Article

Disclosure of APOE Genotype for Risk of Alzheimer's Disease

Boston University School of Medicine, Boston, MA 02118, USA.
New England Journal of Medicine (Impact Factor: 54.42). 07/2009; 361(3):245-54. DOI: 10.1056/NEJMoa0809578
Source: PubMed

ABSTRACT The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial.
We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure.
There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon4 allele (which is associated with increased risk) also revealed no significant differences. However, the epsilon4-negative subgroup had a significantly lower level of test-related distress than did the epsilon4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon4-positive and epsilon4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons).
The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE epsilon4-negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)

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    • "Participants were randomized to either disclosure of results for the risk allele or non-disclosure. The authors reported no significant differences between the two groups in anxiety or depression up to one year [14]. However, Dr. Clayton noted that the REVEAL study was comprised of individuals who were already aware of their AD risk because of family history, were extensively counseled about AD risk as part of their participation, and had consented to the study. "
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    • "These results also indicate the importance of genetic background in determining likelihood and extent of amyloid accumulation, even in preclinical stages, which may be particularly important in clinical trial enrollment. Further, in the era of personalized medicine, the implications of APOE genotype disclosure to patients in a clinical setting must be carefully considered, given the impact of APOE on AD risk and amyloid deposition (Green et al., 2009; Roberts et al., 2011 "
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    • "APOE susceptibility testing. In the REVEAL I study, Green et al. (2009) found that disclosure of APOE genotype did not lead to significant short-term psychological risks. In a qualitative component assessing a sub-sample of the same cohort, participants (n = 29, 48%) reported feelings of relief after APOE result disclosure, including four participants who received e4-positive results (Gooding et al., 2006). "
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