Longitudinal multi-modality imaging in non-fluent/agrammatic primary progressive aphasia

不流利/语法障碍的原发性进行性失语症的纵向多模态成像

基本信息

  • 批准号:
    10665296
  • 负责人:
  • 金额:
    $ 69.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-07-01 至 2028-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative disorder defined by the presence of agrammatic aphasia and/or apraxia of speech that commonly results from a 4- repeat tauopathy. During the previous 2 cycles of the R01 we used neuroimaging to characterize the patterns of neurodegeneration and structural and functional breakdowns in connectivity associated with nfvPPA. However, little is known about how these brain changes are related to, or driven by, underlying biological processes. Two important biological mechanisms relevant to nfvPPA are deposition of the protein tau and neuroinflammation. In the 2nd cycle of the R01 we assessed tau deposition in vivo using PET. In the 3rd cycle we will focus on assessing the role of neuroinflammation and other biological processes. The first aim of the grant is to characterize the patterns of neuroinflammation in the brain using PET imaging with the 3rd generation ligand 11C-ER176 and determine whether neuroinflammation changes over time and is associated with clinical disease severity. The second aim is to determine whether biomarkers of pathological processes measured from blood plasma, including neurofilament light chain, plasma glial fibrillary acidic protein, tau, and inflammation biomarkers, are abnormal in nfvPPA. We will also assess whether these biomarkers change over time and are associated with clinical disease severity. These first two aims will determine whether neuroinflammation PET and blood plasma biomarkers are useful disease biomarkers in nfvPPA, and we will determine whether these measures could be useful prognostic markers of future clinical decline. Our third objective is to build upon knowledge gained from the first 2 cycles and determine how structural and functional abnormalities in the brain, measured using structural MRI, diffusion tractography and resting state fMRI, are related to neuroinflammation PET and blood plasma biomarkers. This aim will help model the degree to which these biological processes relate to other more established breakdowns in brain structure and function. To accomplish these aims we will recruit 50 patients with nfvPPA, and each participant will undergo three serial assessments one year apart. At each assessment, patients will have a neurological and speech-language assessment, 11C-ER176 neuroinflammation PET and a 3T magnetic resonance imaging scan that will include resting-state functional MRI and diffusion tensor imaging sequences. A blood sample will be collected from all patients at both visits. Blood samples were also collected in the 2nd cycle of the R01 and hence blood plasma biomarkers will be measured in 100 nfvPPA patients. We will also recruit 50 cognitively normal healthy controls who will undergo identical neuroimaging and provide a blood sample. This renewal is highly significant as results gained will be critical to understand the biology of nfvPPA and mechanisms of disease spread. Furthermore, this work may also help provide potential mechanistic treatment targets for nfvPPA and establish disease biomarkers for prognosis and for future research studies and clinical trials in patients with nfvPPA.
项目摘要 原发性进行性失语症的非流利/语法缺失变体(nfvPPA)是一种神经退行性疾病 定义为存在语法性失语症和/或言语失用症,通常由4- 重复tau蛋白病。在R 01的前2个周期中,我们使用神经成像来表征模式 与nfvPPA相关的神经退行性变以及连接性的结构和功能故障。 然而,人们对这些大脑变化如何与潜在的生物学特性相关或受其驱动知之甚少。 流程.与nfvPPA相关的两个重要的生物学机制是tau蛋白的沉积和 神经炎症在R 01的第2个周期中,我们使用PET评估了体内tau沉积。第3次循环中 我们将集中评估神经炎症和其他生物过程的作用。第一个目标 该基金的目的是利用第三代PET成像技术来表征大脑中神经炎症的模式。 生成配体11 C-ER 176,并确定神经炎症是否随时间变化, 临床疾病的严重程度。第二个目的是确定病理过程的生物标志物是否 从血浆测量,包括神经丝轻链、血浆神经胶质细胞酸性蛋白、tau,和 炎症生物标志物在nfvPPA中是异常的。我们还将评估这些生物标志物是否会发生变化 时间和临床疾病的严重程度相关。前两个目标将决定 神经炎症PET和血浆生物标志物是nfvPPA中有用的疾病生物标志物,我们将 确定这些措施是否可能是未来临床下降的有用的预后指标。我们的第三 目标是建立在前2个周期获得的知识基础上, 使用结构磁共振成像、弥散纤维束成像和静息状态功能磁共振成像测量的大脑异常, 与神经炎症PET和血浆生物标志物相关。这一目标将有助于模拟 这些生物学过程与大脑结构和功能中其他更确定的故障有关。到 为了实现这些目标,我们将招募50名nfvPPA患者,每名参与者将接受三个系列 一年一评。在每次评估中,患者将有一个神经和言语语言 评估,11 C-ER 176神经炎症PET和3 T磁共振成像扫描,包括 静息态功能性MRI和弥散张量成像序列。血液样本将从所有 两次访视的患者。还在R 01的第2个循环中采集了血样,因此采集了血浆 将在100名nfvPPA患者中测量生物标志物。我们还将招募50名认知正常的健康对照者 他们将接受相同的神经成像并提供血样这一更新意义重大,因为 所获得的结果对于理解nfvPPA的生物学和疾病传播的机制至关重要。 此外,这项工作也可能有助于为nfvPPA提供潜在的机制治疗靶点,并建立 用于预后的疾病生物标志物以及用于nfvPPA患者的未来研究和临床试验。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
In Vivo Imaging and Autoradiography in a Case of Autopsy-Confirmed Pick Disease.
一例尸检确诊的皮克病病例的体内成像和放射自显影。
  • DOI:
    10.1212/cpj.0000000000000755
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Utianski,ReneL;Schwarz,ChristopherG;Murray,MelissaE;Tranovich,JessicaF;Scott,NancyE;Lowe,ValJ;Whitwell,JenniferL;Josephs,KeithA
  • 通讯作者:
    Josephs,KeithA
Assessing Change in Communication Limitations in Primary Progressive Apraxia of Speech and Aphasia: A 1-Year Follow-Up Study.
评估原发性进行性言语失用和失语症的沟通限制变化:一项为期一年的随访研究。
  • DOI:
    10.1044/2021_ajslp-20-00402
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Utianski,ReneL;Martin,PeterR;Duffy,JosephR;Botha,Hugo;Clark,HeatherM;Josephs,KeithA
  • 通讯作者:
    Josephs,KeithA
Diffusion tensor imaging-based multi-fiber tracking reconstructions can regionally differentiate phonetic versus prosodic subtypes of progressive apraxia of speech.
基于扩散张量成像的多纤维跟踪重建可以在区域上区分进行性言语失用的语音亚型和韵律亚型。
Electroencephalography in Primary Progressive Aphasia and Apraxia of Speech.
原发性进行性失语症和言语失用症的脑电图。
  • DOI:
    10.1080/02687038.2018.1545991
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    2
  • 作者:
    Utianski,ReneL;Caviness,JohnN;Worrell,GregoryA;Duffy,JosephR;Clark,HeatherM;Machulda,MaryM;Whitwell,JenniferL;Josephs,KeithA
  • 通讯作者:
    Josephs,KeithA
Communication Limitations in Patients With Progressive Apraxia of Speech and Aphasia.
进行性言语失用和失语症患者的沟通限制。
  • DOI:
    10.1044/2020_ajslp-20-00012
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Utianski,ReneL;Clark,HeatherM;Duffy,JosephR;Botha,Hugo;Whitwell,JenniferL;Josephs,KeithA
  • 通讯作者:
    Josephs,KeithA
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Jennifer Louise Whitwell其他文献

Jennifer Louise Whitwell的其他文献

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{{ truncateString('Jennifer Louise Whitwell', 18)}}的其他基金

Molecular and structural imaging in atypical Alzheimer's disease: a longitudinal study
非典型阿尔茨海默病的分子和结构成像:一项纵向研究
  • 批准号:
    10605186
  • 财政年份:
    2016
  • 资助金额:
    $ 69.94万
  • 项目类别:
Molecular and structural imaging in atypical Alzheimer's disease: a longitudinal study
非典型阿尔茨海默病的分子和结构成像:一项纵向研究
  • 批准号:
    9889014
  • 财政年份:
    2016
  • 资助金额:
    $ 69.94万
  • 项目类别:
Molecular and structural imaging in atypical Alzheimer's disease: a longitudinal study
非典型阿尔茨海默病的分子和结构成像:一项纵向研究
  • 批准号:
    10372031
  • 财政年份:
    2016
  • 资助金额:
    $ 69.94万
  • 项目类别:
Molecular and structural imaging in atypical Alzheimer's disease: a longitudinal study
非典型阿尔茨海默病的分子和结构成像:一项纵向研究
  • 批准号:
    9104818
  • 财政年份:
    2016
  • 资助金额:
    $ 69.94万
  • 项目类别:
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:
    8499542
  • 财政年份:
    2013
  • 资助金额:
    $ 69.94万
  • 项目类别:
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:
    10436959
  • 财政年份:
    2013
  • 资助金额:
    $ 69.94万
  • 项目类别:
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
  • 财政年份:
    2013
  • 资助金额:
    $ 69.94万
  • 项目类别:
Longitudinal multi-modality imaging in progressive apraxia of speech (Diversity Supplement)
进行性言语失用的纵向多模态成像(多样性补充)
  • 批准号:
    10590477
  • 财政年份:
    2013
  • 资助金额:
    $ 69.94万
  • 项目类别:
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:
    10200748
  • 财政年份:
    2013
  • 资助金额:
    $ 69.94万
  • 项目类别:
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
  • 财政年份:
    2013
  • 资助金额:
    $ 69.94万
  • 项目类别:

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Bilingualism as a cognitive reserve factor: the behavioral and neural underpinnings of cognitive control in bilingual patients with aphasia
双语作为认知储备因素:双语失语症患者认知控制的行为和神经基础
  • 批准号:
    10824767
  • 财政年份:
    2024
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    $ 69.94万
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Neurocognitive Mechanisms of Sentence Production Impairment in Aphasia
失语症句子产生障碍的神经认知机制
  • 批准号:
    10735595
  • 财政年份:
    2023
  • 资助金额:
    $ 69.94万
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Characterising and predicting apraxic deficits in patients with chronic aphasia caused by left hemisphere stroke
左半球卒中引起的慢性失语症患者的失语症特征和预测
  • 批准号:
    MR/W030268/1
  • 财政年份:
    2023
  • 资助金额:
    $ 69.94万
  • 项目类别:
    Research Grant
Neural Mechanisms of Song vs Speech Production: Insights from Aphasia and Intracranial Recording
歌曲与言语产生的神经机制:失语症和颅内记录的见解
  • 批准号:
    10648716
  • 财政年份:
    2023
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    $ 69.94万
  • 项目类别:
Functional anomaly mapping of aphasia recovery
失语症恢复的功能异常图谱
  • 批准号:
    10837812
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    2023
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    $ 69.94万
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Computational modeling of language impairment and control in bilingual individuals with post-stroke aphasia and neurodegenerative disorders
中风后失语症和神经退行性疾病双语个体语言障碍和控制的计算模型
  • 批准号:
    10680656
  • 财政年份:
    2023
  • 资助金额:
    $ 69.94万
  • 项目类别:
Toward Personalized Prognosis and Outcomes in Primary Progressive Aphasia
原发性进行性失语症的个性化预后和结果
  • 批准号:
    10634041
  • 财政年份:
    2023
  • 资助金额:
    $ 69.94万
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Exercising language: Behavioral and neurophysiological changes after high-intensity exercise training in post-stroke aphasia.
运动语言:中风后失语症高强度运动训练后的行为和神经生理变化。
  • 批准号:
    10862024
  • 财政年份:
    2023
  • 资助金额:
    $ 69.94万
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Transactional Success in the Texting Exchanges of People with Aphasia
失语症患者短信交流的交易成功
  • 批准号:
    10730224
  • 财政年份:
    2023
  • 资助金额:
    $ 69.94万
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数学和失语症的神经基础
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    10606120
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