Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk

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.