Precision-Mapping Functional Connectivity in Parkinson's Disease

精确绘制帕金森病的功能连接图

• 批准号: 10583322
• 负责人: MEGHAN C CAMPBELL
• 金额: $ 63.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583322
• 关键词: Address; Affect; Age; Amyloid beta-Protein; Attention; Behavioral; Biological Markers; Brain; Brain Pathology; Clinical; Cognition; Cognitive; Cognitive deficits; Complex; Data; Defect; Dementia; Deposition; Disease Progression; Dorsal; Economic Burden; Evaluation; Exhibits; Family; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gait; Genetic; Impaired cognition; Impairment; Individual; Link; Location; Magnetic Resonance Imaging; Maps; Measures; Mental disorders; Methods; Morbidity - disease rate; Motor; Motor Cortex; Neurodegenerative Disorders; Neurotransmitters; Parkinson Disease; Parkinson' s Dementia; Participant; Pathology; Pathway Analysis; Patient Selection; Patients; Persons; Phenotype; Positron-Emission Tomography; Prognostic Marker; Proteins; Research Design; Rest; Rewards; Scanning; Societies; Symptoms; System; Testing; Time; Work; abeta deposition; alpha synuclein; behavioral impairment; brain dysfunction; cholinergic; clinical application; clinical development; clinical heterogeneity; cohort; denoising; disease heterogeneity; improved; individual variation; innovation; magnetic resonance imaging biomarker; mortality; motor deficit; network dysfunction; neuroimaging; neuropathology; neurophysiology; non-demented; non-motor symptom; novel; novel strategies; patient stratification; personalized intervention; personalized medicine; predictive marker; psychiatric symptom; recruit; research clinical testing; tau Proteins

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 in PD likely reflects underlying variability in brain pathology. Although current treatments provide dramatic motor benefit in PD, they fail to fully alleviate gait impairment and non-motor symptoms and may exacerbate cognitive and psychiatric features. These more complex symptoms are linked to the function of large-scale brain networks, which can be measured with resting-state functional connectivity MRI (RSFC). In our past work, we demonstrated that PD participants, as a group, show differences in RSFC relative to healthy controls. However, development of clinical applications requires reliable individual- level biomarkers that capture the widespread neuropathology and respects the clinical heterogeneity of PD, opening the avenue to “personalized medicine” in PD. Recently developed precision-mapping RSFC approaches now permit identification of individual-level differences in brain network organization with high reliability and may provide a non-invasive biomarker for PD. Therefore, we propose to identify individual-level RSFC markers of PD, examine the relationship of these precision RSFC markers with the clinical manifestations and neuropathology of PD, and determine if precision RSFC markers predict cognitive decline and dementia in PD.

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 PD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。 尽管目前的治疗在PD中提供了显著的运动益处，但它们不能完全缓解步态障碍， 非运动症状，并可能加剧认知和精神病学特征。这些更复杂的症状 与大规模大脑网络的功能有关，这可以用静息态功能来衡量。 连接性MRI（RSFC）。在我们过去的工作中，我们证明了PD参与者作为一个群体， 在RSFC中相对于健康对照。然而，临床应用的发展需要可靠的个人- 水平生物标志物，捕获广泛的神经病理学，并尊重PD的临床异质性， 为PD的“个性化医疗”开辟了道路。最近开发的精确映射RSFC方法 现在允许以高可靠性识别大脑网络组织中的个体水平差异，并且可以 为PD提供非侵入性生物标志物。因此，我们建议确定个体水平的RSFC标记， PD，检查这些精确RSFC标志物与临床表现的关系， 本发明还提供了一种用于PD神经病理学研究的方法，并确定精确的RSFC标记物是否预测PD中的认知下降和痴呆。