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

Abstract 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 ɛ4 allele was detected; whereas a 28% decreased mortality-risk was detected in those with the ɛ2 allele compared to those with the ɛ3ɛ3 genotype. IHCD adjustment did not change the mortality-risk in those with the ɛ4 allele or the ɛ2 allele. Dementia accounted for the majority of the increased mortality-risk associated with the ɛ4 allele, but the protective effect of the ɛ2 allele remained. Both effects of the ɛ4 allele and the ɛ2 allele were strongly modified by gender. A 49% elevated risk for death in men was related to the ɛ4 allele, and a 36% decreased mortality-risk was found in women with the ɛ2 allele. These findings suggest different roles for the APOE alleles in survival by gender in old age.