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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的帕金森氏病（PD）是一种进行性神经退行性疾病，其特征是运动，认知和异常蛋白质沉积和神经递质缺陷引起的精神病表现。这临床表现和进展的变异性可能反映了脑病理学的潜在变异性。尽管目前的治疗可为PD提供巨大的运动益处，但它们无法减轻步态的某些方面障碍和非运动症状，可能会加剧认知和精神病特征。发展更多 “个性化医学”干预，防止或预防这些功能，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需的，预测新治疗的进展，发展和评估。因此，我们建议识别和基于综合运动，认知和精神病学评估验证PD临床亚型；决定 PD临床亚型通过纵向行为评估的预测效用；并检查来自多模式神经成像，CSF和尸检数据的PD临床亚型的生物标记。