The clinical introduction of genetic testing for Alzheimer disease: an ethical perspective

A panel of experts convened by the National Institutes of Health recommends that genetic testing for Alzheimer's disease (AD) should only be offered to people with a family history of early-onset AD. Early-onset AD is associated with mutations in genes on chromosomes 1, 14 and 21. The apolipoprotein E (APOE) epsilon4 gene has also been linked to AD, but the presence of this gene does not automatically cause AD. Widespread screening of asymptomatic people could cause severe anxiety in those who test positive for APOE epsilon4. In addition, they could be denied long-term care insurance.
Objective.--Primary caregivers should be aware of recent progress in the genetics of Alzheimer disease (AD) and of the clinical and ethical considerations raised regarding the introduction of genetic testing for purposes of disease prediction and susceptibility (risk) analysis in asymptomatic individuals and diagnosis in patients who present clinically with dementia. This statement addresses arguments for and against clinical genetic testing. Participants.--The 20 participants were selected by the investigators (S.G.P., T.H.M., A.B.Z., and P.J.W.) to achieve balance in the areas of genetics, counseling, ethics, and public policy, and to include leadership from related consensus projects. The consensus group met twice in closed meetings and carried on extensive correspondence over 2 years (1995-1997). The project was supported by the National Human Genome Research Institute of the National Institutes of Health. Evidence.--All 4 involved chromosomes were discussed in group meetings against a background of information from several focus group sessions with ADaffected families. The focus groups comprised volunteers identified by the Cleveland Area Chapter of the Alzheimer's Disease and Related Disorders Association and represented a variety of ethnic populations. Consensus Process.--The first draft was written in April 1996 by the principal investigator (S.G.P.) after the consensus group had met twice. The draft was mailed to all consensus group members 3 times over 6 months for extensive response and redrafting by the principal investigator until all members were satisfied. Conclusions.--Except for autoscmal dominant early-onset families, genetic testing in asymptomatic individuals is unwarranted. Use of APOE genetic testing as a diagnostic adjunct in patients already presenting with dementia may prove useful but it remains under investigation. The premature introduction of genetic testing and possible adverse consequences are to be avoided. JAMA. 1997;277:832-836