Longitudinal multi-modality imaging in progressive apraxia of speech

描述（由申请人提供）：言语失用症（AOS）是一种影响言语运动规划的障碍，可能与神经退行性疾病有关。它可以单独发生，也可以存在语言障碍，即患者有语法和口语问题，称为非流利性失语症（NFA）。目前尚不清楚大脑的纵向结构和功能变化如何与该疾病的异质性临床特征相关。表征神经退行性AOS的进展将对患者预后和进一步定义这些疾病的未来研究和临床试验至关重要。本应用程序中概述的研究目的是确定脑结构和功能变化与AOS患者言语和语言、神经和神经心理特征进展之间的关系。为了实现我们的目标，我们将利用一组特征明确的神经退行性AOS受试者，这些受试者在明尼苏达州罗切斯特市梅奥诊所接受了评估，并接受了标准化的言语和语言、神经学和神经心理学评估、磁共振成像（MRI）扫描和[18-F]-氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）扫描。在这项研究中，我们将对每位患者进行两次额外的系列评估，第一次在他们最初评估的2.5年后进行，第二次在他们最初评估的一年后进行。每次评估将包括相同的语音和语言，神经学和神经心理学评估以及核磁共振和FDG-PET扫描。因此，本研究将采用三个系列评估进行分析。我们将评估脑组织损失的速度，并检查哪些特定的大脑区域和白质束随着时间的推移而改变。脑代谢和功能连接的变化也将被评估。然后，我们将研究这些影像学指标与临床衰退的不同方面之间的关系，并开发基于影像学的模型来预测临床结果，如孤立性AOS患者的AOS恶化和NFA的发展。重要的是，由于我们将跟踪患者数年，我们预计一些受试者将在研究期间死亡，因此我们将能够进行脑尸检以确定大脑中存在哪些疾病，并开发神经成像模型来预测大脑病理。该申请的重点是神经影像学，将由一位在涉及这些神经退行性疾病的神经影像学研究方面有10年经验的首席研究员领导。她还将得到世界知名科学家团队的支持，包括痴呆症、运动障碍和语言病理学专家、核医学科学家、神经心理学家和生物统计学家。我们研究的长期目标是开发神经退行性AOS的神经成像生物标志物，并提供有助于改善临床衰退过程预测的结果。

DESCRIPTION (provided by applicant): Apraxia of speech (AOS) is a disorder affecting the motor planning of speech and can be associated with neurodegenerative diseases. It can occur in isolation or in the presence of a language disorder whereby patients have problems with grammar and spoken language, known as non-fluent aphasia (NFA). It is unclear how longitudinal structural and functional changes in the brain are related to the heterogeneous clinical features of the disorder. Characterizing progression in neurodegenerative AOS will be critical for patient prognosis and for further defining these disorders for future research and clinical trials. The objectives of the studies outlined in this application are to determine the relationship between structural and functional changes in the brain and progression of speech and language, neurological and neuropsychological features in patients with AOS. To accomplish our aims we will utilize a well characterized cohort of neurodegenerative AOS subjects that were evaluated at the Mayo Clinic, Rochester MN, and have undergone standardized speech and language, neurological and neuropsychological evaluations, a magnetic resonance imaging (MRI) scan and a [18-F]-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) scan. In this study, we will perform two additional serial assessments of each patient, with the first performed 2.5 years after their original assessment, and the second performed one year later. Each assessment will include identical speech and language, neurological and neuropsychological evaluations and an MRI and FDG-PET scan. Therefore, three serial assessments will be available for analysis in this study. We will assess the rate of brain tissue loss, and examine which specific brain regions and white matter tracts change over time. Changes in brain metabolism and functional connectivity will also be assessed. We will then investigate associations between these imaging measures and different aspects of clinical decline, as well as develop imaging-based models that predict clinical outcomes, such as worsening of AOS and the development of NFA in patients with isolated AOS. Importantly, since we would have followed patients for a number of years, we anticipate that some subjects will die during the study and hence we will be able to perform brain autopsies to determine what disease(s) are present in the brain and develop neuroimaging models to predict brain pathology. The application focuses on neuroimaging and will be led by a Principal Investigator with 10 years experience in neuroimaging research involving these neurodegenerative disorders. She will also have support from a team of world renowned scientists including dementia, movement disorders and speech pathology specialists, a nuclear medicine scientist, neuropsychologists, and biostatisticians. The long term goal of our research is to develop neuroimaging biomarkers in neurodegenerative AOS and provide results that will help improve predictions about the course of clinical decline.