PURPOSE: Multiple studies have reported a positive association between missing teeth and cognitive impairment. While some authors have postulated causal mechanisms, existing designs preclude assessing this. METHODS: We sought evidence of a causal effect of missing teeth on early-onset cognitive impairment in a natural experiment, using differential exposure to fluoridated water during critical childhood years (ages 5-20 years) in England as the instrument. We coded missing teeth from 0 (≤ 12 missing) to 3 (all missing) and measured the association with cognitive impairment in the English Longitudinal Study of Ageing data (2014-5), covering 4958 persons aged 50-70 years. RESULTS: We first replicated previous evidence of the strongly positive association of missing teeth with cognitive impairment (β = 0.25 [0.11, 0.39]), after adjusting for socio-demographic covariates, such as age, gender, education, and wealth. Using an instrumental variable design, we found that childhood exposure to water fluoridation was strongly associated with fewer missing teeth, with being exposed to fluoridated water during childhood (16 years) associated with a 0.96 reduction in the missing teeth scale (β = - 0.06 [- 0.10, - 0.02]). However, when using the instrumented measure of missing teeth, predicted by probability of fluoride exposure, we found that missing teeth no longer had an association with cognitive impairment (β = 1.48 [- 1.22, 4.17]), suggesting that previous oral health-cognitive impairment associations had unobserved confounding. CONCLUSIONS: Our findings are consistent with the possibility that unobserved confounding leads to the oft-observed association between missing teeth and early-onset cognitive impairment, suggesting that the relationship is spurious rather than causal.