The neurobiology of two distinct types of progressive apraxia of speech

两种不同类型的进行性言语失用的神经生物学

• 批准号: 10224718
• 负责人: Keith A Josephs
• 金额: $ 47.1万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224718
• 关键词: Acoustics; Acute; Address; Affect; Aggressive course; Aphasia; Apraxias; Area; Atrophic; Autopsy; Behavioral; Biological; Brain; Brain Diseases; Brain Stem; Brain region; Brain scan; Characteristics; Chronic; Classification; Clinical; Clinical Data; Clinical assessments; Cognitive; Consensus; Corpus striatum structure; Data; Deposition; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Dopamine; Dopamine Receptor; Dysarthria; Equipment; Functional Magnetic Resonance Imaging; Goals; Grant; Histologic; Image; Individual; Language; Language Tests; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Molecular; Morbidity - disease rate; Motor; Neocortex; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Neurologic; Neuropsychology; Pathologic; Pathology; Patients; Pattern; Prognosis; Progressive Supranuclear Palsy; Proteins; Protocols documentation; Reporting; Research Project Grants; Rest; Scanning; Societies; Speech; Speech Disorders; Stroke; Structure; Syndrome; Testing; Time; Work; base; clinical phenotype; clinically relevant; cohort; corticobasal degeneration; demographics; dopamine transporter; gray matter; improved; loved ones; neurocognitive test; neuroimaging; neuropathology; novel; prognostic; recruit; single photon emission computed tomography; sound; spasticity; tau Proteins; therapy development; uptake; white matter

The primary goal of this R01 is to improve understanding of the neurobiology and clinical utility of recognizing two distinct types of primary progressive apraxia of speech (PAOS). Phonetic PAOS is characterized predominantly by distorted sound substitutions and additions, whereas Prosodic PAOS is characterized predominantly by slow, prosodically segmented speech (previously referred to as type 1 and 2, respectively; a third type is characterized by a relatively equal combination of the Phonetic and Prosodic characteristics). Little is known about these PAOS types; however, pilot data suggest biological and clinically meaningful differences between PAOS types. Specifically, Phonetic PAOS seems to be related to degeneration of neocortex, while Prosodic PAOS appears to be more subcortically and brainstem mediated. Pathological underpinnings may also differ across PAOS types. There is some evidence that Prosodic, and not Phonetic, PAOS is associated with the development of a devastating extrapyramidal syndrome and shortened survival. Our approach to the understanding of PAOS types will involve a comprehensive longitudinal assessment of clinical, neuroanatomical, functional, molecular and histopathological data for these patients. By the end of the R01, we expect to have collected and analyzed clinical data - including demographic, speech and language (perceptual and acoustic), neurological, and neuropsychological variables - for 80 PAOS patients. Of these 80, 33 have already been recruited and 47 will be recruited via this R01 mechanism. All 47 new patients will complete the identical volumetric brain MRI protocol which will allow us to assess grey matter atrophy on structural MRI, white matter tract degeneration on diffusion tensor imaging, and functional network disruption on task free fMRI. All new patients to be recruited via this R01 mechanism will also complete a dopamine transporter SPECT scan to assess for striatal dopamine receptor integrity. All tests will be completed annually. Postmortem brain examinations and additional histological analyses of specific brain regions will also be performed on the PAOS patients who are expected to die during this R01. This will be the first study to systematically investigate PAOS types, as well as follow the course of disease longitudinally, and hence is highly novel. The PI of this grant, Dr. Josephs, will be working with a team of experts in AOS (Drs. Duffy and Utianski), structural neuroimaging (Dr. Whitwell), functional neuroimaging (Dr. Jones), molecular neuroimaging (Dr. Lowe), neuropsychology (Drs. Machulda and Butts), and neuropathology (Dr. Dickson) who will work among state of the art facilities and equipment to collectively to reach the aims. At the completion of the R01, we will 1) better understand the neurobiology of PAOS and 2) validate the clinical validity and utility of PAOS types through perceptual consensus, acoustic correlates, and data driven analysis to support prognostication and the development of targeted treatments.

本R 01的主要目标是提高对神经生物学和识别的临床效用的理解。 两种不同类型的原发性进行性言语失用症（PAOS）。语音PAOS的特点是 主要是通过扭曲的声音替换和添加，而韵律PAOS的特点是 主要通过缓慢的、韵律分段的语音（先前分别称为类型1和2; 第三种类型的特点是语音和韵律特征的相对平等的组合）。小 已知这些PAOS类型;然而，初步数据表明生物学和临床上有意义的差异 不同的PAOS类型。具体而言，语音PAOS似乎与新皮层的退化有关， 韵律PAOS似乎更皮质下和脑干介导。病理基础可能 不同的PAOS类型也不同。有一些证据表明，韵律，而不是语音，PAOS与 伴随着毁灭性的锥体外系综合征的发展和生存期的缩短。我们处理 对PAOS类型的理解将涉及对临床， 这些患者的神经解剖、功能、分子和组织病理学数据。在R 01结束时，我们 我希望收集和分析临床数据-包括人口统计学，言语和语言（感知 和听觉），神经学和神经心理学变量-80例PAOS患者。在这80人中，有33人 已经征聘了47人，将通过这一R 01机制征聘47人。所有47名新患者都将完成 相同的体积脑MRI协议，这将允许我们在结构MRI上评估灰质萎缩， 弥散张量成像显示白色束变性，无任务成像显示功能网络中断 功能磁共振成像。通过该R 01机制招募的所有新患者也将完成多巴胺转运蛋白 SPECT扫描以评估纹状体多巴胺受体完整性。所有测试将每年完成。 尸检脑检查和特定脑区域的额外组织学分析也将在 在预计在R 01期间死亡的PAOS患者中进行。这将是第一项研究， 系统地调查PAOS类型，以及纵向跟踪疾病的过程，因此， 非常新颖。本补助金的PI，约瑟夫博士，将与AOS的专家团队（达菲博士和 Utianski）、结构神经成像（Whitwell博士）、功能神经成像（Jones博士）、分子神经成像 (Dr. Lowe），神经心理学（Machulda和Butts博士）和神经病理学（Dickson博士）谁将工作 最先进的设施和设备，共同实现目标。在R 01完成时， 我们将1）更好地了解PAOS的神经生物学，2）验证PAOS的临床有效性和实用性 类型通过感知共识，声学相关，和数据驱动的分析，以支持演示 以及靶向治疗的发展。