Disclosure of APOE genotype for risk of Alzheimer's disease - PubMed (original) (raw)
Randomized Controlled Trial
. 2009 Jul 16;361(3):245-54.
doi: 10.1056/NEJMoa0809578.
J Scott Roberts, L Adrienne Cupples, Norman R Relkin, Peter J Whitehouse, Tamsen Brown, Susan LaRusse Eckert, Melissa Butson, A Dessa Sadovnick, Kimberly A Quaid, Clara Chen, Robert Cook-Deegan, Lindsay A Farrer; REVEAL Study Group
Collaborators, Affiliations
- PMID: 19605829
- PMCID: PMC2778270
- DOI: 10.1056/NEJMoa0809578
Randomized Controlled Trial
Disclosure of APOE genotype for risk of Alzheimer's disease
Robert C Green et al. N Engl J Med. 2009.
Abstract
Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.)
2009 Massachusetts Medical Society
Figures
Figure 1. Enrollment and Outcomes
Of the 21 subjects who were excluded before randomization, 7 had low neurocognitive scores, and 2 had high depression scores. The other 12 subjects withdrew from the study for other reasons.
Comment in
- Effect of genetic testing for risk of Alzheimer's disease.
Kane RA, Kane RL. Kane RA, et al. N Engl J Med. 2009 Jul 16;361(3):298-9. doi: 10.1056/NEJMe0903449. N Engl J Med. 2009. PMID: 19605835 No abstract available. - ACP Journal Club: Disclosure of genetic risk for Alzheimer disease did not increase anxiety or depression in asymptomatic adults.
Pramanik J. Pramanik J. Ann Intern Med. 2009 Nov 17;151(10):JC5-9. doi: 10.7326/0003-4819-151-10-200911170-02009. Ann Intern Med. 2009. PMID: 19920267 No abstract available. - Disclosure of the genetic risk of Alzheimer's disease.
Gordon SC, Landa D. Gordon SC, et al. N Engl J Med. 2010 Jan 14;362(2):181-2; author reply 182. doi: 10.1056/NEJMc096300. N Engl J Med. 2010. PMID: 20071713 No abstract available.
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