Early life environment and later life dementia, cognition, neuropathology, and reserve

总结 认知储备是指对大脑病理学的缓冲能力，包括通常在 被诊断患有阿尔茨海默病的人的大脑中的死亡（例如，淀粉样斑块和神经原纤维 缠结）。我假设，保留是一些老年人具有正常认知功能的关键原因 尽管存在神经病理学。近年来，研究者开始对准备金进行实证研究 神经病理学和大脑功能之间的差异，如认知测试所测量的。研究 已经发现早期生活环境不利与晚年临床痴呆症之间的关系， 包括阿尔茨海默病和相关痴呆症。然而，目前还不清楚早期的生命是否 与更大的晚年储备或更低水平的神经病理学本身有关。因为大脑的发育 加速到5岁，早期生活可能是认知储备的敏感时期。我建议使用 四个独特的数据集，包含有关早期生活社会环境，后期生活认知测试和 来自地理上不同的研究人群的基于尸检的神经病理学测量： 思想研究，檀香山亚洲老龄化研究，宗教秩序研究，和匆忙的记忆和老化 项目我测试的假设，一个早期的生活环境，独立和协同 与成人的社会优势，与更大的晚年认知储备，即使在存在显着的 神经病理学我也将能够测试早期生活环境是否与实际认知水平有关 和神经病理学我在人口学和流行病学方面的背景，包括3年的博士后工作 研究员和5年的初级教员，准备我领导这些项目，在指导下， 该团队反映了拟议研究的领导力和神经流行病学的领先专家， 神经病理学、认知测量以及社会和生命过程流行病学的整合。拟议 在这个项目中的培训和研究经验将是建立分析基础的组成部分， 认知结果和对痴呆症的恢复力，并增强我现有生活技能的体验 课程和老龄化流行病学，这将使我能够在这些领域的交叉点领导未来的项目。

SUMMARY Cognitive reserve refers to the ability to buffer against brain pathology, including types commonly found post- mortem in the brains of people diagnosed with Alzheimer's disease (e.g., amyloid plaques and neurofibrillary tangles). I hypothesize that reserve is a key reason why some older adults have normal cognitive function despite the presence of neuropathology. Recently, researchers have begun to empirically investigate reserve as the discrepancy between neuropathology and brain function, as measured with cognitive tests. Studies have found a relationship between a disadvantaged early life environment and later life clinical dementia, including Alzheimer's disease and related dementias. However, it is not known if an advantaged early life is related to greater later life reserve or lower levels of neuropathology itself. As brain development is particularly accelerated through age 5 years, early life could be a sensitive period for cognitive reserve. I propose to use four unique datasets that contain information on early life social environment, later life cognitive tests, and autopsy-based neuropathology measures from geographically diverse study populations: the Adult Changes in Thought Study, the Honolulu Asia Aging Study, the Religious Orders Study, and the Rush Memory and Aging Project. I test the hypotheses that an advantaged early life environment, independently of and synergistically with adult social advantage, is related to greater later life cognitive reserve, even in the presence of significant neuropathology. I will be able to test also whether early life environment is related to actual levels of cognition and neuropathology. My background in demography and epidemiology, including 3 years as a postdoctoral fellow and 5 years as a junior faculty member, prepares me to lead these projects, under the guidance of a team that reflects the leadership of the proposed studies and leading experts in neurological epidemiology, neuropathology, cognitive measures, and the integration of social and life course epidemiology. The proposed training and research experiences in this project will be integral in building a foundation in the analysis of cognitive outcomes and resilience to dementia, and enhancing the experience of my existing skills in life course and aging epidemiology that will allow me to lead future projects at the intersection of these fields.