ImportanceLittle is known about the impact of returning Alzheimer disease (AD) biomarkers to cognitively unimpaired (CU) research participants.
ObjectiveDoes return of research results (RoRR) negatively impact longitudinal symptoms of depression and cognition.
DesignRandomized, noninferiority, delayed-start clinical trial, 2021-2025
SettingAD biomarker research results offered to CU participants in a longitudinal study of aging
ParticipantsCU participants age [≥]65 were offered research AD biomarker results (APOE genotype and either plasma A{beta}42/40 or amyloid PET and MRI hippocampal volume) with an estimated 5-year risk of symptomatic AD.
Intervention(s) (for clinical trials) or Exposure(s) (for observational studies)147 participants were randomized to receive results either soon after consent (RoRR arm, N=73) or one year later (delayed-start arm, N=74).
Main Outcome(s) and Measure(s)Longitudinal change in Geriatric Depression Scale (GDS), Clinical Dementia Rating(R) sum of boxes (CDR-SB), and global cognitive composite. Outcomes were measured at annual assessments for a longitudinal study of aging.
Results187 participants received results: 70 in RoRR arm (average age 75, 60% female), 66 in delayed-start arm (average age 73, 53% female). The observed changes in annual measures did not differ between arms in both those with elevated amyloid (A{beta}+) and in those without elevated amyloid (A{beta}-) for GDS (A{beta}+ difference 0.7, 95% CI 0.0-1.3; A{beta}-difference -0.1, 95% CI -0.7-0.5; clinically significant decline >4.0), CDR-SB (A{beta}+ difference 0.0, 95% CI -0.1-0.1; A{beta}-difference 0.0, 95% CI 0.0-0.1; clinically significant decline >0.5), and cognitive composite (A{beta}+ difference -0.10, 95% CI -0.25-0.06; A{beta}-difference -0.05, 95% CI -0.17-0.07; clinically significant decline < -0.26). Secondary analyses found no evidence of association between RoRR and proximity to follow-up testing.
Conclusions and RelevanceIn the first randomized, delayed-start clinical trial of returning AD research results to CU older-adult participants, no effect was seen on longitudinal changes in symptoms of depression or cognition. This supports evidence that there are no harms to returning AD research results, although the results may not apply to more diverse populations not included in this study.
Trial RegistrationNCT04699786