Studies suggest that individuals who are at increased risk for Alzheimer disease (AD) in late life differ on measures of cognition, linguistic performance, and brain metabolism in earlier adult life compared with those with lower risk of this illness. The present study was undertaken to determine whether smaller head circumference (HC), a predictor of AD in late life, could influence educational attainment earlier in life, specifically among individuals at increased risk for AD. Data from the Nun Study, a longitudinal clinicopathologic study of dementia, were analyzed using logistic regression to assess the association between HC and attainment of less than a bachelor's degree. Modification of this association was studied by comparing those with and without evidence of increased AD risk, including possession of apolipoprotein E (APOE)-epsilon 4 alleles, occurrence of dementia before death, and satisfaction of AD neuropathologic criteria at autopsy. Small HC was associated with lower educational attainment in those carrying an APOE-epsilon 4 allele [odds ratio (OR)=6.27, 1.21 to 32.48], those who became demented (OR=3.23, 1.27 to 8.21), and those who fulfilled AD neuropathologic criteria (OR=5.03, 1.29 to 19.66), but not in those without these characteristics. These findings suggest that small HC limits educational attainment only among individuals who have greater risk of AD owing to their APOE genotype or who are destined to develop this illness later in life.