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

Rosvall, Lina; Rizzuto, Debora; Wang, Hui-Xin; Winblad, Bengt; Graff, Caroline; Fratiglioni, Laura

doi:10.1016/j.neurobiolaging.2007.12.003

« Previous Next »Neurobiology of Aging
Volume 30, Issue 10 , Pages 1545-1551, October 2009

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

Lina Rosvall
- Aging Research Center, Karolinska Institutet and Stockholm Gerontology Research Center, SE-11330, Stockholm, Sweden
- Karolinska Institutet, Department NVS, KI-Alzheimer Disease Research Center, SE-14186, Stockholm, Sweden
- The authors contributed equally to this work.
- Corresponding author at: KI Alzheimer Disease Research Center, Department of Neurobiology, Health Care Sciences and Society, Karolinska Institutet, Novum 5th Floor, Karolinska University Hospital, 14157 Huddinge, Sweden. Tel.: +46 8 5858 36 01; fax: +46 8 5858 36 45.
Debora Rizzuto
- Aging Research Center, Karolinska Institutet and Stockholm Gerontology Research Center, SE-11330, Stockholm, Sweden
- The authors contributed equally to this work.
Hui-Xin Wang
- Aging Research Center, Karolinska Institutet and Stockholm Gerontology Research Center, SE-11330, Stockholm, Sweden
Bengt Winblad
- Karolinska Institutet, Department NVS, KI-Alzheimer Disease Research Center, SE-14186, Stockholm, Sweden
Caroline Graff
- Karolinska Institutet, Department NVS, KI-Alzheimer Disease Research Center, SE-14186, Stockholm, Sweden
Laura Fratiglioni
- Aging Research Center, Karolinska Institutet and Stockholm Gerontology Research Center, SE-11330, Stockholm, Sweden

Received 15 October 2007; received in revised form 3 December 2007; accepted 5 December 2007. published online 31 January 2008.

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.