Successful aging without cognitive decline (SA) is apparent in those who escape age-related illnesses, such as cardiovascular disease and dementia. To determine whether there are protective genotypes that increase the probability of successful cognitive aging, a genome-wide screen was conducted on subjects who were 85 years of older, had MMSE scores >26, and had no major illnesses. SNP 500K microarrays were used. The data from the microarrays was analyzed versus that from Alzheimer's patients. Three SNPs in the gene for the low density lipoprotein receptor-related protein 1B (LRP1B) had significant P values, after Bonferroni correction. Additional SNPs were analyzed in this very large gene. Haplotypes in intron 18 were significant for successful aging versus Alzheimer's patients; those haplotypes were not significant when Alzheimer's patients versus CEPH controls were analyzed. These results suggest that haplotypes in the gene LRP1B are significant/protective for successful aging without cognitive decline. © 2009 Wiley-Liss, Inc.