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Apolipoprotein E ?4 allele interacts with sex and cognitive status to influence all-cause and cause-specific mortality in U.S. older adults.

ABSTRACT: OBJECTIVES:To confirm associations of apolipoprotein E (ApoE) ?4 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 ApoE ?4 carriers, particularly those who were older. A Cox proportional hazards model for all-cause mortality yielded a hazard ratio (HR) for ApoE ?4 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 ?4 alleles was found for all-cause mortality (HR = 1.40, 95% CI = 0.94-2.07 for 1 ?4; HR = 2.61, 95% CI = 1.12-6.07 for 2 ?4). After onset of Alzheimer's disease (AD), carrying only one ?4 allele resulted in an approximately 77% greater all-cause mortality risk than in noncarriers. ApoE ?4 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 ?4 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.

SUBMITTER: Beydoun MA

PROVIDER: S-EPMC3628727 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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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.

Beydoun May A MA Beydoun Hind A HA Kaufman Jay S JS An Yang Y Resnick Susan M SM O'Brien Richard R Ferrucci Luigi L Zonderman Alan B AB

Journal of the American Geriatrics Society 20130321 4

<h4>Objectives</h4>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.<h4>Design</h4>Prospective cohort study.<h4>Setting</h4>The Baltimore Longitudinal Study of Aging (BLSA).<h4>Participants</h4>Of 3,047 BLSA participants aged 17 to 98 at first visit (60.1% male), 1,704 with complete ApoE genotype data were inc ...[more]

PMID: 23581910

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Project description:Theoretical background: The Apolipoprotein E (APOE) ε4 genotype is known to be one of the strongest single-gene predictors for Alzheimer disease, which is characterized by widespread brain structural degeneration progressing along with cognitive impairment. The ε4 allele status has been associated with brain structural alterations and lower cognitive ability in non-demented subjects. However, it remains unclear to what extent the visuospatial cognitive domain is affected, from what age onward changes are detectable and if alterations may interact with cognitive deficits in major depressive disorder (MDD). The current work investigated the effect of APOE ε4 homozygosity on visuospatial working memory (vWM) capacity, and on hippocampal morphometry. Furthermore, potential moderating roles of age and MDD were assessed. Methods: A sample of n = 31 homozygous ε4 carriers was contrasted with n = 31 non-ε4 carriers in a cross-sectional design. The sample consisted of non-demented, young to mid-age participants (mean age = 34.47; SD = 13.48; 51.6% female). Among them were n = 12 homozygous ε4 carriers and n = 12 non-ε4 carriers suffering from MDD (39%). VWM was assessed using the Corsi block-tapping task. Region of interest analyses of hippocampal gray matter density and volume were conducted using voxel-based morphometry (CAT12), and Freesurfer, respectively. Results: Homozygous ε4 carriers showed significantly lower Corsi span capacity than non-ε4 carriers did, and Corsi span capacity was associated with higher gray matter density of the hippocampus. APOE group differences in hippocampal volume could be detected but were no longer present when controlling for total intracranial volume. Hippocampal gray matter density did not differ between APOE groups. We did not find any interaction effects of age and MDD diagnosis on hippocampal morphometry. Conclusion: Our results point toward a negative association of homozygous ε4 allele status with vWM capacity already during mid-adulthood, which emerges independently of MDD diagnosis and age. APOE genotype seems to be associated with global brain structural rather than hippocampus specific alterations in young- to mid-age participants.

Dataset Information

Apolipoprotein E ?4 allele interacts with sex and cognitive status to influence all-cause and cause-specific mortality in U.S. older adults.

Publications

Apolipoprotein E ε4 allele interacts with sex and cognitive status to influence all-cause and cause-specific mortality in U.S. older adults.

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