Linking Connectomics to Biochemical Trajectories of Aging: How the Human Brain Ages Differentially in Key Regions of the Default Mode Network

项目摘要 这个项目的最终目标是获得关于代谢机制的顺序和性质的知识 从健康的人脑老化到与以下相关的病理过程 阿尔茨海默病，并将这种顺序与年龄相关的连接性、结构和 微观结构。第一步将是找出神经化学浓度的轨迹是否超过 后扣带回皮质(PCC)和额叶皮质(FC)的年龄跨度相似，或者 该地区的进步年龄比另一个地区更早。PCC和FC是关键的功能连接系统 在默认模式网络(DMN)内，这是与衰老和 阿尔茨海默氏症。我们的假设是，早期表现出恶化迹象的额叶皮质(FC) 在健康老龄化期间，将证明与年龄相关的神经化学改变发生在比 后扣带回皮质(PCC)，在PCC中与阿尔茨海默病相关的病理将是 神经化学特征的改变就是证据。下一步将是找出 神经化学先于或跟随着大脑功能、结构和微结构变化的轨迹。这个 该项目还将允许确定神经化学浓度和核磁共振结果的组合 可以有效地用于区分健康衰老和阿尔茨海默病。基因和基因的影响 对所有这些现象的健康因素也将进行探讨。这项研究旨在利用 最先进的成像数据将存在于国家人类衰老连接组项目(Hcpa)中 以及明尼苏达州阿尔茨海默氏症连接体项目(MACP)。基于图像的详细功能信息， 将从完全相同的FC和PCC的连接体图像中提取结构和微观结构 感兴趣的体积作为磁共振(MR)谱将从测量。一台强大的磁共振扫描仪将 用于检测不常见的神经化学物质，即抗氧化剂抗坏血酸和推定的 髓鞘形成的指示物磷酸乙醇胺，以及神经胶质标记物肌醇， 膜周转胆碱和神经递质谷氨酸。人类群体是 研究设计。衰老将在36岁到89岁之间进行研究，这些人都是已知的 认知健康，没有早期阿尔茨海默病的证据。阿尔茨海默病将在#年进行研究 具有高度临床和代谢特征的患者。早期的阿尔茨海默氏症将是 研究对象是那些经过神经心理和神经学检查看起来很健康的老年人，但 有阳性的淀粉样蛋白PET成像结果。

Project Summary The ultimate goal of this project is to gain knowledge about the order and nature of metabolic mechanisms that underlie the shift from healthy human brain aging to the pathological processes that are associated with Alzheimer's disease, and to relate such order to age-associated alterations in connectivity, structure and microstructure. The first step will be to find out whether the trajectories of neurochemical concentrations over the age span are similar among the posterior cingulate cortex (PCC) and the frontal cortex (FC), or if one region progresses at a younger age than the other. The PCC and FC are key functionally connected systems within the default mode network (DMN), which is one of the most relevant brain networks for aging and Alzheimer's disease. Our hypothesis is that the frontal cortex (FC), which shows signs of deterioration early during healthy aging will evidence age-associated alterations in neurochemistry at a younger age than the posterior cingulate cortex (PCC), and the pathology associated with Alzheimer's disease in the PCC will be evidenced by an altered neurochemical profile. The next step will be to find out whether the trajectory of neurochemistry precedes or follows trajectories of functional, structural and microstructural brain changes. The project will also allow determining whether a combination of neurochemical concentrations and MRI outcomes can be effectively used to distinguish healthy aging from Alzheimer's' disease. The influence of genetic and health factors on all of these phenomena will also be explored. This study is designed to take advantage of state-of-the art imaging data that will be extant within the national human connectome project on aging (HCPA) and the Minnesota Alzheimer's connectome project (MACP). Detailed image-based information on function, structure and microstructure will be extracted from the connectome images from the exact same FC and PCC volumes of interest as magnetic resonance (MR) spectra will be measured from. A powerful MR scanner will be used to detect neurochemicals that are not usually seen, i.e., the antioxidant ascorbate and the putative indicator of myelination phosphorylethanolamine, as well as the glial marker myo-inositol, the marker of membrane turnover choline, and the neurotransmitter glutamate. The human cohorts are key aspects of the study design. Aging will be studied over the range 36 to 89 years old in people who are all known to be cognitively healthy and free of evidence of incipient Alzheimer's disease. Alzheimer's disease will be studied in patients who have been highly characterized clinically and metabolically. Incipient Alzheimer's disease will be studied in older adults who appear to be healthy upon neuropsychological and neurological examination, but have positive amyloid PET imaging outcomes.