• Robert C Green, L Adrienne Cupples, Rodney Go, Kelly S Benke, Timi Edeki, Patrick A Griffith, Mary Williams, Yvonne Hipps, Neill Graff-Radford, David Bachman, Lindsay A Farrer, and MIRAGE Study Group.
• Genetics Program and Alzheimer's Disease Center, Boston University School of Medicine, 715 Albany St, L-320, Boston, MA 02118, USA. rcgreen@bu.edu
• JAMA. 2002 Jan 16; 287 (3): 329336329-36.

ContextEvidence exists that the incidence of Alzheimer disease (AD), as well as risk attributable to specific genetic factors such as apolipoprotein E (APOE) genotype, may vary considerably among ethnic groups. Family studies of probands with AD offer an opportunity to evaluate lifetime risk of dementia among relatives of these probands.ObjectiveTo compare lifetime dementia risk estimates among relatives of white and African American probands with probable or definite AD.Design And SettingRisk analysis using data collected by questionnaire and supplemental records between May 1991 and March 2001 at 17 medical centers contributing to the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study.ParticipantsA total of 17 639 first-degree biological relatives and 2474 spouses of 2339 white AD probands, and 2281 first-degree biological relatives and 257 spouses of 255 African American AD probands.Main Outcome MeasuresCumulative risk of dementia by age 85 years, stratified by ethnicity and sex of relatives and by APOE genotype of probands.ResultsCumulative risk of dementia in first-degree biological relatives of African American AD probands by age 85 years was 43.7% (SE, 3.1%), and the corresponding risk in first-degree biological relatives of white AD probands was 26.9% (SE, 0.8%), yielding a relative risk (RR) of 1.6 (95% confidence interval [CI], 1.4-1.9; P<.001). The risk in spouses of African American AD probands of 18.5% (SE, 8.4%) was also higher than the risk in white spouses of 10.4% (SE, 1.7%) but did not reach statistical significance (RR, 1.8; 95% CI, 0.5-6.0; P =.34), likely due to the smaller sample size of African Americans. The proportional increase in risk of dementia among white first-degree biological relatives compared with white spouses of 2.6 (95% CI, 2.1-3.2) was similar to that of 2.4 (95% CI, 1.3-4.4) in African American first-degree biological relatives compared with African American spouses. Female first-degree biological relatives of probands had a higher risk of developing dementia than did their male counterparts, among whites (31.2% vs 20.4%; RR, 1.5; 95% CI, 1.3-1.7; P<.001) as well as among African Americans, although this was not significant among African Americans (46.7% vs 40.1%; RR, 1.2; 95% CI, 0.9-1.7, P =.30). The patterns of risk among first-degree biological relatives stratified by APOE genotype of the probands were similar in white families and African American families.ConclusionFirst-degree relatives of African Americans with AD have a higher cumulative risk of dementia than do those of whites with AD. However, in this study, the additional risk of dementia conferred by being a first-degree relative, by being female, or by the probability of having an APOE epsilon4 allele appeared similar in African American and white families. These data provide estimates of dementia risk that can be used to offer counseling to family members of patients with AD.

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