Phase 2 Development of a Spoken Language Biomarker of Cognitive Impairment in Parkinson's Disease

帕金森病认知障碍口语生物标志物的二期开发

• 批准号: 9903270
• 负责人: Angela Roberts
• 金额: $ 16.17万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903270
• 关键词: Adult; Advanced Development; Affect; Analysis of Variance; Behavior; Biological Markers; Blinded; Characteristics; Classification; Clinic; Clinical; Code; Cognition; Cognitive; Data; Data Set; Databases; Dementia; Development; Diagnostic; Disease; Early Diagnosis; Education; Enrollment; Environment; Evaluation; Foundations; Future; Genetic Markers; Goals; Hand; Health; Impaired cognition; Impairment; Individual; Language; Linguistics; Manuals; Measures; Methods; Modeling; Monitor; Motor; Neurodegenerative Disorders; Neuropsychology; Parkinson Disease; Parkinson' s Dementia; Participant; Pathogenicity; Persons; Phase; Phenotype; Pilot Projects; Predictive Value; Prevalence; Procedures; Process; Production; Property; Protocols documentation; ROC Curve; Research; Research Personnel; Risk; Sampling; Sensitivity and Specificity; Speech; Standardization; Stimulus; System; Testing; Therapeutic Intervention; Validation; accurate diagnosis; automated analysis; automated speech recognition; biomarker development; candidate marker; clinical care; cognitive change; cognitive impairment in Parkinson' s; cohort; dementia risk; design; improved; innovation; longitudinal dataset; mild cognitive impairment; phase 2 study; phase 3 study; phase 3 testing; primary endpoint; relating to nervous system; repository; response; sex; targeted biomarker; therapy development; tool; treatment response

PROJECT SUMMARY/ABSTRACT Currently, there are limited dementia treatments for the 40-80% of individuals with Parkinson's disease (PD) at risk for developing dementia. Difficulties monitoring early cognitive impairments outside of the clinic, and concomitant delays in treatment initiation, are major barriers to both the accurate diagnosis of and the development of interventions for cognitive impairments in PD. A biomarker is any characteristic that can be measured objectively and indicates pathogenic processes and/or treatment responses. Biomarkers can take a number of forms including observable behaviors. Spoken discourse is sensitive to early cognitive changes in dementia, making it a suitable biomarker target. Yet, to date no study has leveraged the sensitivity of spoken discourse for developing a biomarker of cognitive impairment in PD. The long-term objective of this research is to improve the early and accurate diagnosis of individuals with PD at risk for developing dementia, using a spoken discourse biomarker. Once the biomarker is systematically validated, computational approaches can be used to automate the biomarker analysis. There the lack cognitive and Purpose Phase Aim 1 will rigorously characterize the spoken discourse, cognitive, and motor speech profiles of 129 healthy adults and individuals with PD (with and without cognitive impairment) using a theoretically-grounded model of discourse production. Using methods refined in our pilot studies, Aim 2 will develop and evaluate the classification accuracy of an optimally weighted discourse classification function. Aim 2 will yield a single discourse measure that is comprised of multiple, optimally weighted individual measures. Individual discourse measure values can be `plugged' into the classification function to yield a score, which when compared to a cut-off value, will determine whether the discourse sample are two major barriers toward achieving this objective: 1) of a rigorous, sufficiently-powered, hand-coded dataset of PD spoken discourse (with and without impairment) and 2) the absence of a spoken discourse biomarker that has been rigorously developed tested on a meticulously-characterized cohort of healthy adults and individuals with PD. Using the Fit-for- biomarker framework, the goal of the proposed research is to eliminate these barriers by completing a 2 spoken discourse biomarker study. was produced by a person with PD who has cognitive impairment. The use clinically-grounded, developed longitudinal and phenotypes developing proposed research is innovative in its of an evidence-informed biomarker framework to leverage the sensitivity of spoken discourse to develop a robust biomarker of cognitive impairmen in PD. The resultant biomarker will be further in a future Phase 3 study where the predictive accuracy of the biomarker will be tested in a dataset. Immediately, the proposed project significantly advances research and clinical care in PD, neurodegenerative disorders more broadly, by: 1) expanding our understanding of cognitive-linguistic across the spectrum of PD and 2) providing a rigorous, foundational, discourse dataset for automated analyses of biomarkers that monitor cognition in real world environments. t

项目概要/摘要 目前，40-80% 的帕金森病 (PD) 患者的痴呆症治疗有限。 患痴呆症的风险。难以在诊所外监测早期认知障碍，以及 随之而来的治疗开始延迟是准确诊断和治疗的主要障碍 开发针对 PD 认知障碍的干预措施。生物标志物是任何可以被识别的特征 客观测量并表明致病过程和/或治疗反应。生物标志物可以采取 包括可观察行为在内的多种形式。口语对早期认知变化很敏感 痴呆症，使其成为合适的生物标志物目标。然而，迄今为止还没有研究利用口语的敏感性 关于开发 PD 认知障碍生物标志物的讨论。这项研究的长期目标是 为了提高对有痴呆风险的帕金森病患者的早期和准确诊断，使用 口语话语生物标志物。一旦生物标志物得到系统验证，计算方法就可以 用于自动化生物标志物分析。那里 这 缺少 认知的 和 目的 阶段目标 1 将严格描述口头话语、认知、 129 名健康成人和帕金森病患者（有或没有认知能力）的运动言语特征 损伤）使用基于理论的话语产生模型。使用我们试点中改进的方法 研究中，目标 2 将开发和评估最佳加权话语的分类准确性 分类功能。目标 2 将产生一个单一的话语测量，该测量由多个、最佳的 加权个人措施。单个话语测量值可以“插入”到分类中 函数产生一个分数，与截止值相比，将确定话语样本是否 实现这一目标的两个主要障碍：1) 一个严格的、功能充足的、手工编码的 PD 口语话语数据集（有或没有 损伤）和 2）缺乏经过严格开发的口语生物标志物 在一组经过仔细研究的健康成年人和帕金森病患者身上进行了测试。使用 Fit-for- 生物标志物框架，拟议研究的目标是通过完成一项研究来消除这些障碍 2口语话语生物标志物研究。 是由患有认知障碍的 PD 患者产生的。这 使用 以临床为基础， 发达 纵向 和 表型 发展 拟议的研究具有创新性 一个基于证据的生物标志物框架，利用口语话语的敏感性来开发 PD 认知障碍患者的强有力的生物标志物。由此产生的生物标志物将进一步 在未来的第 3 阶段研究中，生物标志物的预测准确性将在 数据集。拟议的项目立即显着推进了帕金森病的研究和临床护理， 更广泛的神经退行性疾病，通过：1）扩大我们对认知语言的理解 跨越 PD 的各个领域，2) 为以下领域提供严格的、基础的话语数据集： 对监测现实世界环境中认知的生物标志物进行自动分析。 t