Risk of Dementia Among White and African American Relatives of Patients With Alzheimer Disease | Dementia and Cognitive Impairment | JAMA | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.204.185.54. Please contact the publisher to request reinstatement.
1.
Farrer LA. Genetics and the dementia patient.  Neurologist.1997;3:13-30.Google Scholar
2.
Farrer LA, Cupples LA, Haines JL.  et al.  Effects of age, sex and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis.  JAMA.1997;278:1349-1356.Google Scholar
3.
Van Duijn CM, Farrer LA, Cupples LA, Hofman A. Genetic transmission for Alzheimer's disease among families in a Dutch population based survey.  J Med Genet.1993;30:640-646.Google Scholar
4.
Silverman JM, Li G, Zaccario ML.  et al.  Patterns of risk in first-degree relatives of patients with Alzheimer's disease.  Arch Gen Psychiatry.1994;51:577-586.Google Scholar
5.
Farrer LA, Cupples LA, van Duijn CM.  et al.  Apolipoprotein E genotype in patients with Alzheimer's disease: implications for the risk of dementia among relatives.  Ann Neurol.1995;38:797-808.Google Scholar
6.
Lautenschlager NT, Cupples LA, Rao VS.  et al.  Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: what is in store for the oldest old?  Neurology.1996;46:641-650.Google Scholar
7.
Jorm AF, Jolly D. The incidence of dementia: a meta-analysis.  Neurology.1998;51:728-733.Google Scholar
8.
Gao S, Hendrie HC, Hall KS, Hui S. The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis.  Arch Gen Psychiatry.1998;55:809-815.Google Scholar
9.
Hendrie HC, Ogunniyi A, Hall KS.  et al.  Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, Indiana.  JAMA.2001;285:739-747.Google Scholar
10.
Graff-Radford N, Green RC, Go R.  et al.  Association between APOE genotype and Alzheimer disease in African Americans.  Arch Neurol.In press.Google Scholar
11.
Farrer LA, Cupples LA, Blackburn S.  et al.  Interrater agreement for diagnosis of Alzheimer's disease: the MIRAGE study.  Neurology.1994;44:652-656.Google Scholar
12.
Demissie S, Green RC, Mucci L.  et al.  Reliability of information collected by proxy in family studies of Alzheimer's disease.  Neuroepidemiology.2001;20:105-111.Google Scholar
13.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group.  Neurology.1984;34:939-944.Google Scholar
14.
Guo Z, Cupples LA, Kurz A.  et al.  Head injury and the risk of Alzheimer disease in the MIRAGE study.  Neurology.2000;54:1316-1323.Google Scholar
15.
Brandt J, Spencer M, Folstein M. The telephone interview for cognitive status.  Neuropsychiatry Neuropsychol Behav Neurol.1988;1:111-117.Google Scholar
16.
Welsh KA, Breitner JCS, Magruder-Habib KM. Detection of dementia in the elderly using telephone screening of cognitive status.  Neuropsychiatry Neuropsychol Behav Neurol.1993;6:103-110.Google Scholar
17.
 Census of Population and Housing: 1990 Summary Tape File 1, Technical Documentation.  Washington, DC: US Bureau of the Census; 1991.
18.
Wenham PR, Price WH, Blandell G. Apolipoprotein E genotyping by one-stage PCR.  Lancet.1991;337:1158-1159.Google Scholar
19.
Cupples LA, Risch N, Farrer LA, Myers RH. Estimation of morbid risk and age at onset with missing information.  Am J Hum Genet.1991;49:76-87.Google Scholar
20.
Devi G, Ottman R, Tang M.  et al.  Influence of APOE genotype on familial aggregation of AD in an urban population.  Neurology.1999;53:789-794.Google Scholar
21.
Devi G, Ottman R, Tang MX, Marder K, Stern Y, Mayeux R. Familial aggregation of Alzheimer disease among whites, African Americans, and Caribbean Hispanics in northern Manhattan.  Arch Neurol.2000;57:72-77.Google Scholar
22.
Belgrave LL, Wykle ML, Choi JM. Health, double jeopardy, and culture: the use of institutionalization by African-Americans.  Gerontologist.1993;33:379-385.Google Scholar
23.
Ballard EL, Nash F, Raiford K, Harrell LE. Recruitment of black elderly for clinical research studies of dementia: the CERAD experience.  Gerontologist.1993;33:561-565.Google Scholar
24.
Connell CM, Gibson GD. Racial, ethnic and cultural differences in dementia caregiving: review and analysis.  Gerontologist.1997;37:355-364.Google Scholar
25.
Silverman JM, Breitner JC, Mohs RC, Davis KL. Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias.  Am J Psychiatry.1986;143:1279-1282.Google Scholar
26.
Devi G, Marder K, Schofield PW.  et al.  Validity of family history for the diagnosis of dementia among siblings of patients with late-onset Alzheimer's disease.  Genet Epidemiol.1998;15:215-223.Google Scholar
27.
Gurland BJ, Wilder DE, Lantigua R.  et al.  Rates of dementia in three ethnoracial groups.  Int J Geriatr Psychiatry.1999;14:481-493.Google Scholar
28.
Tang MX, Stern Y, Marder K.  et al.  The APOE-e4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics.  JAMA.1998;279:751-755.Google Scholar
29.
Tang MX, Cross P, Andrews H.  et al.  Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan.  Neurology.2001;56:49-56.Google Scholar
30.
Maestre G, Ottman R, Stern Y.  et al.  Apolipoprotein E and Alzheimer's disease: Ethnic variation in genotypic risks.  Ann Neurol.1995;37:254-259.Google Scholar
31.
Tang MX, Maestre G, Tsai WY.  et al.  Effect of age, ethnicity, and head injury on the association between APOE genotypes and Alzheimer's disease.  Ann N Y Acad Sci.1996;802:6-15.Google Scholar
32.
Sahota A, Yang M, Gao S.  et al.  Apolipoprotein E-associated risk for Alzheimer's disease in the African-American population is genotype dependent.  Ann Neurol.1997;42:659-661.Google Scholar
33.
Osuntokun BO, Sahota A, Ogunniyi AO.  et al.  Lack of an association between Apolipoprotein E epsilon 4 and Alzheimer's disease in elderly Nigerians.  Ann Neurol.1995;38:463-465.Google Scholar
34.
Sayi JG, Patel NB, Premkumar DR.  et al.  Apolipiprotein E polymorphism in elderly East Africans.  East Afr Med J.1997;74:668-670.Google Scholar
35.
Farrer LA, Brin MF, Elsas L.  et al.  Statement on use of Apolipoprotein E testing for Alzheimer disease.  JAMA.1995;274:1627-1629.Google Scholar
36.
Lovestone S. The genetics of Alzheimer's disease: new opportunities and new challenges.  Int J Geriatr Psychiatry.1995;10:1-7.Google Scholar
37.
Brodary H, Conneally M, Gauthier S.  et al.  Consensus statement on predictive testing for Alzheimer disease.  Alzheimer Dis Assoc Disord.1995;9:182-187.Google Scholar
38.
Relkin NR, Gandy S. Consensus statements on the use of APOE genotyping in Alzheimer's disease.  Neurol Alert.1996;14:58-59.Google Scholar
39.
Post SG, Whitehouse PJ, Binstock RH.  et al.  The clinical introduction of genetic testing for Alzheimer's disease: an ethical perspective.  JAMA.1997;277:832-836.Google Scholar
40.
McConnell LM, Koenig BA, Greely HT.  et al.  Genetic testing and Alzheimer disease: has the time come? Alzheimer Disease Working Group of the Stanford Program in Genomics, Ethics & Society.  Nat Med.1998;4:757-759.Google Scholar
Original Contribution
January 16, 2002

Risk of Dementia Among White and African American Relatives of Patients With Alzheimer Disease

Author Affiliations

Author Affiliations: Genetics Program and Department of Neurology, Department of Medicine, School of Medicine (Drs Green and Farrer and Ms Benke) and Department of Epidemiology and Biostatistics, School of Public Health (Drs Cupples and Farrer), Boston University, Boston, Mass; Department of Epidemiology, University of Alabama School of Public Health, Birmingham (Dr Go); Departments of Medicine and Pharmacology, Morehouse School of Medicine, Atlanta, Ga (Drs Edeki, Griffith, Williams, and Hipps); Department of Neurology, Mayo Clinic, Jacksonville, Fla (Dr Graff-Radford); and Department of Psychiatry, Medical University of South Carolina, Charleston (Dr Bachman).

JAMA. 2002;287(3):329-336. doi:10.1001/jama.287.3.329
Abstract

Context Evidence 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.

Objective To compare lifetime dementia risk estimates among relatives of white and African American probands with probable or definite AD.

Design and Setting Risk 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.

Participants A 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 Measures Cumulative risk of dementia by age 85 years, stratified by ethnicity and sex of relatives and by APOE genotype of probands.

Results Cumulative 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.

Conclusion First-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 ∊4 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.

×