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