In the largest prospective cohort study to date we have found quite strong evidence that EEE is not importantly associated with subsequent risk of incident dementia. We also failed to replicate a previously reported interaction between APOE genotype and reproductive period. The precision of our null estimates for the hypothesised main effects of proxy indicators of EEE, observed consistently across diverse settings, exclude the possibility of other than trivial effects. The possible exception is premature ovarian failure, a rare exposure, with an upper confidence interval for the ASHR of 1.55, and with suggestive trends towards positive associations in some Latin American sites. While we did observe an association between greater parity and incident dementia, this seems unlikely to be mechanistically explained by cumulative EEE, since the impact of reproductive period on this pathway would be expected to be much greater. Of note, grand multiparity is linked to increased mortality from both diabetes and cardiovascular diseases.