Comparing test-specific distress of susceptibility versus deterministic genetic testing for Alzheimer's disease

Genetic risk for Alzheimer's disease (AD) can be conferred by the susceptibility polymorphism apolipoprotein E (APOE), where the epsilon 4 allele increases the risk of developing late-onset AD but is not a definitive predictor of the disease, or by autosomal dominant mutations (eg, the presenilins), which almost inevitably result in early-onset familial AD. The purpose of this study was to compare the psychological impact of using these two different types of genetic information to disclose genetic risk for AD to family members of affected patients.

Data were compared from two separate protocols. The Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study is a randomized, multi-site clinical trial that evaluated the impact of susceptibility testing for AD with APOE in 101 adult children of AD patients. A separate study, conducted at the University of Washington, assessed the impact of deterministic genetic testing by disclosing presenilin-1, presenilin-2, or TAU genotype to 22 individuals at risk for familial AD or frontotemporal dementia. In both protocols, participants received genetic counseling and completed the impact of event scale (IES), a measure of test-specific distress. Scores were analyzed at the time point closest to 1 year after disclosure at which IES data were available. The role of genetic test result (positive vs negative) and type of genetic testing (deterministic vs susceptibility) in predicting log-transformed IES scores were assessed with linear regression, controlling for age, gender, and time from disclosure.

Subjects from the REVEAL Study who learned that they were positive for the susceptibility gene APOE epsilon 4+ experienced similar, low levels of test-specific distress compared with those who received positive results of deterministic testing in the University of Washington study (P = .78). APOE epsilon 4+ individuals in the susceptibility protocol experienced more test-specific distress than those who tested epsilon 4- in the same study (P = .04); however, among those receiving deterministic test disclosure, the subjects who received positive results did not experience significantly higher levels of distress when compared with those who received negative results (P = .88).

The findings of this preliminary study, with limited sample size, suggest that the test-related distress experienced by those receiving positive results for a deterministic mutation is similar to the distress experienced by those receiving positive results from genetic susceptibility testing, and that the majority of participants receiving genotype disclosure do not experience clinically significant distress as indicated by IES scores 1 year after learning of their test results.