title: Apolipoprotein E ε4 allele interacts with sex and cognitive status to influence all-cause and cause-specific mortality in U.S. older adults.
abstract: OBJECTIVE
  To confirm associations of apolipoprotein E (ApoE) ε4 carrier status, sex, and time-dependent cognitive status with mortality risk and to investigate these joint effects of these associations in a cohort of community-dwelling U.S. adults.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  The Baltimore Longitudinal Study of Aging (BLSA).
  
  
  METHODS
  Of 3,047 BLSA participants aged 17 to 98 at first visit (60.1% male), 1,704 with complete ApoE genotype data were included, of whom 1,461 aged 50 and older with one or more visits were eligible.
  
  
  METHODS
  Time to death from all, cardiovascular, and noncardiovascular causes.
  
  
  RESULTS
  Probability of survival was lower for ApoE ε4 carriers, particularly those who were older. A Cox proportional hazards model for all-cause mortality yielded a hazard ratio (HR) for ApoE ε4 carrier versus noncarriers of 1.31 (95% confidence interval (CI) = 1.02-1.68). This association was also found for cardiovascular mortality. Time-dependent all-cause dementia (HR = 1.73, 95% CI = 1.33-2.26) and mild cognitive impairment (HR = 1.95, 95% CI = 1.42-2.67) increased all-cause mortality risk, associations that were also detected for noncardiovascular mortality. When individuals were free of cognitive impairment, a dose-response relationship with ε4 alleles was found for all-cause mortality (HR = 1.40, 95% CI = 0.94-2.07 for 1 ε4; HR = 2.61, 95% CI = 1.12-6.07 for 2 ε4). After onset of Alzheimer's disease (AD), carrying only one ε4 allele resulted in an approximately 77% greater all-cause mortality risk than in noncarriers. ApoE ε4 carrier status increased all-cause mortality risk in men and interacted with time-dependent AD to increase the risk of this outcome (relative excess risk due to interaction = 2.15, 95% CI = 1.22-3.07).
  
  
  CONCLUSIONS
  ApoE ε4 carrier status was found to increase all-cause and cardiovascular mortality risks and interacted with sex and time-dependent AD status to affect all-cause mortality.
authors.affiliation: National Institute on Aging, National Institutes of Health, Intramural Research Program, Baltimore, MD 21224, USA. baydounm@mail.nih.gov
authors.forename: May A
authors.initials: MA
authors.lastname: Beydoun
authors.forename: Hind A
authors.initials: HA
authors.lastname: Beydoun
authors.forename: Jay S
authors.initials: JS
authors.lastname: Kaufman
authors.forename: Yang
authors.initials: Y
authors.lastname: An
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.forename: Richard
authors.initials: R
authors.lastname: O'Brien
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000401:mortality; D053327:Apolipoprotein E4 / Q000235:genetics*; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics* / Q000401:mortality*; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016017:Odds Ratio; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4