Both leukocyte telomere length and the apolipoprotein epsilon 4 allele have been associated with mortality, cardiovascular disease, cognition, and dementia. The authors investigated whether leukocyte telomere length was associated with APOE genotype or cognitive abilities in the context of APOE genotype. The setting for this cross-sectional study was 427 nondemented individuals aged 41-81 yr. The authors found that epsilon 4 carriers overall exhibited significantly longer telomeres compared with non-carriers (difference of 268 bp, p = 0.001). This difference was greatest at the lower limit of the age span and nonsignificant at the upper limit, which translated into a significantly higher telomere attrition rate (p = 0.049) among epsilon 4 carriers (37 bp/years) compared with non-carriers (21 bp/year). Further, longer telomeres among epsilon 4 carriers significantly predicted worse performance on episodic memory tasks. No significant associations were found on tasks tapping semantic and visuospatial ability, or among epsilon 3/epsilon 3 carriers. In conclusion, APOE epsilon 4 carriers had longer telomeres compared with non-carriers, but higher rate of attrition. Among them, longer telomeres predicted worse performance on episodic memory tasks. These observations suggest that the epsilon 4 allele is associated with abnormal cell turnover of functional and possibly clinical significance.