The authors investigated whether cognitive function may be used as an endophenotype for longevity by assessing the cognitive performance of a family-based cohort consisting of 1380 individuals from 283 families recruited for exceptional survival in field centers in Boston, New York, Pittsburgh, and Denmark. Cognitive performance was assessed in the combined offspring of the Long Life Family Study (LLFS) probands and their LLFS siblings as compared with their spouses' cognitive performance. Our results indicate that the combined offspring of the LLFS probands and their siblings achieve significantly higher scores on both digit forward and backward tasks (p = 5 10(-5) and p = 8 10(-4) respectively) as well as on a verbal fluency task (p = 0.008) when compared with their spouse controls. No differences between groups were found for the other cognitive tests assessed. We conclude that LLFS family members in the offspring generation demonstrate significantly better performance on multiple tasks requiring attention, working memory, and semantic processing when compared with individuals without a family history of exceptional survival, suggesting that cognitive performance may serve as an important endophenotype for longevity.