APOE disclosure in cognitively unimpaired adults: psychological impact in a trial pre-screening cohort

We searched PubMed for publications from database inception up to March 1, 2025, using the terms “APOE”, “genetic counseling”, and “genetic disclosure”, for articles published in English. Although we identified studies that investigated the changes in psychological symptoms following APOE genotype, we did not find any studies that examined the impact of disclosure by APOE4 gene dose (that is, APOE4 non-carriers, heterozygotes, and homozygotes). Furthermore, these studies were primarily US-based and often enrolled participants who were more than a decade younger than the average age for developing symptoms of Alzheimer’s disease.

To our knowledge, this is the first study of its kind that disclosed APOE results to individuals as part of the screening process for participation in a clinical trial and then followed up those participants for up to 12 months to assess the impact of APOE disclosure. Additionally, this study represents the largest experience of disclosing APOE genotypes to date, especially to participants who are homozygotes, and it is notable for the older age of participants compared with previous research.

Our results suggest that APOE disclosure to cognitively unimpaired adults deemed psychologically ready and willing to learn their results from an experienced health-care provider is well tolerated and does not cause persistent, clinically significant psychological symptoms. These results are timely and important given more frequent APOE disclosure to guide clinical decision making for patients considering amyloid-modifying therapies, and the availability of genetic testing for family members interested in APOE testing. Results from this study should be used to inform the development and implementation of scalable programmes for disclosing APOE and other biomarker results for Alzheimer’s disease to cognitively unimpaired adults.

Source: The Lancet Healthy Longevity