Thu T Nguyen1, Eric J Tchetgen Tchetgen2, Ichiro Kawachi3, Stephen E Gilman4, Stefan Walter5, Sze Y Liu6, Jennifer J Manly7, M Maria Glymour5. 1. Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco. Electronic address: Thu.Nguyen@ucsf.edu. 2. Department of Biostatistics, Harvard School of Public Health, Boston, MA; Department of Epidemiology, Harvard School of Public Health, Boston, MA. 3. Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA. 4. Department of Epidemiology, Harvard School of Public Health, Boston, MA; Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA; Health Behavior Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD. 5. Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco. 6. Harvard Center for Population and Development Studies, Harvard School of Public Health, Cambridge, MA. 7. Department of Neurology, Sergievsky Center and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY.
Abstract
PURPOSE: Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies. METHODS: IV analyses in the Health and Retirement Study cohort (1998-2010) used two sets of instruments: (1) a genetic risk score constructed from three single-nucleotide polymorphisms (SNPs; n = 7981); and (2) compulsory schooling laws (CSLs) and state school characteristics (term length, student teacher ratios, and expenditures; n = 10,955). RESULTS: Using the genetic risk score as an IV, there was a 1.1% reduction in dementia risk per year of schooling (95% confidence interval, -2.4 to 0.02). Leveraging compulsory schooling laws and state school characteristics as IVs, there was a substantially larger protective effect (-9.5%; 95% confidence interval, -14.8 to -4.2). Analyses evaluating the plausibility of the IV assumptions indicated estimates derived from analyses relying on CSLs provide the best estimates of the causal effect of education. CONCLUSIONS: IV analyses suggest education is protective against risk of dementia in older adulthood.
PURPOSE: Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies. METHODS: IV analyses in the Health and Retirement Study cohort (1998-2010) used two sets of instruments: (1) a genetic risk score constructed from three single-nucleotide polymorphisms (SNPs; n = 7981); and (2) compulsory schooling laws (CSLs) and state school characteristics (term length, student teacher ratios, and expenditures; n = 10,955). RESULTS: Using the genetic risk score as an IV, there was a 1.1% reduction in dementia risk per year of schooling (95% confidence interval, -2.4 to 0.02). Leveraging compulsory schooling laws and state school characteristics as IVs, there was a substantially larger protective effect (-9.5%; 95% confidence interval, -14.8 to -4.2). Analyses evaluating the plausibility of the IV assumptions indicated estimates derived from analyses relying on CSLs provide the best estimates of the causal effect of education. CONCLUSIONS: IV analyses suggest education is protective against risk of dementia in older adulthood.
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