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

Green, Robert C.; Cupples, L. Adrienne; Go, Rodney C.P.; Benke, Kelly S.; Edeki, Timi; Griffith, Patrick; Williams, Mary; Hipps, Yvonne G.; Graff‐Radford, Neill R.; Bachman, David; Farrer, Lindsay A.

doi:10.1001/jama.287.3.329

Cited by 346 publications

(279 citation statements)

References 38 publications

(38 reference statements)

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“…The MIRAGE study is the largest genetic epidemiological study of its kind to date, focusing on both African American and white families. 13,14,65 As a result, it provided a potential basis for clarifying risk profiles for African Americans and risk estimates to FDRs of persons with AD. The study found significantly higher risk for dementia among FDRs of African Americans compared with whites (RR 1.6; 95% CI 1.4 -1.9).…”

Section: The Mirage Studymentioning

confidence: 99%

“…The study also found similar effects of APOE genotype on overall AD risk for African Americans as reported for whites. 13 A comparison of risk through age 85 by self-identified ethnicity and genotype is provided in Table 1.…”

Section: The Mirage Studymentioning

confidence: 99%

“…The focus on African Americans was warranted not only by the desire to be more inclusive in our clinical research according to NIH guidelines, but also because this group seems to be at increased risk for AD. 13,36 Scholars have argued whether and how to include ethnicity as a focus in genetic research. [37][38][39][40][41][42] Despite this attention, only a few studies provide data about the challenges and impact of expanding ethnic diversity in research about genetic susceptibility testing.…”

mentioning

confidence: 99%

“…45 Indeed, we are seeing increased attention to what has been called "race-based medicine," a trend that may overemphasize genetic factors and distract attention from social, environmental, and structural contributions to health disparities. 46 -49 On the other hand, the epidemiological data on which risk estimates are typically based suggest significant differences in the lifetime risk of AD between African Americans and whites, 13,17 and popular models for genetic cancer risk like the Gail Model incorporate ethnicity into calculations. Some argue that ignoring variations between ethnic groups will not eliminate disparities; and only by focusing attention on these issues will we be able to understand how social, environmental, and behavioral differences interact with biological factors, including genotype.…”

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confidence: 99%

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Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

Christensen

Roberts

Royal

et al. 2008

Genetics in Medicine

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Purpose: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. Methods: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicityspecific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. Results: Review of epidemiological data suggested notable differences in risk between African Americans and whites and that Apolipoprotein E genotype predicts risk in both groups. Discussions about the benefits and risks of stratified risk assessments reached consensus that estimates based on data from whites should not preclude enrolling African Americans, but population-specific risk curves should be created if feasible. Risk models specific to ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for the randomized clinical trial that oversampled African Researchers are identifying a growing number of genetic markers that are associated with increased or decreased risk for common, complex diseases. Consequently, the development of genetic risk assessment and risk communication strategies are areas of critical importance, especially given that laypersons often have a difficult time in understanding probabilistic information. 1,2 Protocols for disclosing genetic information have been developed and refined for various forms of cancer, 3-6 but similar efforts have been made only recently for other diseases. 7,8 One area of recent focus is Alzheimer disease (AD).AD is the most common form of dementia among the elderly, affecting an estimated five million individuals in the United States. Well over 10 million Americans are expected to have the condition by 2050 as the population continues to age. 9 Many risk factors are well-characterized, including age and family history, 10 -14 whereas many others are under investigation, including education level, 15,16 head trauma, 17,18 high blood pressure, 19 caloric intake, and high cholesterol. 20,21 Regarding genetic factors, rare mutations on genes coding for amyloid precursor protein, presenilin 1, and presenilin 2 have been identified that are deterministic for early-onset AD. 22 Apolipoprotein E (APOE), in contrast, affects susceptibility to AD and has three major forms. APOE ⑀3, the most common allele, is found in over half the US population. The ⑀4 allele is associated with increased risk for AD whereas the ⑀2 allele has a protective effect. 23,24 The ⑀4 allele is neither necessary nor sufficient for AD though, and individuals with the ⑀2 allele still have risk for AD. APOE variants are also associated with other conditions such as hyperlipoproteinemia and atherosclerosis 25 and may play a role in the development of ma...

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Section: The Mirage Studymentioning

confidence: 99%

Section: The Mirage Studymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

Christensen

Roberts

Royal

et al. 2008

Genetics in Medicine

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“…Risk estimates were formulated using two sources: (1) agespecific incidence curves for first-degree relatives of individuals affected by AD from a genetic epidemiology study of AD families [17][18] ; and (2) odds ratio estimates reported in a metaanalysis encompassing 40 studies worldwide. 19 Bayes' rule was used to stratify risk according to APOE genotype.…”

Section: Risk Estimatesmentioning

confidence: 99%

Genetic susceptibility testing versus family history–based risk assessment: Impact on perceived risk of Alzheimer disease

LaRusse

Roberts

Marteau

et al. 2005

Genetics in Medicine

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Association Between Apolipoprotein E Genotype and Alzheimer Disease in African American Subjects

Graff‐Radford¹,

Green²,

Go³

et al. 2002

Arch Neurol

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100

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

Cited by 346 publications

References 38 publications

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the REVEAL study experience

Genetic susceptibility testing versus family history–based risk assessment: Impact on perceived risk of Alzheimer disease

Association Between Apolipoprotein E Genotype and Alzheimer Disease in African American Subjects

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