Disclosure of APOE Genotype for Risk for Alzheimer's Disease

Laurie Barclay, MD


August 12, 2009

Disclosure of APOE Genotype for Risk of Alzheimer's Disease

Green RC, Roberts JS, Cupples LA, et al
N Engl J Med. 2009;361:245-254


Although the apolipoprotein E (APOE) genotype is known to help predict risk for Alzheimer's disease, genotyping of patients and their family members has not been recommended, in part for fear of inflicting emotional distress.

This prospective, randomized, controlled trial aimed to evaluate the effect of genotype disclosure in 162 asymptomatic adults who had a parent with Alzheimer's disease. Participants were randomly assigned to receive the results of their own APOE genotyping (disclosure group) or not to receive these results (nondisclosure group). Symptoms of anxiety, depression, and test-related distress were determined at 6 weeks, 6 months, and 1 year after disclosure or nondisclosure.

The 2 groups did not differ significantly in changes in time-averaged measures of anxiety (4.5 in the disclosure group vs 4.4 in the nondisclosure group; P = .84), depression (8.8 vs 8.7; P = .98), or test-related distress (6.9 vs 7.5, respectively; P = .61). There were also no significant differences in secondary comparisons between the nondisclosure group and a disclosure subgroup of participants carrying the APOE ε4 allele, which predicts increased risk for Alzheimer’s disease. Compared with the ε4-positive subgroup, however, the ε4-negative subgroup had significantly less test-related distress (P = .01).

The nondisclosure group and the ε4-positive and ε4-negative subgroups had similar proportions of participants with clinically meaningful changes in psychological outcomes. Postdisclosure scores for anxiety and depression were strongly associated with baseline scores for these symptoms (P < .001 for both comparisons).


Disclosing results of APOE genotyping to adult children of patients with Alzheimer's disease was not associated with significant short-term psychological harm, and participants who learned that they were negative for APOE ε4 had decreased levels of test-related distress. Emotional symptoms after disclosure were more likely to occur in participants who already had high levels of emotional distress before undergoing genetic testing.

Limitations of this study include follow-up of just 1 year, testing of only a single polymorphism linked to Alzheimer's disease, and a homogeneous study sample with similar ancestry and known family history of Alzheimer’s disease. The persons who agreed to participate and to accept randomization regarding whether they would learn their APOE status may not be representative of those who have a strong desire to know or not to know their genetic test results. Potential effects on financial or employment decisions or on eligibility for long-term care or disability insurance also were not addressed.

Some caution is therefore needed when considering genetic testing in adults not known to have a positive family history particularly because disclosure at this stage has no clear medical benefit. An additional caveat is that genetic risk may be poorly understood by both the lay public and medical professionals.



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