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

总结

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.