Occurrence Of Parkinson's Disease Research Articles

Essential tremor-Parkinson's disease syndrome: clinical characteristics and subtypes using cluster analysis.

Essential tremor (ET) and Parkinson's disease (PD) are common movement disorders. ET-PD syndrome is characterized by the occurrence of PD in patients with a previous history of ET, which may be an independent phenotype distinct from PD. This study aims to identify clinical characteristics and subtypes in ET-PD. A total of 93 newly diagnosed ET-PD patients and 93 newly diagnosed PD patients matched for age, sex, education, and disease duration of PD were selected using propensity score matching analysis. The K-means cluster analysis was performed for 11 variables derived from the ET-PD group, and cluster profiles were established through statistical analysis of demographic and clinical variables. The ET-PD group consisted of a high number of patients with a family history of ET exhibiting evident tremor with milder hypokinesia and postural instability symptoms, as compared to the PD group. Through the cluster analysis, two clusters of ET-PD patients were identified. The ET-PD cluster 1 ( n = 34) had a shorter ET duration before PD onset, lower number of patients with a family history of ET, higher unified PD rating scale instability scores, higher non-motor symptoms scores (non-motor symptoms scale D1 scores, Hamilton depression scale scores, Hamilton anxiety scale scores, and PD sleep scale-2 scores), and higher Chinese version of the PD questionnaire-39 scores relative to the ET-PD cluster 2 ( n = 59). ET-PD patients had significantly different characteristics for motor symptoms as compared to PD patients, and may be distinctly divided into two clinical subtypes, namely, the ET-PD complex type and the ET-PD simple type.

Relationship Between Annual Airborne Pollen Levels and Occurrence of Parkinson Disease, Amyotrophic Lateral Sclerosis, Myasthenia Gravis, Multiple Sclerosis, Spinocerebellar Degeneration, Huntington’s Disease, Shy-Drager Syndrome, Moyamoya Disease and Creutzfeldt- Jakob Disease Based on the National Registry Database of Specific Intractable Disease in Japan, 1974-2014: A Retrospective Study

Background: In Japan, pollen counts increased between 1977 and 1987, including three peaks (1978- 1980, 1982, 1984-1986) coinciding with triphasic Kawasaki disease (KD) outbreaks. Epidemiological findings have been then extensively accumulated that KD and related specific intractable diseases such as systemic vasculitis, collagen diseases, inflammatory bowel diseases, idiopathic dilated cardiomyopathy and further various cancers may be correlated to pollen exposure (PE). Methods and results: To elucidate the effects of PE on outbreaks of neurological intractable diseases (NIDs), we evaluated the annual occurrence of disorders in relation to pollen counts using data from a national database. Specifically, we evaluated the occurrence of Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Myasthenia Gravis (MG), multiple sclerosis (MS), spinocerebellar degeneration (SCD), Huntington’s disease (HUNTG), Shy-Drager syndrome, moyamoya disease and CreutzfeldtJakob disease (CJD). During 1975–2014, the 1984-86 peak of pollen scatter was the earliest big peak with which simultaneous increase in occurrence of PD, ALS, MG, MS, SCD and HUNTG coincided. Furthermore, simultaneous outbreaks of each NID coincided with subsequent ten peaks of pollen scatter till 2014. Our results showed statistically significant correlations for PD, ALS, MG, MS and SCD between the annual number of newly registered patients (nRPs) in the patient-registry year and annual pollen levels in the same patient-registry year. Significant correlations were also shown between the number of nRPs in the patient-registry year and annual pollen levels measured 3 years (PD), 6 years (PD, MG, MS, MMD), 9 years (PD, MS, MMD, CJD), 14 years (PD, CJD), and 16 years MG, MS, HUNTG and MMD before the patient-registry year. Conclusion: We assume that cumulative effects of PE during a decade or more before the diagnosis of NIDs might possibly trigger onset of NIDs when cumulative effects of PE as environmental stress overwhelmed immunoreactive threshold.

PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease (PD). However, the mechanisms underlying this association remain unclear. In the present study, we found that high glucose (HG) levels in the cerebrospinal fluid (CSF) of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine (6-OHDA) on the development of motor disorders, and the damage to the nigrostriatal dopaminergic neuronal pathway. In vitro, HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor (NGF) (NGF-PC12). Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle (TCA cycle) activity, which was closely related to abnormal mitochondrial fusion, thus resulting in mitochondrial loss. Interestingly, HG-induced upregulation of pyruvate kinase M2 (PKM2) combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells. In addition, we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA. Furthermore, we found that shikonin (SK), an inhibitor of PKM2, restored the mitochondrial number, promoted TCA cycle activity, reversed hyperglycolysis, enhanced the tolerance of cultured neurons to 6-OHDA, and reduced the risk of PD in diabetic rats. Overall, our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upregulation of PKM2, leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA. Thus, the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Clinical and Genetic Features of Multiplex Families with Multiple System Atrophy and Parkinson's Disease.

While multiple system atrophy (MSA) has been considered a sporadic disease, there were previously reported multiplex families with MSA. Furthermore, several families with multiple patients with MSA and Parkinson's disease (PD) have been reported. As genetic risk factors for MSA, functionally impaired variants in COQ2 and Gaucher-disease-causing GBA variants have been reported. While it has been established that GBA variants are associated with PD, COQ2 may also be associated with PD. In 672 patients with MSA, we identified 12 multiplex families of patients with MSA and PD in first-degree relatives. We conducted a detailed analysis of the clinical presentations of these patients and genetic analyses of GBA and COQ2. In the multiplex families, a patient with MSA with predominant parkinsonism (MSA-P) was observed in nine families, while a patient with MSA cerebellar subtype (MSA-C) was observed in three families. Six families had siblings with MSA and PD, five families had a parent-offspring pair with MSA and PD, and in one family, a sibling and a parent of an MSA patient had PD. In genetic analyses of these patients, GBA variants were identified in one of the 12 MSA patients and two of the seven PD patients. Functionally impaired variants of COQ2 were identified in two of the 12 MSA patients and not identified in the seven PD patients. This study further emphasizes the occurrence of MSA and PD in first-degree relatives, raising the possibility that a common genetic basis underlies MSA and PD. Even though variants of COQ2 and GBA were identified in some patients in multiplex families with MSA and PD, it is necessary to further explore as yet unidentified genetic risk factors shared by MSA and PD.

Influence of heavy metals in Parkinson's disease: an overview.

Parkinson's disease (PD) is an ageing disorder with deterioration of dopamine neurons which leads to motor complications like tremor, stiffness, slow movement and postural disturbances. In PD, both genetics as well as environmental factors both play a major role in causing the pathogenesis. Though there are surfeit of risk factors involved in PD occurrence, till now there is lack of an exact causative agent as a risk for PD with confirmative findings. The role of heavy metals reported to be a significant factor in PD pathogenesis. Heavy metal functions in cell maintenance but growing pieces of evidences reported to cause dyshomeostasis with increased PD rate. Metals disturb the molecular processes and results in oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis. The present review elucidates the role of cobalt, nickel, mercury, chromium, thallium metals in α-synuclein aggregation and its involvement in blood brain barrier flux. Also, the review explains the plausible role of aforementioned metals with a mechanistic approach and therapeutic recommendations in PD.

Identification of alpha‐Synuclein Disaggregator from Camellia sp. Insight of Molecular Docking and Molecular Dynamics Simulations

AbstractMisfolded protein formation and aggregation are the central hallmarks for various neurodegenerative disorders. When it comes to Parkinson's disease (PD), alpha‐synuclein (α‐syn) is the culprit protein. The presence of α‐syn protein in lewy bodies and lewy neurites confirmed its presence in the occurrence of PD. The protein is natively present in the soluble monomeric forms, but certain factors such as oxidative stress convert the structure into insoluble oligomeric formats. This study focuses on the inhibitory effects of various antioxidant compounds on α‐syn oligomerization. We had collected the list of compounds present in the Camellia sp. plant. Using a computational approach, we found the potential interaction sites between the antioxidant compounds and α‐syn using a computational approach. Molecular docking and simulation studies suggest that the compound Theaflavin‐3‐3‐digallate shows best interactions with −7.1 kcal/mol and can reduce the alpha‐sheet structure of α‐syn structure to loop region.

Association between Antidiabtic Medications and Worsening of Parkinson’s Symptoms: A Case Report

Introduction: Parkinson's disease (PD) is one of the most prevalent neurologic disorders, leading to progressive disability; it is characterized by tremors, slow movements, stiffness in arms and legs, and balance impairment; PD symptoms can be slowed but not stopped by treatment such as a combination of Carbidopa/ Levodopa. Although it's widely used for PD, it risks dyskinesia, orthostatic hypotension, and dizziness. The prevalence of PD in Saudi Arabia has been estimated to be 27 per 100,000 populations, and the occurrence of PD in the U.S. is approximately 20 cases per 100,000 people per year.
 Case presentation: A 61 years old male presented with worsening PD symptoms, especially dysarthria symptom; he had a history of diabetes with A1C of 8.5%, on metformin, insulin glargine, liraglutide, and linagliptin, with good adherence, and he had a history of Parkinson on levodopa/carbidopa. Even there are no known drug-drug interactions between antidiabetic medication and levodopa/ carbidopa, he reported that coadministration of antidiabetic medications with levodopa/carbidopa cause PD symptoms worsening, especially dysarthria worsening. This drug-drug interaction was noticed when the patient tried to stop all of his antidiabetic medication except insulin mixtard, when he noticed dysarthria symptoms improved. He is currently on insulin mixtard for diabetes with an A1C of 6.7%. 
 Conclusion: Unintentional drug-drug interaction poses a challenge to the healthcare provider, so this report highlights the importance of adverse drug-drug interaction of antidiabetic with levodopa/carbidopa, its presentation, and management.

Association of serum cholesterol with Parkinson's disease in a cohort of statin-free individuals.

IntroductionThe role of serum cholesterol in the pathogenesis of Parkinson's disease (PD) remains unclear. The objective of this study was to assess the association between serum cholesterol and PD in a cohort of statin‐free newly diagnosed PD patients.MethodsThis retrospective study used fasting lipid profiles obtained from 672 consecutive statin‐free newly diagnosed PD individuals and 540 controls. These PD individuals were identified from three medical institutions during 2017–2021, and the controls were identified from three physical examination centers during the same time period. Logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment of age, sex, and tobacco use history.ResultsAmong 672 PD individuals, 112 were excluded in accordance with the current criteria, leaving 560 PD patients. The multivariate binary logistic regression analysis showed that LDL‐C was the only variable contributing to the occurrence of PD (OR 1.39, 95% CI: 1.07‐2.31, p < .001) after adjusting for age, sex, and tobacco use history; this association persisted following further adjustment for TC and HDL‐C. In the subgroup analysis of the adjusted results of LDL‐C after correcting for TC and HDL‐C, lower LDL‐C was associated with a higher risk of PD.ConclusionAmong selected populations of statin‐free newly diagnosed PD individuals, low LDL‐C might be associated with the occurrence of PD.

Alterations of gut microbiota and metabolome with Parkinson's disease

Gut microbiota and amino acids that are one of their metabolites play important roles in the mechanism of pathology of Parkinson's disease (PD). It has been reported that the level of amino acids in vivo participate in neurodegeneration by regulating adaptive immune response, while the current researches on alteration of amino acids in gut microbiota are still insufficient. We hypothesized that alterations in gut microbiota might be accompanied by altered concentrations of amino acids, leading to the occurrence of PD. In this study, we collected stool samples from PD and healthy controls to analyse fecal microbiome and targeted metabolome by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography coupled to mass spectrometry (GC-MS). At the genus level, there was a greater abundance of Alistipes, Rikenellaceae_RC9_gut_group, Bifidobacterium, Parabacteroides, while Faecalibacterium was decreased in fecal samples from PD patients. Moreover, fecal branched chain amino acids (BCAAs) and aromatic amino acids concentrations were significantly reduced in PD patients compared to controls. Our study not only finds the abundance of certain gut microbiota in PD,but also reveals that it is related to BCAAs and aromatic amino acids. These findings are beneficial to identifying new therapeutic targets for PD by regulating diet and/or gut microbiota.

PLA2G6 mutations cause motor dysfunction phenotypes of young-onset dystonia–parkinsonism type 14 and can be relieved by DHA treatment in animal models

Parkinson's disease (PD), the most common neurodegenerative motor disorder, is currently incurable. Although many studies have provided insights on the substantial influence of genetic factors on the occurrence and development of PD, the molecular mechanism underlying the disease is largely unclear. Previous studies have shown that point mutations in the phospholipase A2 group VI gene (PLA2G6) correlate with young-onset dystonia–parkinsonism type 14 (PARK14). However, limited information is available regarding the pathogenic role of this gene and the mechanism underlying its function. To study the role of PLA2G6 mutations, we first used zebrafish larvae to screen six PLA2G6 mutations and revealed that injection of D331Y, T572I, and R741Q mutation constructs induced phenotypes such as motility defects and reduction in dopaminergic neurons. The motility defects could be alleviated by treatment with L-3, 4-dihydroxyphenylalanine (L-dopa), indicating that these mutations are pathological for PARK14 symptoms. Furthermore, the injection of D331Y and T572I mutation constructs reduced phospholipase activity of PLA2G6 and its lipid metabolites, which confirmed that these two mutations are loss-of-function mutations. Metabolomic analysis revealed that D331Y or T572I mutation led to higher phospholipid and lower docosahexaenoic acid (DHA) levels, indicating that reduced DHA levels are pathological for defective motor functions. Further, a dietary DHA supplement relieved the motility defects in PLA2G6D331Y/D331Y knock-in mice. This result revealed that the D331Y mutation caused defective PLA2G6 phospholipase activity and consequently reduced the DHA level, which is the pathogenic factor responsible for PARK14. The results of this study will facilitate the development of therapeutic strategies for PARK14.

Organothiophosphate Induced Acute and Reversible Parkinsonism: Case Report and Literature Review

Introduction: Organophosphate compound poisoning is one of the most common causes for admission to the Medical Intensive Care Unit. Parkinsonism is a primary neurotoxic manifestation of organophosphate intoxication. In this case report, we present the case of a 26 year old man who had the experience of organothiophosphate poisoning. Case presentation: A 26 year old man was admitted with tremors in upper and lower limbs together with the rigidity of all 4 limbs as well as difficulty in swallowing and in daily activities like walking, rising from chair, and turning on bed. He had consumed organophosphorus compound quinalphos, 15 days before. The basal ganglia changes were documented radiologically by Magnetic Resonance Imaging (MRI). Gradual recovery was observed by treatment with dopaminergic agents and central anticholinergics over few weeks. Only 0.5% of organophosphate poisoning patients develop neurotoxic manifestations in the form of extrapyramidal syndromes such as Parkinsonism. Discussion: The occurrence of Parkinsonism as a complication of organophosphate poisoning raises safety concerns, especially in developing countries. Yet, this study is the first case report on Organothiophospahate induced Parkinsonism. Conclusion: Clinicians should be aware of the possibility of extrapyramidal manifestations following organophosphate poisoning and the patients should be asked for regular follow-ups as the symptoms may appear even 1 month after the poisoning.

MicroRNA-3473b regulates the expression of TREM2/ULK1 and inhibits autophagy in inflammatory pathogenesis of Parkinson disease.

Parkinson disease (PD) is a neurodegenerative disease characterized by selective loss of dopaminergic (DA) neurons in the midbrain. The regulatory role of a variety of microRNAs in PD has been confirmed, and our study is the first to demonstrate that miR-3473b is involved in the regulation of PD. In vitro, an miR-3473b inhibitor can inhibit the secretion of inflammatory factors (TNF-α and IL-1β) in moues microglia cell line (BV2) cells induced by lipopolysaccharide (LPS) and promote autophagy in BV2 cells. In vivo, miR-3473b antagomir can inhibit the activation of substantia nigra pars compacta (SNpc) microglia of C57BL/6 mice induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and promote autophagy. Deletion of TREM2, one of the most highly expressed receptors in microglia, leads to the occurrence and development of PD. ULK1 is a component of the Atg1 complex. Deletion of ULK1 aggravates the pathological reaction of PD. TREM2 and ULK1 are predicted potential targets of miR-3473b by Targetscan. Then, the results of our experiments indicate that transfection with a miR-3473b mimic can inhibit the expression of TREM2 and ULK1. Data from a double luciferase experiment indicate that the 3'-UTR of TREM2, but not ULK1, is the direct target of miR-3473b. Then we aim to investigate the regulation of TREM2 and ULK1 in PD. We found that the expression of p-ULK1 was significantly increased via up-regulation of TREM2. The increased expression of p-ULK1 can promote autophagy and inhibit the expression of inflammatory factors. The regulation of ULK1 by miR-3473b may be accomplished indirectly through TREM2. Thus, miR-3473b may regulate the secretion of proinflammatory mediators by targeting TREM2/ULK1 expression to regulate the role of autophagy in the pathogenesis of inflammation in Parkinson's disease, suggesting that mir-3473b may be a potential therapeutic target to regulate the inflammatory response in PD.

Gut Microbiota and Parkinson's Disease: Implications for Faecal Microbiota Transplantation Therapy.

Parkinson's disease (PD) ranks the second place among neurodegenerative diseases in terms of its morbidity, which affects 1-2% people aged over 65 years. In addition to genetics, some environmental factors may exert vital parts in PD occurrence as well. At present, more and more studies are conducted to elucidate the association between gut microbial dysbiosis and the incidence of PD. Gut microbial dysbiosis has a certain effect on both the central nervous system (CNS) and the enteric nervous system (ENS), which indicates that there is a gut-microbiota-brain axis that induces CNS disorders. Some gut microbial strains are suggested to suppress or weaken the neuroinflammation- and gut-inflammation-immune responses, which suggests the protective and pathogenic effects of certain gut microbial species on PD progression. Therefore, gut microbiome may contain plenty of targets for preventing and managing PD. Faecal microbiota transplantation (FMT) may serve as a direct and useful treatment for PD in the future. Nonetheless, there is little available scientific research in this field. The present work reviewed the latest research to examine the association of gut microbiota with PD, and the future prospects of FMT treatment.

Ferritinophagy-Mediated Ferroptosis Involved in Paraquat-Induced Neurotoxicity of Dopaminergic Neurons: Implication for Neurotoxicity in PD.

Parkinson's disease (PD) is a progressive nervous system disorder. Until now, the molecular mechanism of its occurrence is not fully understood. Paraquat (PQ) was identified as a neurotoxicant and is linked to increased PD risk and PD-like neuropathology. Ferroptosis is recognized as a new form of regulated cell death. Here, we revealed a new underlying mechanism by which ferritinophagy-mediated ferroptosis is involved in PD induced by PQ. The effect of PQ on movement injury in mice was investigated by the bar fatigue and pole-climbing test. SH-SY5Y human neuroblastoma cells were used to evaluate the mechanism of ferroptosis. Our results showed that PQ induced movement injury by causing the decrease in tyrosine hydroxylase in mice. In vitro, PQ significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression significantly, which were important markers in ferroptosis. Fer-1, an inhibitor of ferroptosis, could significantly ameliorate the ferroptosis induced by PQ. Meanwhile, Bcl2, Bax, and p-38 were involved in apoptosis induced by PQ. In conclusion, ferritinophagy-mediated ferroptosis pathway played an important role in PD occurrence. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of PD occurrence. The inhibition of the ferroptosis and apoptosis together may be a new strategy for the prevention of neurotoxicity or PD in the future.

Parkinson Disease and Occupational and Environmental Exposure to Pesticides in a Region of Intense Agribusiness Activity in Brazil

To evaluate the relationship between occupational and environmental exposure to pesticides and Parkinson disease in a region of intense agribusiness activity in the state of Mato Grosso/Brazil. Case-control study carried out in a referral hospital for chronic neurodegenerative diseases. Non-conditional logistic regression analyses were performed. Having performed direct management of pesticides in the workplace (odds ratio [OR]: 3.43; 95% confidence interval [CI]: 1.55 to 7.28), having a family history of Parkinson (OR: 3.42; 95% CI: 1.61 to 7.28) and being men (OR: 3.01; 95% CI: 1.66 to 5.45) were all factors that contributed to a greater chance for the development of the disease. Our study reinforces the associations between occupational and environmental exposure to pesticides and the occurrence of Parkinson disease in regions of intense agribusiness activity in Brazil.

Orthostatic Hypotension: A Prodromal Marker of Parkinson's Disease?

BackgroundOrthostatic hypotension is common in patients with Parkinson's disease (PD). However, it remains unknown whether orthostatic hypotension is a marker of prodromal PD or more advanced disease. The objectives of this study were to assess whether orthostatic hypotension is a prodromal marker of PD in the general population.MethodsThis study was embedded in the Rotterdam Study, a large prospective population‐based cohort in the Netherlands. We measured orthostatic hypotension in 6910 participants. First, we determined the relation between prevalent PD and orthostatic hypotension using logistic regression. Second, we followed PD‐free participants for the occurrence of PD until 2016 and studied the association between orthostatic hypotension and the risk of PD using Cox proportional hazards models. All models were adjusted for age and sex.ResultsAt baseline, the mean age ± standard deviation of the study population was 69.0 ± 8.8 years, and 59.1% were women. Orthostatic hypotension was present in 1245 participants (19.8%), and 62 participants (1.0%) had PD at the time of orthostatic hypotension measurement. Participants with PD were significantly more likely to have orthostatic hypotension (odds ratio, 1.88; 95% confidence interval, 1.09–3.24). During a median (interquartile range) follow‐up of 16.1 years (8.5–22.7 years), 122 participants were diagnosed with incident PD. Orthostatic hypotension at baseline was not associated with an increased risk of PD (hazard ratio, 0.97; 95% confidence interval, 0.59–1.58).ConclusionsOur study suggests that orthostatic hypotension is common in patients with PD, but that orthostatic hypotension is not associated with an increased risk of PD and thus is not a prodromal marker of PD in the general population. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

The association of serum vitamin K2 levels with Parkinson's disease: from basic case-control study to big data mining analysis

Although it is known that inflammation is involved in Parkinson’s disease (PD) pathogenesis and vitamin K2 (VK2) has anti-inflammatory effects, to date few studies have been reported on the relationship between VK2 and PD development. Herein we presented a case-control study involving 93 PD patients and 95 healthy controls. Overall, the serum VK2 level of PD patients (3.49 ± 1.68 ng/ml) was significantly lower than that of healthy controls (5.77 ± 2.71 ng/ml). When the PD patients were stratified by disease progression, we observed that the serum VK2 level of late stage patients was further decreased to 3.15 ± 1.18 ng/ml while the serum VK2 level of early stage patients was 3.92 ± 2.09 ng/ml. Furthermore, the curve analysis showed that the serum VK2 level decreased gradually with the increment of PD Hoehn-Yahr (H-Y) stage. We also confirmed the dysregulated inflammatory responses and coagulation cascades in PD patients by public dataset, which are associated to the decreased VK2 level. In summary, we found the serum VK2 level in PD patients is lower than that in healthy controls. The decrease of VK2 level may be related to the occurrence and progression of PD by loosening the regulation of inflammatory responses and coagulation cascades signal.

Polydatin alleviates parkinsonism in MPTP-model mice by enhancing glycolysis in dopaminergic neurons

Parkinson's disease (PD) is a common neurodegenerative disease. Damage to energy metabolism and reduced adenosine triphosphate (ATP) levels in dopaminergic neurons are common features of PD. Previous studies suggested that the occurrence of PD often affects glucose metabolism and ATP production in the brain, and increased glycolysis or ATP production protects dopaminergic neuronal degeneration in the brain of PD patients. These systems may provide new potential therapeutic targets for the prevention of PD. The present study investigated the inhibitory action of polydatin (PLD) on early dopaminergic neuronal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that PLD protected against MPTP-induced early dopaminergic neuronal degeneration. PLD reduced the MPTP-induced loss of dopaminergic neurons in substantia nigra and striatum, inhibited the occurrence of neural apoptosis, and restored motor function in mice. PLD also increased the continuous activity duration and rhythm amplitude in mice during the circadian activity test. PLD improved glucose metabolism in the brain and restored ATP production levels. These observations suggest that PLD attenuates MPTP-induced early PD-like symptoms, and its mechanism of action may be associated with the promotion of glucose metabolism in neurons.

Visual Acuity and Development of Parkinson's Disease: A Nationwide Cohort Study.

Visual dysfunction in Parkinson's disease (PD) is well known from previous reports, but the association of visual deficits with PD development has not yet been studied. The aim of this research was to evaluate the association of visual acuity with the risk of PD occurrence using a nationwide cohort in South Korea. Among the population participating in the National Health Insurance Service, which is mandatory for all South Koreans, 6,055,113 individuals who had taken part in health screening programs between January 1, 2009, and December 31, 2012, were included in the cohort and followed until December 31, 2017. The hazard ratio was calculated for groups with high and low visual acuity using multivariate adjusted Cox regression analysis. A total of 22,872 subjects (0.38%) were diagnosed as having PD within the study period. Groups with low visual acuity showed a higher incidence of PD compared with groups with good visual acuity. Compared with the reference group (visual acuity better than 20/20), the adjusted hazard ratios and 95% confidence intervals (CIs) was 1.315 (95% CI, 1.261-1.371) for the group with visual acuity between 20/20 and 20/60, 1.357 (95% CI, 1.277-1.442) for the group with visual acuity between 20/60 and 10/100, and 1.267 (95% CI, 1.193-1.343) for the group with visual acuity less than 10/100. Low visual acuity was associated with the development of PD. This suggests that visual dysfunction is one of the premotor symptoms for PD development. © 2020 International Parkinson and Movement Disorder Society.

Clostridium difficile infection and risk of Parkinson's disease: a Swedish population-based cohort study.

Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). The aim of this study was to examine whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD. We performed a population-based cohort study using Swedish national register data. Adults aged ≥35years were identified from the Swedish Population and Housing Census 1990 and followed during the period 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs. outpatient), presence of recurrent infections, and pre-infection use of antibiotics. Amongst the study population (N=4670423), 34868 (0.75%) had a history of CDI. A total of 165 and 47035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among the CDI group [hazard ratio 1.16, 95% confidence interval (CI)1.00-1.36], which was mainly driven by increased PD risk within the first 2years after CDI diagnosis (hazard ratio 1.38, 95% CI 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups. Clostridium difficile may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.