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

 描述(申请人提供)：认知储备是指对大脑病理的缓冲能力，包括在被诊断为阿尔茨海默病的人的大脑中常见的类型(例如淀粉样斑块和神经原纤维缠结)。我假设，储备是一些老年人尽管存在神经病理，但仍具有正常认知功能的关键原因。最近，研究人员已经开始通过认知测试对储备作为神经病理和大脑功能之间的差异进行实证研究。研究发现，不利的早期生活环境与晚年的临床痴呆症之间存在关系，包括阿尔茨海默病和相关的痴呆症。然而，目前尚不清楚早年的有利生活是否与更多的晚年生活储备或较低的神经病理水平有关。由于大脑发育在5岁时尤其加速，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，其中包含来自不同地理位置的研究人群的早期生活社会环境、晚年认知测试和基于尸检的神经病理测量的信息：成人思维变化研究、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。我测试了这样的假设，即一个有利的早期生活环境，独立于成年人的社交优势，并与成年人的社交优势协同作用，与更大的晚年认知储备有关，即使存在显著的神经病理。我还将能够测试早期生活环境是否与认知和神经病理的实际水平有关。我在人口学和流行病学方面的背景，包括3年的博士后和5年的初级教员，为我领导这些项目做好了准备，指导我的团队反映了拟议研究的领导力，巴尔的摩马里兰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，以及社会和生命过程流行病学整合的领先专家。该项目中拟议的培训和研究经验将是在分析认知结果和痴呆症复原力方面建立基础所不可或缺的，并加强我在生命历程和老龄化流行病学方面的现有技能的经验，使我能够领导未来这些领域的交叉项目。

 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.