Adult children of patients with Alzheimer’s disease are not at significant short-term psychologic risk after learning their apolipoprotein E (APOE) genotype status, according to a study in the July 16 New England Journal of Medicine. However, researchers found that persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure.
“These data support the psychologic safety of disclosing data regarding genetic-counseling protocols to screened adult children of patients with Alzheimer’s disease who request such information, despite the frightening nature of the disease and the fact that disclosure has no clear medical benefit,” stated Robert C. Green, MD, Professor of Neurology at Boston University School of Medicine, and colleagues.
In an accompanying editorial, Rosalie A. Kane, PhD, and Robert L. Kane, MD, noted that this specific test “warrants extra caution.”
Learning APOE Status
For the Risk Evaluation and Education for Alzheimer’s Disease (REVEAL) study, Dr. Green and coinvestigators hypothesized that patients who learned their APOEstatus via an education and disclosure protocol would not have greater symptoms of anxiety, depression, or test-related distress than those not receiving this information. Genetics counselors monitored all subjects for psychologic effects throughout the trial.
Dr. Green’s group randomly assigned 162 asymptomatic adults who had a parent with Alzheimer’s disease to the disclosure group or the nondisclosure group. Symptoms of anxiety and depression were the primary outcome measure, noted at six weeks, six months, and one year following disclosure or nondisclosure, and assessed with use of the Beck Anxiety Inventory (BAI) and the Center for Epidemiological Studies Depression Scale (CES-D). Test-related distress was the secondary outcome and was measured with use of the Impact of Event Scale (IES). A secondary analysis compared the APOE ε 4-positive subgroup with either the ε 4-negative subgroup or the nondisclosure group.
Effects of Genotype Disclosure
No significant differences were found between the disclosure and nondisclosure groups regarding changes in time-averaged anxiety (4.5 vs. 4.4, respectively), depression (8.8 vs. 8.7, respectively), or test-related distress (6.9 vs. 7.5, respectively). Between-group differences in scores were stable over time. A post-hoc analysis for equivalence was completed after no significant differences were observed in prespecified analyses. “Post-disclosure scores on the BAI and the CES-D were strongly associated with respective baseline scores on these measures for both comparisons,” Dr. Green’s group noted.
Secondary comparisons between the nondisclosure group and the disclosure subgroup that were ε 4-positive revealed no significant differences. However, the ε 4-negative subgroup showed a significantly lower level of test-related distress than the ε 4-positive subgroup.
The investigators observed no significant differences between the nondisclosure group and the ε 4-positive subgroup using the longitudinal model or at any time point. Mean adjusted IES scores did not substantially differ at any time point or over time (6.9 in the disclosure group vs. 7.5 in the nondisclosure group).
The adjusted IES scores were lower in the ε 4-negative subgroup than in the nondisclosure group at six months and over time. Significant differences were also seen between the IES scores in the ε 4-negative and ε 4-positive subgroups over time (4.8 vs. 8.5, respectively) and at six weeks, six months, and marginally at 12 months.
Drs. Kane and Kane posited that more distress may occur after this time point and suggested that “persons who tested positive for the allele (or simply received disclosure) might react years later, perhaps when they first forget a name or observe distress in a relative with dementia.”
Subjects with clinically meaningful changes in psychologic outcomes were distributed evenly across groups, and none attributed his or her psychologic state to the disclosure results. In addition, those in the ε 4-positive subgroup were more likely than others to report being negatively affected by learning their genotype.
“This finding suggests that the subjects in the ε 4-positive group understood the information they received with respect to risk, and that they had some negative feelings about receiving their results,” the editorialists commented. Subjects in both groups said they would undergo testing again.
Although disclosure of APOE genotyping did not result in significant short-term psychologic risks, further investigation is needed to identify the effects of learning these results after longer periods of time, according to Dr. Green and colleagues. They noted that the study results might have been different if participants with low neurocognitive scores and high depression scores had been included, if subjects did not have a family history of Alzheimer’s disease, or if genetics counselors were not available.
—Laura Sassano