ serum BDNF concentrations were measured. Their motor abilities and activity were assessed by the Unified PD Rating Scale and the Hoehn and Yahr (H-Y) staging scale. Results Serum BDNF was significantly lower in patients with PD than in patients with ET and controls. BDNF decreased only in the early disease stages (H-Y stages I and II), but increased markedly in the advanced stages (H-Y stages III–V). There was no significant difference between patients with ET and controls. The BDNF concentration was negatively correlated with age at PD onset and positively associated with disease duration, severity of PD symptoms, and treatment with L-DOPA. Conclusions A low serum BDNF concentration may serve as a biomarker in the early stages of PD, whereas a high concentration with PD progression may be due to treatment with L-DOPA in the advanced stages.

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Cerebral Microbleeds are Associated with Postural Instability and Gait Disturbance Subtype in People with Parkinson’s Disease

European Neurology ◽

10.1159/000499378 ◽

2018 ◽

Vol 80 (5-6) ◽

pp. 335-340 ◽

Cited By ~ 2

Author(s):

Wei Ting Chiu ◽

Lung Chan ◽

Dean Wu ◽

Tzu Hsiang Ko ◽

David Yen-Ting Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Brain Magnetic Resonance Imaging ◽

Postural Instability ◽

Gait Disturbance ◽

Medical Chart Review ◽

Taiwanese People ◽

Magnetic Resonance Imaging Mri ◽

Student’S T

Objectives: The motor symptoms of Parkinson’s disease (PD) vary among patients and have been categorized into 3 subtypes: tremor dominant, akinetic rigidity, and postural instability and gait disturbance (PIGD). Cerebral microbleed (CMB) is prevalent in people with PD and is associated with some nonmotor symptoms. The present study investigated the association between CMB and the motor subtypes of PD. Materials and Methods: From 2009 to 2017, medical records and brain magnetic resonance imaging (MRI) reports of 134 Taiwanese people with early- and mid-stage PD were reviewed. CMBs were quantified according to the Microbleed Anatomical Rating Scale through susceptibility-weighted MRI. Motor subtypes were determined by medical chart review. Student’s t test and multivariable logistic regression were used to analyze the association between the motor subtypes and CMB. Statistical analyses were performed using SPSS 19.0. Results: Overall, 72 (53.7%) participants were women with a mean age of 69.5 ± 9.8 years. The prevalence of CMB was 33.6%, and lobar, deep, and infratentorial CMBs comprised 21.6, 19.4, and 11.9% of cases, respectively. PIGD subtype PD was associated with a significantly higher prevalence of any CMB as well as deep or lobar CMB. After adjustment for age and sex, the PIGD subtype was significantly positively associated with the presence of any, deep, and white matter (WM) and thalamic CMB. Conclusions: CMB was prevalent in Taiwanese people with early- and mid-stage PD, especially the PIGD subtype. Deep, especially thalamic and WM, CMBs exhibited the highest association with the PIGD subtype.

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Antidepressant treatment restores brain-derived neurotrophic factor (BDNF) serum levels and ameliorates motor function in parkinson's disease patients

European Psychiatry ◽

10.1016/s0924-9338(11)72190-3 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 483-483

Author(s):

V. Ricci ◽

M. Pomponi ◽

G. Martinotti ◽

A. Bentivoglio ◽

G. Loria ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurotrophic Factor ◽

Antidepressant Drugs ◽

Serum Levels ◽

Brain Derived Neurotrophic Factor ◽

Antidepressant Therapy ◽

Enzyme Linked Immunosorbent Assay ◽

List Type ◽

Depressed Patients

IntroductionDepression is a common psychiatric disorder in Parkinson's disease (PD). It has been proposed that antidepressant drugs may bust brain production of trophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF), an effect associated with improvement of clinical symptoms. However, BDNF and GDNF play also a role in the maintenance of dopaminergic neurons, which undergo to neuronal death during PD course.AimsBased on these findings we explored the hypothesis that PD depressed patients may have altered BDNF or GDNF serum levels and that antidepressant drugs may restore them and potentially have beneficial effects not only for depressive but also parkinsonian symptoms.MethodsWe measured by enzyme linked immunosorbent assay (ELISA) the serum levels of BDNF and GDNF in depressed PD patients, non depressed PD patients and healthy subjects and correlated them with clinical observations.ResultsWe found:(1)BDNF serum levels were decreased in PD depressed as compared to non depressed patients and control subjects;(2)antidepressant therapy restored BDNF serum levels to those of controls; and(3)antidepressant therapy in association with Parkinson's therapy significantly ameliorated motor performance in PD depressed patients.ConclusionOur data suggest that PD patients are characterized by a reduction of BDNF serum levels and that depression may exacerbate this effect and worse PD symptoms. It is proposed that association between anti-parkinsonian treatment and SSRI could be a good therapeutic chance not only for treating depression in PD but also for improving PD symptoms.

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37 Postural Instability in Parkinson’s Disease: The Association of Cognitive Impairment and Non-Motor Symptoms

Age and Ageing ◽

10.1093/ageing/afz164.37 ◽

2019 ◽

Vol 48 (Supplement_4) ◽

pp. iv9-iv12

Author(s):

Tien K Khoo ◽

Melanie Cusso ◽

Allka Sewram ◽

Dean Pountney ◽

Kenneth Donald

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Rating Scale ◽

Geriatric Depression Scale ◽

Depression Scale ◽

Postural Instability ◽

Motor Symptoms ◽

Yahr Scale ◽

Non Motor Symptoms

Abstract Introduction Parkinson’s disease (PD) is the second most common neurodegenerative condition after Alzheimer’s. Historically considered as a movement disorder, the multitude of non-motor symptoms (NMS) are now a recognised cause of significant disease burden. This study aimed to explore the relationship between postural instability and NMS in PD. Methodology We recruited individuals (n=100) in South East Queensland with a pre-existing diagnosis of idiopathic PD into this prospective observational study. Motor assessment was performed via the Movement Disorders Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Assessment of postural instability was based on the Hoehn & Yahr Scale (H&Y) with a score of ≥3 considered indicative of postural instability. NMS were assessed via the Non-Motor Symptoms Scale (NMSS). Further neuropsychiatric and affective assessment was evaluated with the Geriatric Depression Scale (GDS-15), Geriatric Anxiety Inventory (GAI), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Montreal Cognitive Assessment (MoCA). Results Cohort demographics comprised of 62% male and 38% female with a mean age of 69.1 years (SD 7.35) and mean H&Y 2.34 (SD 0.59). Sixty four participants were H&Y 1 & 2 whilst 36 participants were H&Y ≥3. Participants with postural instability were significantly older (p = 0.033) and had lower MoCA scores (p=0.039). Among the MoCA domains, only the Visuospatial / Executive domain was associated with postural instability (p= 0.005). Among the NMSS domains, only the sexual function domain was significantly associated with the latter group (p=0.029). GDS scores tended to be higher in the postural instability group (p=0.054) but there was no significance in major depressive disorder (p=0.436). Conclusion Postural instability in PD is significantly associated with age and cognitive impairment, in-particular frontal lobe function. The association of sexual dysfunction is supportive of the notion that disorders in dopaminergic and non-dopaminergic systems underpin the pathophysiology substrate of postural instability.

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Boxing vs Sensory Exercise for Parkinson’s Disease: A Double-Blinded Randomized Controlled Trial

Neurorehabilitation and Neural Repair ◽

10.1177/15459683211023197 ◽

2021 ◽

pp. 154596832110231

Author(s):

Kishoree Sangarapillai ◽

Benjamin M. Norman ◽

Quincy J. Almeida

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Randomized Controlled Trial ◽

Repeated Measures ◽

Rating Scale ◽

Controlled Trial ◽

Motor Symptoms ◽

Post Intervention ◽

Randomized Controlled ◽

Double Blinded

Background. Exercise is increasingly becoming recognized as an important adjunct to medications in the clinical management of Parkinson’s disease (PD). Boxing and sensory exercise have shown immediate benefits, but whether they continue beyond program completion is unknown. This study aimed to investigate the effects of boxing and sensory training on motor symptoms of PD, and whether these benefits remain upon completion of the intervention. Methods. In this 20-week double-blinded randomized controlled trial, 40 participants with idiopathic PD were randomized into 2 treatment groups, (n = 20) boxing or (n = 20) sensory exercise. Participants completed 10 weeks of intervention. Motor symptoms were assessed at (week 0, 10, and 20) using the Unified Parkinson’s Disease Rating Scale (UPDRS-III). Data were analyzed using SPSS, and repeated-measures ANOVA was conducted. Results. A significant interaction effect between groups and time were observed F(1, 39) = 4.566, P = .036, where the sensory group improved in comparison to the boxing group. Post hoc analysis revealed that in comparison to boxing, the effects of exercise did not wear off at washout (week 20) P < .006. Conclusion. Future rehabilitation research should incorporate similar measures to explore whether effects of exercise wear off post intervention.

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Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

Microbial Cell Factories ◽

10.1186/s12934-021-01589-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xiao-yi Kuai ◽

Xiao-han Yao ◽

Li-juan Xu ◽

Yu-qing Zhou ◽

Li-ping Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Neurodegenerative Disorder ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Motor Symptoms ◽

Gastrointestinal Dysfunction ◽

Before And After ◽

Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

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The Parkinson’s Disease Comprehensive Response (PDCORE): a composite approach integrating three standard outcome measures

Brain Communications ◽

10.1093/braincomms/fcaa046 ◽

2020 ◽

Vol 2 (2) ◽

Cited By ~ 2

Author(s):

Matthias Luz ◽

Alan Whone ◽

Niccolò Bassani ◽

Richard K Wyse ◽

Glenn T Stebbins ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Line ◽

Glial Cell ◽

Neurotrophic Factor ◽

Rating Scale ◽

Initial Development ◽

Disease Rating ◽

Recent Phase ◽

Data Source

Abstract There is an increasing need for improved endpoints to assess clinical trial effects in Parkinson’s disease. We propose the Parkinson’s Disease Comprehensive Response as a novel weighted composite endpoint integrating changes measured in three established Parkinson’s outcomes, including: OFF state Movement Disorder Society Unified Parkinson’s Disease Rating Scale Motor Examination scores; Motor Experiences of Daily Living scores; and total good-quality ON time per day. The data source for the initial development of the composite described herein was a recent Phase II trial of glial cell line-derived neurotrophic factor. A wide range of clinically derived relative weights was assessed to normalize for differentially scoring base rates with each endpoint component. The Parkinson’s disease comprehensive response, in contrast to examining practically defined OFF state Unified Parkinson’s Disease Rating Scale Motor Examination scores alone, showed stability over 40 weeks in placebo patients, and all 432 analyses in this permutation exercise yielded significant differences in favour of glial cell line-derived neurotrophic factor. The findings were consistent with results obtained employing three different global statistical test methodologies and with patterns of intra-patient change. Based on our detailed analyses, we conclude it worth prospectively evaluating the clinical utility, validity and regulatory feasibility of using clinically supported final Parkinson’s disease comprehensive response formulas (for both the Unified Parkinson’s Disease Rating Scale-based and Movement Disorders Society-Unified Parkinson’s Disease Rating Scale-based versions) in future disease-modifying Parkinson’s trials. Whilst the data source employed in the initial development of this weighted composite score is from a recent Phase II trial of glial cell line-derived neurotrophic factor, we wish to stress that the results are not described to provide post hoc evidence of the efficacy of glial cell line-derived neurotrophic factor but rather are presented to further the debate of how current regulatory approved rating scales may be combined to address some of the recognized limitations of using individual scales in isolation.

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Dance Rhythms Improve Motor Symptoms in Individuals with Parkinson’s Disease: A Randomized Clinical Trial

Journal of Dance Medicine & Science ◽

10.12678/1089-313x.031522a ◽

2021 ◽

Author(s):

Jéssica A. Moratelli ◽

Kettlyn H. Alexandre ◽

Leonessa Boing ◽

Alessandra Swarowsky ◽

Clynton L. Corrêa ◽

...

Keyword(s):

Parkinson’S Disease ◽

Clinical Trial ◽

Parkinson's Disease ◽

Randomized Clinical Trial ◽

Rating Scale ◽

Freezing Of Gait ◽

Motor Symptoms ◽

Score Change ◽

Significant Difference ◽

Binary Group

Background: Evidence-based practices involving dance modalities found in binary (two-beat rhythm) or quaternary (four-beat rhythm) show that dance positively influences the motor aspects of disease.Aim: This randomized clinical trial aimed to analyze the effect of two dance rhythm (binary and quaternary) on the balance, gait, and mobility in individuals with Parkinson’s disease (PD). Methods: Thirty-one individuals with PD were randomized into the binary group (n = 18) and the quaternary group (n = 13). Both groups participated in different dance rhythms lasting 12 weeks, twice a week, for 45 minutes. Results: The binary group showed a significant difference in balance (p = 0.003), freezing of gait (p = 0.007), as well as in the motor aspects of MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), with emphasis on the total values with a score change of 3.23. In the quaternary group, significant differences were found in balance (p = 0.021) with a score change of -2.54 and in the motor aspects of the MDS-UPDRS Part III where the total values stood out with a change of 3.54. Discussion: When comparing the possible effects of binary and quaternary rhythms on the motor symptoms of individuals with PD, it was demonstrated that binary rhythm improved balance, freezing gait, and UPDRSIII. As for the quaternary rhythm, the benefits were in balance and the UPDRSIII. Conclusion: The binary and the quaternary rhythm dance protocols positively influenced the motor symptoms of individuals with PD after 12 weeks of intervention.

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