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: We examined longitudinal associations between the apolipoprotein E ε4 allele (ApoE4(+) status) and several cognitive outcomes and tested effect modification by sex. Data on 644 non-Hispanic Caucasian adults, from the Baltimore Longitudinal Study of Aging (BLSA) were used. Dementia onset, cognitive impairment and decline were assessed longitudinally. After 27.5 years median follow-up, 113 participants developed dementia. ApoE4(+) predicted dementia significantly (hazard ratio [HR] = 2.89; 95% confidence interval [CI], 1.93-4.33), with nonsignificant sex differences. Taking all time points for predicting cognition, women had significantly stronger positive associations than men between ApoE4(+) status and impairment or decline on the California Verbal Learning Test (CVLT; delayed recall and List A total recall) and on Verbal Fluency Test-Categories. This ApoE4 × sex interaction remained significant with Bonferroni correction only for CVLT-delayed recall. Taking time points prior to dementia for cognitive predictions, the positive association between impairment in CVLT-delayed recall and ApoE4(+) status remained stronger among women, though only before Bonferroni correction. While ApoE4(+) status appears to be a sex neutral risk factor for dementia, its association with verbal memory and learning decline and impairment was stronger among women.Neurobiology of aging 04/2012; 33(4):720-731.e4. DOI:10.1016/j.neurobiolaging.2010.05.017 · 4.85 Impact Factor
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ABSTRACT: The apolipoproteinE epsilon4 (APOE epsilon4) allele and a history of depression are each separate risk factors for cognitive decline (CD). However, little research has investigated whether a history of depression influences the relationship between APOE epsilon4 and CD. The present study examined whether depressive symptoms had greater influence on subsequent CD among participants with APOE epsilon4 than those without the allele. Prospective 6-year longitudinal study. Community in-home interviews. A biracial sample of community dwelling older adults (N = 1,992) from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Data were drawn from Waves 1 to 3 of the EPESE, which were conducted 6 years apart. Cognitive functioning and depressive symptoms were assessed at both waves, and APOE genotyping was completed during the Wave 3 assessment. Regression analyses revealed that depressive symptoms and the APOE epsilon4 allele independently predicted CD. Importantly, the influence of depressive symptoms on CD was greater for individuals with the APOE epsilon4 allele compared with those without the allele. Depressive symptoms and the APOE epsilon4 allele are independent contributors to CD. Moreover, the influence of depressive symptoms on CD is greater among individuals with the APOE epsilon4 allele. Depression and the APOE epsilon4 allele may act together in disrupting neurological functioning, which may in turn lower an individual's cognitive reserve capacity. Given the efficacious treatments currently available for depression, future research should investigate the extent to which interventions for depression may reduce the risk for subsequent CD.The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 03/2009; 17(2):155-65. DOI:10.1097/JGP.0b013e31818f3a6b · 3.52 Impact Factor
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ABSTRACT: Objectives: The ApolipoproteinE ε4 (APOE ε4) allele influences cognitive decline (CD) in some but not in all individuals. The purpose of this study was to investigate whether problems meeting basic needs (BN) (e.g., having enough money to meet needs, having enough money for emergencies, having adequate housing, and having enough heat) influences the relationship between the APOE ε4 allele and CD. We predicted that problems meeting BN would have a greater influence on CD among those with the APOE ε4 allele than those without the allele.Methods: Participants consisted of community-dwelling older adults from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Data were drawn from Waves 1 and 2, which were 3 years apart. Cognitive functioning was assessed at both waves so that change in cognitive status was examined over time, and cognitive status was controlled at baseline. Genotyping, however, was not obtained until Wave 3.Results: The APOE ε4 allele and problems meeting BN independently predicted CD. Importantly, the influence of BN on CD was greater for individuals with the APOE ε4 allele compared to those without the allele. Other indicators of socioeconomic status (e.g., education, income) did not interact with the APOE ε4 allele in predicting CD.Conclusions: There is a synergistic effect of perceived problems meeting BN and the APOE ε4 allele on jointly influencing cognitive functioning. Although genetic risk factors are not easily modifiable, resource deprivation may be more amenable to interventions, which may reduce risk for CD.Aging and Mental Health 03/2010; 14(2):138-144. DOI:10.1080/13607860903421060 · 1.78 Impact Factor