APOE-related mortality: effect of dementia, cardiovascular disease and gender

Allele-frequency comparisons between younger and older populations suggest an effect of apolipoprotein E gene (APOE) on mortality, not consistently confirmed by longitudinal data. Our aim was to assess the effect of APOE on survival taking into account the possible contribution of Alzheimer's disease, other dementias, ischemic heart- and cerebrovascular disease (IHCD). In a community-based longitudinal study, the Kungsholmen Project, 75+ year-old individuals (n=1094) were examined, and followed for 18 years. An increased mortality-risk of 22% in those with the epsilon4 allele was detected; whereas a 28% decreased mortality-risk was detected in those with the epsilon2 allele compared to those with the epsilon3epsilon3 genotype. IHCD adjustment did not change the mortality-risk in those with the epsilon4 allele or the epsilon2 allele. Dementia accounted for the majority of the increased mortality-risk associated with the epsilon4 allele, but the protective effect of the epsilon2 allele remained. Both effects of the epsilon4 allele and the epsilon2 allele were strongly modified by gender. A 49% elevated risk for death in men was related to the epsilon4 allele, and a 36% decreased mortality-risk was found in women with the epsilon2 allele. These findings suggest different roles for the APOE alleles in survival by gender in old age.