Journal of Parkinson's disease最新文献

{"title":"Remote Sensing Data as a Tool for Studying Environmental Aspects of Parkinson's Disease.","authors":"Mohamed N Hegazi, Shaimaa El-Jaafary, Nourhan Shebl, Hassan El-Fawal, Mie Rizig, Mohamed Salama","doi":"10.3233/JPD-230382","DOIUrl":"10.3233/JPD-230382","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"619-622"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do Bacterial Outer Membrane Vesicles Contribute to Chronic Inflammation in Parkinson's Disease?","authors":"Tiana F Koukoulis, Leah C Beauchamp, Maria Kaparakis-Liaskos, Rachel M McQuade, Adityas Purnianto, David I Finkelstein, Kevin J Barnham, Laura J Vella","doi":"10.3233/JPD-230315","DOIUrl":"10.3233/JPD-230315","url":null,"abstract":"<p><p>Parkinson's disease (PD) is an increasingly common neurodegenerative disease. It has been suggested that the etiology of idiopathic PD is complex and multifactorial involving environmental contributions, such as viral or bacterial infections and microbial dysbiosis, in genetically predisposed individuals. With advances in our understanding of the gut-brain axis, there is increasing evidence that the intestinal microbiota and the mammalian immune system functionally interact. Recent findings suggest that a shift in the gut microbiome to a pro-inflammatory phenotype may play a role in PD onset and progression. While there are links between gut bacteria, inflammation, and PD, the bacterial products involved and how they traverse the gut lumen and distribute systemically to trigger inflammation are ill-defined. Mechanisms emerging in other research fields point to a role for small, inherently stable vesicles released by Gram-negative bacteria, called outer membrane vesicles in disease pathogenesis. These vesicles facilitate communication between bacteria and the host and can shuttle bacterial toxins and virulence factors around the body to elicit an immune response in local and distant organs. In this perspective article, we hypothesize a role for bacterial outer membrane vesicles in PD pathogenesis. We present evidence suggesting that these outer membrane vesicles specifically from Gram-negative bacteria could potentially contribute to PD by traversing the gut lumen to trigger local, systemic, and neuroinflammation. This perspective aims to facilitate a discussion on outer membrane vesicles in PD and encourage research in the area, with the goal of developing strategies for the prevention and treatment of the disease.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"227-244"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental Animal Models of Prodromal Parkinson's Disease.","authors":"Hodaka Yamakado, Ryosuke Takahashi","doi":"10.3233/JPD-230393","DOIUrl":"10.3233/JPD-230393","url":null,"abstract":"<p><p>There is an estimated 35-45% loss of striatal dopamine at the time of diagnosis of Parkinson's disease (PD), and cases clinically diagnosed in the early stages may already be pathologically in advanced stages. Recent large-scale clinical trials of disease-modifying therapies (DMT) also suggest the necessity of targeting patients at earlier stages of the disease. From this perspective, the prodromal phase of PD is currently the focus of attention, emphasizing the need for a prodromal mouse model that accurately reflects the pathophysiology, along with early biomarkers. To establish prodromal animal model of PD with high face validity that reflects the disease state, the model must possess high construct validity that accurately incorporates clinical and pathological features in the prodromal phase. Furthermore, as a preclinical model of DMT, the model must possess high predictive validity to accurately evaluate the response to intervention. This review provides an overview of animal models which reflect the characteristics of prodromal PD, including alpha-synuclein (aS) accumulation and associated early non-motor symptoms, with a focus on the aS propagation model and genetic model. In addition, we discuss the challenges associated with these models. The genetic model often fails to induce motor symptoms, while aS propagation models skip the crucial step of initial aS aggregate formation, thereby not fully replicating the entire natural course of the disease. Identifying factors that induce the transition from prodromal to symptomatic phase is important as a preclinical model for DMT to prevent or delay the onset of the disease.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S369-S379"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Another Step Forward for Freezing of Gait in Parkinson's Disease.","authors":"Anton Fomenko, Alfonso Fasano, Suneil K Kalia","doi":"10.3233/JPD-230412","DOIUrl":"10.3233/JPD-230412","url":null,"abstract":"<p><p>The study \"A spinal cord neuroprosthesis for locomotor deficits due to Parkinson's disease\" by Milekovic et al. introduces a novel neuroprosthesis for treating locomotor deficits in late-stage Parkinson's disease (PD). This approach employs an epidural spinal array targeting dorsal roots and electromyography to create a spatiotemporal map of muscle activation, aiming to restore natural gait patterns. Significant improvements in gait freezing and balance were observed in both non-human primate models and a human patient, resulting in improved mobility and quality of life. This innovative method, integrating real-time feedback and non-invasive motor intention decoding, marks a significant advancement in PD treatment.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"353-355"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10977400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Antibodies to Advance Glucocerebrosidase Research.","authors":"Nicolas Dzamko","doi":"10.3233/JPD-249000","DOIUrl":"10.3233/JPD-249000","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"79-80"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Importance of Digital Health Literacy in an Evolving Parkinson's Disease Care System.","authors":"Christine D Esper, Blanca Y Valdovinos, Ruth B Schneider","doi":"10.3233/JPD-230229","DOIUrl":"10.3233/JPD-230229","url":null,"abstract":"<p><p>Digital health technologies are growing at a rapid pace and changing the healthcare landscape. Our current understanding of digital health literacy in Parkinson's disease (PD) is limited. In this review, we discuss the potential challenges of low digital health literacy in PD with particular attention to telehealth, deep brain stimulation, wearable sensors, and smartphone applications. We also highlight inequities in access to digital health technologies. Future research is needed to better understand digital health literacy among individuals with PD and to develop effective solutions. We must invest resources to evaluate, understand, and enhance digital health literacy for individuals with PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S181-S189"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Diet in Parkinson's Disease.","authors":"Kira N Tosefsky, Julie Zhu, Yolanda N Wang, Joyce S T Lam, Amanda Cammalleri, Silke Appel-Cresswell","doi":"10.3233/JPD-230264","DOIUrl":"10.3233/JPD-230264","url":null,"abstract":"<p><p>The aim of this review is to examine the intersection of Parkinson's disease (PD) with nutrition, to identify best nutritional practices based on current evidence, and to identify gaps in the evidence and suggest future directions. Epidemiological work has linked various dietary patterns and food groups to changes in PD risk; however, fewer studies have evaluated the role of various diets, dietary components, and supplements in the management of established PD. There is substantial interest in exploring the role of diet-related interventions in both symptomatic management and potential disease modification. In this paper, we evaluate the utility of several dietary patterns, including the Mediterranean (MeDi), Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), Alternative Healthy Eating Index (AHEI), vegan/vegetarian, and ketogenic diet in persons with PD. Additionally, we provide an overview of the evidence relating several individual food groups and nutritional supplements to PD risk, symptoms and progression.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S21-S34"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oculomotor Dysfunction in Idiopathic and LRRK2-Parkinson's Disease and At-Risk Individuals.","authors":"Carmen Lage, Antonio Sánchez-Rodríguez, María Rivera-Sánchez, María Sierra, Isabel González-Aramburu, Jorge Madera, Manuel Delgado-Alvarado, Sara López-García, Francisco Martínez-Dubarbie, Marta Fernández-Matarrubia, Néstor Martínez-Amador, Isabel Martínez-Rodríguez, Alberto Calvo-Córdoba, Eloy Rodríguez-Rodríguez, Cecilia García-Cena, Pascual Sánchez-Juan, Jon Infante","doi":"10.3233/JPD-230416","DOIUrl":"10.3233/JPD-230416","url":null,"abstract":"<p><strong>Background: </strong>Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson's disease (PD).</p><p><strong>Objective: </strong>To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2.</p><p><strong>Methods: </strong>The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, and memory saccade tests.</p><p><strong>Results: </strong>We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy.</p><p><strong>Conclusions: </strong>iPD and LRRK2-G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"797-808"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Misfolded α-Synuclein Derived from Neuronal Exosomes in Blood with Parkinson's Disease Diagnosis and Duration.","authors":"Eva Schaeffer, Annika Kluge, Claudia Schulte, Christian Deuschle, Josina Bunk, Julius Welzel, Walter Maetzler, Daniela Berg","doi":"10.3233/JPD-230390","DOIUrl":"10.3233/JPD-230390","url":null,"abstract":"<p><strong>Background: </strong>Misfolded α-synuclein can be detected in blood samples of Parkinson's disease (PD) patients by a seed amplification assay (SAA), but the association with disease duration is not clear, yet.</p><p><strong>Objective: </strong>In the present study we aimed to elucidate whether seeding activity of misfolded α-synuclein derived from neuronal exosomes in blood is associated with PD diagnosis and disease duration.</p><p><strong>Methods: </strong>Cross-sectional samples of PD patients were analyzed and compared to samples of age- and gender-matched healthy controls using a blood-based SAA. Presence of α-synuclein seeding activity and differences in seeding parameters, including fluorescence response (in arbitrary units) at the end of the amplification assay (F60) were analyzed. Additionally, available PD samples collected longitudinally over 5-9 years were included.</p><p><strong>Results: </strong>In the cross-sectional dataset, 79 of 80 PD patients (mean age 69 years, SD = 8; 56% male) and none of the healthy controls (n = 20, mean age 70 years, SD = 10; 55% male) showed seeding activity (sensitivity 98.8%). When comparing subgroups divided by disease duration, longer disease duration was associated with lower α-synuclein seeding activity (F60: p < 0.001). In the longitudinal analysis 10/11 patients showed a gradual decrease of α-synuclein seeding activity over time.</p><p><strong>Conclusions: </strong>This study confirms the high sensitivity of the blood-based α-synuclein SAA applied here. The negative association of α-synuclein seeding activity in blood with disease duration makes this parameter potentially interesting as biomarker for future studies on the pathophysiology of disease progression in PD, and for biologically oriented trials in this field.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"667-679"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Continuous Dopaminergic Stimulation on Parkinson's Disease Gait: A Longitudinal Prospective Study with Levodopa Intestinal Gel Infusion.","authors":"Gabriele Imbalzano, Carlo Alberto Artusi, Claudia Ledda, Elisa Montanaro, Alberto Romagnolo, Mario Giorgio Rizzone, Marco Bozzali, Leonardo Lopiano, Maurizio Zibetti","doi":"10.3233/JPD-240003","DOIUrl":"10.3233/JPD-240003","url":null,"abstract":"<p><strong>Background: </strong>Gait issues, including reduced speed, stride length and freezing of gait (FoG), are disabling in advanced phases of Parkinson's disease (PD), and their treatment is challenging. Levodopa/carbidopa intestinal gel (LCIG) can improve these symptoms in PD patients with suboptimal control of motor fluctuations, but it is unclear if continuous dopaminergic stimulation can further improve gait issues, independently from reducing Off-time.</p><p><strong>Objective: </strong>To analyze before (T0) and after 3 (T1) and 6 (T2) months of LCIG initiation: a) the objective improvement of gait and balance; b) the improvement of FoG severity; c) the improvement of motor complications and their correlation with changes in gait parameters and FoG severity.</p><p><strong>Methods: </strong>This prospective, longitudinal 6-months study analyzed quantitative gait parameters using wearable inertial sensors, FoG with the New Freezing of Gait Questionnaire (NFoG-Q), and motor complications, as per the MDS-UPDRS part IV scores.</p><p><strong>Results: </strong>Gait speed and stride length increased and duration of Timed up and Go and of sit-to-stand transition was significantly reduced comparing T0 with T2, but not between T0-T1. NFoG-Q score decreased significantly from 19.3±4.6 (T0) to 11.8±7.9 (T1) and 8.4±7.6 (T2) (T1-T0 p = 0.018; T2-T0 p < 0.001). Improvement of MDS-UPDRS-IV (T0-T2, p = 0.002, T0-T1 p = 0.024) was not correlated with improvement of gait parameters and NFoG-Q from T0 to T2. LEDD did not change significantly after LCIG initiation.</p><p><strong>Conclusion: </strong>Continuous dopaminergic stimulation provided by LCIG infusion progressively ameliorates gait and alleviates FoG in PD patients over time, independently from improvement of motor fluctuations and without increase of daily dosage of dopaminergic therapy.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"843-853"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140904232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}