Longitudinal multi-modality imaging in progressive apraxia of speech

进行性言语失用症的纵向多模态成像

• 批准号: 9096020
• 负责人: Jennifer Louise Whitwell
• 金额: $ 31.29万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9096020
• 关键词: Address; Affect; Aphasia; Apraxias; Autopsy; Basal Ganglia; Biological Markers; Brain; Brain Diseases; Brain Pathology; Brain Stem; Brain region; Broca' s area; Characteristics; Clinic; Clinical; Clinical Treatment; Clinical Trials; Collaborations; Data; Dementia; Development; Diffusion Magnetic Resonance Imaging; Discipline of Nuclear Medicine; Disease; Disease Progression; Evaluation; Executive Dysfunction; Functional Magnetic Resonance Imaging; Future; Glucose; Goals; Grant; Grouping; Health; Histology; Image; Inferior; Language; Language Disorders; Lead; MRI Scans; Magnetic Resonance Imaging; Measures; Modality; Modeling; Motor; Movement Disorders; Nerve Degeneration; Neurocognitive Deficit; Neurodegenerative Disorders; Neurologic; Neurons; Outcome; Pathology; Patient Care; Patients; Performance; Positron-Emission Tomography; Prefrontal Cortex; Principal Investigator; Psychometrics; Research; Resources; Rest; Scientist; Severities; Specialist; Speech; Speech Development; Speech Disorders; Speech Pathology; Symptoms; Synapses; Testing; Time; Work; base; brain metabolism; brain tissue; cohort; experience; fluorodeoxyglucose positron emission tomography; frontal lobe; imaging biomarker; imaging modality; improved; motor impairment; motor symptom; neuroimaging; neuropsychological; outcome forecast; patient subsets; predict clinical outcome; protein TDP-43; rate of change; tau Proteins; treatment trial; white matter

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.

描述(申请人提供)：言语失用症(AOS)是一种影响言语运动计划的障碍，可与神经退行性疾病有关。它可以单独发生，也可以在存在语言障碍的情况下发生，即患者在语法和口语方面存在问题，称为非流利失语症(NFA)。目前尚不清楚大脑的纵向结构和功能变化与这种疾病的不同临床特征之间的关系。确定神经退行性AOS的进展对于患者的预后以及为未来的研究和临床试验进一步定义这些疾病至关重要。本申请中概述的研究的目标是确定AOS患者的大脑结构和功能变化与言语和语言进展、神经和神经心理特征之间的关系。为了实现我们的目标，我们将利用在明尼苏达州罗切斯特市梅奥诊所接受评估的一组具有良好特征的神经退行性AOS受试者，并进行标准化的言语和语言、神经和神经心理评估、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)。在这项研究中，我们将对每个患者进行另外两次系列评估，第一次在最初评估后2.5年进行，第二次在一年后进行。每项评估将包括相同的言语和语言，神经和神经心理评估，以及核磁共振和FDG-PET扫描。因此，本研究将提供三个系列评估以供分析。我们将评估脑组织损失率，并检查哪些特定的脑区和白质束随着时间的推移而变化。还将评估大脑新陈代谢和功能连接的变化。然后，我们将调查这些成像指标与临床下降的不同方面之间的关联，以及开发基于成像的模型来预测临床结果，例如AOS的恶化和孤立性AOS患者的NFA的发展。重要的是，由于我们将跟踪患者多年，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部尸检，以确定大脑中存在什么疾病(S)，并开发神经成像模型来预测大脑病理。这项申请的重点是神经成像，将由一名首席调查员领导，他在涉及这些神经退行性疾病的神经成像研究方面拥有10年的经验。她还将得到一个由世界著名科学家组成的团队的支持，其中包括痴呆症、运动障碍和语言病理专家、一名核医学科学家、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的神经成像生物标记物，并提供有助于改善对临床衰退过程的预测的结果。