Alzheimer's testing less distressing than thought
Subjects should get education, counseling, but it need not be elaborate, researcher says
As genetic testing becomes better able to pinpoint risk factors for various diseases, is there potential harm to subjects in giving them test results, particularly when there are limited treatment and prevention options?
Current models of genetic testing and counseling are based on those created for Huntington's disease, says J. Scott Roberts, PhD, who studies health education and health behavior at the University of Michigan School of Public Health in Ann Arbor.
With Huntington's, "Pretty much, if you have the mutation, you're almost inevitably going to get the disease, and it's fatal, incurable, with an earlier onset," Roberts says. That's very different, he says, from genetic testing for conditions such as Alzheimer's disease.
Currently, for the most common form of Alzheimer's disease, the most prominent genetic marker is a variant of a plasma protein called apolipoprotein E. (APOE). However, existence of this variant is less predictive than the genetic marker for Huntington's.
Roberts and his colleagues set out to look at how subjects would respond to learning whether they had this APOE variant. The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) study is a series of multisite trials that look at the result of APOE testing on more than 700 adults, some of them with immediate family history of Alzheimer's disease.
REVEAL's results can help inform researchers and IRBs as they deal with how to disclose potential genetic risks to research subjects for a variety of diseases, particularly in cases where doctors can't prescribe a prevention or cure.
"It's not like we can say, 'If you're at higher risk for Alzheimer's, here's a regimen that will lower your risk' — we're not at that point," Roberts says. "However, what we've found is that some of the speculated harms haven't come to fruition in our studies.
"We haven't found that people are reacting to bad news with the kind of psychological distress that I think some had been concerned about. I think it does suggest that if you have research participants who are particularly interested in this information and you have a research team with enough resources and inclination to disclose this, it might be something that could be considered."
In each of the four stages of the REVEAL study, researchers developed risk estimates for subjects, based on age, gender, family history and whether the subjects tested positive for a specific APOE allele (APOE-e4), which is a risk factor for late-onset Alzheimer's disease. Subjects were given various types of counseling — a full, face-to-face education, a condensed program or phone consultations. They were followed for a year to assess the impact of their risk assessment.
Roberts says researchers wanted to see if the extensive education and counseling model used with Huntington's testing was necessary for other testing situations.
"Our take is that we don't need to be that elaborate, when you're talking about something like APOE, which is much less predictive," Roberts says. "It's not like our phone disclosure people were reacting with much greater distress.
"We think it's important to have some knowledgeable expert involved and we think it's important to have people try to think through the decision, but on the other hand, we think we can make some accommodations so we don't have to replicate a Huntington's model to do this."
Other issues that came up in the REVEAL study:
• Ethnicity – Roberts says epidemiological studies suggest that African Americans are at higher risk for Alzheimer's disease than whites, although it's unclear why. He says the risk estimates for African American subjects in the REVEAL study did reflect that difference.
"So that was a bit tricky because we were giving them higher numbers, but I think that does reflect the state of the science," Roberts says.
• Insurance risks – Although the Genetic Information Nondiscrimination Act (GINA) protects subjects from discrimination in employment and health insurance based on their genetic information, that protection does not extend to long-term care insurance. This is key in Alzheimer's testing, since many Alzheimer's patients spend many years in long-term care as their disease progresses.
In the one-year REVEAL follow-up, subjects who tested positive for APOE-e4 were about four times more likely to report having made changes in long-term care coverage. If that trend continues, it's possible that insurance companies will begin to ask about APOE testing. It's important that those insurance risks be spelled out in informed consent, Roberts says.
"Basically we often encourage people if they're going to make (insurance) decisions, to consider making them before they actually find out their genetic test results," Roberts says. "That way they can say they weren't influenced by their genetic test results. But our data suggests that people still do make decisions after the fact."
• Preventative measures – There is limited evidence about the effectiveness of lifestyle changes (diet, exercise, mental activity) in preventing or lessening the effects of Alzheimer's disease. However, subjects in the REVEAL studies tended to cite disease risk reduction a prime motivation for seeking a genetic test.
Scott says education to subjects did include lifestyle suggestions, but made it clear that there is no consensus on how effective they are.
"We've tended to frame it by saying, "There are no proven methods, however, some research has suggested these as possible ways,' and we point out that they have other health benefits as well," he says. "We don't want to give these people false hope. On the other hand, I don't think it's unreasonable for people to try these things because, what's the downside?
"And I think from a psychological point of view, people think, 'At least I'm doing something, I'm not just sitting here passively and waiting to see what happens.'"
Roberts says his own IRB required that his group document that it was using a CLIA-approved laboratory for the tests. They obtained a certificate of confidentiality from the National Institutes of Health and created an external advisory board of experts in genetics, bioethics and even insurance law, to review the study.
While not all studies may require an expert panel, he says, the other protections are not overly burdensome and make good sense.
He also notes that there are existing guidelines by bodies such as the National Heart, Lung and Blood Institute for returning genetic research results that can assist IRBs in reviewing these types of studies.
"Our take is there isn't enough empirical evidence to really guide us, but a lot of expert consensus statements," he says. "We need a little bit more empirical research to help us along as well."
Reference
Roberts JS, Christensen KD, Green RC. Using Alzheimer's disease as a model for genetic risk disclosure: implications for personal genomics. Clin Genet 2011:80:407-414.
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