Background: 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. Objective: 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. Methods: 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 ε4 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. Results: We found the APOE ε4 allele to predict CD for both African Americans and whites. Having at least one ε4 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 ε4 allele. Conclusion: 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.

Keywords:
APOE genotype, Cognitive decline, Racial differences, APOE epsilon 4 allele
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© 2008 S. Karger AG, Basel
2008
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