Precision-Mapping Functional Connectivity in Parkinson's Disease

精确绘制帕金森病的功能连接图

基本信息

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
项目类别：
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&apos 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

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 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.

抽象的帕金森病（PD）是一种进行性神经退行性疾病，其特征为运动、认知和神经功能障碍。由异常蛋白质沉积和神经递质缺陷引起的精神表现。 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。尽管目前的治疗方法对帕金森病的运动功能有显着的改善，但它们未能完全缓解步态障碍，并且非运动症状，并可能恶化这些更复杂的症状。与大规模大脑网络的功能相关，可以通过静息态功能来测量在我们过去的工作中，我们证明了 PD 参与者作为一个群体表现出差异。然而，临床应用的开发需要可靠的个体。水平生物标志物捕捉广泛的神经病理学并尊重帕金森病的临床异质性，最近开发的精确绘图 RSFC 方法为 PD 的“个性化医疗”开辟了道路。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，并且可能为PD提供非侵入性生物标志物因此，我们建议鉴定个体水平的RSFC标志物。 PD，检查这些精密RSFC标记物与临床表现的关系以及 PD 的神经病理学，并确定精确的 RSFC 标记是否可以预测 PD 的认知能力下降和痴呆。