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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: Clinical trials now test promising therapies in the preclinical stages of Alzheimer's disease (AD). Participant willingness to enroll in different types of preclinical AD trials is understudied and whether the FDA approval of aducanumab affected these attitudes is unknown.Objective: To evaluate preferences toward three preclinical AD trial scenarios and whether the FDA approval of aducanumab changed willingness to participate among potential trial participants.Methods: Through an electronic survey, we asked enrollees in a recruitment registry age 50-79 to rate their willingness (using a 6-point Likert scale) to enroll in three hypothetical preclinical AD trial scenarios: an in-clinic infused monoclonal antibody intervention, a home-infused monoclonal antibody intervention, and an oral BACE inhibitor intervention. We administered the survey before and after the FDA approval of aducanumab. We used a generalized estimating equation model to assess group differences in preference for the trial scenarios. We used a paired t-test to determine if willingness to participate (using total willingness across three scenarios as the outcome) changed after the FDA decision.Results: At baseline, the mean participant willingness was highest in the in-clinic infusion scenario. There was no significant change in willingness to participate, overall, after the FDA decision. Participants who were independently aware of the FDA's decision (prior to the second survey) demonstrated reduced willingness to participate; participants unaware of the FDA decision demonstrated no change.Conclusion: Willingness to participate in preclinical AD trials may have been negatively affected by the FDA's decision to approve aducanumab among those aware of the decision. [ABSTRACT FROM AUTHOR]

Background: Best approaches for retaining research participants in Alzheimer's disease cohort studies are understudied.Objective: Using data from the National Alzheimer's Coordinating Center Uniform Data Set, we evaluated the associations of unique strategies with participant retention across Alzheimer's Disease Research Centers and explored potential effect modification by race, ethnicity and diagnostic group.Methods: We examined retention at the first follow-up visit among participants enrolled during 2015-2017. Structured surveys ascertained 95 retention tactics among 12 strategies. Strategy-specific summary scores were created based on the number of implemented tactics for each strategy and grouped into tertiles. Generalized estimating equations were constructed to evaluate associations between strategy scores and the odds of retention, controlling for age, sex, education, study partner type, marital status, visit length, battery length, diagnostic group, race and ethnicity. Separate models were stratified by race, ethnicity and diagnostic group. Effect modification was formally tested with interaction terms.Results: Among 5,715 total participants enrolled, 4,515 were Non-Hispanic White (79%), 335 were Hispanic/Latino (6%), 651 were Non-Hispanic Black (11%), and 214 were Non-Hispanic Asian (4%). Compared to the lowest tertile of scores, the highest tertile of scores involving improvement in study personnel and communication of study requirements and details were associated with 61% higher odds of retention in fully adjusted models (adjusted Odds Ratios [aOR] = 1.61, 95% Confidence Interval [CI] = 1.05-2.47 and aOR = 1.55, 95% CI = 1.03-2.35, respectively). We did not find evidence for effect modification.Conclusion: In the setting of limited resources, specific retention strategies may be more valuable than others. [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]

Background: Meta-analyses on the effects of probiotics on specific gastrointestinal diseases have generally shown positive effects on disease prevention and treatment; however, the relative efficacy of probiotic use for treatment and prevention across different gastrointestinal diseases, with differing etiology and mechanisms of action, has not been addressed. Methods/Principal Findings: We included randomized controlled trials in humans that used a specified probiotic in the treatment or prevention of Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, Antibiotic Associated Diarrhea, Traveler's Diarrhea, or Necrotizing Enterocolitis. Random effects models were used to evaluate efficacy as pooled relative risks across the eight diseases as well as across probiotic species, single vs. multiple species, patient ages, dosages, and length of treatment. Probiotics had a positive significant effect across all eight gastrointestinal diseases with a relative risk of 0.58 (95% (CI) 0.51-0.65). Six of the eight diseases: Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, and Antibiotic Associated Diarrhea, showed positive significant effects. Traveler's Diarrhea and Necrotizing Enterocolitis did not show significant effects of probiotcs. Of the 11 species and species mixtures, all showed positive significant effects except for Lactobacillus acidophilus, Lactobacillus plantarum, and Bifidobacterium infantis. Across all diseases and probiotic species, positive significant effects of probiotics were observed for all age groups, single vs. multiple species, and treatment lengths. Conclusions/Significance: Probiotics are generally beneficial in treatment and prevention of gastrointestinal diseases. Efficacy was not observed for Traveler's Diarrhea or Necrotizing Enterocolitis or for the probiotic species L. acidophilus, L. plantarum, and B. infantis. When choosing to use probiotics in the treatment or prevention of gastrointestinal disease, the type of disease and probiotic species (strain) are the most important factors to take into consideration. [ABSTRACT FROM AUTHOR]