Speech markers of cognitive impairment in Parkinson's disease

摘要 博士卡拉·史密斯是马萨诸塞州医学院的运动障碍神经学家 学校（UMMS），其目标是成为一个独立的调查员，专注于早期认知障碍， 帕金森病（PD）。她的长期目标是开发PD认知障碍的言语标记。 大多数PD患者发生认知障碍，导致死亡率增加， 生活质量目前的诊断工具是资源密集型的，灵敏度有限。治疗是 通常在认知衰退的后期提供，并且不能提供最佳益处。语音标记可以 改善PD认知功能障碍检测、监测和治疗。言语标记可能是 通过移动的技术进行频繁和远程监控，捕获有关认知的敏感定量数据， 在患者的日常生活中以及对治疗的反应中发挥作用。史密斯博士作为一名临床医生 运动障碍专家的理想位置，她领导先进的语音和语言的应用 研究为现实生活中的临床实践和临床试验的可行的，以病人为导向的工具。 博士史密斯已经组建了一个专家跨学科的导师团队，非常适合本项目的目标。 创新提案。史密斯博士和她的团队先前已经证明，a）语音声学标记是 B）PD患者中存在轻度认知障碍， 语言缺陷包括话语中的停顿和语法性。根据这些 结果，史密斯博士建议更全面地研究PD患者的言语和语言， 没有轻度认知障碍和对照，以确认这些初步结果，并确定其他 生物标志物。本研究的目的是：1）开发使用语音声学标记的算法， 根据认知状态分类，2）鉴定与PD中轻度认知损害相关的语言标记， （3）评估有轻度认知障碍的PD受试者的在线句法加工。的总目标 该建议是识别早期认知功能障碍言语和语言标记， 使用移动的技术将其细化、验证并实施为更大规模的纵向R01提案。 进一步的工作也将解决这些语音标记的神经生物学机制。 博士史密斯严格的培训计划包括硕士学位，语言学和言语运动生理学课程， 具有信号处理和语音声学分析经验。通过她的训练目标，她将 提高她在以患者为中心的结果测量和仪器验证方面的知识和技能。她将 获得研究领导，介绍和传播科学工作的经验，并在赠款写作， 最终提出了R 01提案。这个K23奖将是至关重要的史密斯博士建立一个独立的职业生涯 作为一名PD临床科学家，在言语和语言科学与认知障碍的独特交叉点。

ABSTRACT Dr. Kara Smith is a Movement Disorders neurologist at the University of Massachusetts Medical School (UMMS) whose goal is to become an independent investigator focused on early cognitive impairment in Parkinson disease (PD). Her long-term goal is to develop speech markers of cognitive impairment in PD. Cognitive impairment occurs in the majority of PD patients, leading to increased mortality and decreased quality of life. The current diagnostic tools are resource-intensive and have limited sensitivity. Treatments are often offered late in the course of cognitive decline and do not provide optimal benefit. Speech markers could improve detection, monitoring and treatment of cognitive impairment in PD. Speech markers could be monitored frequently and remotely via mobile technology, capturing sensitive, quantitative data about cognitive function in the context of patients’ daily life and in response to therapeutics. Dr. Smith’s role as a clinical movement disorders specialist ideally positions her to lead the application of advanced speech and language research to feasible, patient-oriented tools for real-life clinical practice and clinical trials. Dr. Smith has assembled an expert interdisciplinary mentorship team ideally suited for the goals of this innovative proposal. Dr. Smith and her team have previously shown that a) speech acoustic markers are associated with cognitive function in non-demented PD patients, and b) PD patients with mild cognitive impairment had linguistic deficits including pauses within utterances and grammaticality. Building on these results, Dr. Smith proposes to study speech and language more comprehensively in PD patients with and without mild cognitive impairment and controls to confirm these preliminary results and identify additional biomarkers. The aims of this study will be 1) to develop algorithms using speech acoustic markers to categorize by cognitive status, 2) to identify linguistic markers associated with mild cognitive impairment in PD, and 3) to assess on-line syntactic processing in PD subjects with mild cognitive impairment. The overall goal of the proposal is to identify speech and language markers of early cognitive dysfunction that can be further refined, validated and implemented using mobile technology into a larger scale, longitudinal R01 proposal. Further work will also address the underlying neurobiological mechanisms of these speech markers. Dr. Smith’s rigorous training plan includes a Master’s degree, linguistics and speech motor physiology courses, and experience in signal processing and speech acoustic analysis. Through her training goals, she will advance her knowledge and skills in patient-centered outcomes measures and instrument validation. She will gain experience in research leadership, presentation and dissemination of scientific work, and in grant writing, culminating in an R01 proposal. This K23 award will be critical for Dr. Smith to establish an independent career as a PD clinician-scientist at the unique intersection of speech and language science and cognitive impairment.