NEW YORK (GenomeWeb News) – Receiving information regarding apolipoprotein E, or APOE, status — a genetic risk factor for Alzheimer's disease — did not increase psychological risk in adult children of Alzheimer's patients, a new study has concluded. The research appears in today's issue of the New England Journal of Medicine.
Researchers involved in the Risk Evaluation and Education for Alzheimer's Disease, or REVEAL, program, a multi-center project funded by the National Human Genome Research Institute and the National Institute on Aging, did a randomized, controlled trial involving 162 asymptomatic adults who had a parent with Alzheimer's disease to assess the psychological consequences of learning APOE status.
When they measured anxiety, depression, and test-related distress in the subjects several weeks or months after testing, the team didn't see a significant difference in psychological risk in subjects who had received the APOE test results compared with those who didn't.
"Our participants were quite well adjusted to the news," lead author Robert Green, a neurology, genetics, and epidemiology researcher affiliated with Boston University and Harvard Medical School, told GenomeWeb Daily News.
The researchers reported a small, temporary increase in test-related distress in the higher risk, ε4 positive group compared with the lower risk, ε4 negative group. In contrast, those who did not carry the riskier ε4 variant had significantly less distress, they found. Individuals who carry one copy of the ε4 APOE variant have about a three times higher relative risk for late-onset Alzheimer's disease risk, Green explained, whereas those with two copies of ε4 have about 15 times the relative risk.
A second paper in NEJM today found that memory decline tends to be more rapid and begins at a younger age for those carrying ε4 than for those who do not.
At the moment, several experts and organizations have cautioned against routine APOE testing in individuals who don't have Alzheimer's symptoms, due to possible emotional and other side effects of learning, the authors noted. Even so, Green said, several direct-to-consumer genetic testing companies test SNPs that provide information related to APOE status.
In an effort to actually collect data on the psychological effects of APOE testing, Green and his team enrolled 162 adults who did not have any Alzheimer's symptoms but who did have a living or deceased parent with the disease. The study took place at several sites in Boston, Cleveland, and New York. The researchers excluded individuals from the study if they tested high for depression or anxiety at the time of enrollment.
The researchers obtained blood samples from the subjects and Athena Diagnostics performed the APOE genotyping. Then, subjects were randomly assigned to two groups — one that received the test results and another that did not. Twice as many individuals were assigned to the disclosure group as to the non-disclosure group, and 14 individuals withdrew from the study following randomization.
Genetic counselors helped participants interpret their Alzheimer's risk information based on family history and, for the disclosure group, APOE results.
In general, Green said, those involved in the study seemed to understand the nature of the information they were receiving. "People understood quite well that APOE could increase your risk or lower your risk but it did not decide whether you have Alzheimer's," he said.
When they assessed psychological factors such as anxiety, depression, and test-related distress six weeks, six months, and a year after testing, the researchers did not find a significant difference between the individuals who received the test results and those who didn't.
Even so, they noted, subjects in the disclosure group who tested negative for the risk genotype had significantly lower test-related distress than the group that tested positive. "Study participants who learned they were ε4 positive and were therefore at increased risk for Alzheimer's disease showed no more anxiety, depression, or test-related distress than those who did not learn their genotype," Green said in a statement, "but those who learned they were ε4 negative experienced considerable relief."
"The study by Green et al. is a rare and welcome trial of a process that might inform ethics guidelines," University of Minnesota researchers Rosalie Kane and Robert Kane wrote in an editorial appearing in the same issue of NEJM. Nevertheless, the duo cautioned, the results may not necessarily represent the general population.
"Presumably, subjects who agreed to participate were sufficiently indifferent to the potential test results to accept randomization and thus are not representative of those who have a strong perceived need to know or need not to know," they noted.
They also said that the study did not provide information about subjects' relationship with the affected parent, the time course of parental disease, and other pertinent factors. In addition, they added, the study cannot offer insights into other types of test-related risk — such as the social or financial effects of testing.
Green agreed that his team's results don't necessarily throw open the door for widespread APOE testing. But, he said, it is a step toward gaining a view of such tests that is based on science rather than assumptions about psychological and other types of risk. He said his group is currently doing related studies.
In the future, Green said he'd like to see even more research into genetic testing and related translational genomics areas, including larger clinical trials evaluating psychological and other effects of such tests.