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Apolipoprotein E ε4 Allele Interacts with Sex and Cognitive Status to Influence All‐Cause and Cause‐Specific Mortality in U.S. Older Adults
Author(s) -
Beydoun May A.,
Beydoun Hind A.,
Kaufman Jay S.,
An Yang,
Resnick Susan M.,
O'Brien Richard,
Ferrucci Luigi,
Zonderman Alan B.
Publication year - 2013
Publication title -
journal of the american geriatrics society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.992
H-Index - 232
eISSN - 1532-5415
pISSN - 0002-8614
DOI - 10.1111/jgs.12156
Subject(s) - medicine , hazard ratio , proportional hazards model , apolipoprotein e , dementia , cohort , confidence interval , prospective cohort study , cohort study , cause of death , gerontology , cognitive decline , demography , disease , sociology
Objectives To confirm associations of apolipoprotein E ( A po E ) 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. Design Prospective cohort study. Setting The Baltimore Longitudinal Study of Aging ( BLSA ). Participants 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. Measurements Time to death from all, cardiovascular, and noncardiovascular causes. Results Probability of survival was lower for A po E ε4 carriers, particularly those who were older. A Cox proportional hazards model for all‐cause mortality yielded a hazard ratio ( HR ) for A po E 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 A lzheimer'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). Conclusion 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.