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: 9309771
• 负责人: MEGHAN C CAMPBELL
• 金额: $ 48.03万
• 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 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9309771
• 关键词: Amyloid beta-Protein; Autopsy; Behavior assessment; Behavioral; Biological; Biological Markers; Brain Pathology; Classification; Clinical; Cognition; Cognitive; Cognitive deficits; Complex; Corpus striatum structure; Data; Data Set; Dementia; Deposition; Development; Disease; Disease Progression; Economic Burden; Evaluation; Family; Gait; Growth; Hallucinations; Impaired cognition; Impairment; Individual; Intervention; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Methods; Modality; Morbidity - disease rate; Motor; Neurodegenerative Disorders; Neurotransmitters; Parietal; Parkinson Disease; Parkinsonian Disorders; Participant; Pathology; Patients; Performance; Phenotype; Pittsburgh Compound-B; Proteins; Rest; Societies; Statistical Models; Subgroup; Testing; Time; Tremor; Validation; alpha synuclein; base; behavior measurement; clinically relevant; cohort; disorder control; disorder subtype; experience; falls; improved; mortality; motor deficit; multimodality; network dysfunction; neuroimaging; non-motor symptom; novel; patient stratification; personalized intervention; personalized medicine; posture instability; prevent; psychiatric symptom; 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 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 medicine” interventions to treat, forestall or prevent these features, classification of PD clinical subtypes and identification of the associated biological mechanisms are necessary for patient stratification, predicting progression, development and evaluation of novel treatments. Therefore, we propose to identify and validate PD clinical subtypes based on comprehensive motor, cognitive, and psychiatric evaluations; determine the predictive utility of PD clinical subtypes through longitudinal behavioral assessments; and examine biological markers of the PD clinical subtypes from multimodal neuroimaging, CSF, and autopsy data.

摘要 帕金森病（PD）是一种进行性神经退行性疾病，其特征在于运动、认知和神经功能障碍。 由于蛋白质沉积异常和神经递质缺乏而引起的精神症状。的 临床表现和进展的可变性可能反映了脑病理学的潜在可变性。 虽然目前的治疗提供了显着的运动优势，PD，他们未能减轻步态的某些方面， 损伤和非运动症状，并可能加剧认知和精神病学特征。开发更多 “个性化药物”干预治疗，预防或预防这些功能，PD临床分类 亚型和相关生物学机制的鉴定对于患者分层是必要的， 预测进展、开发和评价新的治疗方法。因此，我们建议确定和 基于综合运动、认知和精神评估验证PD临床亚型;确定 通过纵向行为评估预测PD临床亚型的效用;并检查 来自多模式神经成像、CSF和尸检数据的PD临床亚型的生物标志物。