Neural substrates of diffusion imaging in cognitively aging rhesus monkeys

7.抽象的。 识别和跟踪大脑成熟和衰老过程中发生的神经生物学变化的能力是 这不仅是我们理解认知的基础，也是临床研究的关键， 神经发育或神经退行性疾病，包括临床试验。虽然死后研究 提供的数据在局部组织学变化方面得到了很好的表征，但这些数据可能是有限的 由于它们的横截面性质和小样本量。相比之下，非侵入性体内成像允许 在更大的人群中收集纵向数据，是研究生命的更有力的工具 跨越大脑成熟和衰老的轨迹。 神经影像学的最新发展为影像学改变之间的关系提供了证据 和人类的认知老化。不幸的是，认知年龄的细胞基础是一个 这是一个有争议的主题，因此，现有成像措施的生物特异性尚未得到很好的确立。 更令人担忧的是，虽然旧的成像措施仍然缺乏彻底的验证，但新的“更具体”的措施 这些被不断引入临床研究的方法离验证更远了。过去 在资助期间，我们使用了大量的组织学，认知和成像遗留数据库， 认知老化的恒河猴，测试神经炎症和髓鞘变性发挥作用的假设， 研究人员还发现，神经影像学生物标志物可以反映这些生物过程。 我们建议进一步我们的工作在这个方向上，提出翻译实验，将包括1）。 获得新的、高分辨率的“人类连接组计划（HCP）”兼容的成像数据，2）。扩大我们 通过添加神经炎症和髓鞘特异性PET放射性配体进行神经成像，3）。发展神经影像学 轻度认知障碍的白色物质特异性生物标志物-阿尔茨海默病的危险因素，和4）。 研究衰老中性别差异的生物学基础。这是通过三个PI的协作实现的， 在MRI成像、形态测量学、神经解剖学、 免疫组织化学和认知老化，并将进一步促进通过获取和分析行为， 来自24只恒河猴（雌雄各半）、8只年轻成年猴（4 男4女）和16名老年人（男8女8，半数诊断为轻度认知障碍 （MCI））。 这项研究的结果将极大地影响我们对衰老过程的理解， 机制，并提供组织验证的成像措施，可应用于研究 正常的人类衰老以及中枢神经系统的许多神经发育和神经退行性疾病 神经系统

7. Abstract. The ability to identify and follow-up neurobiological changes that occur during brain maturation and aging is not only fundamental to our understanding of cognition, but is also crucial for clinical studies that focus on either neurodevelopmental or neurodegenerative disorders, including clinical trials. While post-mortem studies provide data that are well characterized in terms of localized histological changes, these data can be limited due to their cross sectional nature and small samples sizes. In contrast, non-invasive in vivo imaging allows for the collection of longitudinal data in much larger populations, and is a more powerful tool to investigate life span trajectories of brain maturation and aging. Recent developments in neuroimaging have provided evidence for the relationship between imaging changes and cognitive aging in monkeys, and humans. Unfortunately, the cellular underpinnings of cognitive age are a subject of debate and hence the biological specificity of available imaging measures is not well established. More alarming, while older imaging measures still lack thorough validation, newer “more specific” measures that are being constantly introduced into clinical research are even further from validation. Over the past funding period, we have worked with a large repository of histological, cognitive and imaging legacy data from cognitively aging rhesus monkeys, testing the hypothesis that neuroinflammation and myelin degeneration play crucial roles in cognitive aging, and that neuroimaging biomarkers can reflect those biological processes. We propose to further our work in this direction, by proposing translational experiments that will include 1). acquiring new, high resolution “Human Connectome Project (HCP)” compatible imaging data, 2). Expand our neuroimaging by adding neuroinflammation- and myelin-specific PET radioligands, 3). Develop neuroimaging white matter-specific biomarkers of mild cognitive impairment- a risk factor for Alzheimer’s disease, and 4). Investigate biological underpinnings of sex differences in aging. This is enabled by a collaboration of three PIs, with unique and complementary expertise in MRI imaging, morphometry, neuroanatomy, immunohistochemistry and cognitive aging, and will be further facilitated by acquiring and analyzing behavioral, imaging, blood and post mortem data from a cohort of 24 rhesus monkeys of both sexes, 8 young adults (4 males and 4 females) and 16 old adults (8 males and 8 females, half diagnosed with mild cognitive impairment (MCI)). The results of this proposed study will greatly impact our understanding of aging processes and their mechanisms and provide tissue validated understanding of imaging measures that can be applied to studies of normal human aging as well as many neurodevelopmental and neurodegenerative diseases of the central nervous system.