An article in the New York Times is the latest to highlight the safety risks associated with recently approved new treatments for Alzheimer’s disease, lecanemab and donanemab. Being a carrier of the e4 genotype for the apolipoprotein (APOE) gene, is a known risk factor for the most serious side effects of these medications—swelling and bleeding in the brain collectively known as Amyloid Related Imaging Abnormalities (ARIA). The article highlights that in some of the earlier studies of these drugs, participants were not given the opportunity to learn their APOE genotypes.
The field has historically been reluctant to disclose APOE results inside and outside of research. The reason is that, aside from the well documented impact on disease risk (e4 carriers are more likely to develop Alzheimer’s disease than people who do not carry this gene), there were rather mixed data as to whether APOE genotype had an impact on clinical outcomes once disease was present—for things like the rate of disease progression or treatment outcomes. Further, while some legal protections are in place to prevent discrimination against people based on their APOE genotype, current laws are imperfect and don’t prevent discrimination from long-term care insurers (which studies suggest people who learn they are carrier of the e4 allele are more likely to pursue), for example.
The approval of lecanemab and donanemab changed this. Now, APOE genotype has a demonstrated impact on the risks associated with these treatments and the field must adjust. In fact, UCI MIND investigators have offered important guidance on this. And in new clinical trials of these medications, such as the landmark AHEAD Study (of lecanemab) at UCI MIND, every participant had the opportunity to learn their APOE results before deciding whether to fully enroll in the study.
More broadly, it is not always appropriate or possible to disclose research results to participants. Faculty at UCI MIND have long had an academic interest in this. In fact, we helped develop guidance for all nationally funded Alzheimer’s Disease Research Centers on this topic. This guidance highlights a number of important considerations, including that even when investigators are interested in returning individual research results to participants, they have to be mindful of what doing so might mean to participants and that a certain level of understanding of the meaning of the returned result is essential before even considering returning it to participants. This takes time and study and is a critical responsibility of investigators. They cannot simply give participants “all of their results.” They must deliver them with information about their meaning and implications. To do any less would be inappropriate and could place participants at risk for misunderstanding or worse, if they are left to scour the internet for answers about what results mean.
And so the desire to return as much information to participants as possible must be balanced with ensuring their safety. What can and cannot be shared changes over time, with new knowledge and research progress. We understand that this progress is not possible without the amazing people who participate in our studies. Our goal, after all, is to find solutions that work for them and all others who may face these diseases.
