Onset Parkinson's Disease Research Articles

Effect of Shashti Shali Pinda Swedan and Sahchar Tail Matra Basti in the management of Young Onset of Parkinson Disorder (YOPD) - A Case Report

The young onset Parkinson disease is a progressive neurodegenerative disease characterized by both motor and non motor features. The diseases affect families and caregivers through its progressive degenerative effect on mobility and the muscle control.[1] The main difference between young onset of Parkinson disorder (YOPD)and the late onset of Parkinson disorder (LOPD) is genetic etiology and clinical symptoms e.g., dystonia and levodopa induced per dyskinesia are common in YOPD. YOPD person carrying a greater social economic burden compared to late onset of Parkinson disease due to age factor. YOPD Patients more prone to levodopa related motor complication. Parkinson’s disease is referred to in the ancient Indian medical system of Ayurveda under the name Kampavata which is characterized by Kampa (Tremors), Stambha (Rigidity), Chesthahani (Akinesia) & Gativikriti (Gait Disorders). The case study is of a 45 years old male who has been diagnosed with early stage idiopathic Parkinson’s disease. No satisfactory treatment is seen in contemporary system of medicine so treatment is planned in here study.

Radiomics and Hybrid Models Based on Machine Learning to Predict Levodopa-Induced Dyskinesia of Parkinson's Disease in the First 6 Years of Levodopa Treatment.

Current research on the prediction of movement complications associated with levodopa therapy in Parkinson's disease (PD) is limited. levodopa-induced dyskinesia (LID) is a movement complication that seriously affects the life quality of PD patients. One-third of PD patients develop LID within 1 to 6 years of levodopa treatment. This study aimed to construct models based on radiomics and machine learning to predict early LID in PD. We extracted radiomics features from the T1-weighted MRI obtained in the baseline of 49 PD control and 54 PD with LID in the first 6 years of levodopa therapy. Six brain regions related to the onset of PD were segmented as regions of interest (ROIs). The least absolute shrinkage and selection operator (LASSO) was used for feature selection. Using the machine learning methods of support vector machine (SVM), random forest (RF), and AdaBoost, we constructed radiomics models and hybrid models. The hybrid models combined the radiomics features and the Unified Parkinson's Disease Rating Scale part III (UPDRS III) total score. The five-fold cross-validation was performed and repeated 20 times to validate the stability of the classifiers. We used sensitivity, specificity, accuracy, receiver operating characteristic (ROC) curves, and area under the ROC curve (AUC) for model validation. We selected 33 out of 6138 radiomics features. In the testing set of the radiomics model, the AUC values of the SVM, RF, and AdaBoost classifiers were 0.905, 0.808, and 0.778, respectively, and the accuracies were 0.839, 0.742, and 0.710. The hybrid models had better prediction performance. In the testing set, the AUC values of SVM, RF, and AdaBoost classifiers were 0.958, 0.861, and 0.832, respectively, and the accuracies were 0.903, 0.806, and 0.774. Our results indicate that T1-weighted MRI is valuable in predicting early LID in PD. This work demonstrates that the combination of radiomics features and clinical features has good potential and value for identifying early LID in PD.

A study on the correlations between acoustic speech variables and bradykinesia in advanced Parkinson's disease.

Very few studies have assessed the presence of a possible correlation between speech variables and limb bradykinesia in patients with Parkinson's disease (PD). The objective of this study was to find correlations between different speech variables and upper extremity bradykinesia under different medication conditions in advanced PD patients. Retrospective data were collected from a cohort of advanced PD patients before and after an acute levodopa challenge. Each patient was assessed with a perceptual-acoustic analysis of speech, which included several quantitative parameters [i.e., maximum phonation time (MPT) and intensity (dB)]; the Unified Parkinson's Disease Rating Scale (UPDRS) (total scores, subscores, and items); and a timed test (a tapping test for 20 s) to quantify upper extremity bradykinesia. Pearson's correlation coefficient was applied to find correlations between the different speech variables and the tapping rate. A total of 53 PD patients [men: 34; disease duration: 10.66 (SD 4.37) years; age at PD onset: 49.81 years (SD 6.12)] were included. Levodopa intake increased the MPT of sustained phonation (p < 0.01), but it reduced the speech rate (p = 0.05). In the defined-OFF condition, MPT of sustained phonation positively correlated with both bilateral mean (p = 0.044, r-value:0.299) and left (p = 0.033, r-value:0.314) tapping. In the defined-ON condition, the MPT correlated positively with bilateral mean tapping (p = 0.003), left tapping (p = 0.003), and right tapping (p = 0.008). This study confirms the presence of correlations between speech acoustic variables and upper extremity bradykinesia in advanced PD patients. These findings suggest common pathophysiological mechanisms.

Late Presentation of Chronic Traumatic Encephalopathy in a Former Association Football Player.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by widespread accumulation of hyperphosphorylated tau that typically occurs in people who have suffered repetitive head impacts. To date, very few cases have been reported in association football players. To describe the clinicopathological features of a case of CTE in an 84-year-old former football player who was clinically diagnosed as having dementia with Lewy bodies (DLB). A retrospective review of the patient's primary care and hospital medical records was performed along with a comprehensive neuropathological examination. This patient presented at age 84 with symmetrical parkinsonism and cognitive impairment that was exacerbated by prochlorperazine. His condition was rapidly progressive with recurrent falls within 1 year. Other features included headaches, depression, anxiety, suicidal ideation, disturbed sleep and aggression. He received a clinical diagnosis of DLB and died approximately 2 years after the onset of symptoms. A post-mortem examination revealed stage 4 CTE. While the contemporaneous onset of parkinsonism and cognitive symptoms in the context of possible neuroleptic sensitivity is suggestive of DLB, the additional symptoms of aggressive behavior, depression and suicidality in a former football player are consistent with the neuropathological diagnosis of CTE. This case, which is notable for the late presentation, demonstrates that CTE may masquerade as other dementias and highlights the importance of seeking a history of repetitive head impacts.

Metagenomics of the Gut Microbiome in Parkinson's Disease: Prodromal Changes.

Prior studies on the gut microbiome in Parkinson's disease (PD) have yielded conflicting results, and few studies have focused on prodromal (premotor) PD or used shotgun metagenomic profiling to assess microbial functional potential. We conducted a nested case-control study within 2 large epidemiological cohorts to examine the role of the gut microbiome in PD. We profiled the fecal metagenomes of 420 participants in the Nurses' Health Study and the Health Professionals Follow-up Study with recent onset PD (N = 75), with features of prodromal PD (N = 101), controls with constipation (N = 113), and healthy controls (N = 131) to identify microbial taxonomic and functional features associated with PD and features suggestive of prodromal PD. Omnibus and feature-wise analyses identified bacterial species and pathways associated with prodromal and recently onset PD. We observed depletion of several strict anaerobes associated with reduced inflammation among participants with PD or features of prodromal PD. A microbiome-based classifier had moderate accuracy (area under the curve [AUC] = 0.76 for species and 0.74 for pathways) to discriminate between recently onset PD cases and controls. These taxonomic shifts corresponded with functional shifts indicative of carbohydrate source preference. Similar, but less marked, changes were observed in participants with features of prodromal PD, in both microbial features and functions. PD and features of prodromal PD were associated with similar changes in the gut microbiome. These findings suggest that changes in the microbiome could represent novel biomarkers for the earliest phases of PD. ANN NEUROL 2023;94:486-501.

Decreased serum BDNF contributes to the onset of REM sleep behavior disorder in Parkinson’s disease patients

BackgroundBrain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. BDNF enhances the survival of dopaminergic neurons and improves dopaminergic neurotransmission and motor performance in patients with Parkinson's disease (PD). However, the association between BDNF levels and rapid eye movement (REM) sleep behavior disorder (RBD) in PD patients has received limited attention. MethodsWe employed the Rapid Eye Movement Sleep Behavior Disorder Questionnaire-Hong Kong version (RBDQ-HK) and the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) for RBD diagnosis. Patients were categorized into three groups: healthy controls (n = 53), PD patients without RBD (PD-nRBD; n = 56), and PD patients with RBD (PD-RBD; n = 45). Serum BDNF concentrations, demographic information, medical history, and motor/non-motor manifestations were compared between the three groups. Logistic regression analysis was performed to identify independent factors associated with PD and RBD. P-trend analysis was used to assess the relationship between BDNF levels and the risk of PD and RBD onset. Interaction effects were analyzed between BDNF, patients’ age, and gender on the risk of RBD onset in PD patients. ResultsOur findings indicate that serum BDNF levels were significantly lower in PD patients compared to healthy controls (p < 0.001). PD-RBD patients exhibited higher motor symptom scores (UPDRS III) than PD-nRBD patients (p = 0.021). Additionally, the PD-RBD group demonstrated lower cognitive function scores as measured by the Montreal Cognitive Assessment (MoCA) (p < 0.001) and Mini-Mental State Examination (MMSE) (p = 0.015). PD-RBD patients displayed significantly lower BDNF levels compared to both PD-nRBD and healthy control groups (p < 0.001). Univariate and multivariate logistic regression analyses showed that reduced BDNF levels were associated with an increased risk of RBD in PD patients (p = 0.005). P-trend analysis further confirmed the progressive relationship between decreased BDNF levels and the risk of PD and RBD onset. Furthermore, our interaction analysis highlighted the importance of monitoring younger PD patients with low serum BDNF levels for potential RBD onset. ConclusionsThis study illustrates that decreased serum BDNF levels may be linked to the development of RBD in PD patients, highlighting the potential utility of BDNF as a biomarker in clinical practice.

Characteristics and influencing factors of 11C-CFT PET imaging in patients with early and late onset Parkinson's disease.

This study aims to explore the difference between 11C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (11C-CFT) positron emission tomography (PET) imaging in the early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD), and to analyze the correlation between 11C-CFT PET imaging and disease duration, Hoehn & Yahr (H&Y) stage, motor symptoms, and non-motor symptoms in patients with idiopathic Parkinson's disease (PD), so as to explore its application value in assessing the severity of Parkinson's disease. A total of 113 patients with idiopathic PD were included in this study. The patients were divided into EOPD and LOPD groups according to the age of 60 years, of which 58 were early-onset and 55 were late-onset. All patients underwent 11C-CFT PET imaging and manually sketched regions of interest (ROI) to delineate the caudate nucleus, anterior putamen, and posterior putamen ROI layer-by-layer, and the corresponding values were recorded. Clinical data [age of onset, disease duration, H&Y stage, total Unified Parkinson's Disease Rating Scale (UPDRS) score, UPDRS III score, tremor score, postural instability/gait difficulty (PIGD) score, rigidity score, bradykinesia score, and Montreal Cognitive Assessment (MoCA) score] were collected from all patients. The differences in striatal 11C-CFT uptake between patients with EOPD and LOPD were compared, and the correlation between striatal 11C-CFT uptake and the clinical data of patients with idiopathic PD was evaluated. The caudate nucleus 11C-CFT uptake was higher in EOPD than in the LOPD group (t = 3.002, p = 0.003). 11C-CFT uptake in the caudate nucleus in patients with PD was negatively correlated with the age of onset, H&Y stage, disease duration, total UPDRS score, UPDRS III score, rigidity score, and bradykinesia score (p < 0.05). The anterior and posterior putamen 11C-CFT uptake was negatively correlated with H&Y stage, disease duration, total UPDRS score, UPDRS III score, PIGD score, rigidity score, and bradykinesia score (p < 0.05). 11C-CFT PET provides an objective molecular imaging basis for the difference in disease progression rates between patients with EOPD and LOPD. Secondly, 11C-CFT PET can be used as an important objective indicator to assess disease severity and monitor disease progression.

"It just makes you more vulnerable as an employee": Understanding the effects of disability stigma on employment in Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the United States, affecting approximately 1 million Americans. However, there is a dearth of research on the employment experiences of individuals with PD. This research article makes a crucial contribution to the literature by examining the role of disability stigma in shaping employment options in PD, with relevance to the experiences of adults with chronic and/or progressive diseases more broadly. The author conducted individual semi-structured interviews with 23 adults under the age of 65 with PD. Interviews were audio-recorded and transcribed. The author utilized an integrated approach to analysis, primarily employing a thematic analysis approach. Additionally, a narrative analysis strategy, the Listening Guide, was integrated into the broader thematic analysis to deepen analysis of discrimination and stigma. Findings demonstrate how internalized, anticipated and/or experienced disability-related stigma profoundly affects employment experiences, influencing participants' work outcome expectations and acting as an employment barrier. Findings have implications for health care practice and education, disability policy, early intervention strategies after the onset of PD and priorities for future research.

Study of the relationship between onset lateralization and hemispheric white matter asymmetry in Parkinson's disease.

Parkinson's disease (PD) is characterized by a lateralized onset, but its cause and mechanism are still unclear. Obtaining diffusion tensor imaging (DTI) data from the Parkinson's Progression Markers Initiative (PPMI). Tract-based spatial statistics analysis and region-of-interest-based analysis were performed to evaluate the white matter (WM) asymmetry using original DTI parameters, Z Score normalized parameters, or the asymmetry index (AI). Hierarchical cluster analysis and least absolute shrinkage and selection operator regression were performed to construct predictive models for predicting the PD onset side. DTI data from The Second Affiliated Hospital of Chongqing Medical University were obtained for external validation of the prediction model. 118 PD patients and 69 healthy controls (HC) from PPMI were included. Right-onset PD patients presented more asymmetric areas than left-onset PD patients. The inferior cerebellar peduncle (ICP), superior cerebellar peduncle (SCP), external capsule (EC), cingulate gyrus (CG), superior fronto-occipital fasciculus (SFO), uncinate fasciculus (UNC), and tapetum (TAP) showed significant asymmetry inleft-onset and right-onset PD patients. An onset-side-specific pattern of WM alterations exists in PD patients, and a prediction model was constructed. The predicting models based on AI and ΔZ Score presented favorable efficacy in predicting PD onset side by external validation in 26 PD patients and 16 HCs from our hospital. Right-onset PD patients may have more severe WM damage than left-onset PD patients. WM asymmetry in ICP, SCP, EC, CG, SFO, UNC, and TAP may predict PD onset side. Imbalances in the WM network may underlie the mechanism of lateralized onset in PD.

Detection of a Parkinson's Disease-Specific MicroRNA Signature in Nasal and Oral Swabs.

Biomaterials from oral and nasal swabs provide, in theory, a potential resource for biomarker development. However, their diagnostic value has not yet been investigated in the context of Parkinson's disease (PD) and associated conditions. We have previously identified a PD-specific microRNA (miRNA) signature in gut biopsies. In this work, we aimed to investigate the expression of miRNAs in routine buccal (oral) and nasal swabs obtained from cases with idiopathic PD and isolated rapid eye movement sleep behavior disorder (iRBD), a prodromal symptom that often precedes α-synucleinopathies. We aimed to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression. Healthy control cases (n = 28), cases with PD (n = 29), and cases with iRBD (n = 8) were prospectively recruited to undergo routine buccal and nasal swabs. Total RNA was extracted from the swab material, and the expression of a predefined set of miRNAs was quantified by quantitative real-time polymerase chain reaction. Statistical analysis revealed a significantly increased expression of hsa-miR-1260a in cases who had PD. Interestingly, hsa-miR-1260a expression levels correlated with diseases severity, as well as olfactory function, in the PD and iRBD cohorts. Mechanistically, hsa-miR-1260a segregated to Golgi-associated cellular processes with a potential role in mucosal plasma cells. Predicted hsa-miR-1260a target gene expression was reduced in iRBD and PD groups. Our work demonstrates oral and nasal swabs as a valuable biomarker pool in PD and associated neurodegenerative conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Evaluation of type 1 diabetes mellitus as a risk factor of Parkinson's disease in a Drosophila model.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood glucose levels, resulting from insulin dysregulation. Parkinson's disease (PD) is the most common neurodegenerative motor disorder caused by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta. DM and PD are both age-associated diseases that are turning into epidemics worldwide. Previous studies have indicated that type 2 DM might be a risk factor of developing PD. However, scarce information about the link between type 1 DM (T1DM) and PD does exist. In this work, we have generated a Drosophila model of T1DM based on insulin deficiency to evaluate if T1DM could be a risk factor to trigger PD onset. As expected, model flies exhibited T1DM-related phenotypes such as insulin deficiency, increased content of carbohydrates and glycogen, and reduced activity of insulin signaling. Interestingly, our results also demonstrated that T1DM model flies presented locomotor defects as well as reduced levels of tyrosine hydroxylase (a marker of DA neurons) in brains, which are typical PD-related phenotypes. In addition, T1DM model flies showed elevated oxidative stress levels, which could be causative of DA neurodegeneration. Therefore, our results indicate that T1DM might be a risk factor of developing PD, and encourage further studies to shed light into the exact link between both diseases.

The Ameliorative Effect of Ashwagandha- Withania somnifera (L.) Dunal on park25 Induced Neurodegeneration in Drosophila melanogaster Parkinson’s Disease Model

Ashwagandha - Withania somnifera (L.) Dunal is a perennial shrub belonging to the family Solanaceae. Ashwagandha has been used for over 3000 years in traditional Indian Ayurveda for treatment of various neurological, and stress disorders. The root of Ashwagandha (ASH) is regarded as a tonic, aphrodisiac, narcotic, diuretic, anthelmintic, astringent, thermogenic and stimulant. Ashwagandha with other herbal decoctions was recognized to treat Kampavatha (Parkinson’s Disease) since 18th century. With this wide array of ethnopharmacological relevance, Ashwagandha has been recognized as one of the prominent complementary and alternative medicine to treat many neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s disease (PD). There is a prominent increase in the cases of AD and PD all over the world and it demands the requirement of complementary and alternative herbal remedies with no/minimal side effects. Many genetic factors are responsible for the onset and progression of PD. Loss-of-function mutations in the parkin gene are a major cause of early onset of autosomal recessive juvenile parkinsonism (AR-JP). Drosophila park25 loss of function mutants exhibit significantly increased number of mitochondria-endoplasmic reticulum contacts and a significantly decreased number of dopaminergic neurons in the adult brain which is the main cause of PD condition. Several studies have demonstrated the ability of Ashwagandha in imparting neuroprotection, improved locomotory ability, memory and learning abilities. The challenge lies in scrutinizing the mechanism and the pathways involved in the neuroprotective properties of this well-known herb. Here in our study, we test the possible neuroprotective effect of Ashwagandha on park25 mutants of Drosophila using lifespan analysis and climbing disability as a disease marker. Parkinson’s mimicking flies were administered with aqueous extraction of Ashwagandha-root mixed with the fly food and subjected to negative geotaxis assay. We observed that there is a prominent increase in the climbing ability in park25 treated flies compared to its age-matched untreated flies. This is the first report showing that, aqueous extraction of Ashwagandha-root extract was able to ameliorate the disease phenotype in the park25 Drosophila Parkinson’s disease model.

Therapeutic Potential of Heterocyclic Compounds Targeting Mitochondrial Calcium Homeostasis and Signaling in Alzheimer's Disease and Parkinson's Disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases in the elderly. The key histopathological features of these diseases are the presence of abnormal protein aggregates and the progressive and irreversible loss of neurons in specific brain regions. The exact mechanisms underlying the etiopathogenesis of AD or PD remain unknown, but there is extensive evidence indicating that excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with a depleted antioxidant system, mitochondrial dysfunction, and intracellular Ca2+ dyshomeostasis, plays a vital role in the pathophysiology of these neurological disorders. Due to an improvement in life expectancy, the incidence of age-related neurodegenerative diseases has significantly increased. However, there is no effective protective treatment or therapy available but rather only very limited palliative treatment. Therefore, there is an urgent need for the development of preventive strategies and disease-modifying therapies to treat AD/PD. Because dysregulated Ca2+ metabolism drives oxidative damage and neuropathology in these diseases, the identification or development of compounds capable of restoring Ca2+ homeostasis and signaling may provide a neuroprotective avenue for the treatment of neurodegenerative diseases. In addition, a set of strategies to control mitochondrial Ca2+ homeostasis and signaling has been reported, including decreased Ca2+ uptake through voltage-operated Ca2+ channels (VOCCs). In this article, we review the modulatory effects of several heterocyclic compounds on Ca2+ homeostasis and trafficking, as well as their ability to regulate compromised mitochondrial function and associated free-radical production during the onset and progression of AD or PD. This comprehensive review also describes the chemical synthesis of the heterocycles and summarizes the clinical trial outcomes.

Casein Reactivates Dopaminergic Nerve Injury and Intestinal Inflammation with Disturbing Intestinal Microflora and Fecal Metabolites in a Convalescent Parkinson's Disease Mouse Model

Parkinson's disease (PD) is the fastest-growing neurodegenerative disease, with pathogenic causes elusive and short of effective treatment options. Investigations have found that dairy products positively correlate with the onset of PD, but the mechanisms remain unexplored. As casein is an antigenic component in dairy products, this study assessed if casein could exacerbate PD-related symptoms by stimulating intestinal inflammation and unbalanced intestinal flora and be a risk factor for PD. Using a convalescent PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the results showed casein reduced motor coordination, caused gastrointestinal dysfunction, reduced dopamine content, and induced intestinal inflammation. Meanwhile, casein disturbed gut microbiota homeostasis by increasing the Firmicutes/Bacteroidetes ratio, decreasing α-diversity, and caused abnormal alterations in fecal metabolites. However, these adverse effects of casein attenuated much when it had hydrolyzed by acid or when antibiotics inhibited the intestinal microbiota of the mice. Therefore, our results suggested that casein could reactivate dopaminergic nerve injury and intestinal inflammation and exacerbate intestinal flora disorder and its metabolites in convalescent PD mice. These damaging effects might be related to disordered protein digestion and gut microbiota in these mice. These findings will provide new insights into the impact of milk/dairy products on PD progression and supply information on dietary options for PD patients.

People with Early Onset Parkinson's Disease: Empowered to Improve Care.

Patient organizations play an ever-growing role in modern societies by providing organized resources for patients and care partners. Importantly, patient organizations enable patients to define and share their needs and views. In Parkinson's disease (PD), patient organizations play significant roles in different countries. However, there is limited support and resources tailored for people with early onset Parkinson's disease (EOPD). These individuals face unique social, professional, and personal challenges that are often not accounted for by general PD organizations, which play very important roles for a significant proportion of individuals with PD. In Portugal, this was the situation until 2022, when Young Parkies Portugal (YPP) was founded to allow people with EOPD and various stakeholders to join forces to cover their specific needs. In this manuscript, we aim to share our experience in building an association for people with EOPD, reflecting on the reasons for this need, the activities developed thus far, challenges in implementation, and future directions. In summary, we believe that nonprofit organizations like YPP play an essential role in shaping the care and support of people with PD care and should be considered key partners of care alongside the larger multidisciplinary team. We are confident that sharing our experience can inspire and guide the implementation of similar initiatives in other countries.

Substantia Nigra Echogenicity Signal Correlated with Clinical Features in Patients with Parkinson's Disease in Xinjiang.

Transcranial sonography (TCS) is a noninvasive test that can reveal structural changes in the substantia nigra (SN) in Parkinson's disease (PD). The purpose of this study was to investigate the relationship between SN signatures and clinical features in PD patients in a multiethnic region of China. A total of 147 patients with PD were included in the study, and all of whom had underwent a TCS examination. Clinical information was collected from PD patients, and motor and nonmotor symptoms were assessed using assessment scales. There were differences in the substantia nigra hyperechogenicity (SNH) area between age of onset, visual hallucinations (VH), and UPDRS3.0 II scores (P < 0.05), patients with late onset PD had a greater SNH area than early onset (0.326 ± 0.352 vs. 0.171 ± 0.194), and PD patients presenting with VH had a greater SNH area than those without hallucinations (0.508 ± 0.670 vs. 0.278 ± 0.659), and further multifactorial analysis showed that a high SNH area was an independent risk factor for development of VH. The area under the ROC curve for predicting VH from the SNH area in PD patients was 0.609 (95% CI: 0.444-0.774). There was a positive correlation between the SNH area and UPDRS3.0-II scores, but further multifactorial analysis showed that SNH was not an independent predictor of the UPDRS3.0-II score. A high SNH area is an independent risk factor for development of VH, there is a positive correlation between the SNH area and UPDRS3.0 II score, and TCS has guiding significance in predicting clinical VH symptoms and activities of daily living in PD patients.

Associations between gut microbiota and Parkinson disease: Abidirectional Mendelian randomization analysis.

Parkinson disease (PD)-associated alterations in the gut microbiome have been observed in clinical and animal studies. However, it remains unclear whether this association reflects a causal effect in humans. We performed two-sample bidirectional Mendelian randomization using summary statistics from the international consortium MiBioGen (N = 18,340), the Framingham Heart Study (N = 2076), and the International Parkinson's Disease Genomics Consortium for PD (33,674 cases and 449,056 controls) and PD age at onset (17,996 cases). Twelve microbiota features presented suggestive associations with PD risk or age at onset. Genetically increased Bifidobacterium levels correlated with decreased PD risk (odds ratio = 0.77, 95% confidence interval [CI] = 0.60-0.99, p = 0.040). Conversely, high levels of five short-chain fatty acid (SCFA)-producing bacteria (LachnospiraceaeUCG010, RuminococcaceaeUCG002, Clostridium sensustricto1, Eubacterium hallii group, and Bacillales) correlated with increased PD risk, and three SCFA-producing bacteria (Roseburia, RuminococcaceaeUCG002, and Erysipelatoclostridium) correlated with an earlier age at PD onset. Gut production of serotonin was associated with an earlier age at PD onset (beta = -0.64, 95% CI = -1.15 to -0.13, p = 0.013). In the reverse direction, genetic predisposition to PD was related to altered gut microbiota composition. These results support a bidirectional relationship between gut microbiome dysbiosis and PD, and highlight the role of elevated endogenous SCFAs and serotonin in PD pathogenesis. Future clinical studies and experimental evidence are needed to explain the observed associations and to suggest new therapeutic approaches, such as dietary probiotic supplementation.

C-reactive protein as the biomarker of choice to monitor the effects of exercise on inflammation in Parkinson's disease.

Parkinson's disease (PD), a heterogeneous disease with no disease-modifying treatments available, is the fastest growing neurological disease worldwide. Currently, physical exercise is the most promising treatment to slow disease progression, with evidence suggesting it is neuroprotective in animal models. The onset, progression, and symptom severity of PD are associated with low grade, chronic inflammation which can be quantified by measuring inflammatory biomarkers. In this perspective, we argue that C-reactive protein (CRP) should be used as the primary biomarker for monitoring inflammation and therefore disease progression and severity, particularly in studies examining the impact of an intervention on the signs and symptoms of PD. CRP is the most studied biomarker of inflammation, and it can be detected using relatively well-standardized assays with a wide range of detection, allowing for comparability across studies while generating robust data. An additional advantage of CRP is its ability to detect inflammation irrespective of its origin and specific pathways, an advantageous characteristic when the cause of inflammation remains unknown, such as PD and other chronic, heterogeneous diseases.

Unexpected phenotypic and molecular changes of combined glucocerebrosidase and acid sphingomyelinase deficiency.

Heterozygous variants in GBA1, encoding glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson's disease (PD). Moreover, sporadic PD patients also have a substantial reduction of GCase activity. Genetic variants of SMPD1 are also overrepresented in PD cohorts, whereas a reduction of its encoded enzyme (acid sphingomyelinase or ASM) activity is linked to an earlier age of PD onset. Despite both converging on the ceramide pathway, how the combined deficiencies of both enzymes might interact to modulate PD has yet to be explored. Therefore, we created a double-knockout (DKO) zebrafish line for both gba1 (or gba) and smpd1 to test for an interaction in vivo, hypothesising an exacerbation of phenotypes in the DKO line compared to those for single mutants. Unexpectedly, DKO zebrafish maintained conventional swimming behaviour and had normalised neuronal gene expression signatures compared to those of single mutants. We further identified rescue of mitochondrial Complexes I and IV in DKO zebrafish. Despite having an unexpected rescue effect, our results confirm ASM as a modifier of GBA1 deficiency in vivo. Our study highlights the need for validating how genetic variants and enzymatic deficiencies may interact in vivo.

Frequency of Parkinson disease following COVID-19 infection: A two-year retrospective cohort study

IntroductionCOVID-19 infection is known to cause various neurological symptoms, and potentially increases the risk of developing subsequent neurodegenerative conditions including parkinsonism. To our knowledge, no study to date has used a large data set in the United States to ascertain the risk of developing incident Parkinson disease in patients with history of COVID-19 infection compared to the risk amongst those without prior COVID-19 infection. MethodsWe utilized data from TriNetX electronic health records network which includes 73 healthcare organizations and over 107 million patients. We compared adult patients with and without COVID-19 infection, with health records from January 1, 2020 through July 26, 2022, to determine the relative risk of developing Parkinson disease stratified by 3-month intervals. We used propensity score matching to control for patients’ age, sex, and smoking history. ResultsWe collected data on 27,614,510 patients meeting our study criteria: 2,036,930 patients with a positive COVID-19 infection (COVID-19) and 25,577,580 without a positive COVID-19 infection (non-COVID-19). After propensity score matching, age, sex, and smoking history differences became non-significant, with 2,036,930 patients in each cohort. After propensity score matching, we found significantly increased odds of new onset Parkinson disease in the COVID-19 cohort at three, six, nine, and twelve months from the index event, with peak odds ratio at six months. After twelve months there is no significant difference between the COVID-19 group and non-COVID-19 group. ConclusionsThere may be a transiently increased risk of developing Parkinson disease in the first year following COVID-19 infection.