Motor Symptoms Of Parkinson's Disease Research Articles

Evaluation of the Parkinson's Remote Interactive Monitoring System in a Clinical Setting: Usability Study.

The fastest-growing neurological disorder is Parkinson disease (PD), a progressive neurodegenerative disease that affects 10 million people worldwide. PD is typically treated with levodopa, an oral pill taken to increase dopamine levels, and other dopaminergic agonists. As the disease advances, the efficacy of the drug diminishes, necessitating adjustments in treatment dosage according to the patient's symptoms and disease progression. Therefore, remote monitoring systems that can provide more detailed and accurate information on a patient's condition regularly are a valuable tool for clinicians and patients to manage their medication. The Parkinson's Remote Interactive Monitoring System (PRIMS), developed by PragmaClin Research Inc, was designed on the premise that it will be an easy-to-use digital system that can accurately capture motor and nonmotor symptoms of PD remotely. We performed a usability evaluation in a simulated clinical environment to assess the ease of use of the PRIMS and determine whether the product offers suitable functionality for users in a clinical setting. Participants were recruited from a user sign-up web-based database owned by PragmaClin Research Inc. A total of 11 participants were included in the study based on the following criteria: (1) being diagnosed with PD and (2) not being diagnosed with dementia or any other comorbidities that would make it difficult to complete the PRIMS assessment safely and independently. Patient users completed a questionnaire that is based on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale. Interviews and field notes were analyzed for underlying themes and topics. In total, 11 people with PD participated in the study (female individuals: n=5, 45%; male individuals: n=6, 55%; age: mean 66.7, SD 7.77 years). Thematic analysis of the observer's notes revealed 6 central usability issues associated with the PRIMS. These were the following: (1) the automated voice prompts are confusing, (2) the small camera is problematic, (3) the motor test exhibits excessive sensitivity to the participant's orientation and position in relation to the cameras, (4) the system poses mobility challenges, (5) navigating the system is difficult, and (6) the motor test exhibits inconsistencies and technical issues. Thematic analysis of qualitative interview responses revealed four central themes associated with participants' perspectives and opinions on the PRIMS, which were (1) admiration of purpose, (2) excessive system sensitivity, (3) video instructions preferred, and (4) written instructions disliked. The average system usability score was calculated to be 69.2 (SD 4.92), which failed to meet the acceptable system usability score of 70. Although multiple areas of improvement were identified, most of the participants showed an affinity for the overarching objective of the PRIMS. This feedback is being used to upgrade the current PRIMS so that it aligns more with patients' needs.

Premotor cortical beta synchronization and the network neuromodulation of externally paced finger tapping in Parkinson's disease

Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13–30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency-range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. Following STN-DBS surgery, the magnitude of the post-event beta rebound was negatively correlated with the estimated volume of tissue activated of the zona incerta. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.

THE IMPACT OF FORCED-RATE EXERCISE AND/OR PHOTOBIOMODULATION COMPARED TO USUAL CARE ON METABOLIC SYNDROME SEVERITY IN PEOPLE WITH PARKINSON’S DISEASE

INTRODUCTION/AIMS Metabolic syndrome (MetS) has been postulated to play a role in the progression of Parkinson’s disease (PD). Several lines of evidence also suggest that forced-rate exercise (FRE) is a potent therapy to alleviate motor and non-motor symptoms of PD, and perhaps MetS severity (MSS). However, long-term exercise adherence in people with PD (PWP) is poor. Alternative/adjunct therapies are therefore warranted. Photobiomodulation (PBM) is an emerging non-pharmaceutical/non-exercise therapy that may improve PD symptoms. Thus, this study aimed to determine the impact of FRE and/or PBM relative to usual care on MSS in PWP. METHODS Twenty participants diagnosed with PD (aged 40-80yrs) were randomised into one of four groups assigned to a different sequence of the study interventions or SHAM treatment across four 8-week study periods, each separated by a 4-week wash-out period: (1) Group A-B-C-D (n=5); (2) Group B-D- A-C (n=5); (3) Group C-A-B-D (n=5); (4) Group D-C-B-A (n=5). A-B-C-D represents PBM, FRE, FRE+PBM, and SHAM, respectively. Z-scores were derived from levels of MetS risk factors to determine the MSS (MetS z-score). Responders to a clinically significant change in MetS z-score was classified as those demonstrating a reduction of at least 0.48. RESULTS Our preliminary analysis included 17 participants with 30 complete pre- and post-MetS z-score data sets (FRE, n=5; FRE+PBM, n=7; PBM, n=9; SHAM, n=9). There was no statistically significant difference between groups in MSS change from pre-to-post intervention (p=0.82). However, the FRE group showed the greatest proportion of MSS responders: 60% (3/5) compared to FRE+PBM (43%, 3/7), PBM (44%, 4/9), and SHAM (33%, 3/9). CONCLUSION FRE may be the most efficacious method of clinically improving MSS. However, our study also suggests that a combined FRE+PBM or PBM alone could be used as an initial or supplementary treatment in ameliorating MSS and thus potentially PD progression.

Biosensor Strip for Rapid On-site Assessment of Levodopa Pharmacokinetics along with Motor Performance in Parkinson's Disease.

While levodopa (L-Dopa) is the primary treatment for alleviating Parkinson's disease (PD), its efficacy is hindered by challenges such as a short half-life and inconsistent plasma levels. As PD progresses, the rising need for increased and more frequent L-Dopa doses coupled with symptom fluctuations and dyskinesias underscores the urgency for improved comprehension of the interplay between L-Dopa levels and PD motor symptoms. Addressing this critical need, we present a decentralized testing method using a disposable biosensor strip and a universal slope (U-slope) calibration-free approach. This enables reliable, rapid, simple, and cost-effective decentralized L-Dopa measurements from capillary blood. A pilot study with PD persons demonstrates the ability to monitor real-time L-Dopa pharmacokinetics from fingerstick blood after oral L-Dopa-Carbidopa (C-Dopa) tablet administration. Correlating capillary blood L-Dopa levels with PD motor scores revealed a well-defined inverse correlation with temporal motor fluctuations. We compared the resulting dynamic capillary blood L-Dopa levels with plasma L-Dopa levels using the traditional but clinically impractical high-performance liquid chromatography technique. By providing timely feedback on a proper L-Dopa dosing regimen in a decentralized and rapid fashion, this new biosensing platform will facilitate tailored optimal L-Dopa dosing, towards improving symptom management and enhancing health-related quality of life.

Biosensor Strip for Rapid On‐site Assessment of Levodopa Pharmacokinetics along with Motor Performance in Parkinson’s Disease

While levodopa (L‐Dopa) is the primary treatment for alleviating Parkinson's disease (PD), its efficacy is hindered by challenges such as a short half‐life and inconsistent plasma levels. As PD progresses, the rising need for increased and more frequent L‐Dopa doses coupled with symptom fluctuations and dyskinesias underscores the urgency for improved comprehension of the interplay between L‐Dopa levels and PD motor symptoms. Addressing this critical need, we present a decentralized testing method using a disposable biosensor strip and a universal slope (U‐slope) calibration‐free approach. This enables reliable, rapid, simple, and cost‐effective decentralized L‐Dopa measurements from capillary blood. A pilot study with PD persons demonstrates the ability to monitor real‐time L‐Dopa pharmacokinetics from fingerstick blood after oral L‐Dopa‐Carbidopa (C‐Dopa) tablet administration. Correlating capillary blood L‐Dopa levels with PD motor scores revealed a well‐defined inverse correlation with temporal motor fluctuations. We compared the resulting dynamic capillary blood L‐Dopa levels with plasma L‐Dopa levels using the traditional but clinically impractical high‐performance liquid chromatography technique. By providing timely feedback on a proper L‐Dopa dosing regimen in a decentralized and rapid fashion, this new biosensing platform will facilitate tailored optimal L‐Dopa dosing, towards improving symptom management and enhancing health‐related quality of life.

Effects of Blood Flow Restriction Resistance Training on Autonomic and Endothelial Function in Persons with Parkinson's Disease.

Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one's quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD). To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during LIRT-BFR and HIRT in PwPD using a novel exercise protocol. Thirty-eight PwPD were assigned LIRT-BFR, HIRT or to a control (CNTRL) group. The LIRT-BFR and HIRT groups exercised three days per week for four weeks. The LIRT-BFR protocol used 60% limb occlusion pressure (LOP) and performed three sets of 20 repetitions at 20% of the one-repetition maximum (1RM). The HIRT group performed three sets of eight repetitions at 80% 1RM. The CNTRL group was asked to continue their normal daily routines. LIRT-BFR significantly improved orthostatic hypotension (p = 0.026), homocysteine levels (p < 0.001), peripheral circulation (p = 0.003), supine blood pressure (p = 0.028) and heart rate variability (p = 0.041); LIRT-BFR improved homocysteine levels (p < 0.018), peripheral circulation (p = 0.005), supine blood pressure (p = 0.007) and heart rate variability (p = 0.047) more than HIRT; and hemodynamic loads for LIRT-BFR and HIRT were similar. LIRT-BFR may be more effective than HIRT for autonomic and endothelial function improvements in PwPD and hemodynamic loads may be lessened in LIRT-BFR protocols using single-joint exercises with intermittent blood flow restriction. Further research is needed to determine if non-motor symptoms improve over time and if results are sustainable.

General Treatments Promoting Independent Living in Parkinson's Patients and Physical Therapy Approaches for Improving Gait-A Comprehensive Review.

This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also manifesting in a variety of symptoms that vary greatly among individuals. The complexity of PD symptoms necessitates a comprehensive treatment strategy that integrates surgical interventions, pharmacotherapy, and physical therapy to tailor to the unique needs of each patient. Surgical options, such as deep brain stimulation (DBS), have been pivotal for patients not responding adequately to medication, offering significant symptom relief. Pharmacotherapy remains a cornerstone of PD management, utilizing drugs like levodopa, dopamine agonists, and others to manage symptoms and, in some cases, slow down disease progression. However, these treatments often lead to complications over time, such as motor fluctuations and dyskinesias, highlighting the need for precise dosage adjustments and sometimes combination therapies to optimize patient outcomes. Physical therapy plays a critical role in addressing the motor symptoms of PD, including bradykinesia, muscle rigidity, tremors, postural instability, and akinesia. PT techniques are tailored to improve mobility, balance, strength, and overall quality of life. Strategies such as gait and balance training, strengthening exercises, stretching, and functional training are employed to mitigate symptoms and enhance functional independence. Specialized approaches like proprioceptive neuromuscular facilitation (PNF), the Bobath concept, and the use of assistive devices are also integral to the rehabilitation process, aimed at improving patients' ability to perform daily activities and reducing the risk of falls. Innovations in technology have introduced robotic-assisted gait training (RAGT) and other assistive devices, offering new possibilities for patient care. These tools provide targeted support and feedback, allowing for more intensive and personalized rehabilitation sessions. Despite these advancements, high costs and accessibility issues remain challenges that need addressing. The inclusion of exercise and activity beyond structured PT sessions is encouraged, with evidence suggesting that regular physical activity can have neuroprotective effects, potentially slowing disease progression. Activities such as treadmill walking, cycling, and aquatic exercises not only improve physical symptoms but also contribute to emotional well-being and social interactions. In conclusion, treating PD requires a holistic approach that combines medical, surgical, and therapeutic strategies. While there is no cure, the goal is to maximize patients' functional abilities and quality of life through personalized treatment plans. This integrated approach, along with ongoing research and development of new therapies, offers hope for improving the management of PD and the lives of those affected by this challenging disease.

Dopaminergic Cell Replacement for Parkinson's Disease: Addressing the Intracranial Delivery Hurdle.

Parkinson's disease (PD) is an increasingly prevalent neurological disorder, affecting more than 8.5 million individuals worldwide. α-Synucleinopathy in PD is considered to cause dopaminergic neuronal loss in the substantia nigra, resulting in characteristic motor dysfunction that is the target for current medical and surgical therapies. Standard treatment for PD has remained unchanged for several decades and does not alter disease progression. Furthermore, symptomatic therapies for PD are limited by issues surrounding long-term efficacy and side effects. Cell replacement therapy (CRT) presents an alternative approach that has the potential to restore striatal dopaminergic input and ameliorate debilitating motor symptoms in PD. Despite promising pre-clinical data, CRT has demonstrated mixed success clinically. Recent advances in graft biology have renewed interest in the field, resulting in several worldwide ongoing clinical trials. However, factors surrounding the effective neurosurgical delivery of cell grafts have remained under-studied, despite their significant potential to influence therapeutic outcomes. Here, we focus on the key neurosurgical factors to consider for the clinical translation of CRT. We review the instruments that have been used for cell graft delivery, highlighting current features and limitations, while discussing how future devices could address these challenges. Finally, we review other novel developments that may enhance graft accessibility, delivery, and efficacy. Challenges surrounding neurosurgical delivery may critically contribute to the success of CRT, so it is crucial that we address these issues to ensure that CRT does not falter at the final hurdle.

Bodily Maps of Symptoms and Emotions in Parkinson's Disease.

Emotions are reflected in bodily sensations, and these reflections are abnormal in psychiatric conditions. However, emotion-related bodily sensations have not been studied in neurological disorders. The aim of this study was to investigate whether Parkinson's disease (PD) is associated with altered bodily representations of emotions. Symptoms and emotion-related sensations were investigated in 380 patients with PD and 79 control subjects, using a topographical self-report method, termed body sensation mapping. The bodily mapping data were analyzed with pixelwise generalized linear models and principal component analyses. Bodily maps of symptoms showed characteristic patterns of PD motor symptom distributions. Compared with control subjects, PD patients showed decreased parasternal sensation of anger, and longer PD symptom duration was associated with increased abdominal sensation of anger (PFWE < 0.05). The PD-related sensation patterns were abnormal across all basic emotions (P < 0.05). The results demonstrate altered bodily maps of emotions in PD, providing novel insight into the nonmotor effects of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Predicting Depression in Parkinson's Disease Using Commonly Available PD Questionnaires.

Background: Depression is common in patients with Parkinson's disease (PD) and significantly impacts both the patients and their caregivers. The associations between depression and the responses from commonly used questionnaires for PD patients were assessed. New patients presenting to the Movement Disorder Center completed a number of questionnaires, including assessments of the motor and non-motor symptoms of PD, including depression. Methods: The PD patients were grouped according to severity of depression: none, mild, and moderate-severe, based on the Geriatric Depression Scale (GDS) scores. The mean scores of the Unified PD Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), Non-motor Symptoms Scale (NMSS), PD Quality of life (PDQ-39), Hoehn and Yahr score (H&Y), levodopa equivalent daily dose (LEDD), and number of antidepressants used were collected. There were 1214 PD patients included. Results: Increasing depression scores were associated with worsening motor symptoms (according to the UPDRS and H&Y), non-motor symptoms (according to the NMSS), cognition (according to the MoCA), sleepiness (according to the ESS), and quality of life (according to the PDQ-39) (all p-values of p < 0.001). Only half of the patients with mild or moderate-severe depression were taking antidepressants, and the LEDD increased with depression severity. The risk of depression increased by 16% and 5% for every 1-point increase in the NMSS and PDQ-39 scores, respectively. Conclusions: Depression is often unrecognized and undertreated and should be assessed regularly in PD patients, especially in those who demonstrate changes in motor or non-motor symptoms.

Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review.

Neurodegenerative diseases are progressive disorders characterized by synaptic loss and neuronal death. Optogenetics combines optical and genetic methods to control the activity of specific cell types. The efficacy of this approach in neurodegenerative diseases has been investigated in many reviews, however, none of them tackled it systematically. Our study aimed to review systematically the findings of optogenetics and its potential applications in animal models of chronic neurodegenerative diseases and compare it with deep brain stimulation and designer receptors exclusively activated by designer drugs techniques. The search strategy was performed based on the PRISMA guidelines and the risk of bias was assessed following the Systematic Review Centre for Laboratory Animal Experimentation tool. A total of 247 articles were found, of which 53 were suitable for the qualitative analysis. Our data revealed that optogenetic manipulation of distinct neurons in the brain is efficient in rescuing memory impairment, alleviating neuroinflammation, and reducing plaque pathology in Alzheimer's disease. Similarly, this technique shows an advanced understanding of the contribution of various neurons involved in the basal ganglia pathways with Parkinson's disease motor symptoms and pathology. However, the optogenetic application using animal models of Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis was limited. Optogenetics is a promising technique that enhanced our knowledge in the research of neurodegenerative diseases and addressed potential therapeutic solutions for managing these diseases' symptoms and delaying their progression. Nevertheless, advanced investigations should be considered to improve optogenetic tools' efficacy and safety to pave the way for their translatability to the clinic.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1.

Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Association between fatigue and MDS-UPDRS in individuals with Parkinson's disease: cross-sectional study.

Fatigue is significant in the context of Parkinson's disease (PD), considering that one-third of patients classify it as the most restricting symptom in their daily life activities (DLAs). The objective was to verify the relationship (association) between fatigue and non-motor and motor symptoms of PD. A cross-sectional study which included 100 individuals with PD. Initially, demographic and clinical data (modified Hoehn and Yahr scale-HY, anxiety, and depression) were collected. To assess the non-motor and motor symptoms of PD, the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was applied. Fatigue was evaluated using the Parkinson Fatigue Scale. A higher HY score, greater severity of non-motor aspects of DLAs and motor aspects of DLAs, more motor complications, and higher levels of anxiety as well as depression were observed in the "fatigue" group. Fatigue was associated with a lower daily equivalent levodopa dose (LEDD), a higher body mass index (BMI), anxiety, depression, and the presence of non-motor symptoms. Non-motor symptoms are more determining factors for fatigue than the motor condition itself, with an association between fatigue and higher BMI scores, increased anxiety and depression, lower LEDD, and greater severity of non-motor aspects of DLAs. Individuals in the "fatigue" group had higher HY scores, anxiety, and depression, worse non-motor and motor symptoms related to experiences of daily life, as well as motor complications.

Investigating the efficacy and importance of mobile-based assessments for Parkinson's disease: uncovering the potential of novel digital tests

This study introduces PDMotion, a mobile application comprising 11 digital tests, including those adapted from the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and novel assessments, for remote Parkinson's Disease (PD) motor symptoms evaluation. Employing machine learning techniques on data from 50 PD patients and 29 healthy controls, PDMotion achieves accuracies of 0.878 for PD status prediction and 0.715 for severity assessment. A post-hoc explanation model is employed to assess the importance of features and tasks in diagnosis and severity evaluation. Notably, novel tasks that are not adapted from MDS-UPDRS Part III like the circle drawing, coordination test, and alternative tapping test are found to be highly important, suggesting digital assessments for PD can go beyond digitizing existing tests. The alternative tapping test emerges as the most significant task. Using its features alone achieves prediction accuracies comparable to the full task set, underscoring its potential as an independent screening tool. This study addresses a notable research gap by digitalizing a wide array of tests, including novel ones, and conducting a comparative analysis of their feature and task importance. These insights provide guidance for task selection and future development in PD mobile assessments, a field previously lacking such comparative studies.

Cortical-sparing chronic traumatic encephalopathy (CSCTE): a distinct subtype of CTE.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. Compared to typical high stage CTE, those with CSCTE had a similar age at death and years of contact sports participation and were less likely to carry apolipoprotein ε4 (p<0.05). CSCTE had less overall tau pathology severity, but a proportional increase of disease burden in medial temporal lobe and brainstem regions compared to the neocortex (p's<0.001). CSCTE also had lower prevalence of comorbid neurodegenerative disease. Clinically, CSCTE participants were less likely to have dementia (p= 0.023) and had less severe cognitive difficulties (as reported by informants using the Functional Activities Questionnaire (FAQ); p<0.001, meta-cognitional index T score; p=0.002 and Cognitive Difficulties Scale (CDS); p<0.001,) but had an earlier onset age of behavioral (p=0.006) and Parkinsonian motor (p=0.013) symptoms when compared to typical high stage CTE. Other comorbid tauopathies likely contributed in part to these differences: when cases with concurrent Alzheimer dementia or frontal temporal lobar degeneration with tau pathology were excluded, differences were largely retained, but only remained significant for FAQ (p=0.042), meta-cognition index T score (p=0.014) and age of Parkinsonian motor symptom onset (p=0.046). Overall, CSCTE appears to be a distinct subtype of high stage CTE with relatively greater involvement of subcortical and brainstem regions and less severe cognitive symptoms.

Brazilian dance self-perceived impacts on quality of life of people with Parkinson's.

Parkinson's disease (PD) causes several motor and non-motor symptoms, resulting in negative impacts on physical, mental, emotional, and social aspects of people with PD quality of life. Dance has been considered as a potential non-pharmacological intervention to improve people with PD motor and non-motor symptoms, thereby enhancing quality of life. To analyze the self-perceive impacts of Brazilian Dance on the quality of life (physical, mental, emotional, and social) of PwPD, both before and during the COVID-19 pandemic. Fourteen participants from the "Dança & Parkinson" project were included in this qualitative study. Data collection instruments consisted of a profile and personal data sheet; assessment of accessibility to the online dance classes; Telephone Montreal Cognitive Assessment by phone call; and semi-structured interview conducted through ZOOM video call. The participants characterization data were calculated using mean, standard deviation, and percentages with the Excel Program version 2013. Qualitative data was analyzed using the Thematic Analysis technique in the Nvivo, version 8.0, qualitative analysis of text, sound, and video program. The participants reported facing various challenges in dealing with PD, which negatively impact their quality of life. However, their resilience, acceptance, and dedication to treatment play an important role in coping with the issues related to the disease. Brazilian dance, both in-person before the COVID-19 pandemic and online during the pandemic, led the participants to perceive improvements in physical, mental, emotional, and social aspects of quality of life. The Brazilian dance appears to have a positive impact on the physical, mental, emotional, and social aspects of the participants' quality of life, both before and during the COVID-19 pandemic.

Electroacupuncture at ST25 corrected gut microbial dysbiosis and SNpc lipid peroxidation in Parkinson's disease rats.

Parkinson's disease (PD) remains one kind of a complex, progressive neurodegenerative disease. Levodopa and dopamine agonists as widely utilized PD therapeutics have not shown significant positive long-term outcomes. Emerging evidences indicate that electroacupuncture (EA) have potential effects on the therapy of nervous system disorders, particularly PD, but its specific underlying mechanism(s) remains poorly understood, leading to the great challenge of clinical application and management. Previous study has shown that acupuncture ameliorates PD motor symptoms and dopaminergic neuron damage by modulating intestinal dysbiosis, but its intermediate pathway has not been sufficiently investigated. A rat model of PD was induced using rotenone. The therapeutic effect of EA on PD was assessed using the pole and rotarod tests and immunohistostaining for tyrosine hydroxylase (TH) in the substantia nigra (SN) of brain. The role of gut microbiota was explored using 16S rRNA gene sequencing and metabonomic analysis. PICRUSt2 analysis, lipidomic analysis, LPS and inflammatory factor assays were used for subsequent exploration and validation. Correlation analysis was used to identify the key bacteria that EA regulates lipid metabolism to improve PD. The present study firstly reappeared the effects of EA on protecting motor function and dopaminergic neurons and modulation of gut microbial dysbiosis in rotenone-induced PD rat model. EA improved motor dysfunction (via the pole and rotarod tests) and protected TH+ neurons in PD rats. EA increased the abundance of beneficial bacteria such as Lactobacillus, Dubosiella and Bifidobacterium and decreased the abundance of Escherichia-Shigella and Morganella belonging to Pseudomonadota, suggesting that the modulation of gut microbiota by EA improving the symptoms of PD motility via alleviating LPS-induced inflammatory response and oxidative stress, which was also validated by various aspects such as microbial gene functional analysis, fecal metabolomics analysis, LPS and inflammatory factor assays and SNpc lipidomics analysis. Moreover, correlation analyses also verified strong correlations of Escherichia-Shigella and Morganella with motor symptoms and SNpc lipid peroxidation, explicating targets and intermediate pathways through which EA improve PD exercise symptom. Our results indicate that the improvement of motor function in PD model by EA may be mediated in part by restoring the gut microbiota, which intermediate processes involve circulating endotoxins and inflammatory mediators, SNpc oxidative stress and lipid peroxidation. The gut-microbiome - brain axis may be a potential mechanism of EA treatment for the PD.

Effects and Mechanisms of Exercise on Brain-Derived Neurotrophic Factor (BDNF) Levels and Clinical Outcomes in People with Parkinson's Disease: A Systematic Review and Meta-Analysis.

Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson's disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson's disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I2 = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as "good" in three trials, "fair" in one trial, and "poor" in one trial. Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF.

Effects of dietary supplements, foods, and dietary patterns in Parkinson's disease: meta-analysis and systematic review of randomized and crossover studies.

Diet significantly impacts Parkinson's disease (PD) with plausible biological hypotheses. Although the thesis has been explored in several human clinical trials, no current meta-analyses or reviews summarize the results. We examined the effect of intervention of dietary supplements, foods, and dietary patterns in treating PD. We conducted a meta-analysis and systematic review of randomized and crossover studies published between 1989 and 26 June 2022, searching from PubMed, Embase, Medline, Scopus, Cochrane Library databases, and Chinese databases. Twenty-four studies were included in this review. The meta-analysis results show that dietary supplements intervention significantly increased the quantitative insulin sensitivity check index (QUICKI) [MD = 0.02, 95% CI (0.01, 0.02), p < 0.00001]. Dietary supplement intervention does not significantly affect the total Unified Parkinson Disease Rating Scale (UPDRS) score and six-min walk test (6MWT) distance. We did not find evidence that dietary supplements or food intervention may minimize the UPDRS III score. However, systematic review results indicated that the Mediterranean, low-fat, and ketogenic diets significantly reduced the total UPDRS score; low-protein diets meaningfully mitigated motor symptoms. This meta-analysis result displays that diet and diet supplements had a very modest but statistically significant impact on QUICKI but no effect on motor and non-motor symptoms in PD. The systematic review concludes that dietary patterns intervention may positively attenuate the overall symptoms of PD, including both motor and non-motor symptoms.

The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson's Disease: a New Genetic State of the Art.

Parkinson's disease (PD) is a neurodegenerative disorder affecting 2-3% of those aged over 65, characterized by motor symptoms like slow movement, tremors, and muscle rigidity, along with non-motor symptoms such as anxiety and dementia. Lewy bodies, clumps of misfolded proteins, contribute to neuron loss in PD. Mutations in the GBA1 gene are considered the primary genetic risk factor of PD. GBA1 mutations result in decreased activity of the lysosomal enzyme glucocerebrosidase (GCase) resulting in α-synuclein accumulation. We know that α-synuclein aggregation, lysosomal dysfunction, and endoplasmic reticulum disturbance are recognized factors to PD susceptibility; however, the molecular mechanisms connecting GBA1 gene mutations to increased PD risk remain partly unknown. Thus, in this narrative review conducted according to a systematic review method, we aimed to present the main contributions arising from the molecular impact of the GBA1 gene to the pathogenesis of PD providing new insights into potential impacts for advances in the clinical care of people with PD, a neurological disorder that has contributed to the substantial increase in the global burden of disease accentuated by the aging population. In summary, this narrative review highlights the multifaceted impact of GBA1 mutations in PD, exploring their role in clinical manifestations, genetic predispositions, and molecular mechanisms. The review emphasizes the importance of GBA1 mutations in both motor and non-motor symptoms of PD, suggesting broader therapeutic and management strategies. It also discusses the potential of CRISPR/Cas9 technology in advancing PD treatment and the need for future research to integrate these diverse aspects for improved diagnostics and therapies.