Journal of Parkinson's disease最新文献

{"title":"Psilocybin-assisted psychotherapy for Parkinson's disease without depression: A case-report.","authors":"Vanessa Fleury, Emilie Tomkova, Sabina Catalano Chiuvé, Louise Penzenstadler","doi":"10.1177/1877718X241312604","DOIUrl":"https://doi.org/10.1177/1877718X241312604","url":null,"abstract":"<p><strong>Background: </strong>Psychedelic assisted psychotherapy (PAP) can improve treatment-resistant depression. Its usefulness in Parkinson's disease (PD) is unknown. PD patients may have problems adjusting to their chronic progressive neurological disease. A change from emotional avoidance to acceptance has been reported following psilocybin administration in patients with treatment-resistant depression.</p><p><strong>Objective: </strong>To report for the first time the effect of psilocybin in a PD patient.</p><p><strong>Methods: </strong>A non-depressed 43-year-old female with a 2-year history of PD presented with difficulty adjusting to PD, anxious ruminations and pessimism. The patient declined an increase in dopaminergic medication or the introduction of an anxiolytic. Therapeutic patient education was not beneficial. The patient received four sessions of high-dose PAP within one year. Neurological and psychiatric assessments were performed before and at one year follow-up using qualitative interviews and quantitative assessment of motor status, dispositional optimism, depression, anxiety, apathy, and well-being.</p><p><strong>Results: </strong>PAP was well tolerated. It significantly improved the patient's overall pessimistic outlook on her future and decreased her anxious ruminations and worries about potential handicap due to PD. Her general well-being improved, as well as all psychometric scores except for the apathy scale. Motor status remained unchanged. Better acceptance of PD allowed her to accept pharmacological treatment adjustment.</p><p><strong>Conclusions: </strong>PAP could be a safe and useful treatment for PD patients with dispositional pessimism and difficulties accepting their disease by promoting profound decentration from habitual thoughts and emotions, improving mood and PD acceptance. Randomized, controlled studies are needed to confirm this result.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X241312604"},"PeriodicalIF":4.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457896","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":"Cortical α4β2-nicotinic acetylcholine receptors and cognitive decline in Parkinson's disease.","authors":"Kelly A Mills, Hiroto Kuwabara, Yong Du, Gabriela Gomez, Chelsie S Motley, Yana Skorobogatova, Ergi Spiro, Jennifer M Coughlin, Wojciech Lesniak, Jason Brandt, Vidya Kamath, Martin G Pomper, Gwenn S Smith","doi":"10.1177/1877718X241313373","DOIUrl":"10.1177/1877718X241313373","url":null,"abstract":"<p><strong>Background: </strong>Autopsy and <i>in vivo</i> molecular imaging studies suggest altered binding of the α4β2-nicotinic cholinergic receptor (α4β2-nAChR) with cognitive dysfunction in Parkinson's disease (PD).</p><p><strong>Objective: </strong>To determine the relationship between cortical and hippocampal binding of the α4β2-nAChR with [¹⁸F]XTRA PET, a high-affinity radiotracer that enables quantification of α4β2-nAChR in these regions, and cognitive function in individuals with PD.</p><p><strong>Methods: </strong>Individuals with PD (N = 32) and age-similar, controls without PD or dementia (N = 10) completed a cognitive assessment and one 90-min, [¹⁸F]XTRA PET scan. Metabolite-corrected arterial input function radioactivity time-activity curves were generated to obtain total distribution volume (V_T) across 12 regions of interest (ROIs). [¹⁸F]XTRA binding was compared 1) between controls and people with PD and 2) between controls, persons with PD with normal cognition (PD-NC), and persons with PD with MCI (PD-MCI).</p><p><strong>Results: </strong>[¹⁸F]XTRA binding was higher in the occipital cortex of the combined group of PD participants compared to age-similar controls. No regions showed lower binding in PD. V_T with, but not without, partial volume correction was different between controls, PD-NC, and PD-MCI groups, and this was driven by higher binding in PD-MCI compared to controls. Regression of regional V_T on cognitive domain T-scores, adjusting for age, showed that worse performance in visual-spatial memory tasks was associated with higher V_T in the precuneus and the entire parietal cortex.</p><p><strong>Conclusions: </strong>Higher α4β2-nAChR binding in posterior cortical regions is found in PD and associated with worse visual perception and memory, possibly due to lower receptor occupancy by endogenous acetylcholine.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X241313373"},"PeriodicalIF":4.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458482","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":"How to advance the pharmacological management of cognitive impairment in Parkinson's disease.","authors":"Carla Abdelnour, Lucy L Gibson, Lucia Batzu, Dag Aarsland","doi":"10.1177/1877718X251315645","DOIUrl":"https://doi.org/10.1177/1877718X251315645","url":null,"abstract":"<p><p>Cognitive impairment is a common non-motor symptom in people with Parkinson's disease (PD) and is associated to poor clinical outcomes. Currently, rivastigmine is the only approved medication for PD dementia, and there are no treatments available for people with PD and mild cognitive impairment. To advance the pharmacological management of cognitive impairment in PD, it is essential to optimize clinical trial design. This includes refining cognitive outcome measures, ensuring longer study durations, and incorporating PD-specific cognitive assessments. Biomarkers offer valuable opportunities for screening, stratification, enrichment, and monitoring in trials, increasing the likelihood of detecting treatment effects. Additionally, adopting patient-centered approaches that prioritize inclusivity can enhance trial validity and address the current lack of diversity in PD studies. Digital cognitive assessments offer a promising tool for improving participation and enabling longitudinal monitoring, especially in underrepresented and mobility-challenged populations. By tackling these challenges, this review outlines strategies for advancing the pharmacological management of cognitive impairment in PD. It emphasizes the need for precise, inclusive, and biomarker-driven trials to accelerate drug development.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251315645"},"PeriodicalIF":4.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458432","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":"Aging, cellular senescence and Parkinson's disease.","authors":"Yue Ma, Madalynn L Erb, Darren J Moore","doi":"10.1177/1877718X251316552","DOIUrl":"https://doi.org/10.1177/1877718X251316552","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting 1-2% of people over age 65. The risk of developing PD dramatically increases with advanced age, indicating that aging is likely a driving factor in PD neuropathogenesis. Several age-associated biological changes are also hallmarks of PD neuropathology, including mitochondrial dysfunction, oxidative stress, and neuroinflammation. Accumulation of senescent cells is an important feature of aging that contributes to age-related diseases. How age-related cellular senescence affects brain health and whether this phenomenon contributes to neuropathogenesis in PD is not yet fully understood. In this review, we highlight hallmarks of aging, including mitochondrial dysfunction, loss of proteostasis, genomic instability and telomere attrition in relation to well established PD neuropathological pathways. We then discuss the hallmarks of cellular senescence in the context of neuroscience and review studies that directly examine cellular senescence in PD. Studying senescence in PD presents challenges and holds promise for advancing our understanding of disease mechanisms, which could contribute to the development of effective disease-modifying therapeutics. Targeting senescent cells or modulating the senescence-associated secretory phenotype (SASP) in PD requires a comprehensive understanding of the complex relationship between PD pathogenesis and cellular senescence.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X251316552"},"PeriodicalIF":4.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458451","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":"Narrow-based gait in people with Parkinson's disease: Its mechanisms explored.","authors":"Jamie Af Jansen, Tom Jw Buurke, Lotte van de Venis, Vivian Weerdesteyn, Noël Keijsers, Jorik Nonnekes","doi":"10.1177/1877718X241313333","DOIUrl":"https://doi.org/10.1177/1877718X241313333","url":null,"abstract":"<p><strong>Background: </strong>People with Parkinson's disease (PD) typically exhibit a narrow-based gait. We previously found that walking with reduced trunk rotation and obliquity led to narrow-based gait in healthy adults; a decrease in trunk motion coincided with a decrease in mediolateral extrapolated center of mass (XCoM) excursion, requiring a smaller step width to maintain a constant mediolateral margin of stability (MoS).</p><p><strong>Objective: </strong>To assess whether reduced trunk motion in PD is related to narrow-based gait, without affecting mediolateral MoS. To explore the underlying mechanisms of narrow-based gait, we examined the effects of increasing arm swing (aiming to increase trunk motion), and widening steps on gait in PD.</p><p><strong>Methods: </strong>Fifteen people with PD and narrow-based gait and 17 age-matched controls walked on a treadmill for three minutes at a fixed gait speed during three conditions: baseline, increased arm swing and widened step width. Step width, trunk rotation and obliquity were calculated using marker data, and XCoM excursion and MoS using ground reaction forces.</p><p><strong>Results: </strong>Trunk rotation, XCoM excursion, and step width were significantly smaller in PD compared to controls, while the MoS did not differ. Increased arm swing did not substantially increase trunk motions in PD, though people with PD were able to widen their step width.</p><p><strong>Conclusions: </strong>We provide further evidence for a relation between trunk motion and step width. In PD, reduced trunk motion may contribute to narrow-based gait, without affecting mediolateral MoS; future work is needed to confirm a causal relationship between reduced trunk motion and narrow-based gait in PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X241313333"},"PeriodicalIF":4.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458489","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":"Technology for measuring freezing of gait: Current state of the art and recommendations.","authors":"Martina Mancini, J Lucas McKay, Helena Cockx, Nicholas D'Cruz, Christine D Esper, Benjamin Filtjens, Benedetta Heimler, Colum D MacKinnon, Luca Palmerini, Melvyn Roerdink, William R Young, Jeffrey M Hausdorff","doi":"10.1177/1877718X241301065","DOIUrl":"10.1177/1877718X241301065","url":null,"abstract":"<p><p>This report summarizes the existing literature on the use of technology for the assessment of freezing of gait (FOG) as well as the use of technology to provide insights into the mechanisms of FOG in people with Parkinson's disease. Specifically, this work was carried out for the 3rd International Workshop on Freezing of Gait in Jerusalem in 2023. This review focuses on the most used technologies to quantitatively assess FOG in a laboratory environment and describes the technologies that hold promise for assessing FOG in daily life. Examples of implementation of machine learning algorithms are provided as well as algorithmic biases. Lastly, a standardized assessment using inertial measurement units during a clinical protocol is proposed and a 5-year outlook is discussed. We anticipate this review will help move the field forward in the coming years.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"19-40"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458331","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":"Addressing the need for standardization of symptomatic medication documentation in Parkinson's disease clinical research: A call to action.","authors":"Mikayla Spott, Monica Javidnia, Anne Pedata, Martijn Müller, Laura Carrillo, Tanya Simuni, Gennaro Pagano, Kevin Kwok, Klaus Romero, Diane Stephenson","doi":"10.1177/1877718X241305711","DOIUrl":"10.1177/1877718X241305711","url":null,"abstract":"<p><p>People with Parkinson's disease (PD) are prescribed a variety of medications to mitigate symptoms and improve their quality of life. These symptomatic therapies cover a range of pharmacological classes, including classical dopaminergic treatments, other antiparkinsonian agents, and pharmacotherapies for non-PD conditions. Often, medications are prescribed for concomitant use and in increasing doses, particularly as the disease progresses. Documentation of these interventions in clinical trials is necessary to accurately capture medication usage, compare medication utilization across different studies, understand factors contributing to experimental therapeutic response, and analyze clinical trial data in a precise manner. At the present time, there is no current international standard for how these medications are documented within clinical trials. As a case example, we will highlight medication use documentation in a large international multicenter observational study commonly used as a reference for design of clinical trials. This review aims to raise awareness within the scientific community of the importance of proper medication documentation and the need for standardization to harmonize prescriptive practices, improve treatment interpretability, and perform consistently robust analyses from clinical trials data.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"227-235"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458449","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":"Subcortical tau burden correlates with regional brain atrophy and plasma markers in four-repeat tauopathy parkinsonism.","authors":"Cheng-Hsuan Li, Sung-Pin Fan, Ming-Chieh Shih, Yi-Hsin Weng, Ta-Fu Chen, Hsun Li, Mei-Fang Cheng, Ming-Che Kuo, Pei-Ling Peng, Makoto Higuchi, Ing-Tsung Hsiao, Kun-Ju Lin, Chin-Hsien Lin","doi":"10.1177/1877718X241298192","DOIUrl":"10.1177/1877718X241298192","url":null,"abstract":"<p><p>Background¹⁸F-florzolotau positron emission tomography (PET) assists in the <i>in vivo</i> diagnosis of progressive supranuclear palsy (PSP).ObjectiveWe aimed to investigate the relationship between ¹⁸F-florzolotau uptake and clinical severity, structural volume changes, and plasma markers in four-repeat tauopathies.MethodsA total of 80 participants were recruited: 35 with PSP (11 with PSP-Richardson syndrome and 24 with PSP non-Richardson syndrome), 9 with corticobasal syndrome (CBS), 10 with Alzheimer's disease (AD), 8 with Parkinson's disease, and 18 controls. All participants underwent ¹⁸F-florzolotau PET, brain magnetic resonance imaging (MRI), and plasma biomarker investigation (total and phosphorylated tau [pTau181], neurofilament light chain, and glial fibrillary acidic protein [GFAP]).Results¹⁸F-Florzolotau uptake was significantly higher in the subcortical regions of the pallidum, subthalamic nucleus (STN), midbrain, red nucleus, and raphe nucleus in PSP patients compared to the other groups (all <i>p </i>< 0.01). Subcortical tau tracer retention assisted in distinguishing PSP and CBS from controls (AUC = 0.836, <i>p </i>< 0.001). Tau tracer retention could differentiate PSP and CBS from AD in cortical (<i>p </i>< 0.001) and subcortical regions (<i>p </i>= 0.028). The motor severity of PSP positively correlated with tau burden in STN (<i>p </i>= 0.044) and substantia nigra (<i>p </i>= 0.035). Tau tracer uptake was associated with cortical volume changes in CBS (<i>p </i>= 0.031), PSP non-Richardson syndrome (<i>p </i>= 0.003), and AD (<i>p </i>= 0.044). Cortical tau retention correlated with plasma levels of GFAP (<i>p </i>= 0.001) and pTau181 (<i>p </i>= 0.036).ConclusionsSubcortical ¹⁸F-Florzolotau uptake assist the diagnosis of 4R tauopathy parkinsonism. Additionally, regional tau burden contributes to structural brain volume changes and correlates with plasma levels of GFAP and pTau181.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"214-226"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458437","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":"Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies.","authors":"David Devos, Olivier Rascol, Wassilios G Meissner, Alexandra Foubert-Samier, Simon Lewis, Christine Tranchant, Mathieu Anheim, David Maltête, Philippe Remy, Karla Eggert, Heidi Pape, Christian Geny, Philippe Couratier, Camille Carroll, Ray Sheridan, David Burn, Nicola Pavese, Jason Raw, Daniela Berg, Oksana Suchowersky, Lorraine V Kalia, Andrew Evans, Sophie Drapier, Teodor Danaila, Alfons Schnitzler, Jean-Christophe Corvol, Gilles Defer, Noemi Toiber Temin, Caroline Fradette, Fernando Tricta, Caroline Moreau","doi":"10.1177/1877718X241300295","DOIUrl":"10.1177/1877718X241300295","url":null,"abstract":"<p><p>BackgroundReducing nigrostriatal iron overload reduces neuronal loss in Parkinson's disease (PD) models.ObjectiveExamine the safety and efficacy of deferiprone in reducing motor disability progression in dopaminergic-treated and treatment-naïve patients with early-stage PD.MethodsTwo phase II, multicenter studies, SKY and EMBARK, enrolled patients diagnosed with early PD (<3 years from screening). In SKY, patients on stable dopaminergic therapy were randomized 1:1 to one of four dosage (or placebo-matching) cohorts (300, 600, 900, 1200 mg twice daily [BID]) for 9 months. EMBARK enrolled patients on stable dopaminergic therapy or treatment-naïve patients and received 15 mg/kg BID. For both studies, the primary outcome was the change from baseline to month 9 in motor examination score (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III). ClinicalTrials.gov: NCT02728843; ANZCTR: ACTRN12617001578392.ResultsOverall, 140 patients were randomized in SKY (28 per cohort). Thirty-six patients enrolled in EMBARK (27 dopaminergic-treated; 9 treatment-naïve). In the SKY study, all doses showed the same worsening as the placebo group, with the exception of the 600 mg dose, which was associated with non-significant reductions in MDS-UPDRS Part III least-squares mean (LSM) between baseline and 9 months (-2-8 points versus placebo). In EMBARK, LSM (SE) changes from baseline in MDS-UPDRS Part III were nonsignificant (-1.6 [1.7]) and significant (8.3 [3.9]) for dopaminergic-treated and treatment-naïve patients, respectively, the latter indicating disease worsening. Adverse events possibly related to deferiprone were reported in 35.7%-88.9% across all deferiprone groups vs. 42.9% for placebo.ConclusionsSKY and EMBARK studies indicate that deferiprone combined with L-dopa does not provide significant motor function benefit, while the absence of L-dopa treatment worsens symptoms.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"72-86"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458440","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":"Rong Xue, Xuang Zhang, and Anette Schrag, recipients of the Parkinson Prize 2023.","authors":"Bastiaan R Bloem, Lorraine V Kalia","doi":"10.1177/1877718X241311700","DOIUrl":"10.1177/1877718X241311700","url":null,"abstract":"","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"3-5"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458352","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}