Apolipoprotein E genotype and mortality: Findings from the Cache County Study

Kathleen M. Hayden, Peter P. Zandi, Constantine G. Lyketsos, Jo Ann T. Tschanz, Maria C. Norton, Ara S. Khachaturian, Carl F. Pieper, Kathleen A. Welsh-Bohmer, John C.S. Breitner

Research output: Contribution to journalArticlepeer-review


OBJECTIVES: To evaluate the association between apolipoprotein E (apo E) ε4 and mortality, the population attributable risk for mortality with ε4, and relative contributions of cardiovascular disease (CVD) and Alzheimer's disease (AD). DESIGN: Population-based cohort study. SETTING: Community-based. PARTICIPANTS: Permanent residents of Cache County, Utah, aged 65 and older as of January 1, 1995. MEASUREMENTS: Participants were genotyped at the apo E locus using buccal-swab deoxyribonucleic acid. Cardiovascular health was ascertained using self- or proxy-report interviews at participants' residences. AD was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria. Utah Department of Vital Statistics quarterly reports were reviewed to identify participants who died. RESULTS: Crude evaluations showed nonsignificantly greater risk of death for ε2/2 (hazard ratio (HR) = 1.66, 95% confidence interval (CI) = 0.92-2.76) and ε3/4 (HR = 1.11, 95% CI = 0.97-1.26) genotypes and significantly greater risk for ε4/4 (HR= 1.48, 95% CI = 1.09-1.96). After adjustment for age, age2, sex, and education, risks increased to 1.98 (95% CI = 1.08-3.35), 1.28 (95% CI = 1.12-1.46), and 2.02 (95% CI= 1.47-2.71), respectively, compared with ε3/3 genotypes. Adjustment for presence of any CVD did not change the risk of death for ε3/4 and ε4/4. Adjustment for AD reduced the risk of death for ε3/4 (HR = 1.13, 95% CI = 0.99-1.30) and ε4/4 (HR = 1.59, 95% CI = 1.15-2.14). The population attributable risk of death for ε3/4 and ε4/4 genotypes combined is estimated at 9.6%. CONCLUSION: These findings suggested that the ε2/2, ε3/4, and ε4/4 genotypes have greater early mortality risks. Further analyses showed that AD partially mediates the association between ε3/4, ε4/4, and death.

Original languageEnglish (US)
Pages (from-to)935-942
Number of pages8
JournalJournal of the American Geriatrics Society
Issue number6
StatePublished - Jun 2005


  • Alzheimer's disease
  • Apolipoprotein E
  • Cardiovascular disease
  • Mortality

ASJC Scopus subject areas

  • Geriatrics and Gerontology


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