No cognitive or psychological impact from returning research Alzheimer disease biomarkers: A delayed-start,...

Little is known about the impact of returning Alzheimer disease (AD) biomarkers to cognitively unimpaired (CU) research participants.

Determine whether return of research results (RoRR) negatively impacts longitudinal symptoms of depression and cognition.

Randomized, noninferiority, delayed-start clinical trial, 2021-2025.

AD biomarker research results offered to CU participants in a longitudinal cohort of community-dwelling older adults.

341 CU research participants age >65 with available biomarkers (APOE genotype and either plasma Aβ42/40 or amyloid PET and MRI hippocampal volume) were recruited.

Participants were offered their research AD biomarker results (RoRR) with an estimated 5-year risk of symptomatic AD. After consenting, participants were randomized to either receiving results within several weeks (RoRR arm) or 1 year later (delayed-start arm).

Longitudinal change in Geriatric Depression Scale (GDS), Clinical Dementia Rating^® sum of boxes (CDR-SB), and global cognitive composite. Outcomes were measured at annual assessments for a longitudinal study of aging.

147 participants received results after randomization: 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 (Aβ+) and in those without elevated amyloid (Aβ-) for GDS (Aβ+ difference 0.7, 95% CI 0.0-1.3; Aβ- difference -0.1, 95% CI -0.7-0.5; clinically significant decline >4.0), CDR-SB (Aβ+ difference 0.0, 95% CI -0.1-0.1; Aβ- difference 0.0, 95% CI 0.0-0.1; clinically significant decline >0.5), and cognitive composite (Aβ+ difference -0.10, 95% CI -0.25-0.06; Aβ- 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.

In 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.

NCT04699786.