Motor Symptoms Of Parkinson's Disease Research Articles

Rehabilitation for non-motor symptoms for patients with Parkinson's disease from an α-synuclein perspective: a narrative review.

Parkinson's disease (PD) is a common neurodegenerative disorder affecting aged population around the world. PD is characterized by neuronal Lewy bodies present in the substantia nigra of the midbrain and the loss of dopaminergic neurons with various motor and non-motor symptoms associated with the disease. The protein α-synuclein has been extensively studied for its contribution to PD pathology, as α-synuclein aggregates form the major component of Lewy bodies, a hallmark of PD. In this narrative review, the authors first focus on a brief explanation of α-synuclein aggregation and circumstances under which aggregation can occur, then present a hypothesis for PD pathogenesis in the peripheral nervous system (PNS) and how PD can spread to the central nervous system from the PNS via the transport of α-synuclein aggregates. This article presents arguments both for and against this hypothesis. It also presents various non-pharmacological rehabilitation approaches and management techniques for both motor and non-motor symptoms of PD and the related pathology. This review seeks to examine a possible hypothesis of PD pathogenesis and points to a new research direction focus on rehabilitation therapy for patients with PD. As various non-motor symptoms of PD appear to occur earlier than motor symptoms, more focus on the treatment of non-motor symptoms as well as a better understanding of the biochemical mechanisms behind those non-motor symptoms may lead to better long-term outcomes for patients with PD.

Bradykinesia and rigidity modulated by functional connectivity between the primary motor cortex and globus pallidus in Parkinson's disease.

The mechanisms underlying motor fluctuations in patients with Parkinson's disease (PD) are currently unclear. Regional brain stimulation reported the changing of motor symptoms, but the correlation with functional connectivity (FC) in the brain network is not fully understood. Hence, our study aimed to explore the relationship between motor symptom severity and FC using resting-state functional magnetic resonance imaging (rsfMRI) in the "on" and "off" states of PD. In 26 patients with sporadic PD, FC was assessed using rsfMRI, and clinical severity was analyzed using the motor part of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III) in the on and off states. Correlations between FC values and MDS-UPDRS Part III scores were assessed using Pearson's correlation coefficient. The correlation between FC and motor symptoms differed in the on and off states. FC between the ipsilateral precentral gyrus (PreCG) and globus pallidus (GP) correlated with the total MDS-UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Lateralization analysis indicated that FC between the PreCG and GP correlated with the contralateral total MDS-UPDRS Part III scores and those for bradykinesia/rigidity in the off state. Aberrant FC in cortico-striatal circuits correlated with the severity of motor symptoms in PD. Cortico-striatal hyperconnectivity, particularly in motor pathways involving PreCG and GP, is related to motor impairments in PD. These findings may facilitate our understanding of the mechanisms underlying motor symptoms in PD and aid in developing treatment strategies such as brain stimulation for motor impairment.

The Parkinson's disease waiting room of the future: measurements, not magazines.

Utilizing technology to precisely quantify Parkinson's disease motor symptoms has evolved over the past 50 years from single point in time assessments using traditional biomechanical approaches to continuous monitoring of performance with wearables. Despite advances in the precision, usability, availability and affordability of technology, the "gold standard" for assessing Parkinson's motor symptoms continues to be a subjective clinical assessment as none of these technologies have been fully integrated into routine clinical care of Parkinson's disease patients. To facilitate the integration of technology into routine clinical care, the Develop with Clinical Intent (DCI) model was created. The DCI model takes a unique approach to the development and integration of technology into clinical practice by focusing on the clinical problem to be solved by technology rather than focusing on the technology and then contemplating how it could be integrated into clinical care. The DCI model was successfully used to develop the Parkinson's disease Waiting Room of the Future (WROTF) within the Center for Neurological Restoration at the Cleveland Clinic. Within the WROTF, Parkinson's disease patients complete the self-directed PD-Optimize application on an iPad. The PD-Optimize platform contains cognitive and motor assessments to quantify PD symptoms that are difficult and time-consuming to evaluate clinically. PD-Optimize is completed by the patient prior to their medical appointment and the results are immediately integrated into the electronic health record for discussion with the movement disorder neurologist. Insights from the clinical use of PD-Optimize has spurred the development of a virtual reality technology to evaluate instrumental activities of daily living in PD patients. This new technology will undergo rigorous assessment and validation as dictated by the DCI model. The DCI model is intended to serve as a health enablement roadmap to formalize and accelerate the process of bringing the advantages of cutting-edge technology to those who could benefit the most: the patient.

Suppression of beta oscillations by delayed feedback in a cortex-basal ganglia-thalamus-pedunculopontine nucleus neural loop model.

Excessive neural synchronization of neural populations in the beta (β) frequency range (12-35 Hz) is intimately related to the symptoms of hypokinesia in Parkinson's disease (PD). Studies have shown that delayed feedback stimulation strategies can interrupt excessive neural synchronization and effectively alleviate symptoms associated with PD dyskinesia. Work on optimizing delayed feedback algorithms continues to progress, yet it remains challenging to further improve the inhibitory effect with reduced energy expenditure. Therefore, we first established a neural mass model of the cortex-basal ganglia-thalamus-pedunculopontine nucleus (CBGTh-PPN) closed-loop system, which can reflect the internal properties of cortical and basal ganglia neurons and their intrinsic connections with thalamic and pedunculopontine nucleus neurons. Second, the inhibitory effects of three delayed feedback schemes based on the external globus pallidum (GPe) on β oscillations were investigated separately and compared with those based on the subthalamic nucleus (STN) only. Our results show that all four delayed feedback schemes achieve effective suppression of pathological β oscillations when using the linear delayed feedback algorithm. The comparison revealed that the three GPe-based delayed feedback stimulation strategies were able to have a greater range of oscillation suppression with reduced energy consumption, thus improving control performance effectively, suggesting that they may be more effective for the relief of Parkinson's motor symptoms in practical applications.

Enhancing Quality of Life in Parkinson’s Disease: A Systematic Review of Occupational Therapy Interventions on Balance and Reaction Time

Background: Parkinson's disease (PD) is a common neurodegenerative disorder affecting the elderly population and can lead to impaired balance, reaction time, and overall quality of life (QoL). Occupational therapy interventions have shown promise in managing the motor and non-motor symptoms of PD. This systematic review aims to evaluate the effectiveness of occupational therapy intervention on balance and reaction time to enhance the quality of life in patients with Parkinson's disease.
 Methods: A comprehensive search was conducted on various electronic databases, including PubMed, Google Scholar, and ResearchGate. Studies published between 2010 and 2022 were included in the review. Inclusion criteria were set for age, clinical diagnosis of Parkinson's disease, MoCA score, and cooperation for participation. Studies that did not meet the inclusion criteria or reported other interventions were excluded. Data from selected studies were analyzed for relevance, appropriateness, clarity, and methodology.
 Results: Out of the initial 250 potentially relevant articles, 200 were identified as duplicates and removed. Another 25 studies did not meet the inclusion criteria, and 15 studies did not provide sufficient information on the interventions. Eventually, 10 studies were included in this systematic review. All the studies were qualitative in nature and were published between 2010 and 2023.
 Conclusion: Occupational therapy interventions have shown promising results in enhancing balance, reaction time, and quality of life in patients with Parkinson's disease. The review emphasizes the importance of goal-oriented occupational therapy programs to improve the overall well-being of patients with PD. Further research in this area is warranted to strengthen the evidence and guide clinical practice for better management of Parkinson's disease.

Jumping to conclusions bias, psychosis and impulsivity in early stages of Parkinson’s disease

ObjectivesThe aim was to explore the correlations between Jumping to Conclusions (JtC) tendency and neuropsychiatric features in patients with early Parkinson’s disease (PD).BackgroundAccording to few reports, PD patients with impulsive–compulsive behaviors (ICBs) are prone to working memory difficulties including JtC bias. The correlation of psychotic features and JtC tendency remains still unclear.MethodsHealthy controls and patients within 3 years of PD onset were recruited. Participants were examined for psychotic symptoms using a 10 question PD-specific psychosis severity scale. JtC was measured by a probalistic reasoning scenario (beads task). In PD group, medication use, motor and non-motor symptoms were documented. Impulsivity was evaluated using the Questionnaire for Impulsive–Compulsive Disorders in PD (QUIP).ResultsThe prevalence of JtC bias was 9% (6/70) in healthy individuals, compared to 32% (22/68) of PD group [p = 0.001]. No association was detected between the presence of JtC tendency and PD-associated psychosis (p = 0.216). Patients with JtC had shorter duration of PD, more tremor-dominant PD subtype and higher QUIP scores, regardless of the dopaminergic therapy (p = 0.043, p = 0.015, p = 0.007, respectively). A trend towards attention and inhibition control deficit was noticed in JtC patients.ConclusionsWe found a high prevalence of JtC bias in early, cognitively intact PD population and a potential link between subthreshold ICBs and poor performance on beads task. Additional studies are needed to confirm our results and elaborate on the mechanisms that correlate impulsivity with JtC tendency, which are likely to be different from those mediating psychotic features in early PD.

Distinct amyloid-dependent patterns of nigra dopamine depletion in Lewy body diseases.

Concomitant amyloid pathology is not uncommon and contributes to the clinical characteristics of Lewy body disease (LBD). We investigated the effect of amyloid on striatal18F-FP-CIT uptake patterns in LBD, including Parkinson's disease (PD) and dementia with Lewy bodies. We enrolled 125 patients with LBD who underwent18F-florbetaben positron emission tomography (PET) and18F-FP-CIT PET. Patients were divided into amyloid-positive and amyloid-negative groups. We investigated the effect of amyloid on striatal dopamine transporter (DAT) availability, depending on the type of LBD, using general linear models with interaction analysis after controlling for age, sex, education, deep white matter hyperintensity (WMH), periventricular WMH, and cognitive status. There was a significant interaction effect between the disease group and the presence of amyloid on DAT availability in the anterior putamen, posterior putamen, caudate, and ventral striatum. In the presence of amyloid, only the PD group exhibited decreased DAT availability in the anterior and posterior putamen. In both groups, the presence of amyloid was not associated with DAT availability in the caudate and ventral striatum. The presence of amyloid was not directly related to the worse parkinsonian motor symptoms in both groups. However, there was a significant indirect effect of amyloid on parkinsonian motor symptoms, which was mediated by anterior and posterior putaminal DAT availability in the PD group alone. This study demonstrates different amyloid-dependent or amyloid-independent18F-FP-CIT PET patterns in patients with LBD, suggesting distinctive interactions between α-synuclein and amyloid pathology based on the type of LBD.

Time perception reflects individual differences in motor and non-motor symptoms of Parkinson's disease

Decreasing dopaminergic function is at the core of Parkinson's disease (PD) motor symptoms and changes in dopaminergic action are associated with many comorbid non-motor symptoms in PD. Notably, dopaminergic signaling in the striatum has been shown to play a critical role in the perception of time. We hypothesize that patients with PD perceive time differently and in accordance with their specific comorbid non-motor symptoms and clinical state. This means that individual differences in clinical symptoms may be reflected in individual differences in timing behavior. To test this hypothesis, we recruited patients with PD and compared individual differences in patients' clinical state with their ability to judge intervals of time ranging from 500 ms to 1100 ms while on and off their prescribed dopaminergic medications. We show that medication state (on vs. off medications) did not affect timing behavior, but individual differences in timing behavior are able to predict individual differences in comorbid non-motor symptoms, duration of PD diagnosis, and prescribed dopaminergic medications. We show that comorbid impulse control disorder is associated with temporal overestimation; depression is associated with decreased temporal accuracy; and increased PD duration and prescribed levodopa monotherapy are associated with reduced temporal precision and accuracy. Observed differences in time perception are consistent with hypothesized dopaminergic mechanisms thought to underlie the respective motor and non-motor symptoms in PD. In future work, time perception tasks may augment clinical diagnosis strategies, or help disentangle the neural and cognitive mechanisms underlying PD motor and non-motor symptom etiology.

Antidiabetic agents as a novel treatment for Alzheimer's and Parkinson's disease.

Therapeutic strategies for neurodegenerative disorders have commonly targeted individual aspects of the disease pathogenesis to little success. Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by several pathological features. In AD and PD, there is an abnormal accumulation of toxic proteins, increased inflammation, decreased synaptic function, neuronal loss, increased astrocyte activation, and perhaps a state of insulin resistance. Epidemiological evidence has revealed a link between AD/PD and type 2 diabetes mellitus, with these disorders sharing some pathological commonalities. Such a link has opened up a promising avenue for repurposing antidiabetic agents in the treatment of neurodegenerative disorders. A successful therapeutic strategy for AD/PD would likely require a single or several agents which target the separate pathological processes in the disease. Targeting cerebral insulin signalling produces numerous neuroprotective effects in preclinical AD/PD brain models. Clinical trials have shown the promise of approved diabetic compounds in improving motor symptoms of PD and preventing neurodegenerative decline, with numerous further phase II trials and phase III trials underway in AD and PD populations. Alongside insulin signalling, targeting incretin receptors in the brain represents one of the most promising strategies for repurposing currently available agents for the treatment of AD/PD. Most notably, glucagon-like-peptide-1 (GLP-1) receptor agonists have displayed impressive clinical potential in preclinical and early clinical studies. In AD the GLP-1 receptor agonist, liraglutide, has been demonstrated to improve cerebral glucose metabolism and functional connectivity in small-scale pilot trials. Whilst in PD, the GLP-1 receptor agonist exenatide is effective in restoring motor function and cognition. Targeting brain incretin receptors reduces inflammation, inhibits apoptosis, prevents toxic protein aggregation, enhances long-term potentiation and autophagy as well as restores dysfunctional insulin signalling. Support is also increasing for the use of additional approved diabetic treatments, including intranasal insulin, metformin hydrochloride, peroxisome proliferator-activated nuclear receptor γ agonists, amylin analogs, and protein tyrosine phosphatase 1B inhibitors which are in the investigation for deployment in PD and AD treatment. As such, we provide a comprehensive review of several promising anti-diabetic agents for the treatment of AD and PD.

Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (NPTX1) as synapto-axonal target in late-stage Parkinson's disease.

Parkinson's disease (PD) affects a significant proportion of the population over the age of 60 years, and its prevalence is increasing. While symptomatic treatment is available for motor symptoms of PD, non-motor complications such as dementia result in diminished life quality for patients and are far more difficult to treat. In this study, we analyzed PD-associated alterations in the hippocampus of PD patients, since this brain region is strongly affected by PD dementia. We focused on synapses, analyzing the proteome of post-mortal hippocampal tissue from 16 PD cases and 14 control subjects by mass spectrometry. Whole tissue lysates and synaptosomal fractions were analyzed in parallel. Differential analysis combined with bioinformatic network analyses identified neuronal pentraxin 1 (NPTX1) to be significantly dysregulated in PD and interacting with proteins of the synaptic compartment. Modulation of NPTX1 protein levels in primary hippocampal neuron cultures validated its role in synapse morphology. Our analysis suggests that NPTX1 contributes to synaptic pathology in late-stage PD and represents a putative target for novel therapeutic strategies.

Differential Implications of Cerebral Hypoperfusion and Hyperperfusion in Parkinson's Disease.

Patients with Parkinson's disease (PD) exhibit widespread brain perfusion changes. This study investigated whether cerebral regions with hypoperfusion and hyperperfusion have differential effects on motor and cognitive symptoms in PD using early-phase 18 F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (18 F-FP-CIT) positron emission tomography (PET) scans. We enrolled 394 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET scans. Indices reflecting associated changes in regional cerebral hypoperfusion and hyperperfusion on early-phase 18 F-FP-CIT PET scans were calculated as PD[hypo] and PD[hyper] , respectively. The associations of PD[hypo] and PD[hyper] on motor and cognitive symptoms at baseline were assessed using multivariate linear regression. Also, Cox regression and linear mixed models were performed to investigate the effects of baseline PD[hypo] and PD[hyper] on longitudinal outcomes. There was a weak correlation between PD[hypo] and PD[hyper] (γ = -0.19, P < 0.001). PD[hypo] was associated with baseline Unified Parkinson's Disease Rating Scale Part III scores (β = -1.02, P = 0.045), rapid increases in dopaminergic medications (β = -18.02, P < 0.001), and a higher risk for developing freezing of gait (hazard ratio [HR] = 0.67, P = 0.019), whereas PD[hyper] was not associated. Regarding cognitive function, PD[hypo] was more relevant to the baseline cognitive performance levels of visuospatial, memory, and frontal/executive function than PD[hyper] . However, greater PD[hyper] was associated with future dementia conversion (HR = 1.43, P = 0.004), whereas PD[hypo] was not associated. These findings suggest that PD[hypo] and PD[hyper] may differentially affect motor and cognitive functions in patients with PD. © 2023 International Parkinson and Movement Disorder Society.

What Dietary Vitamins and Minerals Might Be Protective against Parkinson's Disease?

Dietary constituents may affect the progression of Parkinson's disease (PD). This study aimed to assess the contribution of dietary intake of vitamins and minerals to the severity, motor and non-motor symptoms, and risk of PD. In this case-control study, 120 patients with PD and 50 healthy participants participated. Dietary intake of vitamins and minerals was determined using a 147-item food frequency questionnaire. The severity of PD was determined by the Unified Parkinson's Disease Rating Scale (UPDRS). Patients with PD had lower intake of several vitamins and minerals including lycopene, thiamine, vitamin B6, vitamin B12, pantothenic acid, magnesium, zinc, manganese, selenium, chromium, and phosphorus, but had higher intake of α-tocopherol. High dietary intake of vitamin A, α-carotene, β-cryptoxanthin, vitamin C, and α-tocopherol were correlated with increased odds of PD. High intake of lycopene, thiamin, vitamin B6, pantothenic acid, magnesium, zinc, manganese, chromium, and phosphorous correlated with reduced odds of PD. The predictive power of α-tocopherol concerning the risk of PD was stronger relative to other vitamins. Dietary intake of pantothenic acid was negatively correlated with PD severity and symptoms of motor examination and complication. The severity and motor symptoms of PD were also negatively correlated with β-carotene, vitamin C, riboflavin, vitamin B6, and biotin intake. The UPDRS total score and motor symptoms in PD patients were negatively correlated with phosphorus, magnesium, zinc, manganese, and chromium, and strongly with potassium intake. The findings indicate that adequate dietary intake of vitamins and minerals may have a preventive effect on developing PD and progression of motor decline.

A wearable inertial system to evaluate Tai Chi training motor effects in patients with Parkinson's disease.

Physical therapy is strongly recommended for patients with neurological disorders. Tai Chi-based treatments seem to improve physical functions like gait speed and balance. However, assessments after treatment rely on semi-quantitative clinical scales affected by subjectivity with controversial results. This study aims at investigating whether Tai Chi could be a valid alternative to traditional physiotherapy rehabilitation. We propose a wearable system composed of two inertial devices able to objectively measure the effect of the rehabilitation treatment on the range of movement of the trunk. Seventeen patients with Parkinson's Disease (PD) were recruited and assessed. They have been randomly divided into two groups: group 1 followed a Tai Chi-based treatment, while group 2 underwent a traditional physiotherapy rehabilitation. The two groups have been assessed before (t0) and after the treatment (t1). No statistical differences have been found in the relative range of motion between the upper and lower sensors between the two groups at the baseline. Both treatments resulted in a significant improvement in the trunk range of movement (on the right side). Notably, the improvement in the effect size of the treatment was greater in group 1 than in group 2. In fact, even if both the groups benefited from their treatment group 1 gained larger mobility of the trunk if compared to group 2. Interestingly, no differences have been accounted adopting the traditional UPDRS III for motor symptoms of PD, strengthening the idea that objective measurement coming from wearable biomedical sensors could detect information otherwise neglected by traditional clinical tools.Clinical Relevance- This study preliminary confirms that beneficial motor effects after a Tai Chi rehabilitation program are comparable and quite better than after traditional physiotherapy, promoting Tai Chi as a valid alternative treatment for PD patients.

A pilot study for testing a low-cost 3D design with an inertial sensor for the quantitative assessment of finger tapping in patients with Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders worldwide. Current identification and monitoring of its motor symptoms depends on the clinical expertise. Repetitive finger tapping is one of the most common clinical maneuvers to assess for bradykinesia. Despite the increasing use of technology aids to quantitatively characterize the motor symptoms of PD, there is still a relative lack of clinical evidence to support their widespread use, particularly in low-resource settings. In this pilot study, we used a low-cost design prototype coupled with an inertial sensor is coupled to quantify the frequency of the finger tapping movements in four participants with PD. Repetitive finger tapping was performed using both hands before and after taking levodopa as part of their clinical treatment. The proposed 3D design allowed repetitive movements to be performed without issues. The maximum frequency of finger tapping was in the range of 0.1 to 4.3 Hz. Levodopa was associated with variable changes in the maximum frequency of finger tapping. This pilot study shows the feasibility for low-cost technology to quantitatively characterize repetitive movements in people living with PD.Clinical relevance- In this pilot study, a low-cost inertial sensor coupled to a design prototype was feasible to characterize the frequency of repetitive finger tapping movements in four participants with PD. This method could be used to quantitatively identify and monitor bradykinesia in people living with PD.

The Association of the Glymphatic Function with Parkinson's Disease Symptoms: Neuroimaging Evidence from Longitudinal and Cross-Sectional Studies.

Emerging pathological evidence suggests that there is an association between glymphatic dysfunction and the progression of Parkinson's disease (PD). However, the clinical evidence of this association remains lacking. In this study, the index for diffusion tensor image analysis along the perivascular space (ALPS index) was calculated to evaluate glymphatic function. Overall, 289 patients with PD were enrolled in the cross-sectional study. The ALPS index was found to be negatively correlated with age, disease severity, and dyskinesia. In the longitudinal study, the information on a total of 95 PD patients with 5-year follow-up examinations was collected from the Parkinson's Progression Marker Initiative, 33 of which were classified into the low ALPS index group, and all others were classified into the mid-high ALPS index group based on the first tertile of the baseline ALPS index. The results of longitudinal regression indicated that there was a significant main group effect on autonomic dysfunction, as well as on activities of daily living. In addition, the low ALPS index group had faster deterioration in MDS-UPDRS part III and part II, Symbol Digit Modalities Test and Hopkins Verbal Learning Test. Path analysis showed that ALPS index acted as a significant mediator between tTau/ Aβ1-42 and cognitive change in the Symbol Digit Modalities Test score at year 4 and year 5. The ALPS index, an neuroimaging marker of glymphatic function, is correlated with PD disease severity, motor symptoms, and autonomic function, and is predictive of faster deterioration in motor symptoms and cognitive function. Additionally, glymphatic function may mediate the pathological role of toxic protein in cognitive decline. ANN NEUROL 2023;94:672-683.

Parkinson’s disease. Focus on early stages

The review presents current data on the peculiarities of the neurodegenerative process in the early stages of Parkinson’s disease (PD) and considers the hypothesis of the presence of body-first and brain-first subtypes of the disease onset. The earliest manifestations of the disease include symptoms such as parasomnia, constipation, hyposmia, anxiety-depressive disorder, daytime sleepiness, color perception changes, cognitive dysfunction, and mild motor manifestations. The diagnosis of PD can be made when characteristic motor manifestations occur: hypokinesia, rest tremor, muscle rigidity. Substantia nigra ultrasound, magnetic resonance imaging in SWI mode, and functional neuroimaging methods are used as confirmatory methods. The approach to the treatment of early stages of PD is age dependent. Patients over 70 years of age are recommended to start therapy with levodopa; younger patients – with dopamine receptor agonists (ADR), amantadines, MAO-B inhibitors. The mechanisms of ADR action, the possibility of their influence on the motor and non-motor symptoms of PD are analyzed. A special place is given to piribedil, which, due to the dual mechanism of action, has a positive effect on cognitive functions, depression, apathy, as well as a minimal effect on daytime sleepiness.

Irritable bowel syndrome based on Rome IV diagnostic criteria associates with non-motor symptoms of Parkinson's disease

BackgroundRecent concepts suggest that the neuropathological hallmark of Parkinson's disease (PD) may in part originate from the enteric nervous system. We evaluated the frequency of functional gastrointestinal disorders in PD patients using Rome IV criteria and correlated the clinical severity of PD. MethodsPD patients and matched controls were recruited between January 2020 and December 2021. Rome IV criteria were used to diagnose constipation and irritable bowel syndrome (IBS). Severity of PD motor symptoms was evaluated using UPDRS part III scores and non-motor symptoms using Non-motor Symptoms Scale (NMSS). ResultsA total of 99 PD patients and 64 controls were enrolled. The prevalence of constipation (65.7% vs. 34.3%, P < 0.001) and IBS (18.1% vs 5%, P = 0.02) were significantly higher in PD patients than controls. The prevalence of IBS was higher in early-stage PD than advanced-stage PD (14.43% vs. 8.25%, P = 0.02), whereas constipation was more common in advanced stages (71.43% vs. 18.56%, P < 0.001). PD patients with IBS had higher NMSS total scores (P < 0.01) than those without IBS. The severity of IBS correlated with NMSS scores (r = 0.71, P < 0.001), especially subscores in domain 3 assessing mood disorders (r = 0.83, P < 0.001), but not UPDRS part III scores (r = 0.06, P = 0.45). The severity of constipation correlated with the UPDRS part III scores (r = 0.59, P < 0.001) but not the domain 3 mood subscores (r = 0.15, P = 0.07). ConclusionThe prevalence of IBS and constipation was higher in PD patients than controls and phenotypic correlation supported the occurrence of IBS with higher non-motor symptom burden, especially mood symptoms, in PD patients.

An Overview of Animal Models and Symptomatic Treatment of Parkinson’s disease

The broad theory indicate that neurological ailment is caused by intricate interactions between environmental and genetic factors is supported using animal models to better understand the the cause and pathogenesis of Parkinson's disease (PD), as well as its cellular and molecular mechanisms. The more recent models use genetic manipulations that either introduce mutations similar to those found in familial cases of PD (a-synuclein, DJ-1, PINK1, Parkin, etc.) or selectively disrupt nigrostriatal neurons (MitoPark, Pitx3, Nurr1, etc.). "Classic" models are based on neurotoxins that specifically target catecholaminergic neurons. All of these together each model has its own benefits and drawbacks. The use of medication, deep brain stimulation, and physical therapy has been optimised for the symptomatic treatment of the motor symptoms of Parkinson disease (PD). L-dopa, several dopamine agonists, inhibitors of MAO-B and catechol-o-methyltransferase (COMT), and amantadine are among the pharmacotherapies available.&#x0D;

Effect of long-term locomotion and balance exercise on functional mobility considering the Parkinson’s disease subtypes: a pilot study

BACKGROUND: Different clinical subtypes (i.e., Postural Instability and Gait Difficulty -PIGD and Tremor Dominant -TD) have been highlighted in Parkinson's disease (PD). Although physical exercise improves motor symptoms in PD, the knowledge about the effect of physical exercise considering the PD subtype is limited. AIM: To compare the effects of long-term locomotion and balance exercise on lower limb functional strength and functional mobility in PD subtypes. METHOD: Eight individuals PIGD and 10 TD participated in this study. All individuals participated in the interventions with exercises focused on improving locomotion and balance. 48 sessions of exercise were performed three times per week for 60 minutes each session. Functional Mobility was analyzed by the Timed Up and Go test (TUG) in a single (ST) and double-task (DT – i.e., subtraction by three). Lower limb functional strength was analyzed by the 30s sit-to-stand test. Both tests were performed at baseline (pre-test) and post-intervention (post-test). Statistical analysis was performed by two-way ANOVA, with Group (PIGD vs. TD) and Moment (pre vs. post-test) factors, with repeated measures for the second factor. RESULTS: PIGD decreased the time to perform TUG_ST in the post-test compared to the pre-test (p=0.001). Both groups decreased the time in TUG_DT and increased the number of repetitions in sit-to-stand test in the post-test in relation to the pre-test (p&lt;0.05). CONCLUSION: Long-term locomotion and balance exercise programs can improve functional mobility mainly in PIGD. A possible explanation is due to the greater room for improvement of PIGD subtypes and exercise specificity.

Corticostriatal beta oscillation changes associated with cognitive function in Parkinson's disease.

Cognitive impairment is the most frequent non-motor symptom in Parkinson's disease and is associated with deficits in a number of cognitive functions including working memory. However, the pathophysiology of Parkinson's disease cognitive impairment is poorly understood. Beta oscillations have previously been shown to play an important role in cognitive functions including working memory encoding. Decreased dopamine in motor cortico-striato-thalamo-cortical (CSTC) circuits increases the spectral power of beta oscillations and results in Parkinson's disease motor symptoms. Analogous changes in parallel cognitive CSTC circuits involving the caudate and dorsolateral prefrontal cortex (DLPFC) may contribute to Parkinson's disease cognitive impairment. The objective of our study is to evaluate whether changes in beta oscillations in the caudate and DLPFC contribute to cognitive impairment in Parkinson's disease patients. To investigate this, we used local field potential recordings during deep brain stimulation surgery in 15 patients with Parkinson's disease. Local field potentials were recorded from DLPFC and caudate at rest and during a working memory task. We examined changes in beta oscillatory power during the working memory task as well as the relationship of beta oscillatory activity to preoperative cognitive status, as determined from neuropsychological testing results. We additionally conducted exploratory analyses on the relationship between cognitive impairment and task-based changes in spectral power in additional frequency bands. Spectral power of beta oscillations decreased in both DLPFC and caudate during working memory encoding and increased in these structures during feedback. Subjects with cognitive impairment had smaller decreases in caudate and DLPFC beta oscillatory power during encoding. In our exploratory analysis, we found that similar differences occurred in alpha frequencies in caudate and theta and alpha in DLPFC. Our findings suggest that oscillatory power changes in cognitive CSTC circuits may contribute to cognitive symptoms in patients with Parkinson's disease. These findings may inform the future development of novel neuromodulatory treatments for cognitive impairment in Parkinson's disease.