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

摘要 认知储备指的是缓冲大脑病理的能力，包括在脑部疾病后发现的常见类型 诊断为阿尔茨海默病(如淀粉样斑块和神经原纤维)的人的大脑中的身体 纠缠)。我推测，储备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。最近，研究人员开始对储量进行实证调查 因为神经病理和大脑功能之间的差异，通过认知测试来衡量。研究 发现了不利的早期生活环境和晚年临床痴呆症之间的关系， 包括阿尔茨海默病和相关的痴呆症。然而，还不知道早年的有利生活是否 与较高的晚年生活储备或较低的神经病理水平有关。因为大脑的发展尤其是 在5岁以后，早期生活可能是认知储备的敏感期。我建议使用 四个独特的数据集，包含有关早期生活的社会环境、后来的生活认知测试和 来自不同地域研究人群的基于尸检的神经病理学测量：成人的变化 思想研究，火奴鲁鲁亚洲老龄化研究，宗教秩序研究，以及快速记忆和老龄化 项目。我测试了有利的早期生命环境，独立和协同的假设 具有成人社交优势的人，是与较大的晚年生活认知储备有关的，即使在存在显著 神经病理学。我将能够测试早期的生活环境是否与实际的认知水平有关 和神经病理学。我的人口学和流行病学背景，包括3年的博士后生涯 作为一名资深教员和5年的初级教员，我准备好在一名 该团队反映了拟议研究的领导力和神经流行病学方面的领先专家， 神经病理学，认知测量，以及社会和生活过程流行病学的整合。建议数 在这个项目中的培训和研究经验将是建立在分析的基础上不可或缺的 认知结果和对痴呆症的适应能力，并增强我现有生活技能的体验 课程和老龄化流行病学，这将使我能够领导未来的项目，在这些领域的交叉。

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.