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INTRODUCTION: Trialists need a thorough understanding of whether reactions to Alzheimer's disease (AD) biomarker information differ among racial and ethnic groups in preclinical AD trials. METHODS: We used data from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease Study to analyze cognitively unimpaired participants' responses on the Impact of Event Scale (IES) 24 to 72 hours after amyloid disclosure. We fit a linear regression model to test whether mean IES scores differed among participants from specific racial and ethnic groups. We considered potential effect modification by amyloid status. RESULTS: Reactions to disclosure did not significantly differ among participant groups based on self‐reported race and ethnicity. Although the results were not significant when stratified by amyloid status, all racial and ethnic groups except for participants self‐reporting Hispanic/Latino ethnicity were observed to have higher mean IES in the elevated amyloid group. DISCUSSION: These results support continued use of current disclosure methods in preclinical AD trials. [ABSTRACT FROM AUTHOR]

Background: Preclinical Alzheimer's disease (AD) trials require biomarker testing and disclosure. Efforts are underway to improve the diversity and inclusivity of enrollment in these trials. While previous studies have shown that disclosure can be performed safely, trialists need a more thorough understanding of whether reactions to AD biomarker disclosure differ among racial and ethnic groups. Methods: Using data from the Anti‐Amyloid treatment in Asymptomatic AD (A4) study, we analyzed participant responses on the Impact of Events Scale (IES), a 15‐item questionnaire that assesses avoidance and intrusive thoughts after disclosure of amyloid imaging results. We fit a linear regression model to test the hypothesis that mean IES scores differed by racial and ethnic group. Confounding factors included age, sex, years of education, study partner type, family history of AD, and amyloid status. We considered potential effect modification by amyloid status by including an interaction term between race and amyloid group. Results: IES data were available for 4311 participants (3795 = non‐Hispanic [NH] White; 147 = NH Black; 165 = NH Asian; 135 = Hispanic; 69 = Other). Figure 1 illustrates total IES scores for the groups, stratified by amyloid status. NH Asians demonstrated the highest mean IES among those with elevated amyloid. Hispanics demonstrated the lowest mean IES among those with elevated amyloid, but the highest among those with not elevated amyloid. In a regression model, younger age, female sex, and family history of AD were associated with higher IES. Overall, the association between race and ethnicity groups and IES did not significantly differ by amyloid status (p = 0.200). Among not elevated amyloid individuals, Hispanics had a significantly higher mean IES when compared to NH Whites (est: 2.38; 95% CI: 0.57, 4.19; p = 0.10). Among elevated amyloid individuals, this estimate decreased to ‐1.47 (95% CI: ‐4.36, 1.42; p = 0.319). Conclusions: When stratified by amyloid status, all racial and ethnic groups showed higher mean IES in the elevated compared to the not elevated amyloid group, except for Hispanics. This may suggest that, for Hispanics, having an AD biomarker test at all may lead to avoidance and intrusive thoughts, regardless of the specific test result. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that many cognitively unimpaired older individuals are interested in learning their Alzheimer's disease (AD) biomarker results. Yet, little is known about what motivates participation in preclinical AD trials that require amyloid biomarker testing and disclosure, and whether these motivations differ by biomarker results (elevated or not‐elevated amyloid). Method: Using data from the EARLY trial, a preclinical AD trial testing the safety and efficacy of a BACE1 inhibitor, we analyzed participant responses on the Views and Perceptions of Amyloid Imaging (VPAI) scale (Table 1) that was collected during the screening process; that is, before undergoing biomarker testing and disclosure. Participants were asked to rate how important 9 potential reasons for seeking amyloid imaging were to them. Response options included "not at all" (1), "a little" (2), "somewhat" (3), "very" (4), and "extremely" (5). We categorized raw scores into binary responses; those with high endorsement (scores ≥4) and those with low‐to‐moderate endorsement (scores <4). We stratified participant responses by amyloid group to examine whether their biomarker status impacted participant item‐level VPAI scores. Result: Prior to biomarker testing and disclosure, participants most often endorsed the desire to contribute to research as a motivation to participate (Table 1). In general, the not‐elevated amyloid group had higher endorsement for the VPAI items than the elevated amyloid group. The proportions of participants endorsing "confirm feeling that I might be developing dementia" and "preparing family members" were observed to be higher among participants with elevated compared to not‐elevated amyloid; whereas "curiosity" was endorsed by a higher proportion of the not‐elevated amyloid group. Conclusion: While there are individual differences in reasons for seeking an amyloid scan, preclinical AD trial participants may be largely motivated by altruistic factors. Differences in factors that motivate participants to learn biomarker results may be apparent between amyloid groups even before biomarker disclosure. [ABSTRACT FROM AUTHOR]

Background: Participant retention directly affects the validity and generalizability of clinical trial results. Investigators need information about expected attrition when planning trials of varying durations. Method: Using the Alzforum and clinicaltrials.gov databases we reviewed 351 phase 2 and 3 placebo‐controlled trials conducted since 1998. Eighty‐six mild‐to‐moderate Alzheimer's disease (AD) and eleven Mild Cognitive Impairment (MCI) trials met criteria for inclusion in this study. We first assessed the frequency with which trial arms differed in overall retention. When trials included more than one active arm, we combined those arms into a single group. To model associations between trial duration and retention, we used binomial regression. Result: Figure 1 illustrates differences in the observed proportion of participants completing in each trial between active and placebo arms for mild‐to‐moderate AD (Figure 1A) and MCI trials (Figure 1B). For each trial, a 95% confidence interval for the true difference between arms is provided. Since there was no consistent difference between arms, subsequent analyses combined active and placebo arms. Figure 2 illustrates the completion rate by trial duration for mild‐to‐moderate AD (Figure 2A) and MCI trials (Figure 2B). A local smoother along with uncertainty regions is added for visual aid. In general, trials with longer study duration had lower retention rates. Using binomial regression with robust variance estimates to account for within‐trial correlation, we estimated that a 6‐month increase in trial duration is associated with a 34% decrease in the odds of trial completion (OR=0.66; 95% CI: 0.58, 0.75; p<0.001) among mild‐to‐moderate AD trials and a 20% decrease (OR=0.80; 95% CI: 0.68, 0.93; p=0.004) among MCI trials. From the binomial regression model, the proportion of participants completing 6, 12, and 18‐month trials were estimated to be 82.9%, 76.3%, and 68.0% for mild‐to‐moderate AD trials and 82.6%, 79.1%, and 75.2% for MCI trials, respectively. Conclusion: While decisions related to expected trial attrition are guided by several factors, these estimates may assist investigators designing trials and suggest that trial attrition is frequent and related to trial duration. [ABSTRACT FROM AUTHOR]