ApoE Testing in Alzheimer’s Disease

Scientists, ethicists, and other health professionals have joined together to develop a public policy statement about the appropriateness of apolipoprotein E (apoE) testing and the role of genetic counseling in Alzheimer’s disease (AD). Discussions leading to the statement took place at a conference sponsored by the National Institute on Aging (NIA) and the Alzheimer’s Association in Chicago, Illinois, in October 1995. These recommendations come at a time when public interest in genetic tests to predict AD is growing rapidly because the current blood test for apoE gives some information about genetic risk for AD.

Medical tests may be used for different purposes. Some tests can indicate susceptibility (the likelihood or risk of getting a disease); some help confirm diagnoses; and others assist in planning or monitoring treatment. In certain cases, physicians screen people without symptoms to predict who might develop a medical problem in an effort to prevent it. For those with symptoms, doctors try to rule out other disorders and determine, as accurately as possible, what is causing the symptoms.

Many AD researchers are studying apoE because the apoE alleles that people inherit seem to be related to their risk for AD. In addition, researchers, ethicists, and health care providers are developing policies about the appropriate use of the apoE test and its results. What makes these tasks especially difficult are the facts that: apoE status cannot show whether people will develop AD, and the apoE test gives only limited information about AD risk. (See the accompanying article for a more indepth explanation of apoE.)

Many questions have been raised already about whether and how limited information about AD risk can benefit people. For example, people learning through testing that they have an increased risk of getting AD may experience emotional distress and depression about the future because there currently is no effective way to prevent or treat the disease.

Ms. Phyllis Lessin is the Assistant Chief of the Alzheimer’s Disease Research Center (ADRC) at the University of California, San Diego (UCSD). She notes that “We can see how self-fulfilling behaviors might arise–for example, a middle-aged person might falsely attribute momentary absentmindedness to the onset of dementia.” She goes on to say “Although our primary concern is with the misinterpretation of test results, we feel that several other important considerations exist. One is discrimination by insurance companies. Another is the possibility of people giving up on their futures even when symptoms have yet to, and may never, appear.” These concerns point to the need for further research and policy development.

Therefore, the joint statement does not endorse apoE testing as a patient screening (predictive testing) method. The statement supports the use of apoE testing for diagnostic purposes only in conjunction with other tests during medical evaluations of patients who show AD symptoms.

In the research setting, apoE testing is a powerful tool. One use includes helping to recruit study volunteers who may be at risk of getting AD to identify early cognitive changes that may indicate onset. This tool also helps researchers compare the effectiveness of treatments for patients with different apoE status.

For example, Dr. Judes Poirier and his colleagues at the McGill Centre for Studies in Aging at McGill University in Montreal, Canada, used the apoE test in a study of 40 AD patients taking tacrine. They found that 83 percent of the 18 patients with no apoE4 alleles responded well to tacrine. The response of these patients was described as strong, in that their memory and learning scores after treatment returned to what they had been 2 to 3 years before. Sixty percent of the 22 patients with apoE4 alleles were unchanged or worse after 30 weeks.

Predictive testing or screening will make sense only when effective ways to prevent or treat AD are available. In fact, some researchers believe that apoE tests or other screening measures may never be able to predict AD with 100 percent accuracy.

As Ms. Lessin points out, researchers at the ADRC believe that the apoE test is most useful in broadly-based population-risk studies and not for determining a person’s individual risk.

Source: Connection Magazine [Volume 5(1), Winter/Spring 1996]

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