Does selective survival before study enrolment attenuate estimated effects of education on rate of cognitive decline in older adults? A simulation approach for quantifying survival bias in life course epidemiology

Background: The relationship between education and late-life cognitive decline is controversial. Selective survival between early life, when education is typically completed, and late life, when cognitive ageing studies take place, could attenuate effect estimates. Methods: We quantified potential survival bias (collider-stratification bias) in estimation of the effect of education on late-life cognitive decline by simulating hypothetical cohorts of 20-year-olds and applying cumulative mortality from US life tables. For each of four causal scenarios (2000 replications each), we compared the estimated versus causal effect of education on cognitive decline over 9 years, starting at age 60, 75 or 90 in random samples of n ¼ 2000 people who survived to each age. Results: Effects of education on cognitive decline were underestimated when both education and U, another determinant of cognitive decline, influenced mortality (collider-stratification bias). The magnitude of bias was sensitive to the magnitude of the effect of U on cognitive decline and whether there was a multiplicative interaction between education and U on mortality. For example, when there was a multiplicative interaction between education and U on mortality, 95% confidence interval coverage of the causal effect ranged from 83.4% to 50.4% at age 60 and 25.8% to 0.2% at age 90. Conclusions: Selective survival could lead to underestimation of effects of education on late-life cognitive decline. Our simulations map survival bias to testable assumptions about underlying causal structures.