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Georgina M. Aldridge, Matthew Weber and Lauren Walker recipients of the Parkinson Prize 2025. 乔治娜·m·奥尔德里奇、马修·韦伯和劳伦·沃克获得2025年帕金森奖。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-01-22 DOI: 10.1177/1877718X261416959
Bastiaan R Bloem, Lorraine V Kalia
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引用次数: 0
Dual-Risk axis: GBA1 mutations and occupational pesticide exposure in Parkinson's disease. 双风险轴:帕金森病中GBA1突变和职业性农药暴露。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-01-19 DOI: 10.1177/1877718X251412233
Zeynep Hilal Üstündağ, Hazal Özçelik, Ipek Koker, Pınar Özkan, İrem Kar, Buse Elitas Ozmutlu, Elif İpek Gençer Mutlu, Gunal Damla Yildiz, Merve Koç Yekedüz, Fatma Tuba Eminoğlu, M Cenk Akbostancı, Rezzak Yilmaz

BackgroundOccupational pesticide (OcP) exposure and pathogenic GBA1 variants are established risk factors for Parkinson's disease (PD). However, whether they interact to influence disease onset or severity remains uncertain.ObjectiveTo determine the prevalence of OcP exposure and other lifestyle risks in relation to GBA1 status and their interactions on age of onset (AOO) and clinical scores in a well-characterized PD cohort.MethodsWe analyzed 505 people with PD (PwP) enrolled in the Ankara Parkinson's Disease Registry (ANPAR). GBA1 variants were identified using next-generation sequencing; benign or uncertain variants were excluded. Structured, face-to-face interviews collected data on history of OcP exposure, history of head trauma, smoking, coffee and tea consumption habits. PwP with and without GBA1 variants were compared using unadjusted and adjusted tests. General linear models assessed gene-environment interactions on AOO, non-motor, and motor scores.ResultsFifty-two PwP (10.3%) carried pathogenic GBA1 variants. OcP exposure was more common in carriers than non-carriers (36% vs. 22%; adjusted OR 1.98, 95%CI: 1.07-3.67, p = 0.031). No other risk factor differed between groups. Smoking independently delayed AOO, but there were no significant GBA1 × risk/lifestyle factor interactions for AOO or for motor/non-motor scores. Head trauma, coffee, tea, and OcP exposure showed neither main nor interaction effects on severity indices.ConclusionOcP exposure is reported more often by individuals carrying pathogenic GBA1 variants, supporting a gene-environment "dual-hit" model. However, OcPs did not modify AOO or disease severity once PD was manifest.

职业农药(OcP)暴露和致病性GBA1变异是帕金森病(PD)的已知危险因素。然而,它们是否相互作用影响疾病的发病或严重程度仍不确定。目的在一个特征明确的PD队列中,确定OcP暴露率和其他生活方式风险与GBA1状态的关系,以及它们与发病年龄(AOO)和临床评分的相互作用。方法我们分析了在安卡拉帕金森病登记处(ANPAR)登记的505例PD (PwP)患者。利用下一代测序技术鉴定GBA1变异;排除良性或不确定变异。结构化的面对面访谈收集了OcP暴露史、头部外伤史、吸烟、咖啡和茶的消费习惯等数据。使用未调整和调整的测试比较有和没有GBA1变异的PwP。一般线性模型评估了AOO、非运动和运动分数上基因与环境的相互作用。结果52例PwP(10.3%)携带致病性GBA1变异。OcP暴露在携带者中比在非携带者中更常见(36%比22%;调整后比值为1.98,95%CI: 1.07-3.67, p = 0.031)。两组之间没有其他风险因素的差异。吸烟单独延迟AOO,但在AOO或运动/非运动评分中没有显著的GBA1 ×风险/生活方式因素相互作用。头部创伤、咖啡、茶和OcP暴露对严重程度指数没有主要影响,也没有相互作用。结论携带致病性GBA1变异的个体更常报告ocp暴露,支持基因-环境“双重打击”模型。然而,一旦PD出现,ocp并没有改变AOO或疾病严重程度。
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引用次数: 0
The road for developing new pharmacological therapies for Parkinson's disease: Current trends and targets in clinical trials. 帕金森氏病新药物治疗的发展之路:临床试验的当前趋势和目标。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-01-16 DOI: 10.1177/1877718X251412671
Tiago Machado, Gonçalo S Duarte, Tiago F Outeiro, Joaquim J Ferreira

BackgroundDespite substantial research efforts, advances in Parkinson's disease therapeutics remain largely confined to the management of motor symptoms, with comparatively limited progress in addressing non-motor features, and with no proven success in disease-modifying therapies to date.ObjectivesTo describe recent trends in Parkinson's disease therapeutic trials and to characterize the experimental compounds and targets investigated in drug development programs.MethodsWe conducted a cross-sectional analysis of Parkinson's disease therapeutic clinical trials registered in ClinicalTrials.gov, EUCTR, and CTIS since 2013. For the subset of commercially sponsored medicinal product trials, we further described therapeutic objectives and pharmacological targets.ResultsWe identified 1855 trials, of which 29% were ongoing. Commercial trials predominantly investigated drugs and devices, whereas non-commercial trials more often focused on non-pharmacological interventions. Among 294 commercial medicinal product trials, 166 distinct products representing 146 active compounds were identified, mapped to 52 pharmacological targets, with additional compounds acting through multiple or unclear mechanisms. Dopaminergic approaches dominated (dopamine receptor agents, 18%; dopamine replacement, 15%), followed by aSyn-targeted strategies (10%). Advanced therapies, including cell and gene therapies, were investigated in 8%. Motor symptoms, particularly motor fluctuations, were the most frequent objectives (45%), whereas non-motor symptoms were rarely addressed (8%).ConclusionsThe landscape of Parkinson's disease trials has expanded over the past decade, but progress has largely been limited to incremental improvements in dopaminergic therapies. The continued lack of effective treatments for non-motor symptoms and disease modification suggests a need to rethink current approaches to drug development in Parkinson's disease.

背景:尽管进行了大量的研究,但帕金森病治疗的进展仍然主要局限于运动症状的治疗,而在解决非运动特征方面的进展相对有限,并且迄今为止在疾病改善疗法方面尚未取得成功。目的描述帕金森病治疗试验的最新趋势,并描述药物开发计划中研究的实验化合物和靶点的特征。方法:我们对2013年以来在ClinicalTrials.gov、EUCTR和CTIS注册的帕金森病治疗性临床试验进行了横断面分析。对于商业赞助的药品试验子集,我们进一步描述了治疗目标和药理学靶点。结果我们纳入了1855项试验,其中29%仍在进行中。商业试验主要研究药物和设备,而非商业试验更多地侧重于非药物干预。在294项商业药品试验中,鉴定了166种不同的产品,代表146种活性化合物,映射到52个药理靶点,其他化合物通过多种或不明确的机制起作用。多巴胺能途径占主导地位(多巴胺受体药物,18%;多巴胺替代,15%),其次是非靶向策略(10%)。8%的人研究了包括细胞和基因疗法在内的先进疗法。运动症状,特别是运动波动是最常见的目标(45%),而非运动症状很少得到解决(8%)。在过去的十年中,帕金森氏症的临床试验已经扩大,但进展主要局限于多巴胺能疗法的渐进式改进。非运动症状和疾病改善的有效治疗方法的持续缺乏表明需要重新考虑目前帕金森病药物开发的方法。
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引用次数: 0
Anxiety is associated with increased risk of suicidality in Parkinson's disease. 帕金森氏症患者的焦虑与自杀风险增加有关。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-01-06 DOI: 10.1177/1877718X251410887
Joyce St Lam, Kira N Tosefsky, Julie Zhu, Dylan Meng, Petra Uzelman, Fabricio Pio, Nicholas J Ainsworth, Fidel Vila-Rodriguez, Andrew K Howard, Silke Appel-Cresswell

BackgroundSuicide risk in Parkinson's disease (PD) remains understudied, with limited exploration of the impact of neuropsychiatric comorbidities and commonly prescribed PD and psychiatric medications.ObjectiveTo investigate the prevalence and correlates of suicide risk in PD.MethodsThis study comprised 129 people with PD (PwP) undergoing screening for clinical trial participation at a movement disorders clinic. Suicide risk and psychiatric diagnoses were assessed with the Mini International Neuropsychiatric Interview (MINI). The Parkinson Anxiety Scale (PAS) and the Beck Depression Inventory-II (BDI-II) were also administered. Logistic regression models were used to identify correlates of suicide risk.ResultsSuicide risk was present in 22.5% of the sample, with 3.9% reporting a lifetime suicide attempt. No associations were found between suicide risk and demographic or PD-related variables. Suicide risk was independently associated with higher PAS score (odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.07-1.29; p = 0.001), higher BDI-II suicidal ideation item score (OR = 32.43; 95% CI: 7.78-135.12; p < 0.001), and benzodiazepine use (OR = 13.88; 95% CI: 2.77-69.57; p = 0.001). Furthermore, the BDI-II suicidal ideation item missed nearly 45% of at-risk individuals identified by the MINI, with only 16 scoring above 0.ConclusionsDespite no documented suicide risk in participants' medical charts or neurologists' referrals, over one-fifth were found to be at risk. Correlates of suicide risk in PD warrant further investigation. This study highlights the importance of screening PwP for suicidality during routine care, and that a one-item screen might not adequately capture at-risk individuals.ClinicalTrials.gov IdentifierNCT03968133.

帕金森氏病(PD)的自杀风险仍未得到充分研究,对神经精神合并症和常用PD和精神药物影响的探索有限。目的了解PD患者自杀风险的发生率及相关因素。方法本研究纳入了129名PD (PwP)患者,他们在一家运动障碍诊所接受了临床试验的筛查。自杀风险和精神诊断通过迷你国际神经精神病学访谈(Mini)进行评估。同时进行帕金森焦虑量表(PAS)和贝克抑郁量表- ii (BDI-II)。使用逻辑回归模型来确定自杀风险的相关因素。结果22.5%的人有自杀风险,3.9%的人一生都有自杀企图。没有发现自杀风险与人口统计学或pd相关变量之间存在关联。自杀风险与较高的PAS评分独立相关(优势比(OR) = 1.17;95%置信区间(CI): 1.07-1.29;p = 0.001), BDI-II自杀意念项目得分较高(OR = 32.43; 95% CI: 7.78 ~ 135.12; p = 0.001)。此外,BDI-II自杀意念项缺失了近45%的MINI识别的高危个体,只有16个得分在0分以上。结论:尽管在参与者的医疗图表或神经科医生的转诊中没有记录自杀风险,但超过五分之一的人被发现有自杀风险。PD患者自杀风险的相关因素有待进一步调查。这项研究强调了在常规护理中筛查PwP是否有自杀倾向的重要性,而且单项筛查可能无法充分捕捉到有自杀风险的个体。
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引用次数: 0
Acknowledgment to reviewers 2025. 感谢审稿人2025。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-01-05 DOI: 10.1177/1877718X251409485
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引用次数: 0
An online platform to increase access to gait rehabilitation for underserved Parkinson's disease communities. 一个在线平台,为服务不足的帕金森病社区增加步态康复的机会。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2025-12-30 DOI: 10.1177/1877718X251410104
Tamine Tc Capato, Anouk Tosserams, Bastiaan R Bloem, Jorik Nonnekes

Compensation strategies are a key element of gait rehabilitation in Parkinson's disease, ideally requiring involvement of specialized therapists. However, access to allied healthcare is not universally guaranteed. We evaluated an online platform to deliver compensation strategies for gait in 25 individuals with Parkinson's in rural Brazil. After three weeks of use, median patient-reported impact of gait impairment on daily activities [rated on visual analogue scale, 0-10] decreased from 7 to 4 (p < 0.001), without reported falls. This suggest that the platform is a safe and effective tool for supporting gait rehabilitation in underserved communities with limited access to healthcare services.

补偿策略是帕金森病步态康复的关键因素,理想情况下需要专业治疗师的参与。然而,获得联合医疗保健并不是普遍保证。我们评估了一个在线平台,为巴西农村25名帕金森患者提供步态补偿策略。使用三周后,患者报告的步态障碍对日常活动的影响中位数[按视觉模拟量表评分,0-10分]从7降至4
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引用次数: 0
Discrepancies between patient and caregiver reports of daily living abilities in Parkinson's disease. 帕金森病患者和护理者日常生活能力报告之间的差异。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2025-12-29 DOI: 10.1177/1877718X251408292
Bora Jin, Sang-Myung Cheon

BackgroundPatients with Parkinson's disease (PD) frequently experience a progressive decline in their activities of daily living (ADL), necessitating caregiver support. Discrepancies between patient and caregiver ADL ratings are common and may hinder optimal care.ObjectivesTo quantify patient-caregiver differences in ADL ratings and identify the clinical factors associated with these discrepancies.MethodsWe conducted a cross-sectional study involving 217 patients with PD and their primary caregivers. Both groups independently completed the Activities of Daily Living Questionnaire (ADLQ). Discrepancy (dADLQ) was defined by subtracting the caregiver-rated score from the patient-rated score; its absolute value (δADLQ) reflected the degree of disagreement. Associations with clinical variables, including motor and non-motor symptoms (cognition, mood, sleep, and autonomic function), were examined using multivariate regression.ResultsThe mean ADLQ scores were similar between patients and caregivers, but individual differences varied. The no-discrepancy group was characterized by younger age, shorter disease duration, and lower caregiver burden than those with any discrepancy. Larger δADLQ was associated with more severe motor and non-motor symptoms, as well as increased caregiver burden and depression. The dADLQ scores showed directional associations with patient mood and caregiver burden. Multivariate analysis revealed that δADLQ was independently predicted by greater motor symptom severity and gastrointestinal dysfunction.ConclusionsDiscrepancies in ADL ratings were common in patients with PD and increased with disease severity. They were associated with motor and non-motor symptoms, particularly gastrointestinal dysfunction and mood factors. These findings underscore the importance of integrating both perspectives in clinical assessment, particularly for advanced diseases.Plain language summary titleUnderstanding the Gap Between Patients with Parkinson's Disease and Their Caregivers in Daily Life Abilities.

帕金森氏病(PD)患者经常经历日常生活活动(ADL)的进行性下降,需要护理人员的支持。患者和护理人员ADL评分之间的差异是常见的,可能会阻碍最佳护理。目的量化患者与护理者在ADL评分上的差异,并确定与这些差异相关的临床因素。方法对217例PD患者及其主要护理人员进行横断面研究。两组独立完成日常生活活动问卷(ADLQ)。差异(dADLQ)通过从患者评分中减去护理者评分来定义;其绝对值δADLQ反映了分歧的程度。使用多变量回归检查与临床变量的关联,包括运动和非运动症状(认知、情绪、睡眠和自主神经功能)。结果患者和护理人员的平均ADLQ得分相似,但个体差异存在差异。无差异组的特点是年龄较年轻,病程较短,照顾者负担较低。较大的δADLQ与更严重的运动和非运动症状,以及增加的照顾者负担和抑郁有关。dADLQ得分与患者情绪和照顾者负担有方向性关联。多因素分析显示,δADLQ与运动症状严重程度和胃肠功能障碍有独立预测关系。结论ADL评分差异在PD患者中很常见,且随疾病严重程度的增加而增加。它们与运动和非运动症状有关,特别是胃肠道功能障碍和情绪因素。这些发现强调了在临床评估中整合两种观点的重要性,特别是对于晚期疾病。了解帕金森病患者与其照护者在日常生活能力上的差距。
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引用次数: 0
Gut microbial shifts toward inflammation in Parkinson's disease: Insights from pilot shotgun metagenomics Egyptian cohort. 帕金森氏病的肠道微生物转向炎症:来自试验霰弹枪宏基因组学埃及队列的见解。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2025-12-01 Epub Date: 2025-09-17 DOI: 10.1177/1877718X251370156
Ali Shalash, Shahd Ezzeldin, Sara Hashish, Yara Salah, Noha L Dawood, Ahmed Moustafa, Mohamed Salama

Gut microbiome alterations are increasingly linked to Parkinson's disease (PD), yet regional signatures remain underexplored. We performed shotgun metagenomic sequencing of stool samples from Egyptian PD patients and healthy controls. PD patients exhibited depletion of short-chain fatty acid-producing taxa, and enrichment of pathobionts. Our findings suggested a pro-inflammatory gut shift in PD and emphasized the need for geographically diverse microbiome studies. While limited in sample size (n = 7 PD patients and n = 6 controls), this pilot addressed a critical gap in African PD microbiome research.

肠道微生物组的改变越来越多地与帕金森病(PD)联系在一起,但区域特征仍未得到充分探索。我们对来自埃及PD患者和健康对照者的粪便样本进行了鸟枪宏基因组测序。PD患者表现出短链脂肪酸产生类群的耗竭和病原菌的富集。我们的研究结果提示了PD患者的促炎肠道转变,并强调需要进行地理上不同的微生物组研究。虽然样本量有限(n = 7名PD患者和n = 6名对照),但该试点解决了非洲PD微生物组研究的关键空白。
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引用次数: 0
A glimpse of the end-of-life of people with Parkinson's disease and atypical parkinsonism: A descriptive analysis of electronic health records. 帕金森氏症和非典型帕金森氏症患者的临终一瞥:电子健康记录的描述性分析。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2025-12-01 Epub Date: 2025-09-02 DOI: 10.1177/1877718X251372875
Herma Lennaerts-Kats, Anke Elbers, Catharina Muente, Rebecca van Stigt, Bastiaan R Bloem, Kris Cp Vissers, Marieke M Groot, Marjan J Meinders

BackgroundThe needs of people with Parkinson's disease (PD) or atypical parkinsonism (AP) change significantly in the final weeks to days of life. A better understanding of this phase can help improve care.ObjectiveTo examine healthcare use and end-of-life care in people with PD.MethodsWe conducted a retrospective study (2022-2023) in three nursing homes, four hospitals, and eleven general practices in the Netherlands. Electronic health records of deceased individuals with PD or AP were reviewed for symptoms, healthcare use, and professional involvement.ResultsWe reviewed 189 records (70.4% PD; mean age 80.2; 68.1% male). In the last two weeks of life, patients had an average of 8.4 symptoms, with a higher burden in AP. Palliative sedation was used in 60.4%, most often in nursing homes (up to 78.3%) and among AP patients. Euthanasia occurred in 11 cases (6 PD, 5 AP), mainly in nursing homes and general practices. Antibiotics and pain medications were commonly used; fluid and oxygen therapy were more frequent in hospitals. Most patients were treated by a GP and 3-4 other healthcare professionals, but only 12.7% received support from a palliative care team.ConclusionsPeople with PD and AP face a high symptom burden at the end of life, yet palliative care involvement is limited. The frequent use of palliative sedation and cases of euthanasia reflect the complexity of this care phase. Better integration of palliative expertise and research into symptom management is urgently needed.

帕金森氏病(PD)或非典型帕金森氏症(AP)患者的需求在生命的最后几周到几天内发生显著变化。更好地了解这一阶段有助于改善护理。目的了解帕金森病患者的医疗保健使用和临终关怀情况。方法:我们在荷兰的3家养老院、4家医院和11家全科医院进行了回顾性研究(2022-2023)。我们回顾了PD或AP患者的电子健康记录,包括症状、医疗使用和专业参与。结果189例患者中,70.4%为PD,平均年龄80.2岁,68.1%为男性。在生命的最后两周,患者平均有8.4种症状,AP患者的负担更高。60.4%的患者使用姑息性镇静,最常见于养老院(高达78.3%)和AP患者。安乐死发生在11例(6例PD, 5例AP),主要是在养老院和一般做法。常用抗生素和止痛药;输液和氧气治疗在医院更为常见。大多数患者由全科医生和3-4名其他医疗保健专业人员治疗,但只有12.7%的患者得到了姑息治疗团队的支持。结论PD和AP患者在生命末期面临较高的症状负担,但参与姑息治疗的人数有限。姑息性镇静和安乐死的频繁使用反映了这一护理阶段的复杂性。迫切需要将姑息治疗专业知识和研究更好地整合到症状管理中。
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引用次数: 0
Prevention of cognitive impairment and dementia in people with Parkinson's disease: A call-to-action. 预防帕金森病患者的认知障碍和痴呆:行动呼吁。
IF 5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI: 10.1177/1877718X251365769
Elke Kalbe, Tobias Warnecke, Carsten Eggers, Anja Ophey, Ann-Kristin Folkerts

Mild cognitive impairment and dementia are common symptoms in people with Parkinson's disease (PwPD) that impair the quality of life of those affected. However, PD-specific concepts for the prevention of cognitive decline are rarely incorporated into routine care. Here, we provide key data on cognitive impairment in PwPD and a framework for primary, secondary, and tertiary prevention in this context. The importance of cognitive reserve as a protective buffer for cognitive decline in PwPD is highlighted. Relevant lifestyle and health-related factors, including cognitive aspects, physical and social activity, diet, hearing loss, and cardiovascular factors, are discussed. Evidence on the efficacy of possible cognition-enhancing interventions in PwPD-pharmacological, cognitive, physical, nutritional, and multidomain interventions-is summarized. On this basis, and the recommendations of the European Task Force for Brain Health Services, a proposal is developed outlining options for preventing cognitive impairment in PwPD that could be implemented in routine care, as well as further developments needed to achieve a best-case scenario. The main pillars of a strategic agenda for this purpose include: (i) regular assessment of cognitive state, overall risk, and risk factors for cognitive decline; (ii) risk communication and education concerning modifiable risk factors with standardized procedures; (iii) risk reduction with multi-domain interventions for secondary prevention; and (iv) cognitive enhancement with cognitive and physical training for tertiary prevention. As the proposal makes clear, the prevention of cognitive impairment in PwPD requires interdisciplinary collaboration organized throughout PD care networks.

轻度认知障碍和痴呆是帕金森病患者(PwPD)的常见症状,会损害患者的生活质量。然而,预防认知能力下降的pd特异性概念很少被纳入常规护理。在这里,我们提供了PwPD患者认知功能障碍的关键数据,并在此背景下提供了一级、二级和三级预防框架。强调了认知储备作为PwPD认知衰退的保护性缓冲的重要性。相关的生活方式和健康相关因素,包括认知方面,身体和社会活动,饮食,听力损失和心血管因素,进行了讨论。总结了在pwpd中可能的认知增强干预措施的有效性的证据-药物,认知,身体,营养和多领域干预。在此基础上,根据欧洲脑健康服务特别工作组的建议,制定了一项建议,概述了可在常规护理中实施的预防PwPD认知障碍的备选方案,以及实现最佳情况所需的进一步发展。为此目的制定的战略议程的主要支柱包括:(i)定期评估认知状态、总体风险和认知能力下降的风险因素;(ii)采用标准化程序就可改变的风险因素进行风险交流和教育;(iii)通过多领域二级预防干预措施降低风险;(四)通过三级预防的认知和体能训练来增强认知能力。正如该提案明确指出的那样,预防PwPD的认知障碍需要在PD护理网络中组织跨学科合作。
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引用次数: 0
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Journal of Parkinson's disease
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