Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors

识别脑铁、神经认知网络和保护因素之间的关联

基本信息

  • 批准号:
    10579909
  • 负责人:
  • 金额:
    $ 53.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-05-01 至 2026-02-28
  • 项目状态:
    未结题

项目摘要

Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors Alzheimer’s disease (AD) involves accumulation of pathological levels of amyloid-beta (Aβ) and phospho-tau proteins. However, a significant proportion of individuals with AD pathology do not have clinical AD, indicating contributions of other factors. Novel in-vivo measures are required to track other factors contributing to AD-related cognitive declines. Increasing evidence suggests that age-related accumulation of brain iron and its correlates contribute to the manifestation of memory declines. Our recent neuroimaging results suggest that high brain iron concentration, measured with in vivo quantitative susceptibility mapping (QSM), is associated poor connectivity within brain memory networks. This proposal seeks to identify associations between QSM-based iron concentration and neurocognitive changes toward a goal of improving AD biomarkers. We will also define the interplay between QSM-based iron signal, AD pathology, inflammatory markers on cognitive declines. Finally, we will test the possibility that brain iron accumulation may be slowed by an antioxidant rich diet. We propose to study 140 healthy older adults using neuroimaging measures including fMRI and QSM, measures of CSF and plasma Aβ, p-tau and t-tau and inflammatory markers. Additional structural neuroimaging measures will include regional volumes, FLAIR imaging for quantification of WMH volumes and diffusion tensor imaging for quantification of regionally distributed white matter connectivity. A subset of participants will be complete the same CSF and imaging measures approximately 3 years later. We aim to identify (1) effects of QSM-based iron signal on functional and structural brain networks supporting cognition; (2) associations between brain iron, inflammatory markers, AD pathology and cognitive declines and; (3) modifiers of brain iron or its effects on cognition. We will test hypotheses that high QSM-based brain iron is associated with low connectivity in memory circuits independently of AD pathology but may and synergistically interacts with AD over time. We will also test the hypothesis that reserve factors will offset the effects of brain iron on cognitive functions via mechanisms of brain maintenance or plastic functional brain reorganization of large-scale brain functional networks in some older adults.
识别脑铁、神经认知网络和 保护因素 阿尔茨海默病 (AD) 涉及病理水平的淀粉样蛋白 - β (Aβ) 的积累 和磷酸 tau 蛋白。然而,很大一部分患有 AD 病理的个体 没有临床AD,表明有其他因素的贡献。新颖的体内措施是 需要跟踪导致 AD 相关认知能力下降的其他因素。增加 有证据表明,与年龄相关的脑铁及其相关物的积累有助于 记忆力下降的表现。我们最近的神经影像学结果表明,高 通过体内定量磁化率图 (QSM) 测量的脑铁浓度为 大脑记忆网络内的连通性较差。该提案旨在确定 基于 QSM 的铁浓度与神经认知变化之间的关联 改善 AD 生物标志物的目标。我们还将定义基于 QSM 的铁之间的相互作用 信号、AD 病理学、认知能力下降的炎症标志物。最后,我们将测试 富含抗氧化剂的饮食可能会减缓脑铁积累的可能性。我们 提议使用神经影像学方法(包括功能磁共振成像和 QSM、CSF 和血浆 Aβ、p-tau 和 t-tau 以及炎症标记物的测量。 其他结构神经影像测量将包括区域体积、FLAIR 成像 用于 WMH 体积的量化和扩散张量成像的量化 区域分布的白质连接。一部分参与者将完成 大约 3 年后进行相同的脑脊液和影像学测量。我们的目标是确定 (1) 影响 基于 QSM 的铁信号对支持认知的功能和结构大脑网络的影响; (2)脑铁、炎症标志物、AD病理和认知之间的关联 拒绝并且; (3)脑铁调节剂或其对认知的影响。我们将测试假设 基于 QSM 的高脑铁与记忆回路的低连接性有关 独立于 AD 病理学,但随着时间的推移可能与 AD 协同相互作用。我们 还将检验储备因子将抵消脑铁对大脑的影响的假设 通过大脑维护机制或可塑性功能大脑实现认知功能 一些老年人大规模大脑功能网络的重组。

项目成果

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BRIAN Timothy GOLD其他文献

BRIAN Timothy GOLD的其他文献

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{{ truncateString('BRIAN Timothy GOLD', 18)}}的其他基金

Reduced BBB Water Exchange as a Preclinical Biomarker of Small Vessel Disease
BBB 水交换减少作为小血管疾病的临床前生物标志物
  • 批准号:
    10369462
  • 财政年份:
    2022
  • 资助金额:
    $ 53.27万
  • 项目类别:
Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors
识别脑铁、神经认知网络和保护因素之间的关联
  • 批准号:
    10206402
  • 财政年份:
    2021
  • 资助金额:
    $ 53.27万
  • 项目类别:
Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors
识别脑铁、神经认知网络和保护因素之间的关联
  • 批准号:
    10395546
  • 财政年份:
    2021
  • 资助金额:
    $ 53.27万
  • 项目类别:
Contributions of Alzheimer's Pathology and Cerebrovascular Factors to Cognitive Aging
阿尔茨海默病病理学和脑血管因素对认知衰老的影响
  • 批准号:
    9448188
  • 财政年份:
    2017
  • 资助金额:
    $ 53.27万
  • 项目类别:
The effects of bilingualism on age-related cognitive and neurobiological declines
双语对与年龄相关的认知和神经生物学衰退的影响
  • 批准号:
    7729395
  • 财政年份:
    2009
  • 资助金额:
    $ 53.27万
  • 项目类别:
The effects of bilingualism on age-related cognitive and neurobiological declines
双语对与年龄相关的认知和神经生物学衰退的影响
  • 批准号:
    8134817
  • 财政年份:
    2009
  • 资助金额:
    $ 53.27万
  • 项目类别:
The effects of bilingualism on age-related cognitive and neurobiological declines
双语对与年龄相关的认知和神经生物学衰退的影响
  • 批准号:
    8516420
  • 财政年份:
    2009
  • 资助金额:
    $ 53.27万
  • 项目类别:
The effects of bilingualism on age-related cognitive and neurobiological declines
双语对与年龄相关的认知和神经生物学衰退的影响
  • 批准号:
    8316218
  • 财政年份:
    2009
  • 资助金额:
    $ 53.27万
  • 项目类别:
The effects of bilingualism on age-related cognitive and neurobiological declines
双语对与年龄相关的认知和神经生物学衰退的影响
  • 批准号:
    7930649
  • 财政年份:
    2009
  • 资助金额:
    $ 53.27万
  • 项目类别:
Neural Substrates of Component Lexical Semantic Processes
成分词汇语义过程的神经基础
  • 批准号:
    7197997
  • 财政年份:
    2006
  • 资助金额:
    $ 53.27万
  • 项目类别:
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