An ongoing longitudinal study in Maracaibo, Venezuela, examined the interaction between apolipoprotein E (APOE) genotypes and Alzheimer's disease (AD) and vascular dementia (VD), evaluating age and gender as potential modifiers of risk. Overall, carriers of at least one epsilon4 allele were at higher risk for AD, not for VD; however, the risk was significant only for subjects older than 65, and it increased 10-fold in subjects older than 85. The risk of AD conferred by APOE-epsilon4, adjusted for age and stratified by gender, was significant only for women. No association was found between the epsilon-2 allele and AD or VD. The results support the notions that APOE-epsilon4 is relevant for late-onset, not early onset AD, and that age and gender act as modulators of this association.