Racial Differences in the Influence of the APOE Epsilon 4 Allele on Cognitive Decline in a Sample of Community-Dwelling Older Adults
ABSTRACT Most, but not all, past studies have suggested that the APOE genotype is a risk factor for dementia in whites but not African Americans. This paper first describes explanations as to why some studies may have failed to detect the effect of APOE genotype in African American samples. Briefly, studies have been limited by various methodological problems including small sample sizes, dichotomous measures of cognitive functioning (which tend to be less sensitive to change), and racial bias in assessing demented status.
This paper suggests methods for increasing the likelihood that genuine racial differences will be identified when examining genetic risk factors. Further, we test our model of racial differences in the relationship of APOE genotype and cognitive decline (CD) in a large prospective community sample.
Building on the work of Fillenbaum and colleagues [J Am Geriatr Soc 2001;49:1148-1155], we used data from the Duke EPESE study collected in four waves over a 10-year period (n = 2,076) to illustrate methods which may better assess racial differences in the influence of the APOE epsilon 4 allele on CD. We used multilevel models for repeated measures to examine racial differences in participants' increase in errors on a continuous measure of cognitive functioning as they aged.
We found the APOE epsilon 4 allele to predict CD for both African Americans and whites. Having at least one epsilon 4 allele predicted more cognitive errors at wave 1 and a faster rate of decline for both African Americans and whites over time. While African Americans experienced a faster rate of CD than whites, there was no additional increase in CD from being both African American and a carrier of the epsilon 4 allele.
The study points to several common methodological issues that arise when examining racial differences in genetic influences on health-related outcomes. Further, the study's results highlight the importance of including both African Americans and Caucasians in research concerning the contribution of APOE genotype to CD.
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ABSTRACT: ABSTRACT Background: There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer's disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline. Methods: In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox's proportional hazards regression and mixed effects models. Results: After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425). Conclusions: In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.International Psychogeriatrics 02/2014; 26(6):1-9. DOI:10.1017/S1041610214000167 · 1.89 Impact Factor
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ABSTRACT: To examine whether observed differences in dementia rates between black and white older people living in the community could be explained by measures of socioeconomic status (income, financial adequacy, education, and literacy) and health related factors. Prospective cohort study. General community from two clinic sites in the United States (Pittsburgh, Pennsylvania and Memphis, Tennessee). 2457 older people (mean age 73.6 years; 1019 (41.5%) black; 1233 (50.2%) women), dementia-free at baseline, in the Health, Aging, and Body Composition study. Dementia was determined over 12 years (ending January 2011) by prescribed dementia drugs, hospital records, and decline in global cognitive scores. The influence of socioeconomic status and health related factors on dementia rates was examined in a series of Cox proportional hazard models in which these variables were added sequentially in covariate blocks. Over follow-up, 449 (18.3%) participants developed dementia. Black participants were more likely than white participants to develop dementia (211 (20.7%) v 238 (16.6%), P<0.001; unadjusted hazard ratio 1.44, 95% confidence interval 1.20 to 1.74). The hazard ratio lessened somewhat after adjustment for demographics, apolipoprotein E e4, comorbidities, and lifestyle factors (1.37, 1.12 to 1.67) but was greatly reduced and no longer statistically significant when socioeconomic status was added (1.09, 0.87 to 1.37). These findings suggest that differences in the burden of risk factors, especially socioeconomic status, may contribute to the higher rates of dementia seen among black compared with white older people. Strategies aimed at reducing these disparities may favorably affect the incidence of dementia.BMJ (online) 12/2013; 347:f7051. DOI:10.1136/bmj.f7051 · 16.38 Impact Factor
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ABSTRACT: Objectives: Biological and environmental factors are thought to contribute to the development of cognitive decline (CD). The Apolipoprotein E (APOE) ϵ4 allele is the greatest known genetic risk factor. The current study focused on the extent to which environmental factors, specifically stress, influence the relationship between the APOE allele and cognitive functioning and whether this relationship is stronger for African-Americans compared to Caucasians.Methods: Participants consisted of community-dwelling older adults from the Duke Established Populations for Epidemiologic Studies of the Elderly (N = 4,162). Data were drawn from two waves, which were three years apart. Cognitive functioning was assessed at both waves using the Short Portable Mental Status (SPMSQ).Results: Whereas there was no main effect of stress, there was a significant interaction between APOE status and stressful life events, such that increased stress in individuals with an ϵ4 allele lead to more errors on the SPMSQ than individuals with no allele. Inconsistent with predictions, there was a significant interaction between stress and race such that increased stressful events predicted CD in Caucasians but not African-Americans.Conclusions: Recent stressful late-life events have a greater impact on the cognitive status of individuals with an ϵ4 allele. While Caucasians appear to be less vulnerable to cognitive losses at lower levels of stress, as the number of stressful life events increases that advantage disappears for Caucasians.Aging and Mental Health 02/2014; 18(6). DOI:10.1080/13607863.2014.880403 · 1.78 Impact Factor