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.
Competing Interests: J.D. Grill reports grant funding from the NIH (P30 AG066519), Eli Lilly, Biogen, Eisai, BrightFocus Foundation, and the Alzheimer's Association. R. Raman reports grant funding from the NIH, Eli Lilly, Eisai, American Heart Association and the Alzheimer's Association. K. Ernstrom reports grant funding from the NIH, Eli Lilly, and Eisai. S. Wang reports grant funding from the NIH, Eli Lilly, and Eisai. M.C. Donohue reports consulting fees from Roche and his spouse is a full time employee of Janssen. P.S. Aisen reports research funding from NIH, the Alzheimer's Association, Janssen, Lilly and Eisai, and consults with Merck, Roche, Genentech, Abbvie, Biogen, ImmunoBrain Checkpoint and Arrowhead. J. Karlawish reports grant funding from Eisai and Biogen. D. Henley is a full time employee of Janssen. G. Romano is a former full time employee of Janssen. G. Novak is a former full time employee of Janssen. H.R. Brashear is a former full time employee of Janssen. R.A. Sperling reports serving as a paid consultant for AC Immune, Alector, Acumen, Alnylam, Cytox, Genentech, Janssen, Neuraly, NervGen, Neurocentria, Oligomerix, Prothena, Renew, Vigil Neuroscience, Ionis and Vaxxinity. She receives research support from Eisai and Eli Lilly as part of public-private partnership clinical trials, and also receives research support from the following grants: P01 AG036694, U24 AG057437, R01 AG063689, R01 AG054029, R01 AG053798, GHR Foundation, National Institute on Aging, Fidelity Biosciences, and the Alzheimer's Association. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
(© 2024 American Academy of Neurology.)