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.

该R01的主要目标是提高对识别神经生物学和临床实用性的理解 两种不同类型的主要渐进性语言（PAO）。语音paos的特征 主要由扭曲的声音替代和加法，而韵律PAO的表征 主要是由缓慢的韵律分割的语音（以前称为1型和类型2； a 第三类的特征是语音和韵律特征的相对相对相等的组合）。小的 这些PAOS类型已知；但是，飞行员数据表明​​生物学和临床意义有意义的差异 在PAO类型之间。具体而言，语音PAO似乎与新皮层的变性有关，而 韵律PAO似乎是细胞皮层和脑干介导的。病理基础可能 PAOS类型也有所不同。有一些证据表明韵律，而不是语音，Paos是相关的 随着毁灭性锥体外综合征的发展并缩短了存活率。我们对 对PAOS类型的了解将涉及对临床的全面纵向评估 这些患者的神经解剖学，功能，分子和组织病理学数据。到R01结束时，我们 期望收集和分析临床数据 - 包括人口统计，语音和语言（感知 和声学），神经系统和神经心理学变量 - 80名PAOS患者。在这80个中，有33个 已经被招募了，将通过此R01机制招募47。所有47位新患者将完成 相同的体积大脑MRI方案，这将使我们能够评估结构MRI上的灰质萎缩， 在扩散张量成像上的白质道变性和无任务的功能网络中断 fMRI。通过此R01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。 事后大脑检查和特定大脑区域的其他组织学分析也将是 对预计在R01期间死亡的PAOS患者进行。这将是第一个研究 系统地研究PAOS类型，并遵循纵向疾病的过程，因此 高度新颖。这笔赠款的PI Josephs博士将与AOS专家团队合作（Duffy和Dr. UTIANSKI），结构神经影像学（惠特威尔博士），功能性神经影像学（琼斯博士），分子神经成像 （Lowe博士），神经心理学（Machulda和Butts博士）和神经病理学（Dickson博士） 在最先进的设施和设备中，以共同达到目标。 R01完成时， 我们将更好地理解PAO的神经生物学和2）验证PAO的临床有效性和效用 通过知觉共识，声学相关性和数据驱动分析的类型，以支持预后 以及有针对性治疗的发展。