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

 描述（由申请人提供）：认知储备是指缓冲脑病理的能力，包括在被诊断患有阿尔茨海默病的人的大脑中通常发现的类型（例如，淀粉样斑块和神经纤维缠结）。我假设，储备是一个关键原因，为什么一些老年人有正常的认知功能，尽管存在神经病理学。最近，研究人员已经开始实证研究储备作为神经病理学和大脑功能之间的差异，如认知测试所测量的。研究发现，不利的早期生活环境与晚年临床痴呆症（包括阿尔茨海默病和相关痴呆症）之间存在关系。然而，目前尚不清楚早期生活是否与更大的后期生活储备或更低水平的神经病理学本身有关。由于大脑发育在5岁时特别加速，因此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，包含信息的早期生活的社会环境，以后的生活认知测试，和基于尸检的神经病理学措施，从地理上不同的研究人群：成人的思想变化研究，檀香山亚洲老龄化研究，宗教秩序研究，和拉什记忆和衰老项目。我测试的假设，一个独立的早期生活环境，并与成人的社会优势协同作用，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认知和神经病理学的实际水平有关。我在人口学和流行病学方面的背景，包括3年的博士后研究员和5年的初级教员，使我准备好领导这些项目，在一个反映拟议研究领导力的团队的指导下，巴尔的摩的马里兰州大学神经病理学和流行病学的当地专家，认知测量分析的当地专家，也是整合社会和生命过程流行病学的领先专家。在这个项目中提出的培训和研究经验将是不可或缺的，在认知结果和抗痴呆能力的分析建立基础，并提高我在生命历程和老龄化流行病学的现有技能的经验，这将使我能够在这些领域的交叉点领导未来的项目。

 DESCRIPTION (provided by applicant): 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, local experts in neuropathology and epidemiology at the University of Maryland, Baltimore, a local expert in the analysis of cognitive measures, and a leading expert in 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.