Clinical Manifestations

Background: The impact of knowledge of β-amyloid status on cognitively unimpaired persons' cognitive test performance is unknown.

Method: Cognitively unimpaired adults aged 65-80 with a first-degree relative with AD received a dementia risk estimate and were randomly assigned to disclosure (D+) or non-disclosure (D-) of their β-amyloid PET scan result. At 6 weeks and 6 months post-disclosure, participants completed the ADCS-PACC, a composite of Free and Cued Selective Reminding (free portion), Logical Memory IIa test, Digit-Symbol Substitution, and MMSE. Scores from each test are standardized to a Z-score metric and a composite score calculated by summing the standardized Z-scores.

Result: 315 participants were randomized (84 elevated (41 A+D+/43 A+D-)) and 231 not elevated (118 A-D+, 113 A-D-)). After adjusting for baseline PACC scores, analyses compared PACC scores between (1.) A+D+ and A+D- and (2.) A-D+ and A-D- and stratified by race. A+ participants who learned their result (D+) had lower mean follow-up PACC scores than participants who did not learn their β-amyloid PET scan result (D-) at 6 weeks (β = -0.89, 95% CI: -1.65, -0.13, p = 0.023) but not at 6 months post-disclosure (β = -0.50, 95% CI -1.28, 0.27, p = .21). Mean follow-up PACC scores did not differ between A- who did or did not learn their result at both 6 weeks (β -0.02, 95% CI: -0.42, 0.37, p = 0.91) and 6 months post-disclosure (β -0.15, 95% CI -0.54, 0.25, p = .47). Analyses stratified by race showed Black/African American A+D+ had lower scores than A+D- at 6 weeks (β -2.01, 95% CI: -3.57, -0.45, p = 0.01) and 6 months post-disclosure (β -1.63, 95% CI -3.19, -0.06, p = .04). Disclosure had no impact on scores of nonblack participants with elevated amyloid and the scores of any of not elevated participant groups.

Conclusion: Knowledge of an elevated amyloid result reduced cognitively unimpaired persons PACC scores. A greater impact was observed in Black/African American participants' test performance compared to non-Black participants. In contrast, knowledge of not-elevated amyloid showed no impact on test performance in any of the groups. Clinical trials should consider the potential impact of AD biomarker knowledge on cognitive outcomes.