Parkinson's Disease最新文献

Introduction: Parkinson's disease (PD) is a chronic, neurodegenerative disease of the central nervous system (CNS). Complications in PD are related to impaired cardiorespiratory capacity, and the presence of motor and nonmotor symptoms, such as reduced cardiorespiratory fitness, decreased respiratory muscle strength and lung volumes and capacities, bradykinesia, muscle rigidity, attenuation of strength and lower limb muscle power, sleep disorders, anxiety, and depressive symptoms. The practice of high-intensity exercise and the examination of the aquatic environment may help to minimize these symptoms and slow disease progression. Objective: To develop a water physical exercise program (WPEP) focusing on high-intensity interval training (HIIT) for individuals with DP. Methods: This is a protocol for a single blinded controlled clinical trial. The sample will consist of individuals with PD between Stages 1 and 4 on the Hoehn and Yahr (HY) Scale, divided into a control group and a WPEP group (which will participate in the WPEP). The outcomes will be divided into three categories: cardiorespiratory, motor, and nonmotor aspects. The WPEP will last 12 weeks, and the intervention will take place two times a week, with a duration of approximately 35 min, with an interval between 48 and 72 h between training sessions for muscle recovery, for a total of 24 sessions. It is expected that this study will establish parameters for prescribing and monitoring a WPEP for individuals with PD Stages 1-4 on the HY scale, enhancing the practice of exercise prescription. Trial Registration: Brazilian Register of Clinical Trials: RBR-3hp5yvh.

Oxidative stress (OS), a condition that occurs when the balance between reactive oxygen species production and antioxidant defense mechanisms is disrupted, has been implicated in the pathogenesis of several neurological conditions, including neurodegenerative and vascular disorders. Ferroptosis is a mechanism mediating OS-induced damage, with growing evidence of specific involvement in both Parkinson's disease (PD) and ischemic stroke. Regular physical activity may have an antioxidant effect by increasing the production and activity of nonenzymatic and enzymatic antioxidants. Among the biological mediators of physical activity, irisin may act as an agent capable of inducing systemic changes and crossing the brain-blood barrier. This review aims to describe the main role of OS in the pathophysiology of PD, highlighting putative neurodegenerative mechanisms and emphasizing the potential targeting by physical activity as a possible shared preventive and symptomatic treatment approach.

Background: Hallucinations and delusions are severe long-term complications of Parkinson's disease (PD). Clozapine is the only antipsychotic with proven efficacy in PD psychosis (PDPsy) available outside the United States but apprehensions about its adverse event profile result in a substantial underuse of clozapine. Objectives: To investigate the practical use and long-term efficacy of clozapine in severe psychotic disorders in PD. Methods: In this retrospective study, the author used data collected over a period of 20 years and included all PD patients under his care, who were treated with clozapine for psychotic disorders. Results: During the observation period, 41 PD patients (38 with PDPsy, 2 with psychotic depression, and one with schizoaffective disorder) were started on clozapine. They had responded poorly or only transiently to quetiapine. An overnight switch to clozapine was tolerated in most. Maximum clozapine doses ranged from 12.5 to 150 mg (72.9 ± 29.9 mg). A significant reduction in psychotic symptoms was achieved in 2 days to 6 months. Among the cases tolerating clozapine, 10 had a full, 25 had a good, 3 had a moderate, and 2 had a poor clinical response to clozapine. Treatment lasted up to 12 years. The long-term response was full or good in 23, moderate in 3, and poor in 2 patients. Conclusions: Clozapine is often effective in the treatment of psychotic disorders in PD including PDPsy poorly or only transiently responding to quetiapine. Side effects including agranulocytosis are manageable in the majority of cases. Clozapine treatment should not be delayed if other measures against PDPsy prove ineffective.

Parkinson's disease is an age-related progressive neurodegenerative disorder. A large majority of Parkinson's disease patients have an unknown etiology, which is classified as idiopathic Parkinson's disease. Generating disease models directly from idiopathic Parkinson's disease patients may improve the understanding of the disease pathology. Both neuroprotective and neurodegenerative roles have been suggested for cystatin C in neurodegenerative disease. In Parkinson's disease, investigations assessing cystatin C levels in different types of biospecimens such as blood, cerebrospinal fluid, and in vitro models have had conflicting results. We present a study assessing cystatin C levels in different biospecimen types originating from the same subjects. Using a sandwich ELISA, we compared cystatin C concentration in blood derivatives (plasma and serum) and culture media of derived models (stem cells, neuroepithelial stem cells, and midbrain organoids) of three idiopathic Parkinson's disease and three age-matched healthy control subjects with the same CST3 genotype. Genotyping analyses confirmed that all subjects were homozygous AA. The identity of the derived models was confirmed using immunohistochemical staining. Secreted cystatin C concentration was measured in each biospecimen tested. No statistically significant differences in cystatin C concentrations were found between the subjects in any of the biospecimen types. As a personalized marker, a higher cystatin C concentration was shown for some individual patients in the culture medium of midbrain organoids, suggesting a potential involvement in Parkinson's disease physiopathology. This proof of concept demonstrates that cystatin C is secreted by various idiopathic Parkinson's disease cell models, including midbrain organoids, which in turn suggests that cystatin C secretion by midbrain organoids might be pertinent in neurodegenerative disease research.

Objected: Parkinson's disease (PD) is an important cause of neurological dysfunction, and the aim of this study was to explore whether neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory response (SIRI), and systemic immune inflammation (SII) are associated with the risk of developing PD. Based on this, we may identify people at high risk for PD and intervene early. Method: Our study included 31,480 participants from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. Basic information and inflammation-related indicators were obtained by questionnaires and laboratory tests, respectively. NLR, PLR, LMR, SIRI, SII, and PD risk were analyzed using weighted logistic regression models. Results: There were 261 and 31,219 in the PD and non-PD groups, respectively, and the prevalence of PD was 0.83%. Separate analyses of NLR and PLR were conducted after fully adjusting for confounding factors. According to our analysis, there was an increased risk of PD for both NLR and PLR in the higher level group (Q4) as compared with the lower level group (Q1) (OR = 1.83 and 95% confidence interval (CI) = 1.09-3.07, and OR = 1.92 and 95% CI = 1.20-3.08). However, we did not find similar relationships in LMR, SIRI, and SII. Conclusions: There was a significant association between elevated levels of NLR, PLR, and PD risk, while LMR, SIRI, and SII were not statistically significant. It suggests that NLR or PLR could be used to screen people at risk of PD at an early stage. It is essential to conduct more large-scale prospective studies to investigate the role that NLR and PLR play in PD.

Cinnamaldehyde (CA), the primary bioactive compound in cinnamon (Cinnamomum cassia Presl, Lauraceae, Cinnamomum), holds potential therapeutic benefits for Parkinson's disease (PD). To scrutinize the impact and mechanisms of CA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD, male C57BL/6 mice were randomly allocated to CA (150, 300, and 600 mg/kg), model, Madopar, and control group (n = 12). The Open Field, Pole-jump, and Rotarod experiments assessed exercise capacity and anxiety levels. HPLC evaluated the levels of neurotransmitters. Immunohistochemistry was utilized to detect the expression of TH and GFAP. WB and RT-qPCR determine the expression levels of apoptosis-related genes and proteins in the substantia nigra and striatum. The findings revealed that CA not only enhanced motor abilities and reduced anxiety but also elevated the levels of TH, DOPAC, DA, 5-HIAA, HVA, and 5-HT in the substantia nigra and striatum. Moreover, it protected DA neurons and downregulated the expression of Bax, Casp3, and Bax/Bcl-2 mRNA and proteins, while increasing the expression of Bcl-2 mRNA compared to the model group. Furthermore, CA was observed to inhibit glial cell activation, leading to reduced levels of GFAP and IBA1 in the substantia nigra and striatum. This resulted in decreased expression of inflammatory factors such as iNOS and NF-κBp65 proteins in these regions, consequently mitigating neuroinflammation. These results suggest that CA exerts a neuroprotective effect in acute PD model mice by suppressing glial cell activation, modulating the expression of apoptotic genes, and alleviating neuroinflammation and apoptosis induced by MPTP.

A cardinal symptom of Parkinson's disease (PD) is motor dysfunction, including bradykinesia and tremors, which is quantified in the Unified PD Rating Scale (UPDRS). Although some medications provide palliative treatments for these motor deficits, their efficacy wanes and can produce unwanted side effects, such as dyskinesia. Deep-brain stimulation (DBS) has provided an alternative treatment strategy that can benefit many patients, but optimal target structures for DBS and its long-term efficacy are not fully understood. The present study represents a meta-analysis of the long-term (> 5 years) effects of DBS on the two most common targets, the subthalamic nucleus (STN) and the globus pallidus interna (GPi), on scores of motor performance using the UPDRS-III. The initial search of PubMed, Cochrane Library, and Clinical Trials resulted in 197 articles, of which 28 met the criteria for our analysis. Of the 1321 patients included, 1179 received STN DBS group and 142 received GPi DBS. UPDRS-III scores for both target groups were analyzed at baseline and at either 5-8 or 10-15 years later for both on- and off-medication phases. The results indicated that the STN stimulation is effective at reducing motor symptoms during off-medication treatment for up to 15 years and that the GPi stimulation can be effective for up to at least 8 years. Our findings further suggest that STN- and GPi-targeted DBS may wear off during the on-medication phase between 5 and 10 years of treatment. This study supports findings that both DBSs of either the STN or GPi have long-term efficacy, especially during off-medication periods.

Background: Cognitive impairment is common in Parkinson's disease (PD) but has limited treatment options. Medication has shown some benefits but accompanied by risk of adverse events. We aimed to investigate effectiveness and feasibility of nonpharmacological interventions for people with PD and cognitive impairment on patient-centred outcomes. Methods: Systematic searches of five databases (MEDLINE, Embase, CINAHL, PsycINFO and Web of Science) were performed for studies evaluating nonpharmacological interventions for people with PD and cognitive impairment, reporting health-related quality of life, function (activities of daily living) or wellbeing outcomes, published up to 15 May 2023. Two reviewers independently assessed full-text articles and one reviewer extracted data, with a second reviewer reliability checking all data extraction. Randomised controlled trials (RCTs) were synthesised through meta-analysis using a random-effects meta-analysis with restricted maximum likelihood method pooled estimate and observational studies through narrative synthesis. Results: Eleven RCTs and three noncontrolled studies were included, studying a range of interventions: cognitive training, cognitive stimulation, cognitive rehabilitation, physical and cognitive exercise, goal management training, psychoeducation with mindfulness, broader rehabilitation programs and a psychological intervention. Feasibility was demonstrated. The majority showed effectiveness for their primary outcome. Meta-analysis showed no significant improvement in HrQoL (seven RCTs: pooled effect, standardised mean difference, -0.20 [-0.57-0.18]) or function (four RCTs: 0.08 [-0.36, 0.52]), and wellbeing measurement was infrequent and indirect. Quality of evidence was judged as very low, limiting the conclusions drawn. Conclusion: Whilst nonpharmacological trials for cognitive impairment in PD have shown promise, we found no evidence of effectiveness on HrQoL, function or wellbeing. However, this is based on very low-quality evidence from a small number of diverse studies, not powered for these outcomes. Feasibility of a range of interventions has been demonstrated in both PD-mild cognitive impairment and PD-dementia. There is a need for more robust, adequately powered studies.

Objective: To assess the psychometric properties of the Spanish King's Parkinson's Disease Pain Scale (KPPS). Design: A descriptive transversal study at a Spanish hospital. Methods: Fifty-three Parkinson's disease (PD) patients suffering from otherwise explained pain (34 females, age = 63.42 ± 10.52 years, time with disease = 7.25 ± 4.65 years) were evaluated by the KPPS, Brief Pain Inventory (BPI), two Pain Pressure Thresholds (PPTs), Widespread Mechanical Hyperalgesia (WMH), and Conditioned Pain Modulation (CPM). A retest of the KPPS was performed 7-15 days later. Internal consistency, test-retest reliability (intraclass correlation coefficient (ICC)), measurement error, factor structure, and criterion/convergent validity were assessed. Results: Internal consistency of the Spanish KPPS was acceptable (Cronbach's alpha = 0.77). The mean test and retest total KPPS scores were similar (test = 34.83 ± 23.50 points, retest = 35.87 ± 26.23 points), and test-retest reliability was good (ICC = 0.85, 95% CI = 0.75-0.91). Standard error of measurement (SEM) was 9.1 points and smallest detectable change (SDC) was 25.22 points. The sampling adequacy was not sufficient to perform factor analysis. The total KPPS score was not correlated to the BPI intensity subscale (r = 0.18, p=0.19), but it was moderately and positively correlated to the interference subscale (r = 0.43, p=0.001). The total KPPS was moderately and negatively correlated to both the remote PPT (r = -0.4, p=0.003) and WMH (r = -0.38, p=0.005). No statistical correlations were found with local PPT or CPM. Conclusion: The present study provides evidence that the Spanish KPPS effectively measures pain in individuals with PD, with its total score demonstrating good reliability, minimal measurement error, and adequate criterion and convergent validity.

Apathy is recognized to be a common, disabling syndrome that occurs across a range of psychiatric and neurological conditions, including Parkinson's disease. It can have a significant impact on quality of life, both for people affected and those around them. Currently, there are no established, evidence-based treatments for this debilitating syndrome. Assessment and treatment have been complicated by overlaps with depression and anhedonia, as well as a lack of understanding of the underlying mechanisms. Emerging lines of evidence conceptualize apathy as a reduction of motivation associated with disordered effort-based decision-making and dysfunction of distinct neural circuitry between the basal ganglia and medial prefrontal cortex. Here, we introduce a novel cognitive-behavioral framework that can inform a clinician's conceptualization and treatment of apathy, using cognitive-behavioral therapy (CBT) techniques. We focus on people with Parkinson's disease in our model, but our approach is transdiagnostic and can be applied to other conditions. It considers both individual targets for therapy as well as maintenance and intervention at a systemic level. The generalizability and parsimony of the framework provides a structured assessment and formulation of apathy, while also allowing clinicians to remain sensitive to other neuropsychiatric symptoms that can occur alongside apathy, such as depression and anxiety.