Immediate Reactions to Alzheimer Biomarker Disclosure in Cognitively Unimpaired Individuals in a Global Truncated Randomized Trial.

Background and Objectives: Preclinical Alzheimer disease (AD) trials simultaneously test candidate treatments and the implications of disclosing biomarker information to cognitively unimpaired individuals. Methods: The EARLY trial was a randomized, double-blind, placebo-controlled, phase 2b/3 study conducted in 143 centers across 14 countries from November 2015 to December 2018 after being stopped prematurely because of treatment-related hepatotoxicity. Participants age 60-85 years deemed cognitively unimpaired were disclosed an elevated or not elevated brain amyloid result by a certified clinician. Among 3,686 participants, 2,066 underwent amyloid imaging, 1,394 underwent CSF biomarker assessment, and 226 underwent both. Among biomarker-tested participants with at least one change score on an outcome of interest, 680 with elevated and 2,698 with not elevated amyloid were included in this analysis. We compared the Geriatric Depression Scale (GDS), the State-Trait Anxiety Scale (STAI), and the Columbia Suicide Severity Rating Scale (CSSRS) before disclosure between amyloid groups. After disclosure, we assessed for differences in the Impact of Events Scale (IES, collected 24-72 hours after disclosure), a measure of intrusive thoughts. Additional scales included the Concerns for AD scale. Results: Among 3378 included participants, the mean (SD) age was 69.0 (5.3); most were female (60%) and White race (84%). No differences were observed before disclosure between participants with elevated and not elevated amyloid for the GDS, STAI, or CSSRS. Participants with elevated amyloid demonstrated higher Concerns for AD scores compared with participants with not elevated amyloid before disclosure. Participants with elevated amyloid demonstrated higher IES scores (9.6 [10.8] vs 5.1 [8.0]) after disclosure and increased Concerns about AD. Patterns of reactions (elevated vs not elevated) were similar for biomarker modalities, although scores were lower among those undergoing CSF compared with PET testing. Although score differences were apparent comparing geographical regions, patterns of group differences were similar. Discussion: Although sample bias must be considered, these results suggest that amyloid disclosure resulted in increased perceived risk and mild distress in those learning an elevated result. Although this study did not assess psychological safety, observed associations intrusive thoughts and distress could be important considerations in the future clinical practice.