Journal of Parkinson's disease最新文献

{"title":"Cerebrospinal ceramides and cognition as a function of striatal asymmetry in early stage of Parkinson's disease.","authors":"Anthony Nuber-Champier, Philippe Voruz, Ioana Constantin, Alexandre Cionca, Julie A Péron","doi":"10.1177/1877718X251319242","DOIUrl":"10.1177/1877718X251319242","url":null,"abstract":"<p><p>BackgroundParkinson's disease (PD) is characterized by heterogeneous clinical phenotypes that may be influenced by the asymmetry of striatal denervation. The alpha-Synuclein Origin site and Connectome (SOC) model proposes that different disease onset patterns-\"body first\" versus \"brain first\"-affect symptom development and cognitive decline.ObjectiveThis study aims to explore the relationship between striatal denervation asymmetry, ceramide metabolism, and cognitive performance in early-stage PD.MethodsWe analyzed data from 329 patients with PD at baseline, categorized by the type of putamen denervation asymmetry predominance at baseline, along with data from 167 healthy controls. We performed generalized linear mixed models introducing ceramides levels and cognitive performance as discriminating factors. Spearman correlations were used to highlight the relationship between cognition and ceramides.ResultsOur findings revealed that patients with asymmetric striatal denervation exhibited higher concentrations of C18:0 ceramides compared to both symmetric patients and healthy controls. Moreover, patients with symmetric denervation demonstrated greater cognitive impairment than those with right or left asymmetry.ConclusionsThe study highlights the importance of striatal denervation asymmetry in influencing ceramide metabolism and cognitive function in early-stage PD. These findings suggest that specific ceramide profiles may serve as metabolic markers to distinguish clinical phenotypes, providing insights into disease progression.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"512-521"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537326","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":"Identification of a circRNA-miRNA-mRNA interactome associated with Parkinson's disease progression.","authors":"Lisa Shrestha, André Leier","doi":"10.1177/1877718X251331930","DOIUrl":"10.1177/1877718X251331930","url":null,"abstract":"<p><p>BackgroundCircular RNAs (circRNAs) constitute a distinctive subclass of RNAs that are known for their regulatory roles in fundamental cellular processes. Due to their increased stability and ubiquitous expression, circular RNAs have been widely studied as potential molecular targets in various diseases, including neurodegenerative diseases. While several studies have found differentially expressed circRNAs associated with Parkinson's disease (PD), none has looked specifically into PD progression.ObjectiveTo elucidate the role of circRNAs in the progression of PD by identifying dysregulated circRNAs associated with PD progression and to pinpoint potential downstream miRNAs and associated differentially expressed gene targets.MethodsIn this study, we have utilized large-scale, longitudinal, and deep RNA-seq data from two independent cohorts, namely the Parkinson's Progression Marker Initiative (PPMI) and the Parkinson's Disease Biomarker Program (PDBP), to characterize circRNA expression in patients of early PD stage.ResultsWe identified six circRNAs significantly differentially expressed in whole blood samples obtained from PD patients over time. Additionally, we were able to map a competing endogenous RNA (ceRNA) network with potential downstream miRNA-mRNA targets and, with the help of co-expression analysis, to identify genes associated with PD progression. Our findings provide compelling evidence for a dysregulated circRNA interactome as an indicator of PD progression, with changes in the expression of these circRNAs and downstream gene targets being significantly associated with changes in UPDRS III scores in PD patients.ConclusionsOur results strongly indicate the association of circular RNAs with PD progression and emphasize its significance as a critical molecular marker.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"495-511"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780362","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":"Association of cholesterol and glycemic state biomarkers with phenotypic variation and Parkinson's disease progression: The Oxford Discovery cohort.","authors":"Nicholas Kwan Ho Chiu, Michael Lawton, Tanja Zerenner, Alireza Morovat, Jessica Welch, Jamil Razzaque, Michele T Hu, Yoav Ben-Shlomo","doi":"10.1177/1877718X251323914","DOIUrl":"10.1177/1877718X251323914","url":null,"abstract":"<p><p>BackgroundParkinson's disease (PD) has marked phenotypic variability. Increased lipids have been suggested as being neuroprotective whilst hyperglycemia may increase α-synuclein aggregation.ObjectiveWe have tested whether high total cholesterol and high-density lipoprotein cholesterol (HDL-C) and low levels of fructosamine are associated with better PD phenotypes and predict less rapid progressionMethodsNon-fasting serum HDL-C, total cholesterol, and fructosamine were measured at baseline in 866 patients with early PD (median duration, 0.96; IQR, 0.43-1.98 years) from the Oxford Discovery cohort. These biomarkers were compared against our data-derived PD subtypes using multinomial logistic regression. We used multilevel models to predict longitudinal motor and non-motor outcomes (e.g., cognition, mood).ResultsHDL-C and total cholesterol differed across baseline PD phenotype clusters, with reduced levels associated with the most severe motor and non-motor phenotypes (psychological well-being, cognitive impairment, REM sleep behavior disorder, and daytime sleepiness). Higher HDL-C and total cholesterol, although the latter was attenuated after adjustment for statin use, were associated with better baseline activities of daily living (e.g., UPDRS-II score with 1 SD increase in HDL-C -0.74, 95%CI -1.22 to -0.26, p = 0.002) and non-motor features. Neither predicted the rate of motor or non-motor progression. Fructosamine levels were not associated with phenotypic variability or rate of disease progression.ConclusionsHypercholesterolemia was associated with a better motor/non-motor disease subtype and daily living impairment at presentation, but did not predict longitudinal change. Future research needs to determine if these associations are causally related or secondary to disease onset by examining prodromal subjects.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"522-530"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014983","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":"Corrigendum to \"Parkinsonian Hand or Clinician's Eye? Finger Tap Bradykinesia Interrater Reliability for 21 Movement Disorder Experts\".","authors":"","doi":"10.1177/1877718X251329129","DOIUrl":"10.1177/1877718X251329129","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"672"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670205","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":"Diverse preferences, different solutions: Exploring remote monitoring preferences in Parkinson's disease through a discrete choice experiment.","authors":"Carlos Antonio Godoy Junior, Laura Mäkitie, Eleonora Fiorenzato, Maija Koivu, Joonas Niskala, Angelo Antonini, Lytske Jantien Bakker, Luis Pilli, Carin Uyl-de Groot, William Ken Redekop, Welmoed Kirsten van Deen","doi":"10.1177/1877718X251327752","DOIUrl":"10.1177/1877718X251327752","url":null,"abstract":"<p><p>BackgroundRemote monitoring solutions (RMS) have the potential to improve Parkinson's disease (PD) management by enabling continuous symptom tracking and personalized care. Understanding patient preferences for RMS features is essential for successful implementation.ObjectiveThis study aimed to investigate the preferences of people with Parkinson's disease (PwP) for RMS features and identify preference heterogeneity across distinct patient subgroups.MethodsFrom November 2023 to February 2024, a discrete choice experiment (DCE) was conducted among PwP in Finland and Italy to elicit preferences for RMS attributes, including monitoring frequency, time spent filling questionnaires, home video recordings, and clinical benefits (delay in advanced symptom onset). Latent class analysis (LCA) was used to identify subgroups with distinct preference patterns, and adoption probabilities under varying RMS scenarios were estimated.ResultsA total of 411 PwP participated, revealing significant heterogeneity in RMS preferences. While clinical benefits, particularly delaying advanced symptom onset, were the most valued attribute overall, preferences diverged across subgroups. Some participants strongly preferred home video recordings, whereas others expressed aversion to this feature. A smaller subgroup exhibited reluctance toward RMS adoption, regardless of its benefits.ConclusionsPwP generally view RMS favorably, but preferences for specific features vary substantially across subgroups. Clinical benefits are a key driver of adoption, while home video recordings elicit both strong preference and aversion, highlighting the impracticality of a one-size-fits-all approach. Tailoring RMS to diverse patient needs, addressing concerns, and enhancing usability through customization are essential for successful implementation and widespread acceptance in PD management.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"619-629"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692388","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":"Investigating the prevalence of the G2019S mutation in Parkinson's disease among a Libyan population.","authors":"Nuri H Awayn, Sara A Hashish, Sultan A Salem, Sulieman Abod, Sana M Elgahmasi, Khalid Ouararhni, Houari Abdesselem, Ilham Y Abdi, Omar A El-Agnaf","doi":"10.1177/1877718X251324407","DOIUrl":"10.1177/1877718X251324407","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder influenced by both environmental and genetic risk factors. This study investigates the prevalence of the <i>LRRK2</i> G2019S mutation in a Libyan population of 140 PD patients and 58 controls. Genetic analysis of blood samples revealed that 19.5% of PD patients carry the G2019S mutation, indicating a genetic association with the disease. The study highlights the G2019S mutation as a potential genetic risk factor for PD in Libya and emphasizes the importance of genetic screening for better understanding and management of the disease.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"664-667"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676631","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":"Feasibility and acceptability of PDConnect, a multi-component intervention to support physical activity in people with Parkinson's disease: A mixed methods study.","authors":"Julie Jones, Lyndsay Alexander, Elizabeth Hancock, Kay Cooper","doi":"10.1177/1877718X251324415","DOIUrl":"10.1177/1877718X251324415","url":null,"abstract":"<p><p>BackgroundPhysical activity (PA) is beneficial for people with Parkinson's (PwP); however, many are classed as sedentary. PDConnect is an online multicomponent intervention combining 1:1 physiotherapy and group-based PA combined with education, behavior change and self-management strategies, promoting PA and self-management among PwP.ObjectiveTo assess feasibility and acceptability of PDConnect.MethodsMixed methods study involving 31 PwP randomly allocated to: (i) usual care: physiotherapy once a week for six weeks, and (ii) PDConnect: physiotherapy once a week for six weeks, followed by 12 weekly sessions of group-based PA, followed by three monthly Teams calls to support engagement. Outcomes included intervention feasibility and acceptability (primary) assessed via survey and interviews; PA, motor, non-motor symptoms, and health and well-being (secondary) assessed at baseline, and at six, 18, and 30 weeks. Fidelity was accessed by post hoc video analysis.ResultsOnline delivery of PDConnect was feasible and safe. Participant retention was 74%. Response rate of self-reported measures was 97%. 95% of participants returned completed activity diaries. Attendance was high, with all participants recommending PDConnect. PDConnect participants reported improved flexibility, muscle strength, and endurance as well as increased PA confidence, PA levels and knowledge of Parkinson's disease. Half of PDConnect participants reported that they were much improved compared to 10% of usual care participants. Small to large effect sizes in PA (d = 0.03) and UPDRS (d = 0.96) ES) were reported, which warrant further exploration in an appropriately powered study.ConclusionsPDConnect is feasible and acceptable among PwP. A future large-scale trial is required to determine the effectiveness of PDConnect.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"603-618"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730485","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":"Recognition, management, and patient perspectives of impulsive-compulsive disorders in Parkinson's disease.","authors":"Mirjam Wolfschlag, Gustav Cedergren Weber, Jonathan Timpka, Daniel Weintraub, Per Odin, Anders Håkansson","doi":"10.1177/1877718X251323922","DOIUrl":"10.1177/1877718X251323922","url":null,"abstract":"<p><p>BackgroundImpulsive-compulsive disorders (ICDs) are commonly acknowledged as side effects of dopaminergic therapy in Parkinson's disease (PD). While many large-scale studies have focused on prevalences and high-risk treatments, little is known about practical management of ICDs in clinical care and patients' experiences.ObjectiveTo investigate how ICDs are recognized in clinical PD care, clinical features of patients with ICDs, and how patients are impacted by their ICD.MethodsQuestionnaires were sent to all patients who reported ICD symptoms in the Swedish quality register for PD in Skåne County (n = 170) and patients' medical records were screened for mention of ICDs. Core subjects were communication between clinician and patient, course and management of ICDs, and impact on different life domains.ResultsDespite sufficient awareness of the ICD risk during PD treatment, there was limited communication between clinical care staff and patients regarding ICDs. Only 49% of patients had reported their ICD as part of clinical care, and only 14% had been asked about it. Additionally, collaboration with psychiatry was rare (12%). ICD severity increased over time with ongoing PD treatment, and most patients reported a mild to moderate impact of their ICD on close relationships, family, mental and physical health.ConclusionsThis study identified insufficient communication about ICDs as part of clinical care in PD and a very limited involvement of mental health services. Thus, to improve prevention and treatment, ICDs should be recognized, monitored and treated more systematically in routine clinical care, and collaboration with mental health services should be increased.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"585-594"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649446","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":"Burden of tremor in Parkinson's disease: A survey study.","authors":"Robert A Hauser, Tara Crowder Skarpaas, Andréa Merriam, Jason Rivera, Valmira Hoxhaj, Luigi M Barbato, Anita Chadha-Patel, Michelle Baladi","doi":"10.1177/1877718X251329328","DOIUrl":"10.1177/1877718X251329328","url":null,"abstract":"<p><p>BackgroundTremor is reported by people with Parkinson's disease (PwP) as being one of the most troublesome symptoms.ObjectiveTo characterize the PwP experience of tremor.MethodsAn internet-based survey of PwP living with tremor was conducted in the US, from September 2023 to March 2024.ResultsSurvey responses from 634 respondents (PwP = 599; care partner = 35) were analyzed. Most (93%) PwP had tremor in their upper extremities and of these, 59% reported ≥2 tremor subtypes (rest/postural/kinetic). Overall, 24% reported little or no effect of medication and a further 25% reported that medication only somewhat improved their tremor. At least mild functional impairment due to tremor was reported by 65% of PwP and most indicated that ≥1 daily activity (83%), sensory experience (77%), or psychosocial function (92%) was impacted. Multinomial logistic regression analyses revealed that the odds [95%CI] of reporting severe functional impairment due to tremor (vs. slight) were increased by worse tremor in the dominant hand (4.9 [1.36, 17.72]); presence of OFF-time (4.7 [1.22, 18.30]), number of body parts affected (2.0 [1.45, 2.88]) and lack of medication effect (1.6 [0.30, 8.22]). The presence of all three tremor subtypes was associated with increased odds of being \"<i>very dissatisfied</i>\" with quality of life (21.5 [2.51, 183.44]).ConclusionsResults from this survey demonstrate that tremor in PD is often more than a rest tremor and frequently impacts function and activities of daily living. Medication response is inadequate in about half of cases, highlighting that effective treatment of tremor is an important unmet need.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"541-551"},"PeriodicalIF":4.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692383","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":"From past to future: Digital approaches to success of clinical drug trials for Parkinson's disease.","authors":"Cen Cong, Madison Milne-Ives, Ananya Ananthakrishnan, Walter Maetzler, Edward Meinert","doi":"10.1177/1877718X251330839","DOIUrl":"https://doi.org/10.1177/1877718X251330839","url":null,"abstract":"<p><p>Recent years have seen successes in symptomatic drugs for Parkinson's disease, but the development of treatments for stopping disease progression continues to fail in clinical drug trials, largely due to the lack of clinical efficacy of drugs. This may be related to limited understanding of disease mechanisms, data heterogeneity, poor target screening and candidate selection, challenges in determining optimal dosage levels, reliance on animal models, insufficient patient participation, and lack of drug adherence in trials. Most of the recent applications of digital health technologies and artificial intelligence (AI)-based tools focused mainly on stages before clinical drug trials. Recent applications used AI-based algorithms or models to discover novel targets, inhibitors and indications, recommend drug candidates and drug dosage, and promote remote data collection. This paper reviews the state of the literature and highlights strengths and limitations in digital approaches to drug discovery and development for Parkinson's disease from 2021 to 2024, and offers recommendations for future research and practice for the success of drug clinical trials.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251330839"},"PeriodicalIF":4.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999005","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}