Mechanisms of Gait and Balance Impairment in Progressive Supranuclear Palsy

进行性核上性麻痹的步态和平衡障碍的机制

基本信息

批准号：
10657768
负责人：
Farwa Ali
金额：
$ 19.01万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10657768
关键词：
3-Dimensional Accreditation Address Age Calibration Cessation of life Clinic Clinical Clinical Research Clinical Treatment Clinical Trials Collaborations Controlled Environment Data Detection Development Devices Diagnosis Diagnostic tests Diffusion Magnetic Resonance Imaging Disease Equilibrium Evaluation Frequencies Future Gait Gait abnormality Goals Grant Heterogeneity Human Image Impairment Knowledge Laboratories Locomotion Magnetic Resonance Imaging Measures Mentorship Methods Minnesota Monitor Morbidity - disease rate Motion Movement Disorders Nerve Degeneration Neuroanatomy Neurodegenerative Disorders Outcome Outcome Measure Outcomes Research Patients Pattern Phenotype Positioning Attribute Posture Productivity Progressive Supranuclear Palsy Qualifying Reporting Research Research Methodology Research Project Grants Research Proposals Severity of illness Standardization Syndrome System Tauopathies Technology Testing Training Translations Universities Validation Work career career development clinical biomarkers clinical examination clinical heterogeneity clinical outcome measures clinical practice clinical training clinically significant comparative cost effective diagnostic tool disability equilibration disorder experience fall risk falls human model improved innovation mortality motor control multidisciplinary multimodality neurobiological mechanism neuroimaging normal aging patient oriented research patient population portability professor prognostic assays programs sex skills statistics structural imaging three-dimensional modeling tractography treatment trial trial planning wearable device

项目摘要

PROJECT SUMMARY/ABSTRACT Progressive supranuclear palsy (PSP) is a fatal, progressive, incurable neurodegenerative tauopathy. Falls resulting from gait and balance impairments are a cardinal feature of the disease and occur in all PSP syndromes. Currently, detection of these abnormalities relies on largely subjective clinical examination and scales. There are no standardized ways to quantify specific features of gait and balance impairments in PSP. Diagnostic, and prognostic tests focusing on patient relevant outcomes such as gait related disability are needed. Motion analysis technology can be used for objective qualification of gait and balance variables. This offers an opportunity to develop patient-centric diagnostic tools that can measure features of gait impairment and its impact on risk for falls. Laboratory-based video motion capture utilizes multiple high frequency cameras in a well calibrated controlled environment to generate a three-dimensional model of human locomotion and balance. This is considered the most accurate and reliable method of motion analysis. Our project will utilize laboratory-based motion capture to identify gait metrics that best characterize PSP Richardson syndrome, PSP-cortical and PSP-subcortical syndromes and distinguish PSP from normal controls. However, accredited motion analysis labs are not readily accessible, and require an elaborate usually expensive set-up. Body-worn motion-sensing devices offer a feasible alternative. They are cost-effective, portable, easy to use in ambulatory settings. However, it is essential to establish reliability and accuracy of these devices in specific patient populations and assess clinical significance of the data captured. Therefore, in this project we will employ a body-worn motion sensing device or inertial monitoring unit (IMU) to detect gait and balance metrics that best characterize PSP. The data from the IMU will then be compared to the motion analysis lab to establish its accuracy. Gait metrics have the potential to serve as patient-centric outcome measures in PSP. In this project we will also use these variables to analyze neurobiological mechanisms underlying gait and balance impairment in PSP. We will correlate the identified gait and balance metrics with volumetric magnetic resonance imaging (MRI), diffusion MRI (dMRI) and tractography to determine patterns of disruption of cortical and subcortical motor control systems in PSP. The effect of sex as a biologically significant variable will be assessed. Age will be a covariate to identify gait abnormalities that are specifically related to disease state and not secondary to normal aging. The outcomes of this research project will contribute to development of patient centric outcome measures, assessment of clinical heterogeneity and understanding of mechanisms of gait impairment in PSP syndromes. Future directions will include longitudinal assessment and comparative analyses across related neurodegenerative diseases to advance diagnosis and development of patient centric outcome measures for clinical trials.

项目概要/摘要进行性核上性麻痹 (PSP) 是一种致命的、进行性的、无法治愈的神经退行性 tau 病。瀑布由步态和平衡障碍引起的症状是该疾病的一个主要特征，并且发生在所有 PSP 中综合症。目前，这些异常的检测很大程度上依赖于主观的临床检查和秤。没有标准化的方法来量化 PSP 中步态和平衡损伤的具体特征。专注于患者相关结果（例如步态相关残疾）的诊断和预后测试需要。运动分析技术可用于客观鉴定步态和平衡变量。这提供了开发以患者为中心的诊断工具的机会，该工具可以测量步态障碍的特征及其对跌倒风险的影响。基于实验室的视频动作捕捉利用多个高频摄像机在校准良好的受控环境中生成人体运动的三维模型平衡。这被认为是最准确、最可靠的运动分析方法。我们的项目将利用基于实验室的运动捕捉来识别最能表征 PSP 理查森综合征的步态指标， PSP-皮质和 PSP-皮质下综合征，并将 PSP 与正常对照区分开来。然而，经认可运动分析实验室并不容易获得，并且需要复杂且通常昂贵的设置。身体佩戴运动传感设备提供了一种可行的替代方案。它们具有成本效益、便携、易于在门诊使用设置。然而，必须确定这些设备在特定患者中的可靠性和准确性人群并评估所捕获数据的临床意义。因此，在这个项目中我们将采用体戴式运动传感设备或惯性监控单元 (IMU)，用于检测最佳步态和平衡指标描述 PSP 的特征。然后将来自 IMU 的数据与运动分析实验室进行比较，以确定其准确性。步态指标有潜力作为 PSP 中以患者为中心的结果衡量指标。在这个项目中我们还将使用这些变量来分析步态和平衡的神经生物学机制 PSP 损伤。我们将把识别的步态和平衡指标与体积磁相关联磁共振成像 (MRI)、扩散 MRI (dMRI) 和纤维束成像以确定皮质破坏模式和 PSP 中的皮层下运动控制系统。性别作为生物学上重要变量的影响将是评估。年龄将是一个协变量，用于识别与疾病状态和特定相关的步态异常。不是继发于正常衰老。该研究项目的成果将有助于患者的发展以结果为中心的测量、临床异质性评估和步态机制的理解 PSP 综合征的损害。未来的方向将包括纵向评估和比较分析相关的神经退行性疾病，以推进以患者为中心的诊断和开发临床试验的结果测量。