Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors

确定脑铁、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β蛋白(Aβ)的积累 和磷酸-tau蛋白。然而，相当大比例的AD病理患者 临床上没有AD，说明有其他因素的贡献。新的体内测量方法是 需要跟踪导致AD相关认知功能下降的其他因素。渐增 有证据表明，与年龄相关的脑铁积累及其相关因素有助于 记忆力的表现形式下降了。我们最近的神经成像结果表明， 用活体定量磁化率图(QSM)测量的脑铁浓度是 与大脑记忆网络内的连接不良相关。这项提案旨在确定 基于QSM的铁浓度与神经认知功能改变之间的关系 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、炎症标记物对认知功能的影响。最后，我们将测试 富含抗氧化剂的饮食可能会减缓大脑中铁的积累。我们 建议使用神经成像方法研究140名健康的老年人，包括功能磁共振成像和 脑脊液和血浆Aβ、p-tau、t-tau和炎症标志物的测定。 其他结构性神经成像措施将包括区域体积、FLAIR成像 用于WMH体积的量化和弥散张量成像 区域分布的脑白质连通性。参与者的子集将完成 大约3年后进行相同的脑脊液和影像检查。我们的目标是确定(1)影响 基于QSM的铁信号在支持认知的功能和结构大脑网络上的研究； (2)脑铁、炎症标志物、AD病理与认知功能的关系 下降；(3)大脑铁的修饰物或其对认知的影响。我们将检验假设 基于QSM的大脑铁含量高与记忆电路中的低连接性有关 独立于AD病理，但随着时间的推移可能与AD协同作用。我们 还将检验储备因素将抵消脑铁对人体健康影响的假设 通过大脑维持机制或可塑性功能脑实现的认知功能 一些老年人的大规模脑功能网络的重组。

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.