No cognitive or psychological impact from returning research Alzheimer disease biomarkers: A delayed-start, noninferiority, randomized clinical trial
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Importance
Little is known about the impact of returning Alzheimer disease (AD) biomarkers to cognitively unimpaired (CU) research participants.
Objective
Determine whether return of research results (RoRR) negatively impacts 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 cohort of community-dwelling older adults.
Participants
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.
Intervention(s) (for clinical trials) or Exposure(s) (for observational studies)
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).
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
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.
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
Key points
Question
Does return of Alzheimer’s disease (AD) research biomarker results to cognitively unimpaired older adults negatively impact longitudinal symptoms of depression and cognition?
Findings
In this randomized, delayed-start clinical trial, no effect of returning research AD biomarkers was seen on longitudinal changes in symptoms of depression or cognition.
Meaning
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.
