Parkinsonism & related disorders最新文献

{"title":"GLP-1 receptor expression and Parkinson's disease: Reassessing the link.","authors":"Qiu-Han Xu, Cheng Wang","doi":"10.1016/j.parkreldis.2025.107799","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107799","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107799"},"PeriodicalIF":3.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721048","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":"Motivational disturbances and cognitive effort-based decision-making in Parkinson's disease","authors":"Bonnie M. Scott ,&nbsp;Robert S. Eisinger ,&nbsp;Roshan Mara ,&nbsp;Amtul-noor Rana ,&nbsp;Anika Bhatia ,&nbsp;Sable Thompson ,&nbsp;Michael S. Okun ,&nbsp;Aysegul Gunduz ,&nbsp;Dawn Bowers","doi":"10.1016/j.parkreldis.2025.107355","DOIUrl":"10.1016/j.parkreldis.2025.107355","url":null,"abstract":"<div><h3>Background</h3><div>Motivational disturbances, such as apathy and impulse control disorders (ICDs), frequently co-occur in patients with Parkinson's disease (PD). The assessment of these motivational disturbances has proven to be challenging due the absence of validated objective behavioral measures for evaluating motivation in older adults. This scenario may contribute to underdiagnosis. The present study aimed to investigate the clinical utility of a modified version of an existing effort-based decision-making task which required cognitive (e.g., working memory) instead of physical (e.g., finger tapping) effort.</div></div><div><h3>Methods</h3><div>Ninety-five non-demented individuals (45–85 years of age) with idiopathic PD completed a cognitive screening measure, self-report questionnaires, and a cognitive adaptation of the Effort Expenditure for Rewards Task (COG-EEfRT), which is a multi-trial game where a participant can choose whether to expend greater effort for larger rewards which vary in magnitude and probability. Patients were classified as having clinically significant symptoms of apathy and/or an ICD based on recommended cut-off scores on the Apathy Scale (AS) and Questionnaire for Impulse Control Disorders in Parkinson's Disease – Rating Scale (QUIP-RS). The methodological cutoffs defined two groups: Apathy (36.8 %), and ICD (48.4 %).</div></div><div><h3>Results</h3><div>The level of effort expended by patients significantly predicted apathy and ICD status with high accuracy (88.2 % and 82.4 %, respectively), above and beyond age, levodopa equivalent dose and self-report measures of motivation. Additionally, we found that greater symptoms of apathy and ICD (i.e., negative urgency) were significantly correlated with patients choosing to expend greater effort. This result varied based on reward probability and outcome.</div></div><div><h3>Conclusion</h3><div>We offer preliminary evidence suggesting the clinical utility of the COG-EEfRT for identifying and quantifying motivational disturbances in PD. Additionally, anticipatory anhedonia and impulsive traits may be important predictors of cognitive effort-based decision-making. Compared to tasks requiring physical effort, the COG-EEfRT may be a more suitable tool for PD and perhaps for people with motor impairment.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"134 ","pages":"Article 107355"},"PeriodicalIF":3.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680835","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":"Moderators of aerobic exercise effects on motor symptoms in patients with Parkinson's disease: A systematic review and meta-analysis.","authors":"Ryul Kim, Nyeonju Kang, Joon Ho Lee, Hanall Lee, Tae Lee Lee, Do Kyung Ko, Hajun Lee, Kyeongho Byun, Kiwon Park, Jee-Young Lee, Beomseok Jeon","doi":"10.1016/j.parkreldis.2025.107779","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107779","url":null,"abstract":"<p><strong>Introduction: </strong>Although growing evidence suggests that aerobic exercise has beneficial effects on motor symptoms in patients with Parkinson's disease (PD), it remains unclear which specific aerobic exercise regimen optimizes improvement in these symptoms. This study aimed to investigate the difference in the effects of aerobic exercise on motor function in patients with PD according to exercise intervention protocols.</p><p><strong>Methods: </strong>Through 28 qualified studies with randomized controlled trials, we assessed motor function using either the Unified PD Rating Scale (UPDRS) III or Movement Disorder Society-UPDRS III as an outcome measure. We employed random effects meta-analysis models to obtain standardized mean differences and 95 % confidence intervals (CIs). Moderator variable analyses were conducted based on exercise type (aerobic exercise vs. aerobic-based combined exercise), duration (<60 min vs. ≥60 min per session), frequency (<four vs. ≥four sessions per week), period (<12 weeks vs. ≥12 weeks), and intensity (low-to-moderate vs. moderate-to-high).</p><p><strong>Results: </strong>Aerobic exercise interventions demonstrated significant improvements in overall motor function. Although all categories were significantly effective in improving motor function, aerobic-based combined exercise had a greater effect size on motor symptoms compared to aerobic exercise alone. Additionally, ≥60 min per session showed a significantly increased effect size compared to <60 min per session. The impact of aerobic exercise did not differ based on exercise frequency, period, or intensity.</p><p><strong>Conclusions: </strong>Our observations suggest that aerobic-based combined exercise and exercise sessions lasting 60 min or longer may be associated with greater improvements in motor symptoms in patients with PD.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107779"},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664226","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":"LONG-NEXT: A new accurate and efficient NGS-based method for GBA1 analysis in Parkinson disease","authors":"Giada Cuconato ,&nbsp;Ilaria Palmieri ,&nbsp;Marco Percetti ,&nbsp;Serena Pagliarani ,&nbsp;Sara Tenace ,&nbsp;Marco J. Morelli ,&nbsp;Ettore Zapparoli ,&nbsp;Micol Avenali ,&nbsp;Valerio Carelli ,&nbsp;Patrizia Dentelli ,&nbsp;Alessia Fiorentino ,&nbsp;Andrea Gaudio ,&nbsp;Claudia Ledda ,&nbsp;Paola Mandich ,&nbsp;Silvia Marino ,&nbsp;Tiziana Martone ,&nbsp;Raffaella Minardi ,&nbsp;Paola Origone ,&nbsp;Danara Ormanbekova ,&nbsp;Barbara Pasini ,&nbsp;Edoardo Monfrini","doi":"10.1016/j.parkreldis.2025.107780","DOIUrl":"10.1016/j.parkreldis.2025.107780","url":null,"abstract":"<div><h3>Introduction</h3><div><em>GBA1</em> variants are the most common genetic risk factor for Parkinson disease (PD). Sequencing of <em>GBA1</em> on a large scale represents a burdensome task with currently adopted diagnostic techniques, namely Sanger sequencing and conventional short read next generation sequencing (sr-NGS). The high degree of sequence homology between <em>GBA1</em> and its pseudogene <em>GBA1LP</em> is the major driver behind this complexity, leading to false positive and false negative results.</div><div>We designed, optimized and validated LONG-NEXT, a new NGS-based strategy to streamline large scale <em>GBA1</em> sequencing.</div></div><div><h3>Methods</h3><div>LONG-NEXT relies on a specific long-range PCR, encompassing the whole <em>GBA1</em> gene, in one fragment (6.5 kb), followed by short-read NGS and a tailored bioinformatic pipeline masking the <em>GBA1LP</em> sequence on the reference genome.</div></div><div><h3>Results</h3><div>This protocol was optimized and tested on selected cases suspected of diagnostic mistakes by conventional testing (n = 13) and then validated on consecutively collected PD patients already screened either by Sanger sequencing (n = 101) or conventional sr-NGS (n = 294). LONG-NEXT reanalysis of 13 patients disclosed: 3 false positive cases due to mismapping of pseudogene reads on <em>GBA1</em>, 4 false homozygotes due to PCR-related allele dropout events, and 6 false negative cases, due to misalignment of <em>GBA1</em> reads against the pseudogene or PCR-related allele dropout events. The validation phase disclosed one additional false homozygote in the Sanger cohort, and one false negative result in the sr-NGS cohort.</div></div><div><h3>Conclusion</h3><div>LONG-NEXT is a reliable, fast, cost-effective alternative for <em>GBA1</em> sequencing and may prove strategic in light of current genotype-based tailored therapies specifically targeting <em>GBA1</em>-PD patients.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"134 ","pages":"Article 107780"},"PeriodicalIF":3.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on Chaparro-Solano et al.: \"Critical evaluation of the current landscape of pharmacogenomics in Parkinson's disease - What is missing? A systematic review.\" Parkinsonism Relat Disord. 2025 Jan;130:107206.","authors":"Anton J M Loonen","doi":"10.1016/j.parkreldis.2025.107774","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107774","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107774"},"PeriodicalIF":3.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674322","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":"Pure autonomic failure, phenoconversion phenomenon and autonomic non-motor subtype of Parkinson disease: The chicken or the egg?","authors":"Daniel Rebolledo-Garcia","doi":"10.1016/j.parkreldis.2025.107773","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107773","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107773"},"PeriodicalIF":3.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664233","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":"Cholinergic basal forebrain atrophy and cortical alterations in Parkinson's disease with apathy","authors":"Qianqian Si ,&nbsp;Caiting Gan ,&nbsp;Aidi Shan ,&nbsp;Huimin Sun,&nbsp;Xingyue Cao,&nbsp;Shiyi Ye,&nbsp;Jiaxin Shi,&nbsp;Chenhui Wan,&nbsp;Xufeng Wang,&nbsp;Yongsheng Yuan,&nbsp;Kezhong Zhang","doi":"10.1016/j.parkreldis.2025.107793","DOIUrl":"10.1016/j.parkreldis.2025.107793","url":null,"abstract":"<div><h3>Introduction</h3><div>Emerging evidences support the contribution of cholinergic deficiency to apathy in Parkinson's disease (PD). We aimed to ascertain the role of structural alterations of cholinergic basal forebrain (BF) and its innervated cortical regions in the pathogenesis of apathy in PD.</div></div><div><h3>Methods</h3><div>Twenty-one PD patients with apathy (PD-A), 28 without apathy (PD-NA), and 20 healthy controls (HCs) were recruited in this study. Changes in subregional volumes of the BF were compared. Cortical thickness and local gyrification index (LGI) analysis were adopted to reveal the concomitant cortical alterations. The correlation with the severity of apathy and the diagnostic capacity were also assessed.</div></div><div><h3>Results</h3><div>Compared to PD-NA and HCs groups, PD-A group showed excessively nucleus basalis of Meynert (NBM/Ch4) atrophy (<em>p</em> &lt; 0.05 after Bonferroni correction), accompanied by cortical thinning and hypergyrification of the right entorhinal cortex (<em>p</em> &lt; 0.001 after Bonferroni correction). Furthermore, regression analysis showing that the Ch4 volume was negatively associated with the severity of apathy in PD-A group (<em>β</em> = −23.198, T = −1.063, <em>p</em> = 0.039). All the above significant neuroimaging alterations showed good performance in identifying apathetic patients (<em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Our findings highlighted that BF cholinergic degeneration driven by Ch4 atrophy may be involved in the pathogenesis of apathy in PD patients without dementia or depression.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"134 ","pages":"Article 107793"},"PeriodicalIF":3.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674406","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 Queasy to Rigid - An amendment on the administration of contraindicated antiemetics in hospitalized people with Parkinson's disease","authors":"Camila C. Piccinin ,&nbsp;Jeryl Ritzi T. Yu ,&nbsp;Claire Sonneborn ,&nbsp;Olivia Hogue ,&nbsp;Roman Popov ,&nbsp;Debolina Ghosh ,&nbsp;Anne Brooks ,&nbsp;James Liao ,&nbsp;Shannon Shaffer ,&nbsp;Scott A. Sperling ,&nbsp;Benjamin L. Walter","doi":"10.1016/j.parkreldis.2025.107782","DOIUrl":"10.1016/j.parkreldis.2025.107782","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"134 ","pages":"Article 107782"},"PeriodicalIF":3.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628103","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":"No causal link between smoking and dementia with Lewy bodies.","authors":"Yu-Liang Gao, Qiu-Han Xu","doi":"10.1016/j.parkreldis.2025.107775","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107775","url":null,"abstract":"<p><p>This letter addresses the findings of Goodheart and Gomperts (2024), which observed an association between smoking and reduced odds of dementia with Lewy bodies (DLB). In contrast, our Mendelian randomization analysis found no causal link, suggesting that further research using genetically informed methods is needed to clarify these results.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107775"},"PeriodicalIF":3.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634343","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":"Comprehensive analysis of SLC17A5 variants in large European cohorts reveals no association with Parkinson's disease risk","authors":"Marya S. Sabir ,&nbsp;Mary B. Makarious ,&nbsp;Marjan Huizing ,&nbsp;William A. Gahl ,&nbsp;Frances M. Platt ,&nbsp;May Christine V. Malicdan","doi":"10.1016/j.parkreldis.2025.107790","DOIUrl":"10.1016/j.parkreldis.2025.107790","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and α-synuclein aggregation. Aging is the primary risk factor, with both rare and common genetic variants playing a role. Previous studies have implicated lysosomal storage disorder (LSD)-related genes, including <em>SLC17A5,</em> in PD susceptibility.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the association of <em>SLC17A5</em> variants, including rare and common variants and the FSASD-associated p.Arg39Cys missense variant, with PD risk in large European ancestry cohorts.</div></div><div><h3>Methods</h3><div>Rare variant burden analyses were performed at minor allele frequency (MAF) thresholds of ≤1 % and ≤0.1 % in 7,184 PD cases and 51,650 controls using whole-genome and whole-exome sequencing data. Association testing of the p.Arg39Cys variant was conducted across five cohorts, encompassing both Finnish and non-Finnish Europeans. Common variant associations were examined using summary statistics from the largest European GWAS of PD.</div></div><div><h3>Results</h3><div>No significant association was observed between rare <em>SLC17A5</em> variants and PD at either MAF threshold. The p.Arg39Cys variant, though enriched in Finnish Europeans, showed no significant association with PD across several cohorts. Similarly, common <em>SLC17A5</em> variants (MAF ≥1%) were not associated with PD risk.</div></div><div><h3>Conclusion</h3><div>Our findings do not support a role for <em>SLC17A5</em> variants in PD susceptibility. While lysosomal dysfunction is central to PD pathogenesis, its contribution appears pathway-specific, with <em>SLC17A5</em> unlikely to influence risk. Larger, multiethnic studies and functional analyses are needed to further investigate sialic acid metabolism in PD and related disorders.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"134 ","pages":"Article 107790"},"PeriodicalIF":3.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143621191","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}