Parkinsonism & related disorders最新文献

{"title":"Rethinking the role of continuous dopaminergic stimulation in Parkinson disease therapy","authors":"Peter A. LeWitt","doi":"10.1016/j.parkreldis.2025.107354","DOIUrl":"10.1016/j.parkreldis.2025.107354","url":null,"abstract":"<div><div>This Viewpoint will examine continuous dopaminergic stimulation (CDS), a concept that has long been invoked as the optimal treatment strategy for improving symptomatic control of Parkinson disease (PD) patients experiencing motor fluctuations. The appeal of CDS has always seemed intuitive and is based, in part, on preclinical investigations implicating pulsatile dopaminergic stimulation as causing motor fluctuations and dyskinesia from levodopa (LD) treatment. However, four large-scale randomized controlled clinical trials testing infused drug delivery have demonstrated only partial effectiveness of CDS at reducing daily OFF time. Other clinical trial data has offered evidence that a reduction in OFF time also can be accomplished from targeting sites in motor pathways downstream from the basal ganglia. Neural plasticity and a CNS calcium receptor signaling compound, ophthalmate, may also hold answers to the regulation of OFF time. Finally, insights derived from neural computational modeling of PD motor pathway pharmacology and the involved electrophysiological connections may guide future understanding of motor fluctuations in PD and their management.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107354"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Front Matter 1 - Full Title Page (regular issues)/Special Issue Title page (special issues)","authors":"","doi":"10.1016/S1353-8020(25)00786-2","DOIUrl":"10.1016/S1353-8020(25)00786-2","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 108045"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inside Front Cover - Aims and Scope, Copyright, Publication information, Orders and Claims, Advertising information, Author inquiries, Permissions, Funding body, Permanence of paper, Impressum (German titles only) and GFA link in double column","authors":"","doi":"10.1016/S1353-8020(25)00785-0","DOIUrl":"10.1016/S1353-8020(25)00785-0","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 108044"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supports available for apomorphine management: How best to facilitate appropriate usage of apomorphine?","authors":"Zvezdan Pirtošek","doi":"10.1016/j.parkreldis.2025.107934","DOIUrl":"10.1016/j.parkreldis.2025.107934","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a chronic neurodegenerative disorder marked by progressive deterioration in both motor and non-motor function. In advanced stages, patients commonly experience motor fluctuations, including unpredictable “off” episodes that severely affect quality of life. Apomorphine, a potent dopamine receptor agonist administered subcutaneously—either as intermittent injections or continuous infusion—offers rapid and effective relief during these episodes. Despite its therapeutic value, apomorphine remains underutilized due to barriers such as limited awareness, initiation complexity, adverse effect management, and the need for specialized infrastructure.</div><div>This review outlines current knowledge regarding support systems necessary for optimizing apomorphine use in PD. A structured, three-stage model—pre-initiation, initiation, and maintenance—is proposed to guide best practices. We describe the roles of key stakeholders, including multidisciplinary healthcare teams, caregivers, pharmaceutical service providers, and patient advocacy organizations. Neurologists and Parkinson's Disease Nurse Specialists (PDNS) are central to treatment coordination, while physiotherapists, occupational therapists, speech-language pathologists, and mental health professionals provide essential complementary care. When adequately informed and supported, caregivers play a critical role in promoting adherence and emotional stability. Pharmaceutical companies offer educational materials, technical assistance, home care resources, and financial support mechanisms. Patient organizations contribute through peer education and emotional reinforcement. Future directions include enhanced training models, broader telemedicine integration, and device innovation. A coordinated, patient-centered approach is needed to ensure sustained, equitable access to apomorphine for individuals living with advanced PD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107934"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining ‘OFF’ time in device-aided therapy criteria for Parkinson’s disease: gaps and opportunities","authors":"Roongroj Bhidayasiri ,&nbsp;Phooi Leng Lean ,&nbsp;K. Ray Chaudhuri","doi":"10.1016/j.parkreldis.2025.107894","DOIUrl":"10.1016/j.parkreldis.2025.107894","url":null,"abstract":"<div><div>Evaluating individuals with Parkinson's to determine if they have progressed to the advanced stage and may be suitable for transitioning from intermittent oral medications to continuous, device-aided therapy (DAT) involves considering multiple clinical factors. A key parameter in this assessment, and an indicator of a declining response to oral medication, is overall daily OFF time and the occurrence of unpredictable OFF episodes. OFF-periods are, however, complex and experienced differently by individual patients, so assessment of duration alone may not provide an accurate picture of the patient's lived experience and the challenges they face, information which can be helpful in deciding appropriate management. A range of useful screening tools are available to assist clinicians in determining if a patient has advanced disease and may be suitable for DAT, but these do not always capture the aspects of OFF periods that are the most important, or the most bothersome, to patients. To improve recognition, enhance patient-clinician communication, and achieve effective, personalized management of OFF periods, we propose expanding these tools to consider additional dimensions in three specific areas. First, incorporate patient insights into the personal and functional impact, including the severity of OFF periods, effects on daily activities, and the types and timing (daytime or nighttime) of episodes. Second, include specialist advice from clinicians to characterise the nature of these symptoms and determine suitable therapies. Finally, support this with objective information from PD diaries or technology-based monitoring.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107894"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay between obesity and triglyceride-glucose index in modulating Parkinson's disease risk: A cross-sectional NHANES study of middle-aged and young adults","authors":"Jincheng Ma ,&nbsp;Mimi Li ,&nbsp;Zhendong Lei","doi":"10.1016/j.parkreldis.2025.108070","DOIUrl":"10.1016/j.parkreldis.2025.108070","url":null,"abstract":"<div><h3>Introduction</h3><div>The triglyceride-glucose (TyG) index is a newly proposed biomarker of insulin resistance, and its relationship with Parkinson's disease (PD) remains to be studied, particularly among individuals with obesity. This study examined the relationship between insulin resistance and PD risk, assessing whether obesity modulates this association.</div></div><div><h3>Methods</h3><div>Data from the National Health and Nutrition Examination Survey (2003–2018) were analyzed, focusing on 6349 participants aged 20–65 years. Participants were stratified by body mass index (BMI), and multivariate logistic regression was used to evaluate the relationship between TyG index and PD risk in individuals with and without obesity. Odds ratio (OR) with 95 % confidence intervals (CIs) were calculated using a logistic regression analysis model.</div></div><div><h3>Results</h3><div>A positive correlation between the TyG index and PD risk was observed in this cross-sectional analysis, specifically among individuals with obesity (OR = 2.21, 95 % CI: 1.32–3.7) but not in those without obesity (OR = 1.16, 95 % CI: 0.67–2.02). A statistically significant multiplicative interaction between obesity and the TyG index was identified(<em>P</em> = 0.005).</div></div><div><h3>Conclusion</h3><div>The TyG index is significantly associated with PD risk, with obesity potentially playing a key role. This exploratory study suggests the TyG index may serve as a possible low-cost marker for identifying individuals with obesity at higher likelihood of having PD, though replication in population-based prospective studies is required before clinical application.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"140 ","pages":"Article 108070"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dyskinesia-hyperpyrexia syndrome due to introduction of continuous subcutaneous infusion of levodopa: A case report","authors":"Kanako Menjo ,&nbsp;Rei Yasuda ,&nbsp;Hiroki Yoshida ,&nbsp;Mitsunori Ishikawa ,&nbsp;Toshiki Mizuno","doi":"10.1016/j.parkreldis.2025.108068","DOIUrl":"10.1016/j.parkreldis.2025.108068","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"140 ","pages":"Article 108068"},"PeriodicalIF":3.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The need for developing consensus-based guidelines in assessing Parkinson's disease laterality","authors":"Emily Houston ,&nbsp;Sean Boyd ,&nbsp;Vivikta Iyer ,&nbsp;James Boyd ,&nbsp;Deepak Gupta","doi":"10.1016/j.parkreldis.2025.108067","DOIUrl":"10.1016/j.parkreldis.2025.108067","url":null,"abstract":"<div><div>This study investigated the correlation between Parkinson's disease laterality, as defined by the <strong>Hoehn and Yahr (HY) scale</strong>, and <strong>appendicular parkinsonism scores</strong> from the <strong>MDS-UPDRS Part III</strong> using the <strong>PPMI dataset</strong>. While most cases (89.6 %) showed congruence, a 10.4 % discordance suggests that factors beyond appendicular parkinsonism influence clinical HY staging, highlighting a need for standardized guidelines.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"140 ","pages":"Article 108067"},"PeriodicalIF":3.4,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenomic profile of GBA1 in Parkinson's disease","authors":"Eloise Berson ,&nbsp;Raphael Zaghroun ,&nbsp;Matteo Santoro ,&nbsp;Syed Bukhari ,&nbsp;David Seong ,&nbsp;Chi-Hung Shu ,&nbsp;Amalia Perna ,&nbsp;Tomin James ,&nbsp;Kathleen S. Montine ,&nbsp;Geidy E. Serrano ,&nbsp;Thomas G. Beach ,&nbsp;C. Dirk Keene ,&nbsp;Howard Y. Chang ,&nbsp;M. Ryan Corces ,&nbsp;Brenna Cholerton ,&nbsp;Nima Aghaeepour ,&nbsp;Thomas J. Montine","doi":"10.1016/j.parkreldis.2025.108066","DOIUrl":"10.1016/j.parkreldis.2025.108066","url":null,"abstract":"<div><h3>Introduction</h3><div>While genome-wide association studies have identified <em>GBA1</em> as a key gene contributing to disease severity and cognitive decline in PD, its molecular effects remain poorly understood.</div></div><div><h3>Methods</h3><div>We used integrative bulk ATAC-seq across six brain regions from autopsied individuals with PD and varying genetic risk to characterize region- and cell type-specific molecular differences. Using Cellformer, an AI-based bulk ATAC-seq-deconvolution tool, we determined cell type-specific effects of <em>GBA1</em> on PD disease progression and then validated our findings using whole transcriptome data from blood samples.</div></div><div><h3>Results</h3><div>Epigenomic differences between PD with (“GBA+”; n = 15) and without (“GBA-”, n = 15) <em>GBA1</em> variants were localized in substantia nigra. Nineteen chromatin-accessible regions strictly separated GBA+ from GBA-, including the promoter sites of key genes such as <em>CACNA1C</em>, <em>EHMT1</em>, and <em>SLC25A48</em>. The effect in GBA + spanned the main cell types in brain, and chromatin differences between GBA- and GBA + increased with neuropathologic progression of disease. Significant differences in the epigenomic profile in GBA+ were observed in neuronal cells (AUROC = 0.8, AUPRC = 0.8, P-value&lt;0.0001). Validation in blood samples distinguished between GBA+ and GBA-subtypes, achieving AUROC values of 0.99. Over 5000 transcripts in blood cells distinguished GBA+ from GBA-, validating key genes and pathways from our epigenomic analysis of brain regions.</div></div><div><h3>Conclusion</h3><div>Our study provides novel insights into the cell type-specific epigenomic and transcriptomic landscape of GBA+ and its molecular divergence from other PD subtypes, and highlights potential therapeutic targets for this genetically defined subset of PD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"140 ","pages":"Article 108066"},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPTBN2- associated early-onset Parkinson's disease: A phenotypic expansion","authors":"Rohan Mahale ,&nbsp;Gautham Arunachal ,&nbsp;Hansashree Padmanabha ,&nbsp;Pooja Mailankody","doi":"10.1016/j.parkreldis.2025.108065","DOIUrl":"10.1016/j.parkreldis.2025.108065","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"140 ","pages":"Article 108065"},"PeriodicalIF":3.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}