This proposal seeks to understand the impact of interactions between genetic risk and social environments at various stages in the life course on genitive decline and Alzheimer?s disease and related dementias (ADRD). Under the guidance of primary mentors Drs. Victor Henderson and Maria Glymour, the training and research plan will build upon Dr. Harrati?s expertise in biodemography and sociogenomics to prepare her for an independent career that integrates social science, genetics, and lifecourse epidemiology into the study of ADRD risk. Dr. Harrati will pursue a program of training at Stanford University, in conjunction with the University of California, San Francisco, that will advance her knowledge and skills in (1) enhanced knowledge of the genetic architecture of Alzheimer?s disease and advances in the analysis of molecular genetic data, (2) methods of longitudinal analysis and analysis of cumulative exposures, (3) clinical assessments of Alzheimer?s disease and (4) use of administrative data linkages for the study of ADRD. The proposed research plan will capitalize on a 60 year-long longitudinal social and health survey spanning birth through age 72 (n=~9,000). The Wisconsin Longitudinal Study (WLS) has a number of unique and important advantages for this proposal: a family design that allow for better controls of unobserved family environments; detailed measures of adolescent cognition; school data from administrative school district records; linkage to individual 1940 Census records (the year of birth for cohort members); longitudinal job histories, rich, longitudinal, neurocognitive assessments; linkage to respondents? Medicare data; and genotype data for cohort members and their siblings, allowing for more power to detect genetic associations. WLS was recently awarded an NIA R01 award to study dementia onset, which Dr. Harrati will use as the starting point for her eventual R01 application. The proposal will explore the role of three important social exposures: early-life family environments, school quality in high school, and job demand at mid-life and how they each moderate genetic risk of ADRD. This proposal seeks to address some of the methodological challenges inherent in studies of cognitive aging? that of recall bias?by using the WLS survey data that were collected contemporaneously from 1957 on and linkages to administrative data. Results from this research program may shed light on the social resources and risk factors that moderate biological risk of ADRD. This evidence can help identify strategies most likely to reduce the population burden of ADRD, as well as the disparities therein.
Little is known about how social environments in infancy, childhood, and adulthood accumulate across the lifecourse and interact with genetic risk to inform late-life ADRD risk. The result of this project will quantify how genetic risk of ADRD is moderated by i) early-life family environments, ii) school quality, and iii) job demand.