No evidence of cognitive or psychological impact after returning research Alzheimer disease biomarkers: A delayed-start, noninferiority, randomized clinical trial
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Importance
Little is known about the impact of returning Alzheimer disease (AD) biomarkers to cognitively unimpaired (CU) research participants.
Objective
Does return of research results (RoRR) negatively impact longitudinal symptoms of depression and cognition.
Design
Randomized, noninferiority, delayed-start clinical trial, 2021-2025
Setting
AD biomarker research results offered to CU participants in a longitudinal study of aging
Participants
CU participants age ≥65 were offered research AD biomarker results ( APOE genotype and either plasma Aβ42/40 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® sum of boxes (CDR-SB), and global cognitive composite. Outcomes were measured at annual assessments for a longitudinal study of aging.
Results
187 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 (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.
Conclusions and Relevance
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.
Trial Registration
NCT04699786
