title: Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco. Electronic address: Thu.Nguyen@ucsf.edu.
authors.forename: Thu T
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA; Department of Epidemiology, Harvard School of Public Health, Boston, MA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Tchetgen Tchetgen
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawachi
authors.affiliation: 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.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Gilman
authors.affiliation: Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco.
authors.forename: Stefan
authors.initials: S
authors.lastname: Walter
authors.affiliation: Harvard Center for Population and Development Studies, Harvard School of Public Health, Cambridge, MA.
authors.forename: Sze Y
authors.initials: SY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Manly
authors.affiliation: Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco.
authors.forename: M Maria
authors.initials: MM
authors.lastname: Glymour
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D004505:Education, Nonprofessional / Q000331:legislation & jurisprudence; D004522:Educational Status; D005260:Female; D020022:Genetic Predisposition to Disease; D006306:Health Surveys; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012307:Risk Factors; D012574:Schools / Q000331:legislation & jurisprudence; D014481:United States
keywords: Causal inference; Dementia; Education; Instrumental variables; Unmeasured confounding