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: 9302347
• 负责人: Jennifer Louise Whitwell
• 金额: $ 32.7万
• 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/9302347
• 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; Deoxyglucose; Development; Diffusion Magnetic Resonance Imaging; Discipline of Nuclear Medicine; Disease; Disease Progression; Evaluation; Executive Dysfunction; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Grouping; Histology; Image; Inferior; Language; Language Disorders; Lead; MRI Scans; Magnetic Resonance Imaging; Measures; Modality; Modeling; Motor; Movement Disorders; Multimodal Imaging; Nerve Degeneration; Neurocognitive Deficit; Neurodegenerative Disorders; Neurologic; Neurons; Neuropsychology; Pathologic; Pathology; Patient Care; Patient-Focused Outcomes; Patients; Performance; Positron-Emission Tomography; Prefrontal Cortex; Principal Investigator; Psychometrics; Research; Resources; Rest; Scientist; Severities; Specialist; Speech; Speech Development; Speech Disorders; Speech Pathology; Standardization; Symptoms; Synapses; Testing; Time; Work; base; brain metabolism; brain tissue; cohort; experience; fluorodeoxyglucose positron emission tomography; frontal lobe; imaging biomarker; imaging potential; improved; motor impairment; motor symptom; neuroimaging; neuroimaging marker; outcome forecast; patient subsets; predict clinical outcome; predictive modeling; protein TDP-43; public health relevance; rate of change; research study; serial imaging; 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（由申请人提供）：语音（AOS）是一种影响语音运动计划的疾病，可以与神经退行性疾病有关。它可以孤立地发生，也可以在患者存在语法和口语问题的情况下发生，被称为非素养失语症（NFA）。目前尚不清楚大脑中的纵向结构和功能变化与该疾病的异质临床特征有关。表征神经退行性AO的进展对于患者预后和进一步定义这些疾病以进行未来的研究和临床试验至关重要。本应用中概述的研究的目的是确定大脑中结构和功能变化之间的关系以及AOS患者的言语和语言，神经和神经心理学特征的发展。 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) 扫描。在这项研究中，我们将对每位患者进行两次额外的序列评估，并在他们的原始评估后2。5年进行，第二次进行一年后进行。每项评估将包括相同的语音和语言，神经和神经心理学评估以及MRI和FDG-PET扫描。因此，在本研究中将进行三个序列评估。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区随时间变化。还将评估大脑代谢和功能连通性的变化。然后，我们将研究这些影像学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，以预测临床结果，例如AOS的恶化和NFA的发展。重要的是，由于我们会跟随患者多年，因此我们预计在研究期间有些受试者会死亡，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发展神经成像模型以预测脑病理学。该申请的重点是神经影像学，将由一位主要研究者领导，在涉及这些神经退行性疾病的神经成像研究方面具有10年的经验。她还将得到一个世界著名科学家团队的支持，包括痴呆症，运动障碍和言语病理学专家，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在神经退行性AOS中开发神经影像标志物，并提供结果，有助于改善对临床下降过程的预测。