Speech markers of cognitive impairment in Parkinson's disease

摘要 卡拉·史密斯博士是马萨诸塞大学医学院的运动障碍神经病学家 学校(UMMS)，其目标是成为关注早期认知障碍的独立调查者 帕金森病(PD)。她的长期目标是开发帕金森病认知障碍的言语标记物。 认知障碍发生在大多数PD患者中，导致死亡率增加和减少 生活质量。目前的诊断工具是资源密集型的，而且灵敏度有限。治疗方法是 通常在认知衰退的过程中后期提供，并不能提供最佳益处。语音标记可以 改进对帕金森病患者认知障碍的检测、监测和治疗。语音标记可能是 通过移动技术进行频繁和远程监控，捕获有关认知的敏感、定量数据 在患者的日常生活和对治疗的反应中发挥作用。史密斯医生作为临床医生的角色 运动障碍专家的理想定位是领导高级语言和语言的应用 为现实生活中的临床实践和临床试验研究可行的、以患者为中心的工具。 史密斯博士已经组建了一支跨学科的专家指导团队，非常适合这一目标 创新的建议。史密斯博士和她的团队此前已经证明，a)语音声学标记 与非痴呆性帕金森病患者的认知功能相关，以及b)轻度认知障碍的帕金森病患者 语言障碍包括话语中的停顿和语法上的缺陷。建立在这些基础上 结果，史密斯博士建议更全面地研究患有和 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。这项研究的目标将是1)开发使用语音声学标记的算法 根据认知状态进行分类，2)识别与帕金森病轻度认知障碍相关的语言标记物， 3)评估轻度认知障碍帕金森病患者的在线句法加工。的总目标是 这项建议是为了确定早期认知功能障碍的言语和语言标志，这些标志可以进一步 使用移动技术将其细化、验证并实施为更大规模的纵向R01提案。 进一步的工作还将解决这些语音标记物的潜在神经生物学机制。 史密斯博士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， 在信号处理和语音声学分析方面有经验。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。她会的 在研究领导、介绍和传播科学工作以及撰写赠款方面积累经验， 最终以R01提案告终。这项K23奖项对于史密斯博士建立独立的职业生涯至关重要。 作为一名PD临床医生兼科学家，在言语和语言科学与认知障碍的独特交汇点。

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.