Objective: To evaluate the cognitive reserve hypothesis by examining whether individuals of greater educational attainment have better cognitive function than individuals with less education in the presence of elevated fibrillar brain amyloid levels. Design, Setting, and Participants: Uptake of carbon 11-labeled Pittsburgh Compound B ([11C]PiB) was measured for participants assessed between August 15, 2003, and January 8, 2008, at the Washington University Alzheimer's Disease Research Center and diagnosed either as nondemented (n=161) or with dementia of the Alzheimer type (n=37). Multiple regression was used to determine whether [11C]PiB uptake interacted with level of educational attainment to predict cognitive function. Main Outcome Measures: Scores on the Clinical Dementia Rating sum of boxes, Mini-Mental State Examination, and Short Blessed Test and individual measures from a psychometric battery. Results: Uptake of [11C]PiB interacted with years of education in predicting scoresonthe Clinical Dementia Rating sum of boxes (P=.003), the Mini-Mental State Examination (P<.001), the Short Blessed Test (P=.03), and a measure of verbal abstract reasoning and conceptualization (P=.02) such that performance on these measures increased with increasing education for participants with elevated PiB uptake. Education was unrelated to global cognitive functioning scores among those with lower PiB uptake. Conclusion: The results support the hypothesis that cognitive reserve influences the association between Alzheimer disease pathological burden and cognition.