Functional imaging and neuropathological studies suggest that individuals with higher education have better cognitive performance at the same level of brain pathology than less educated subjects. No in vivo studies are available that directly test how education modifies the effect of structural pathology on cognition in Alzheimer's disease (AD). The present study therefore aimed to measure this effect using data from a large multi-center study. 270 patients with AD underwent cognitive testing using the Mini Mental State Examination (MMSE), apolipoprotein E (APOE) genotyping, and cerebral magnetic resonance imaging. A linear regression analysis was used to examine the relation of medial temporal lobe atrophy (MTA), as a proxy of AD pathology, to MMSE score, adjusting for age, gender, APOE, cerebrovascular disease, ethnicity, education, and disease duration. An interaction term for MTA and education was introduced to test the hypothesis that education modifies the effect of MTA on cognition. There was a significant inverse association between MTA and cognition. Most interestingly, the interaction term between education and MTA was significant suggesting that education modifies the relation of MTA to cognition. At any level of pathology, cognition remained higher for better educated individuals.