Journal of Parkinson's disease最新文献

{"title":"Depressive symptoms can negatively influence patient reported disease severity after subthalamic nucleus stimulation for Parkinson's disease.","authors":"Christine Girges, Alexis de Roquemaurel, Nirosen Vijiaratnam, Jennifer Foley, Joseph Candelario, Maricel Salazar, Catherine Milabo, John Esperida, Tim Grover, Harith Akram, Jonathan Hyam, Marie T Krüger, Ludvic Zrinzo, Patricia Limousin, Thomas Foltynie","doi":"10.1177/1877718X251354933","DOIUrl":"10.1177/1877718X251354933","url":null,"abstract":"<p><p>BackgroundDepression can negatively influence an individual's perception of their disease. Although subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), some patients do not appreciate benefits despite showing objective improvements in motor function.ObjectiveWe explored the impact of depressive symptoms on self-reported outcomes of PD severity in patients who underwent STN-DBS.MethodsAssessments took place preoperatively and 2-years after surgery. Patients completed the Hospital Anxiety and Depression Scale (HADS), Unified Parkinson's Disease Rating Scale (UPDRS) Parts 2 and 4, Gait and Falls Questionnaire, Parkinson's Disease Questionnaire-39 (PDQ-39), and the Non-motor Symptoms Scale. The UPDRS Part 3 (motor examination) was also performed. Patients were dichotomized into two groups (normal or high) based on their postoperative follow-up HADS depression score.ResultsEighteen patients (33.3%) were assigned to the high group (hHADS-D), and 36 patients (66.7%) were assigned to the normal group (nHADS-D). The UPDRS Part 3 OFF-medication score improved to a similar extent in both groups, and participants experienced a similar reduction in their levodopa equivalent daily dose following STN-DBS. Unlike the nHADS-D group, however, hHADS-D patients did not self-report improvements on any clinical outcome measure at follow-up from baseline, and instead indicated a significant worsening on the UPDRS Part 2 ON-medication and PDQ-39 cognition domain. This was not explicable by their preoperative non-motor symptom burden, nor changes in dopaminergic medications. There were no differences between groups in terms of proportion using anti-depressants, surgical complications or postoperative side effects.ConclusionsDepressive symptoms may play a significant role in subjective self-reporting, and should be carefully considered when evaluating STN-DBS effectiveness and managing patients postoperatively.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"998-1006"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497376","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":"Diffuse putaminal degeneration without iron deposition in multiple system atrophy.","authors":"Shin-Ichi Ueno, Taiji Tsunemi, Daisuke Taniguchi, Nobutaka Hattori","doi":"10.1177/1877718X251355592","DOIUrl":"10.1177/1877718X251355592","url":null,"abstract":"<p><p>BackgroundMultiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia, and autonomic dysfunction. Putaminal hypointensities on T2 magnetic resonance imaging (MRI) are commonly observed in the parkinsonian variant of MSA (MSA-P).ObjectiveTo report a neuropathologically confirmed case of MSA-P with an atypical MRI presentation, characterized by progressive T2 hyperintensity in the putamen, without significant iron accumulation.MethodsWe present the clinical course, imaging findings, and neuropathological results of a 57-year-old woman with MSA-P. Diagnostic evaluations included serial brain MRI, cerebrospinal fluid analysis, magnetic resonance spectroscopy, and post-mortem pathological examination.ResultsThe patient initially presented with L-dopa-responsive bradykinesia and right-dominant rigidity, followed by progressive motor decline, orthostatic hypotension, and urinary retention. Serial T2-weighted MRI revealed diffuse and progressively increasing hyperintensity in the putamen, accompanied by atrophy predominantly on the left side. Autopsy confirmed the diagnosis of MSA, revealing severe neuronal loss, marked gliosis, and abundant glial cytoplasmic inclusions in the putamen, with only mild iron deposition as shown by Prussian blue staining.ConclusionsThis case demonstrates that severe putaminal neurodegeneration in advanced MSA can be associated with progressive T2 hyperintensity on MRI, reflected by the absence of substantial iron deposition. These findings indicate that iron-independent mechanisms contribute to the pathophysiology of MSA-related putaminal damage in patients with MSA.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1019-1023"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575705","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":"Biological definitions of synucleinopathies should be anchored in clinical trajectories and encompass the complex biology of the disease.","authors":"David Bendetowicz, Vincent Planche, Erwan Bezard, Benjamin Dehay, Wassilios G Meissner","doi":"10.1177/1877718X241313443","DOIUrl":"10.1177/1877718X241313443","url":null,"abstract":"<p><p>Recently, two proposals for defining Parkinson's disease and its related pathogenic processes have been published. In this viewpoint, we discuss the primary drivers behind these efforts, the future directions, and the challenges that must be addressed. While finding biomarkers is a mandatory step for better precision medicine and optimal patient stratification in therapeutic trials, we argue that a biological definition of Parkinson's disease based on a single biomarker will struggle to account for the complexity of the mechanisms involved in developing the disease. Additionally, a biological definition of asymptomatic patients should rely on a thorough understanding of patients' clinical trajectories, which is currently not the case in synucleinopathies.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"944-952"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458455","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":"Twenty-five-year experience with apomorphine pump in Parkinson's disease: A real-life long-term retrospective tolerance study.","authors":"Sina R Potel, Maria Chondrogiorgi, Andrea Gozzi, Sandrine Correia, Anna Castrioto, Sara Meoni, Pierre Pelissier, Emmanuelle Schmitt, Valérie Fraix, Elena Moro","doi":"10.1177/1877718X251344896","DOIUrl":"10.1177/1877718X251344896","url":null,"abstract":"<p><p>BackgroundContinuous subcutaneous apomorphine infusion (CSAI) is a standard of care treatment in advanced Parkinson's disease (PD) to treat motor fluctuations. However, literature about its long-term data is scarce.ObjectiveThe aim of this study was to report about CSAI tolerance and discontinuation predictors in a large monocentric cohort.MethodsConsecutive PD patients who had CSAI were included. CSAI duration, discontinuation rates at 3, 12, 24, 36, 48, and 60 months, demographic data, MDS-UPDRS motor score, adverse events (AEs), discontinuation reasons and predictive factors were analyzed with logistic regression.ResultsA total of 208 patients were included from 1999 to 2023 (51% male; age: 67.4 ± 8.3 years; PD duration: 11.2 ± 5.0 years). In the overall group, CSAI duration was 25.0 ± 32.9 months (median: 13.0, range: 0.1-260.0). Ninety-five patients (45.7%) discontinued CSAI after 12.7 ± 15.3 months (median: 8.0). Main discontinuation causes were switching to deep brain stimulation (44.2%) and low efficacy (15.8%). Sixty% of discontinuations occurred within the first year. CSAI duration was the only significant difference between ongoing CSAI (116) and discontinued patients (35.4 ± 39.7 vs. 11.1 ± 18.4 months; <i>p</i> < 0.001), after excluding 42 CSAI-to-DBS. About 79.8% patients had AEs, mainly hallucinations (41.3%) and nodules (24.0%). The best discontinuation predictors were CSAI duration and baseline <i>off</i> medication MDS-UPDRS motor score.ConclusionsThese results may help clinicians better select patients, anticipate and manage AEs, and predict CSAI discontinuation.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"970-981"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302388","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":"Shades of grey: The continuum of therapies for Parkinson's disease along the spectrum of credibility.","authors":"Araceli Alonso-Canovas, Olaf M Dekkers, Bastiaan R Bloem","doi":"10.1177/1877718X251361441","DOIUrl":"10.1177/1877718X251361441","url":null,"abstract":"<p><p>Complementary and alternative therapies (CAT) is an umbrella term applied to a diverse set of approaches, with high interest among persons with Parkinson's disease. However, scientific community regards evidence-based medicine as the only acceptable, creating a black and white dichotomy, which is neither epistemologically correct nor workable in daily practice. CAT are heterogeneous, and the label is dynamic as new scientific insights might accrue. Medicine encompasses a wide range of interventions that can be positioned alongside a spectrum of credibility, with many shades of grey between the extremes. We define credibility along three dimensions: the underlying rationale, the scientific rigor, and patient perceptions. By no means this implies we encourage adoption of weakly grounded therapies, or favor exotic treatments over evidence-based approaches. Credibility serves as basis for a nuanced debate in clinical practice, with attention to adverse effects, interactions, and costs. The degree of credibility also informs the need for further research. This offers a practical road forward for open-minded, yet rational decisions by persons with Parkinson's disease, clinicians, funding bodies and relevant stakeholders.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251361441"},"PeriodicalIF":5.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760380","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":"Progression to Parkinson's dementia is not modulated by genetic risk variants for Alzheimer's or Parkinson's disease.","authors":"Kayenat Parveen, J Alexander Ross, Hendrik van der Wurp, Monika Balzer-Geldsetzer, Daniela Berg, Günther Deuschl, Thomas Gasser, Rüdiger Hilker-Roggendorf, Elke Kalbe, Inga Liepelt-Scarfone, Brit Mollenhauer, Oliver Riedel, Sandra Röske, Jörg B Schulz, Annika Spottke, Alexander Storch, Claudia Trenkwalder, Jan Kassubek, Karsten Witt, Richard Dodel, Ullrich Wüllner, Alfredo Ramirez, Maria Carolina Dalmasso","doi":"10.1177/1877718X251356512","DOIUrl":"https://doi.org/10.1177/1877718X251356512","url":null,"abstract":"<p><p>Parkinson's disease (PD) is marked by motor symptoms and often accompanied by mild cognitive impairment (PD-MCI), affecting up to 50% of patients and preceding PD dementia (PDD). Genetic factors may influence this progression, yet the underlying mechanisms remain unclear. This study investigated genetic factors influencing the progression from PD-MCI to PDD using polygenic risk scores (PRS). A genome-wide association study (GWAS) was conducted using data from the LANDSCAPE study. Multivariable Cox regression, Kaplan-Meier survival analysis, and concordance statistics assessed the relationship between PRS and PDD progression. No significant association was found between PD PRS and the risk of developing PDD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251356512"},"PeriodicalIF":5.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753614","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":"Unmet needs in the pharmacological management of motor symptoms in Parkinson's disease.","authors":"Beatrice Heim, Werner Poewe","doi":"10.1177/1877718X251352416","DOIUrl":"https://doi.org/10.1177/1877718X251352416","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder clinically defined by the presence of cardinal motor features like bradykinesia, rigidity and resting tremor. The mainstay of PD treatment is pharmacological dopamine substitution and responsiveness of motor symptoms to levodopa is a supporting diagnostic feature of this illness. Although the armentarium of drugs to treat the motor symptoms of PD and their efficacy on a variety of motor problems are overall impressive, significant unmet needs persist, particularly in the advanced stages of PD. These include situations of poorly responsive tremor, motor complications associated with sustained levodopa exposure, disorders of gait and balance as well as impairments of posture, speech and swallowing. This review provides an overview of available treatment strategies for these areas of unmet need and emerging therapies under development. Future perspectives include novel pharmacological targets, new modes of drug delivery, combination therapies and the integration of real-time monitoring and wearable technologies to tailor treatments.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251352416"},"PeriodicalIF":4.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698879","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":"SGLT2 inhibitors vs. metformin for Parkinson's disease risk reduction in type 2 diabetes.","authors":"Mingyang Sun, Xiaoling Wang, Zhongyuan Lu, Yitian Yang, Shuang Lv, Mengrong Miao, Wan-Ming Chen, Szu-Yuan Wu, Jiaqiang Zhang","doi":"10.1177/1877718X251359391","DOIUrl":"https://doi.org/10.1177/1877718X251359391","url":null,"abstract":"<p><p>SummaryThis study is the first large-scale, head-to-head comparison suggesting that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may offer greater neuroprotection against Parkinson's disease (PD) compared to metformin in patients with type 2 diabetes mellitus (T2DM). Utilizing a 20-year real-world dataset and propensity score matching, we found that SGLT2i users had a 28% lower adjusted hazard ratio (aHR) for PD (0.72; 95% CI, 0.62-0.84) and reduced all-cause mortality. Unlike previous studies suggesting a potential increased PD risk with SGLT2is, our robust study design, stringent exclusion criteria, and competing risk adjustments support a protective association. The findings highlight the need for further prospective research to explore the neuroprotective benefits of SGLT2is, which may justify prioritizing their use in T2DM patients at risk for neurodegeneration.BackgroundType 2 diabetes mellitus (T2DM) is linked to an increased risk of Parkinson's disease (PD), likely mediated by insulin resistance, inflammation, and mitochondrial dysfunction. While metformin has shown neuroprotective effects, sodium-glucose cotransporter-2 inhibitors (SGLT2is) have emerging benefits in neurodegeneration. This study provides the first real-world head-to-head comparison of SGLT2is and metformin on PD risk in T2DM patients.MethodsUsing the TriNetX platform, we analyzed a 20-year dataset (2005-2025) from 142 healthcare organizations, identifying 913,428 T2DM patients (96,018 SGLT2i, 817,410 metformin users). Patients with prior PD, neurodegenerative diseases, or exposure to neuroprotective/neurotoxic antidiabetic drugs were excluded. Propensity score matching (1:1) balanced cohorts across demographic, clinical, and pharmacological variables. Cox proportional hazards models estimated adjusted hazard ratios (aHRs), validated by positive and negative controls.ResultsSGLT2i use was associated with a 28% lower PD risk than metformin (aHR = 0.72; 95% CI, 0.62-0.84; p < 0.0001). Dementia, a positive control, also showed reduced risk (aHR = 0.73; 95% CI, 0.68-0.78; p < 0.0001), reinforcing the neuroprotective effect. Negative controls confirmed specificity. SGLT2i users had significantly lower all-cause mortality (aHR = 0.85; 95% CI, 0.83-0.89; p < 0.0001).ConclusionsThis first large-scale comparison suggests SGLT2is provide superior neuroprotection against PD compared to metformin in T2DM patients, warranting further investigation.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251359391"},"PeriodicalIF":4.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649779","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":"Proposed mechanisms of neuroprotection for nicotine in Parkinson's disease.","authors":"Namrata Kumari, Lauren E Cooke, Abby L Olsen","doi":"10.1177/1877718X251355112","DOIUrl":"https://doi.org/10.1177/1877718X251355112","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurological disorder that is characterized by the death of dopaminergic neurons in the substantia nigra. Despite extensive research, the exact cause of PD is unknown, and current treatment options are centered on symptom management rather than disease modification. Most, though not all, epidemiologic studies have demonstrated reduced risk of development of PD among smokers, generating interest in nicotine, a key component of tobacco. Many preclinical investigations have investigated nicotine's neuroprotective properties, especially through its interaction with nicotinic acetylcholine receptors in the central nervous system. Nicotine has been linked to a variety of cellular activities, including neurotransmitter release, neuronal survival, and anti-inflammatory responses. Animal studies in PD models have indicated that nicotine administration can attenuate the degeneration of dopaminergic neurons and ameliorate behavioral abnormalities. Clinical investigations evaluating nicotine as a treatment for PD have yielded mixed results in terms of efficacy. Thus, central questions remain about the effects of nicotine in patients with established PD, and neither nicotine nor smoking are recommended for treatment or prevention of PD. Further research on the multiple proposed mechanisms of nicotine is required, with particular emphasis on elucidating symptomatic versus neuroprotective effects. The aim of this scoping review is to provide a comprehensive discussion of the proposed mechanisms of neuroprotection for nicotine in Parkinson's disease.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251355112"},"PeriodicalIF":4.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600824","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":"Gaps in the Parkinson's disease therapeutic clinical pipeline: A focus on approaches targeting disease pathobiology.","authors":"Christos Koros, Brian Fiske, Leonidas Stefanis","doi":"10.1177/1877718X251354935","DOIUrl":"https://doi.org/10.1177/1877718X251354935","url":null,"abstract":"<p><p>The understanding of the pathobiology of Parkinson's disease (PD) is evolving, based largely on genetic discoveries. Despite a rich pipeline of potential therapies addressing aspects of the underlying biology of the disease, there is currently no available disease-modifying therapy for PD. In this short commentary, we review the status of the relevant pipeline and highlight areas where alternative or complementary approaches could also be advanced to the stage of clinical trials, with the ultimate goal of providing meaningful clinical benefit to patients and their families. The further evolution of biomarkers, cellular and animal models of the disease and delivery methods will be crucial to this end.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251354935"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528407","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}