BOSTON—Cognitively normal adults who learn that they are at high risk for Alzheimer’s disease do not, as some clinicians fear, develop depression, anxiety, or distress, investigators reported at the 2013 Alzheimer’s Association International Conference.
An analysis of data from three randomized trials testing the effects of genetic testing disclosure found that cognitively normal adults who learned that they were homozygous for the high-risk APOE ε4 allele had a spike in test-specific distress score until about six months after learning the results. The patients’ distress scores subsequently returned to levels similar to those of heterozygous carriers, reported Jason Karlawish, MD, Professor of Medicine at the University of Pennsylvania in Philadelphia, and his colleagues. Homozygous and heterozygous APOE ε4 carriers, however, had more test-specific distress than carriers of other APOE alleles did.
“While there is no question that learning that you’re at higher risk causes some test-specific distress, this [study] further validates that there is no long-term, sustained psychologic distress,” said Dr. Karlawish in an interview. People who learned that they were at high risk for developing Alzheimer’s disease were significantly more likely to adopt putative risk-reducing behaviors such as dietary changes, exercise, and medication or vitamin supplementation, he said.
Learning of High Risk Was Associated With Distress
The researchers examined participants in three cohorts of the Risk Evaluation and Education for Alz-heimer’s Disease (REVEAL) trial. The REVEAL study is a series of multicenter trials that evaluates the effects of APOE genotyping.
The group pooled data from three randomized REVEAL trials on 648 patients, identifying 399 (62%) participants who were negative for the ε4 allele, 221 (34%) who were heterozygous carriers of the ε4 allele, and 28 (4%) who were ε4 homozygotes. The investigators found that ε4 homozygotes and heterozygotes had significantly higher mean test-specific distress levels, compared with noncarriers, but there were no significant differences between the two ε4-positive groups.
Patient Groups Had Similar Depression Scores
Asked at one-year follow-up how they perceived their risk for Alzheimer’s disease, 64% of heterozygous carriers and 72% of homozygous carriers rated their risk as high or very high, a difference that was not significant. In contrast, about half of all noncarriers rated their risk as average, and about 15% rated it as high, but none rated their risk as very high. The investigators found no significant differences in patients’ mean depression scores on the Center for Epidemiologic Studies Depression Scale.
Approximately 61% of homozygous carriers reported dietary changes at 12 months, compared with 34% of heterozygous carriers and 27% of noncarriers. Homozygotes also were more likely to report increases in exercise (58% vs 39% and 28%, respectively) and to take medication or vitamins to try to stave off Alzheimer’s disease (58% vs 38% and 27%, respectively).
Although only 28 participants carried both copies of the ε4 allele, analysis of individual participants suggested that the data in this group were uniform and not skewed by outliers, said Dr. Karlawish. The distribution of APOE alleles in the study mirrored that of the population at large, he added. The researchers are mailing follow-up surveys to participants and plan to continue long-term follow-up.
—Neil Osterweil
IMNG Medical News