Journal of Parkinson's disease最新文献

{"title":"Reduced volume of the mediodorsal and anteroventral thalamus is associated with anxiety in Parkinson's disease: A cross-sectional 7-tesla MRI study.","authors":"Guillaume Carey, Mark L Kuijf, Stijn Michielse, Amée F Wolters, Kathy Dujardin, Albert Fg Leentjens","doi":"10.1177/1877718X241308141","DOIUrl":"https://doi.org/10.1177/1877718X241308141","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD)-related anxiety occurs frequently and may be associated with imbalance between anxiety-related circuits. While the thalamus is a shared region of these circuits, its role in PD-related anxiety has not been explored so far.</p><p><strong>Objective: </strong>To identify changes in volume of the thalamus and its subnuclei in patients with PD-related anxiety.</p><p><strong>Methods: </strong>Cognitively intact PD patients (n = 105) were divided into two groups based on their score on the Parkinson anxiety scale (PAS): 31 PD patients had anxiety (Anx-PD) and 74 did not have anxiety (non-Anx-PD). Forty-five healthy control subjects were included. Participants underwent 7-Tesla MRI scanning. Using automatic segmentation, the volumes of the thalamus and its subnuclei were measured, compared between the groups and regressed on the PAS.</p><p><strong>Results: </strong>The volumes of the thalamus and its subnuclei did not significantly differ between the groups. However, in anxious PD patients, more severe anxiety was strongly associated with a smaller volume of the right medial thalamic subregion, specifically the right mediodorsal magnocellular nucleus and the right mediodorsal parvocellular nucleus (R = 0.63, ß_PAS= -0.546, p-value_model= 0.007 and R = 0.60, ß_PAS= -0.547, p-value_model= 0.016, respectively), and of the left anteroventral thalamus (R = 0.73, FDR p-value_model= 0.002, ß_PAS= -0.407, p-value_PAS= 0.01).</p><p><strong>Conclusions: </strong>A reduced volume of the mediodorsal and anteroventral thalamus, overlapping structures between the anxiety related circuits, are associated with more severe PD-related anxiety and may explain its high prevalence in the disease.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X241308141"},"PeriodicalIF":4.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458392","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":"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":"Non-motor symptoms in prodromal Parkinson's disease are linked to reduced quality of life.","authors":"Sinah Röttgen, Marie-Sophie Lindner, Aline Seger, Johanna Kickartz, Kim-Lara Weiß, Christopher Ej Doppler, Gereon R Fink, Anja Ophey, Michael Sommerauer","doi":"10.1177/1877718X241310726","DOIUrl":"https://doi.org/10.1177/1877718X241310726","url":null,"abstract":"<p><p>Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) highlights an early α-synucleinopathy. This study compared health-related quality of life (hrQoL) in 62 individuals with iRBD with 19 healthy controls (HC) and 29 individuals with Parkinson's disease (PD) and identified factors linked to poorer hrQoL. HrQoL was significantly lower in individuals with iRBD (83.33 ± 16.96) compared to HC (92.29 ± 5.49, p = 0.027). Poorer hrQoL in individuals with iRBD was linked to severity of multiple non-motor symptoms, most prominently fatigue and depressive symptoms being significant predictors (<i>p </i>< 0.001, adjusted <i>R</i>² = 0.81). This study highlights the importance of non-motor symptoms for hrQoL in prodromal PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X241310726"},"PeriodicalIF":4.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458491","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 blood vessels to brain cells: Connecting the circulatory system and Parkinson's disease.","authors":"Oyedele J Olaoye, Sophie L Farrow, Denis M Nyaga, Antony A Cooper, Justin M O'Sullivan","doi":"10.1177/1877718X241308168","DOIUrl":"https://doi.org/10.1177/1877718X241308168","url":null,"abstract":"<p><p>Parkinson's disease (PD) is traditionally recognized as a neurodegenerative disorder characterized by motor dysfunction and α-synuclein protein accumulation in the brain. However, recent research suggests that the circulatory system may also contribute to PD pathogenesis through the spread of α-synuclein beyond the brain. The blood-brain barrier (BBB), a key regulator of molecular exchange between the bloodstream and the brain, may become compromised in PD, allowing harmful substances, including pathogenic forms of α-synuclein, to infiltrate the brain and promote neurodegeneration. Transport mechanisms such as P-glycoprotein and the low-density lipoprotein (LDL) receptor-related protein (LRP-1) further modulate the movement of α-synuclein across the BBB, influencing disease progression. Additionally, extracellular vesicles are emerging as crucial mediators in the dissemination of α-synuclein between the brain and peripheral tissues, facilitating its spread and accumulation. The lymphatic system, responsible for clearing α-synuclein, may also contribute to PD pathology when impaired. This review highlights the growing evidence for a circulatory axis in the initiation and progression of PD. We propose that future research should explore the hypothesis that the circulatory system contributes to the pathogenesis of PD by aiding the distribution of α-synuclein throughout the body.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X241308168"},"PeriodicalIF":4.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458430","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":"Continuous, subcutaneous apomorphine infusion for Parkinson disease motor fluctuations: Results from the phase 3, long-term, open-label United States InfusON study.","authors":"Stuart H Isaacson, Alberto J Espay, Rajesh Pahwa, Pinky Agarwal, Holly A Shill, Jennifer Hui, Khashayar Dashtipour, Mark Lew, Peibing Qin, Andrea E Formella, Gianpiera Ceresoli-Borroni, Peter A LeWitt","doi":"10.1177/1877718X241310727","DOIUrl":"https://doi.org/10.1177/1877718X241310727","url":null,"abstract":"<p><strong>Background: </strong>Continuous subcutaneous apomorphine infusion (CSAI) has been used globally since the 1980s for Parkinson disease (PD) motor fluctuations but has not been available in the United States (US).</p><p><strong>Objective: </strong>Evaluate CSAI for motor fluctuations in the US setting.</p><p><strong>Methods: </strong>This open-label study (NCT02339064) enrolled patients with PD experiencing ≥3 hours (h) daily OFF time despite optimized levodopa and current/prior use of at least one other adjunctive therapy. CSAI was initiated with a 1-2 mg bolus followed by 1 mg/h infusion titrated to optimal efficacy and tolerability. Following titration, patients entered a 52-week maintenance period.</p><p><strong>Results: </strong>Of 99 patients treated, 85 completed the titration period, 69 completed maintenance week 12 and 48 completed maintenance week 52. Common treatment-related adverse events included infusion site nodules and erythema, dyskinesia, nausea, and somnolence, each of which occurred more frequently during the titration period. Reduction in OFF time began at CSAI initiation and reached a mean of 3.0 ± 3.18 h/day by maintenance week 12 (primary efficacy endpoint), with a corresponding increase in Good ON time of 3.1 ± 3.35 h/day. By maintenance week 12, 68% of patients rated themselves as much or very much improved, 62% had at least a 2-h reduction in daily OFF time, and mean concomitant oral levodopa and levodopa equivalent doses (excluding CSAI) had been reduced by 198 mg/day and 283 mg/day, respectively. Improvements were maintained through week 52.</p><p><strong>Conclusions: </strong>This study supports the clinical utility of CSAI to reduce OFF time and increase Good ON time in patients with motor fluctuations inadequately controlled with oral therapy.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X241310727"},"PeriodicalIF":4.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458480","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":"<i>Lactobacillaceae</i> and Parkinson's disease: An apparent paradox.","authors":"Marieke Me van der Maden, Marcel M Verbeek, Milan Beckers","doi":"10.1177/1877718X241312401","DOIUrl":"https://doi.org/10.1177/1877718X241312401","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder predominantly known for its motor symptoms such as bradykinesia, rigidity and tremor, but the disorder is also increasingly recognized for its association with impaired gastrointestinal function. The composition of the gut microbiome is known to be different in PD compared with healthy individuals. One of the bacterial families with increased abundance in people with PD is <i>Lactobacillaceae</i>. Interestingly, opposite effects have been ascribed to <i>Lactobacillaceae</i> in PD. A number of studies have linked <i>Lactobacillaceae</i> spp. in the gut to worse motor function, and to premature degradation of levodopa. However, other studies have linked administration of <i>Lactobacillaceae</i>-containing probiotics to improved motor function and reduced gastrointestinal problems. In this narrative review, we investigate this apparent paradox. The key to its understanding appears to lie in the specific species of <i>Lactobacillaceae</i>. The species <i>L. plantarum</i> in particular seemed to show a correlation with improved motor symptoms, as well as a reduction in intestinal inflammation, whereas <i>L. brevis, L. curvatus</i> and <i>L. fermentum</i> have properties that might be detrimental to people with PD.</p>","PeriodicalId":16660,"journal":{"name":"Journal of Parkinson's disease","volume":" ","pages":"1877718X241312401"},"PeriodicalIF":4.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458444","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}