Ethnic and Genetic Risks for AD

Abstract & Commentary

Synopsis: Increased risk of developing Alzheimer’s disease is found in first-degree relatives of both whites and African Americans, although African American relatives have a 1.6 times more risk than whites. Female gender and the presence of specific alleles also increase cumulative risk.

Source: Green RC, et al. JAMA. 2002;287:329-336.

Using 17 major medical centers for subject recruitment over the last 10 years, this Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) study now publishes cumulative risk estimates by age from the families of 2339 white and 255 African American patients with Alzheimer disease (AD). The patients were identified at specialty clinics for dementia by published research criteria, and questionnaires collected health information and dementia status on the entire family. This information was supplemented with other medical records including death certificates and nursing home records. Ethnicity was established by self-report and reclassified according to 1990 US Census definitions. Blood for apolipoprotein E (APOE e4) allele was collected from a subset of 46% of the patients.

Curves illustrating the cumulative risks at different ages were created, showing risk for first-degree relatives for dementia by age 85 of 44% for African Americans and 27% for non-Hispanic whites. The risk for spouses by this age was 18.5% for African Americans and 10% for whites. Women in both groups had increased risk, 1.2 times higher for African Americans and 1.5 for white women. The presence of the APOE e4 allele raised the risk further by 1.3 in African American relatives and 1.5 in whites.

Comment by Mary Elina Ferris, MD

At least a 2-fold cumulative increased risk of AD in African-American elderly populations compared to whites has been reported by age 90, which does not change even when adjusted for history of diabetes, stroke, hypertension, heart disease, or years of education.1 In white populations, previous studies have established that relatives of AD patients are more likely to develop the disease, along with higher risk for female sex, increasing age, and carrying the APOE e4 allele. Siblings of patients have a 1.8 relative risk and parents a 1.2, giving an overall 1.5 risk increase to first-degree relatives of AD patients compared to relatives of control groups. Relatives who were women showed a further 1.5 increase in relative risk.2

This new article has collected the largest number of African American families ever studied for risk of AD, and the same risk factors as white populations were shown. However, the overall incidence of AD was still higher in African Americans. Although these results are limited somewhat by small numbers of African American families and by proxy reporting of family information, they still provide the most comprehensive data to date on the inheritance of AD in this population, and the published tables in the article can be useful for counseling patients on their age-specific risks.

The reason for the disturbing increased risk among African Americans is not entirely clear, but intriguing clues currently suggest both genetics and environment contribute to the difference. This article suggests that there may be both a higher baseline risk of dementia and a higher degree of familial aggregation, including the possibility that other genetic alleles may be involved. When spouses of Alzheimer patients were matched for age and compared between ethnic groups, African Americans’ spouses were 1.8 times more likely to develop dementia than white spouses. Environmental causes were also suggested in a recent 5-year prospective incidence study of dementia and AD comparing African Americans in Indianapolis with residents of Nigeria, which found an annual age-standardized rate of 2.52% for Indianapolis compared to 1.35% in Nigeria.3 These issues merit further research and should be expanded to include other ethnic groups.

References

1. Tang MX, et al. Neurology. 2001;56:49-56.

2. Devi G. Arch Neurol. 2000;57:72-77.

3. Hendrie HC. JAMA. 2001;285:739-747.

Dr. Ferris, Clinical Associate Professor, University of Southern California, is Associate Editor of Internal Medicine Alert.