Parkinson Disease Clinical Subtypes: Validation, Clinical Utility, and Biological Correlates

帕金森病临床亚型：验证、临床实用性和生物学相关性

• 批准号: 10659637
• 负责人: MEGHAN C CAMPBELL
• 金额: $ 60.33万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659637
• 关键词: Abbreviations; Amyloid beta-Protein; Atrophic; Autonomic Dysfunction; Autopsy; Behavior assessment; Behavioral; Biological; Biological Markers; Brain; Brain Pathology; Classification; Clinical; Clinical Data; Clinical assessments; Cognition; Cognitive; Corpus striatum structure; Data; Data Set; Dementia; Deposition; Development; Disease Progression; Economic Burden; Evaluation; Family; Freezing; Functional Magnetic Resonance Imaging; Functional disorder; Gait; Hallucinations; Impaired cognition; Impairment; Individual; Intervention; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Medical Records; Methods; Midbrain structure; Morbidity - disease rate; Motor; Movement Disorders; Neurobiology; Neurodegenerative Disorders; Neurotransmitters; Orthostasis; Outcome; Outcome Study; Parkinson Disease; Participant; Pathology; Patient Selection; Patients; Pattern; Positron-Emission Tomography; Proteins; Research; Severity of illness; Societies; Statistical Models; Subgroup; System; Testing; Time; Tracer; Translating; Validation; alpha synuclein; cholinergic; clinical application; clinical movement disorder; clinical subtypes; clinically relevant; cognitive function; cohort; dementia risk; disorder subtype; falls; improved; mortality; motor deficit; motor impairment; multimodal neuroimaging; multimodality; non-motor symptom; noradrenaline transporter; noradrenergic; novel; patient health information; patient stratification; personalized intervention; personalized medicine; prevent; prognostic value; psychiatric symptom; screening; tau Proteins; tool

ABSTRACT Parkinson disease (PD) is a progressive neurodegenerative disease characterized by motor, cognitive, and psychiatric manifestations resulting from abnormal protein deposition and neurotransmitter deficits. The variability in clinical presentation and progression likely reflects different PD subtypes, which may be associated with the underlying variability in brain pathology. Although current treatments provide dramatic motor benefit in PD, they fail to alleviate some aspects of gait impairment and non-motor symptoms and may exacerbate cognitive and psychiatric features. To develop more personalized interventions to treat, forestall or prevent these features, more information regarding PD subtypes is necessary for patient selection and stratification, predicting progression, and evaluation of novel treatments. Therefore, we propose to examine the clinical and prognostic utility of PD subtypes and their stability through longitudinal behavioral assessments; determine the biological markers of PD subtypes from multimodal neuroimaging, CSF, and brain autopsy data; and translate the PD subtypes to a clinical setting.

摘要 帕金森病(PD)是一种进行性神经退行性疾病，其特征是运动、认知和 由蛋白质异常沉积和神经递质缺陷引起的精神症状。这个 临床表现和进展的变异性可能反映了不同的PD亚型，这可能与 大脑病理中的潜在变异性。尽管目前的治疗方法在运动方面提供了巨大的好处 帕金森病，它们未能缓解步态损害和非运动症状的某些方面，并可能加剧 认知和精神特征。开发更个性化的干预措施来治疗、预防或预防这些 特征，更多关于PD亚型的信息对于患者选择和分层、预测 新疗法的进展和评价。因此，我们建议检查临床和预后。 通过纵向行为学评估PD亚型的实用性及其稳定性；确定生物学上的 来自多模式神经成像、脑脊液和脑尸检数据的帕金森病亚型的标记；并翻译帕金森病 临床环境下的亚型。

项目成果

Detecting associations between intact connectomes and clinical covariates using recursive partitioning object-oriented data analysis.

使用递归分区面向对象的数据分析来检测完整连接组和临床协变量之间的关联。

• DOI: 10.1002/sim.8374
• 发表时间: 2019
• 期刊: Statistics in medicine
• 影响因子: 2
• 作者: Yang,Dake;Deych,Elena;Shands,Berkley;Campbell,MeghanC;Perlmutter,JoelS;Petersen,Steve;Schlaggar,BradleyL;Shannon,William
• 通讯作者: Shannon,William

Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy?

• DOI: 10.1016/j.toxicon.2017.09.004
• 发表时间: 2018-06-01
• 期刊: TOXICON
• 影响因子: 2.8
• 作者: Jinnah, H. A.;Comella, Cynthia L.;Hallett, Mark
• 通讯作者: Hallett, Mark

Head tremor in cervical dystonia: Quantifying severity with computer vision.

• DOI: 10.1016/j.jns.2022.120154
• 发表时间: 2022-03-15
• 期刊: JOURNAL OF THE NEUROLOGICAL SCIENCES
• 影响因子: 4.4
• 作者: Vu, Jeanne P.;Cisneros, Elizabeth;Lee, Ha Yeon;Le, Linh;Chen, Qiyu;Guo, Xiaoyan A.;Rouzbehani, Ryin;Jankovic, Joseph;Factor, Stewart;Goetz, Christopher G.;Barbano, Richard L.;Perlmutter, Joel S.;Jinnah, Hyder A.;Richardson, Sarah Pirio;Stebbins, Glenn T.;Elble, Rodger;Comella, Cynthia L.;Peterson, David A.
• 通讯作者: Peterson, David A.

Quantitative, clinically relevant acoustic measurements of focal embouchure dystonia.

局灶性口型肌张力障碍的定量、临床相关声学测量。

• DOI: 10.1002/mds.27298
• 发表时间: 2018
• 期刊: Movement disorders : official journal of the Movement Disorder Society
• 作者: Morris,AimeeE;Norris,ScottA;Perlmutter,JoelS;Mink,JonathanW
• 通讯作者: Mink,JonathanW

ESM-CT: a precise method for localization of DBS electrodes in CT images.

• DOI: 10.1016/j.jneumeth.2018.09.009
• 发表时间: 2018-10-01
• 期刊: Journal of neuroscience methods
• 影响因子: 3
• 作者: Milchenko M;Snyder AZ;Campbell MC;Dowling JL;Rich KM;Brier LM;Perlmutter JS;Norris SA
• 通讯作者: Norris SA