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

将连接组学与衰老的生化轨迹联系起来：人脑默认模式网络关键区域的衰老方式如何差异

• 批准号: 9926788
• 负责人: Silvia Mangia
• 金额: $ 69.77万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926788
• 关键词: Adult; Advocate; Age; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Amyloid; Anisotropy; Antioxidants; Biochemical; Brain; Brain Chemistry; Brain region; Choline; Clinical; Cognitive; Communities; Data; Data Set; Deterioration; Development; Diffuse; Discipline; Elderly; Evaluation; Event; Functional disorder; Future; Genetic; Gliosis; Glutamates; Glycosylated hemoglobin A; Goals; Health; Human; Image; Inositol; Intervention; Knowledge; Link; Longevity; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Membrane; Metabolic; Minnesota; Monitor; Nature; Neurologic Examination; Neurologist; Neuropsychology; Neurotransmitters; Outcome; Oxidative Stress; Participant; Pathologic Processes; Pathology; Patients; Positron-Emission Tomography; Process; Research Design; Scanning; Site; Specialist; Structure; Subgroup; System; T2 weighted imaging; Techniques; Technology; Work; aging brain; apolipoprotein E-4; ascorbate; base; brain abnormalities; cingulate cortex; clinical phenotype; cohort; connectome; design; effective intervention; frontal lobe; gray matter; healthy aging; human data; indexing; interest; molecular phenotype; myelination; neurochemistry; neurotransmission; phosphoethanolamine; regional difference; response

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.

项目摘要 该项目的最终目标是获得有关代谢机制的顺序和性质的知识， 从健康的人类大脑衰老到与之相关的病理过程的转变 阿尔茨海默病，并将这种顺序与年龄相关的连接，结构和 微观结构第一步将是找出神经化学物质浓度的轨迹是否超过 年龄跨度在后扣带皮层（PCC）和额叶皮层（FC）之间是相似的，或者如果一个 一个区域比另一个区域在更小的年龄发展。PCC和FC是关键的功能连接系统 在默认模式网络（DMN）中，这是与衰老最相关的大脑网络之一， 老年痴呆症我们的假设是，额叶皮层（FC），其中显示出恶化的迹象，早期 在健康的老龄化过程中，将在比老年人更年轻的年龄证明与年龄相关的神经化学变化。 后扣带皮层（PCC），并且PCC中与阿尔茨海默病相关的病理学将是 神经化学成分的改变证明了这一点下一步将是找出 神经化学先于或跟随功能、结构和微结构脑变化的轨迹。的 该项目还将允许确定神经化学物质浓度和MRI结果的组合是否 可以有效地用于区分健康衰老和阿尔茨海默病。基因的影响， 此外，亦会探讨影响这些现象的健康因素。本研究旨在利用 国家人类连接体衰老项目（HCPA）中现存的最先进的成像数据 明尼苏达阿尔茨海默氏症连接体项目（MACP）基于图像的详细功能信息， 将从来自完全相同的FC和PCC的连接体图像中提取结构和微观结构 作为磁共振（MR）谱的感兴趣体积将从其测量。强大的MR扫描仪将 用于检测通常不常见的神经化学物质，即，抗氧化剂抗坏血酸和假定的 髓鞘形成磷酸乙醇胺的指示剂，以及神经胶质标记物肌醇， 膜更新胆碱和神经递质谷氨酸。人类队列是 研究设计.老化将在36至89岁的人群中进行研究，这些人群都是已知的 认知健康且无早期阿尔茨海默病的迹象。阿尔茨海默病将在 在临床和代谢方面具有高度特征的患者。早期的阿尔茨海默氏症 在老年人中进行了研究，这些老年人在神经心理学和神经学检查后似乎是健康的，但 淀粉样蛋白PET成像结果呈阳性。