Journal of Parkinson's disease最新文献

{"title":"Tissue Factor and Its Cerebrospinal Fluid Protein Profiles in Parkinson's Disease.","authors":"Milan Zimmermann, Madeleine Fandrich, Meike Jakobi, Benjamin Röben, Isabel Wurster, Stefanie Lerche, Claudia Schulte, Shahrzad Zimmermann, Christian Deuschle, Nicole Schneiderhan-Marra, Thomas O Joos, Thomas Gasser, Kathrin Brockmann","doi":"10.3233/JPD-240115","DOIUrl":"10.3233/JPD-240115","url":null,"abstract":"<p><strong>Background: </strong>Prior investigations have elucidated pathophysiological interactions involving blood coagulation and neurodegenerative diseases. These interactions pertain to age-related effects and a mild platelet antiaggregant function of exogenous α-Synuclein.</p><p><strong>Objective: </strong>Our study sought to explore whether cerebrospinal fluid (CSF) levels of tissue factor (TF), the initiator of the extrinsic pathway of hemostasis, differ between controls (CON) compared to patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB), considering that these conditions represent a spectrum of α-Synuclein pathology. We further investigated whether TF levels are associated with longitudinal progression in PD.</p><p><strong>Methods: </strong>We examined CSF levels of TF in 479 PD patients, 67 patients diagnosed with DLB, and 16 CON in order to evaluate potential continuum patterns among DLB, PD, and CON. Of the 479 PD patients, 96 carried a GBA1 variant (PD GBA1), while the 383 non-carriers were classified as PD wildtype (PD WT). We considered both longitudinal clinical data as well as CSF measurements of common neurodegenerative markers (amyloid-β 1-42, h-Tau, p-Tau, NfL, α-Synuclein). Kaplan-Meier survival and Cox regression analysis stratified by TF tertile levels was conducted.</p><p><strong>Results: </strong>Higher CSF levels of TF were associated with an older age at examination in PD and a significant later onset of postural instability in PD GBA1. TF levels were lower in male vs. female PD. DLB GBA1 exhibited the lowest TF levels, followed by PD GBA1, with CON showing the highest levels.</p><p><strong>Conclusions: </strong>TF as representative of blood hemostasis could be an interesting CSF candidate to further explore in PD and DLB.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1405-1416"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140305","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":"Introduction: The Earliest Phase of Parkinson's Disease: Possibilities for Detection and Intervention.","authors":"Daniela Berg, Bastiaan R Bloem, Lorraine V Kalia, Ron B Postuma","doi":"10.3233/JPD-249011","DOIUrl":"10.3233/JPD-249011","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S253-S255"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348605","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":"Factors Associated with Preferred Place of Care and Death in Patients with Parkinson's Disease: A Cross-Sectional Study.","authors":"Anna J Pedrosa, Sarah Feldmann, Jan Klippel, Christian Volberg, Christiane Weck, Stefan Lorenzl, David J Pedrosa","doi":"10.3233/JPD-230311","DOIUrl":"10.3233/JPD-230311","url":null,"abstract":"<p><strong>Background: </strong>A significant proportion of people with Parkinson's disease (PwPD) die in hospital settings. Although one could presume that most PwPD would favor being cared for and die at home, there is currently no evidence to support this assumption.</p><p><strong>Objective: </strong>We aimed at exploring PwPD's preferences for place of end-of-life care and place of death, along with associated factors.</p><p><strong>Methods: </strong>A cross-sectional study was conducted to investigate PwPD's end-of life wishes regarding their preferred place of care and preferred place of death. Using different approaches within a generalized linear model framework, we additionally explored factors possibly associated with preferences for home care and home death.</p><p><strong>Results: </strong>Although most PwPD wished to be cared for and die at home, about one-third reported feeling indifferent about their place of death. Preferred home care was associated with the preference for home death. Furthermore, a preference for dying at home was more likely among PwPD's with informal care support and spiritual/religious affiliation, but less likely if they preferred institutional care towards the end of life.</p><p><strong>Conclusions: </strong>The variation in responses regarding the preferred place of care and place of death highlights the need to distinguish between the concepts when discussing end-of-life care. However, it is worth noting that the majority of PwPD preferred care and death at home. The factors identified in relation to preferred place of care and death provide an initial understanding of PwPD decision-making, but call for further research to confirm our findings, explore causality and identify additional influencing factors.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"589-599"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059612","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":"Investigating the Shared Genetic Etiology Between Parkinson's Disease and Depression.","authors":"Paula Reyes-Pérez, Luis M García-Marín, Asma M Aman, Tarek Antar, Victor Flores-Ocampo, Brittany L Mitchell, Alejandra Medina-Rivera, Miguel E Rentería","doi":"10.3233/JPD-230176","DOIUrl":"10.3233/JPD-230176","url":null,"abstract":"<p><strong>Background: </strong>Depression is a common symptom in Parkinson's disease (PD), resulting from underlying neuropathological processes and psychological factors. However, the extent to which shared genetic risk factors contribute to the relationship between depression and PD is poorly understood.</p><p><strong>Objective: </strong>To examine the effects of common genetic variants influencing the etiology of PD and depression risk at the genome-wide and local genomic regional level.</p><p><strong>Methods: </strong>We comprehensively investigated the genetic relationship between PD and depression using genome-wide association studies data. First, we estimated the genetic correlation at the genome-wide level using linkage-disequilibrium score regression, followed by local genetic correlation analysis using the GWAS-pairwise method and functional annotation to identify genes that may jointly influence the risk for both traits. Also, we performed Latent Causal Variable, Latent Heritable Confounder Mendelian Randomization, and traditional Mendelian Randomization analyses to investigate the potential causal relationship.</p><p><strong>Results: </strong>Although the genetic correlation between PD and depression was not statistically significant at the genome-wide level, GWAS-pairwise analyses identified 16 genomic segments associated with PD and depression, implicating nine genes. Further analyses revealed distinct patterns within individual genes, suggesting an intricate pattern. These genes involve various biological processes, including neurotransmitter regulation, senescence, and nucleo-cytoplasmic transport mechanisms. We did not observe genetic evidence of causality between PD and depression.</p><p><strong>Conclusions: </strong>Our findings did not support a genome-wide genetic correlation or a causal association between both conditions. However, we identified genomic segments but identified genomic segments linked to distinct biological pathways influencing their etiology.Further research is needed to understand their functional consequences.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"483-493"},"PeriodicalIF":5.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059613","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":"Hidden Gems in the Neurological Literature of Progressive Supranuclear Palsy.","authors":"Peter A LeWitt","doi":"10.3233/JPD-230301","DOIUrl":"10.3233/JPD-230301","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"639-642"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074384","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":"Remote Delivery of Allied Health Therapies in Parkinson's Disease.","authors":"Ryan P Duncan, Gammon M Earhart","doi":"10.3233/JPD-230214","DOIUrl":"10.3233/JPD-230214","url":null,"abstract":"<p><p>Remote delivery of allied health therapies has long been possible, but adoption has been limited in some disciplines until relatively recently. The COVID-19 pandemic drove dramatic increases in use of remote delivery within allied health. This review summarizes the latest evidence on remotely-delivered physical therapy, occupational therapy, and speech therapy and discusses associated challenges and opportunities.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S219-S226"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11234339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440877","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":"Relationships of B12 and Homocysteine with Outcomes in the SURE-PD, SURE-PD3, and STEADY-PDIII Trials.","authors":"Chadwick W Christine, Peggy Auinger, Esther A R Forti, Lyvin Tat, Noemi Cannizzaro, Arshi Mustafa, Jay M Iyer, David Oakes, Ralph Green","doi":"10.3233/JPD-240035","DOIUrl":"10.3233/JPD-240035","url":null,"abstract":"<p><strong>Background: </strong>DATATOP was a study of early Parkinson's disease (PD) conducted in the 1980 s, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369 pg/mL and homocysteine (tHcy) of 9.5μmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15μmol/L) predicted greater declines in cognitive function.</p><p><strong>Objective: </strong>We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression.</p><p><strong>Methods: </strong>We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials.</p><p><strong>Results: </strong>Baseline geometric mean B12 levels for these studies ranged from 484- 618 pg/ml and for tHcy ranged from 7.4- 10μmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcy > 15μmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC.</p><p><strong>Conclusions: </strong>In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":"14 6","pages":"1243-1255"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140307","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":"Advancing Parkinson's Disease Research in Canada: The Canadian Open Parkinson Network (C-OPN) Cohort.","authors":"Marisa Cressatti, Gabriel D Pinilla-Monsalve, Mathieu Blais, Catherine P Normandeau, Clotilde Degroot, Iris Kathol, Sarah Bogard, Anna Bendas, Richard Camicioli, Nicolas Dupré, Ziv Gan-Or, David A Grimes, Lorraine V Kalia, Penny A MacDonald, Martin J McKeown, Davide Martino, Janis M Miyasaki, Michael G Schlossmacher, A Jon Stoessl, Antonio P Strafella, Edward A Fon, Oury Monchi","doi":"10.3233/JPD-240213","DOIUrl":"10.3233/JPD-240213","url":null,"abstract":"<p><strong>Background: </strong>Enhancing the interactions between study participants, clinicians, and investigators is imperative for advancing Parkinson's disease (PD) research. The Canadian Open Parkinson Network (C-OPN) stands as a nationwide endeavor, connecting the PD community with ten accredited universities and movement disorders research centers spanning, at the time of this analysis, British Columbia, Alberta, Ontario, and Quebec.</p><p><strong>Objective: </strong>Our aim is to showcase C-OPN as a paradigm for bolstering national collaboration to accelerate PD research and to provide an initial overview of already collected data sets.</p><p><strong>Methods: </strong>The C-OPN database comprises de-identified data concerning demographics, symptoms and signs, treatment approaches, and standardized assessments. Additionally, it collects venous blood-derived biomaterials, such as for analyses of DNA, peripheral blood mononuclear cells (PBMC), and serum. Accessible to researchers, C-OPN resources are available through web-based data management systems for multi-center studies, including REDCap.</p><p><strong>Results: </strong>As of November 2023, the C-OPN had enrolled 1,505 PD participants. The male-to-female ratio was 1.77:1, with 83% (n = 1098) residing in urban areas and 82% (n = 1084) having pursued post-secondary education. The average age at diagnosis was 60.2±10.3 years. Herein, our analysis of the C-OPN PD cohort encompasses environmental factors, motor and non-motor symptoms, disease management, and regional differences among provinces. As of April 2024, 32 research projects have utilized C-OPN resources.</p><p><strong>Conclusions: </strong>C-OPN represents a national platform promoting multidisciplinary and multisite research that focuses on PD to promote innovation, exploration of care models, and collaboration among Canadian scientists.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1481-1494"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289616","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":"Designing the First Trials for Parkinson's Prevention.","authors":"Grace F Crotty, Samuel J Ayer, Michael A Schwarzschild","doi":"10.3233/JPD-240164","DOIUrl":"10.3233/JPD-240164","url":null,"abstract":"<p><p>For decades the greatest goal of Parkinson's disease (PD) research has often been distilled to the discovery of treatments that prevent the disease or its progression. However, until recently only the latter has been realistically pursued through randomized clinical trials of candidate disease-modifying therapy (DMT) conducted on individuals after they received traditional clinical diagnosis of PD (i.e., tertiary prevention trials). Now, in light of major advances in our understanding of the prodromal stages of PD, as well as its genetics and biomarkers, the first secondary prevention trials for PD are beginning. In this review, we take stock of DMT trials to date, summarize the breakthroughs that allow the identification of cohorts at high risk of developing a traditional diagnosis of PD, and describe key design elements of secondary prevention trials and how they depend on the prodromal stage being targeted. These elements address whom to enroll, what interventions to test, and how to measure secondary prevention (i.e., slowed progression during the prodromal stages of PD). Although these design strategies, along with the biological definition, subtype classification, and staging of the disease are evolving, all are driven by continued progress in the underlying science and integrated by a broad motivated community of stakeholders. While considerable methodological challenges remain, opportunities to move clinical trials of DMT to earlier points in the disease process than ever before have begun to unfold, and the prospects for PD prevention are nowtangible.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"S381-S393"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289617","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":"Clinical Trial Highlights: Anti-Inflammatory and Immunomodulatory Agents.","authors":"Bina Patel, Julia C Greenland, Caroline H Williams-Gray","doi":"10.3233/JPD-240353","DOIUrl":"10.3233/JPD-240353","url":null,"abstract":"<p><p> Inflammation and immune dysregulation have been linked to the pathogenesis and progression of Parkinson's disease (PD), and represent an attractive target for therapeutic intervention, given the potential for repurposing of existing anti-inflammatory and immunomodulatory agents. Despite the fact that initial studies of drugs with secondary anti-inflammatory effects did not yield positive results, agents specifically targeting immune and inflammatory pathways may hold more promise. This article will briefly review the evidence base for targeting the immune system and neuroinflammation in PD, and discuss in detail the recently completed and currently active trials of primary anti-inflammatory/immunomodulatory drugs in PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1283-1300"},"PeriodicalIF":4.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348602","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}