This is the first analysis to explore how perceptions about the pros and cons about genetic susceptibility tests change after actual testing. Our data supported the hypothesis that people who seek and obtain APOE
genetic testing as part of obtaining AD risk assessment retain strong positive attitudes about the experience but generally reduce their endorsements of the pros and increase their concerns about risk of discrimination after undergoing testing. Among the topics where perceptions of the pros were diminished after disclosure, this drop was particularly striking in the items “to seek information about preventative measures” and “to know about risk in case better treatments become available.” Similarly, there was an increase in the perceived con item “lack of a cure or prevention.” One of the main reasons APOE
testing of asymptomatic patients for AD risk is not part of standard clinical practice is the absence of options to prevent or delay disease onset,38–40
and educational materials in the REVEAL Study emphasized that “there are no proven ways to prevent Alzheimer disease.” Despite this clear disclaimer, it is possible that some participants sought susceptibility testing thinking that genetic susceptibility testing would expose them to new strategies for reducing or delaying AD risk, especially when conducted as part of research. Anecdotally, many participants asked REVEAL Study personnel whether the investigative team was also associated with prevention and treatment trials, although such queries were not formally tracked.
At the same time, APOE ε
4 carriers did not lower their rating of “to seek information on preventative measures” as much as noncarriers did, suggesting that they found greater utility to the genetic risk assessment in terms of thinking about prevention measures. This finding is consistent with prior analyses of REVEAL Study data showing ε
4 carriers to be more likely to report health behavior changes than noncarriers, particularly in their consumption of dietary supplements and vitamins.41,42
It seems that those who learn they are ε
4 carriers may feel justified in using unproven preventative measures. If so, clinicians who provide predictive genetic testing should be sure that efficacy expectations about such measures are realistic and that test recipients do not pursue strategies—such as off-label use of pharmaceuticals—that may be detrimental to their health.
Another theme that emerged in the data related to the risk of future disability. “To make arrangements for long-term care” and “to start doing things sooner” were reasons for testing that were, on average, rated lower after testing than before. This finding was surprising given prior REVEAL Study data showing that APOE
genetic susceptibility test results can inform the purchase of LTC insurance.30,43
It is possible that participants who hoped to use testing to inform decisions about the future, such as LTC insurance purchasing, were dissuaded because of greater sensitivity to the limited positive and negative predictive value of APOE
for AD. Supporting this argument, participants rated the lack of a definitive answer about future AD onset as a stronger con at follow-up.
Participants also tended to rate the reason “to give information about my children’s possible risk for AD” lower at follow-up than at baseline. The change varied by APOE
status, with ε
4 carriers lowering their ratings more than noncarriers. This difference may be attributable to concern or guilt about passing increased risk for AD risk along to children, supported by evidence that carriers feel more test-specific distress in the short-term than noncarriers.31
Another possibility is that carriers may consider sharing “bad” news to be more stressful than sharing “good” news.
A final benefit that was rated lower after testing was “the desire to contribute to research on AD.” This finding is interesting given prior findings that endorsement of this reason predicted follow-through on intentions to seek testing in prior analyses.10
It is possible that the burdens of study participation—which included regular follow-ups and completion of questionnaires over a 1-year period after disclosure—tempered the altruism many participants felt when they originally enrolled in the study, and anecdotal evidence suggested that some participants thought the surveys and time required for the study were excessive. On the other hand, participants tended to rate testing burdens lower at follow-up than at baseline. It may simply be that testing was interesting while study follow-up was less so.
The increases in concern about discrimination merit attention considering federal legislation enacted after data collection ended in 2006. The Genetic Information Nondiscrimination Act of 2008 has been hailed as a success for genomic medicine because it provides federal protections against employment and health insurance discrimination based on genetic information, including genetic test results.44
Although many such protections had already been provided in a patchwork of state legislations—including all states and districts hosting REVEAL Study sites at the time of the study—the passage of Genetic Information Nondiscrimination Act has likely raised awareness about the existence of legal protections, especially considering the media attention its passage has generated after 13 years of debate. Discrimination fears related to genetic testing may not be so strong in the future.
Several limitations should be kept in mind while interpreting results. Our methodology does not allow us to make determinations about what reasons may have caused the changes in perceptions of pros and cons. After participants completed the baseline assessment, participants received educational preparation for the study, underwent a second informed consent step, and had in-person discussions with a clinician. In each of those steps, participants received information about the benefits, risks, and limitations of AD genetic susceptibility testing, and any or all of these activities could have contributed to changes in perceptions of pros and cons. Furthermore, participants lacking data at 12 months were omitted from analysis, possibly biasing results. Among this group were those with lower presumed socioeconomic status (those with the less education, lower household incomes, or were not currently employed) in addition to those who perceived greater pros and greater cons at baseline. In addition, our close-ended survey items are unlikely to have captured all pros and cons relevant to a given participant. Finally, significance levels were not adjusted to account for the number of comparisons conducted because the study was not powered for this secondary analysis, thus increasing the risk for false-positive findings.
Nevertheless, the findings from this analysis have important implications for the way genetic services are delivered. Our analyses show strong positive attitudes toward genetic susceptibility testing for AD, even after a genetic risk assessment that includes APOE
genotyping. Additional genetic tests associated with risk for AD and tests for other untreatable diseases are likely to become available in the future.24
If so, we can expect those who have already undergone AD susceptibility testing to have favorable attitudes toward the new ones.
Finally, if post-test ratings represent a more accurate appraisal of the benefits, risks, and limitations of APOE
genetic testing for AD risk, then the minor changes observed in our analysis demonstrate slight discordance between how participants anticipated they would use genetic risk information and how they actually used it. Experts tend to agree that the best decisions are made when expectations are brought into alignment with true outcomes through a process of education and deliberation.45
The condensed educational protocol tested in the second REVEAL Study trial imposed substantially less burdens on both clinicians and test recipients (i.e., one fewer study visit and a reduction in clinic time of over 40 minutes). The lack of differences in perceptions of cons and pros by educational protocol in our study suggests that condensed protocols can have the same effect as more time-consuming ones, at least on altering the perceptions individuals have about what APOE
testing can achieve. As genetic testing for susceptibility becomes more common, providers will need to seek the right balance between feasibility and effectiveness in pretest education to ensure that people seeking such testing are making informed decisions.