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Abstract INTRODUCTION In Alzheimer's disease (AD) clinical trials, participants must enroll with a study partner informant who completes validated study instruments. We hypothesized that mid‐trial informant replacement impacts study data in industry‐sponsored trials. METHODS We conducted a retrospective analysis of two industry‐sponsored AD clinical trials testing semagacestat in mild‐to‐moderate AD dementia. We assessed the relationships between informant replacement and Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS‐ADL) scores. Using generalized estimating equations, we assessed bias and variability using mean (bias) and mean absolute (variance) change in ADCS‐ADL between successive visits as outcomes. Both models adjusted for a priori–specified potential confounding variables including participant sex, age, informant type, trial, time, previous ADCS‐ADL score, and region. To analyze the impact on end‐of‐study change‐from‐baseline results, we used an analysis of covariance model to estimate the association between replacement and end‐of‐study change‐from‐baseline in ADCS‐ADL, in which we adjusted for participant sex, age, informant type, trial, baseline measurement, and region. We conducted an F‐test to compare the variances of this change. RESULTS Among N = 2637 randomized participants, 69 participants (2.6%) experienced 78 occurrences of replacement. For visits standardized to be 3 months apart, the difference in mean between‐visit change in ADCS‐ADL was approximately −1.61 points (95% confidence interval [CI]: −3.79, 0.57; P = 0.147), comparing participants who experienced replacement to similar participants who had stable informants. The difference in the mean between‐visit absolute change was approximately 2.02 points (95% CI: 0.34, 3.70; P = 0.019). We did not estimate a statistically significant difference in end‐of‐study change‐from‐baseline (Est. = −0.70 points; 95% CI: −5.88, 4.48; P = 0.790) or a significant ratio of variances (Est. = 1.13; 95% CI: 0.67, 2.28; P = 0.600) for participants with replacement compared to those with stable informants. DISCUSSION Informant replacement was associated with increased between‐visit variability but had limited impact on overall trial outcomes. Highlights Informant replacement occurred in 2.6% of participants in these industry trials. Informant replacement was associated with increased variance in acute Alzheimer's Disease Cooperative Study Activities of Daily Living reporting. Informant replacement had a limited impact on overall change‐from‐baseline outcomes.

Summary: Advances in treatment are changing not only the therapeutic options for patients with Alzheimer's disease; they're also changing their diagnostic options. Technologies to detect amyloid such as PET imaging and blood or CSF testing now have a central role in Alzheimer's disease care. Notably, this role has been made possible by regulatory approval and coverage by payers of therapies. Access to treatments and the diagnostic tests needed to prescribe them is encourageing but it reveals a problem. These tests are tailored to the needs of the therapies, not to the needs of patients. Patients and families need to understand the causes of their impairments and their prognosis. This requires access to the best available diagnostic tests and this access should not depend on the availability of treatments. These tests should be used to their fullest capacity to inform patients of the causes of their cognitive impairments and their prognosis. Unfortunately, compared to diagnostic testing, treatment options are overvalued. We call this problem the tyranny of treatment.

Abstract Background Participant retention is a key factor that affects clinical trial integrity. Trial protocols estimate attrition as a function of sample size calculations. Alzheimer’s disease (AD) is an area of active treatment development. We aimed to quantify the association between trial duration and completion rates and provide guidance for estimating attrition in AD trial protocols. Methods Using the Alzforum and ClinicalTrials.gov databases, we analyzed retention data from 125 mild-to-moderate AD and 12 mild cognitive impairment (MCI) clinical trials. We compared the rates of completion between trial arms (active vs. control) and ran regression models to test the hypothesis that trials with longer study duration have lower trial completion using all available data and restricting to placebo data. Our primary outcome was the odds of trial completion for a 6-month increase in trial duration. From the regression model, we estimated the proportion of participants completing 6-, 12-, and 18-month trials. Results We found that 21 (17%) mild-to-moderate AD trials and 1 (8%) MCI trial demonstrated greater dropout in treatment compared to placebo arms. For every 6-month increase in trial duration, there was a 27% decrease in the odds of trial completion (OR = 0.73; 95% CI 0.66, 0.81; p

Abstract Background Recruiting to multi-site trials is challenging, particularly when striving to ensure the randomized sample is demographically representative of the larger disease-suffering population. While previous studies have reported disparities by race and ethnicity in enrollment and randomization, they have not typically investigated whether disparities exist in the recruitment process prior to consent. To identify participants most likely to be eligible for a trial, study sites frequently include a prescreening process, generally conducted by telephone, to conserve resources. Collection and analysis of such prescreening data across sites could provide valuable information to improve understanding of recruitment intervention effectiveness, including whether traditionally underrepresented participants are lost prior to screening. Methods We developed an infrastructure within the National Institute on Aging (NIA) Alzheimer’s Clinical Trials Consortium (ACTC) to centrally collect a subset of prescreening variables. Prior to study-wide implementation in the AHEAD 3–45 study (NCT NCT04468659), an ongoing ACTC trial recruiting older cognitively unimpaired participants, we completed a vanguard phase with seven study sites. Variables collected included age, self-reported sex, self-reported race, self-reported ethnicity, self-reported education, self-reported occupation, zip code, recruitment source, prescreening eligibility status, reason for prescreen ineligibility, and the AHEAD 3–45 participant ID for those who continued to an in-person screening visit after study enrollment. Results Each of the sites was able to submit prescreening data. Vanguard sites provided prescreening data on a total of 1029 participants. The total number of prescreened participants varied widely among sites (range 3–611), with the differences driven mainly by the time to receive site approval for the main study. Key learnings instructed design/informatic/procedural changes prior to study-wide launch. Conclusion Centralized capture of prescreening data in multi-site clinical trials is feasible. Identifying and quantifying the impact of central and site recruitment activities, prior to participants signing consent, has the potential to identify and address selection bias, instruct resource use, contribute to effective trial design, and accelerate trial enrollment timelines.

Abstract To estimate causal effects, analysts performing observational studies in health settings utilize several strategies to mitigate bias due to confounding by indication. There are two broad classes of approaches for these purposes: use of confounders and instrumental variables (IVs). Because such approaches are largely characterized by untestable assumptions, analysts must operate under an indefinite paradigm that these methods will work imperfectly. In this tutorial, we formalize a set of general principles and heuristics for estimating causal effects in the two approaches when the assumptions are potentially violated. This crucially requires reframing the process of observational studies as hypothesizing potential scenarios where the estimates from one approach are less inconsistent than the other. While most of our discussion of methodology centers around the linear setting, we touch upon complexities in non-linear settings and flexible procedures such as target minimum loss-based estimation and double machine learning. To demonstrate the application of our principles, we investigate the use of donepezil off-label for mild cognitive impairment. We compare and contrast results from confounder and IV methods, traditional and flexible, within our analysis and to a similar observational study and clinical trial.

Abstract Background Timely accrual of a representative sample is a key factor in whether Alzheimer’s disease (AD) clinical trials successfully answer the scientific questions under study. Studies in other fields have observed that, over time, recruitment to trials has become increasingly reliant on larger numbers of sites, with declines in the average per-site recruitment rate. Here, we examined the trends in recruitment over a 20-year period of NIH-funded AD clinical trials conducted by the Alzheimer’s Disease Cooperative Study (ADCS), a temporally consistent network of sites devoted to interventional research. Methods We performed retrospective analyses of eleven ADCS randomized clinical trials. To examine the recruitment planning, we calculated the expected number of participants to be enrolled per site for each trial. To examine the actual trial recruitment rates, we quantified the number of participants enrolled per site per month. Results No effects of time were observed on recruitment planning or overall recruitment rates across trials. No trial achieved an overall recruitment rate greater than one subject per site per month. We observed the fastest recruitment rates in trials with no competition and the slowest in trials that overlapped in time. The highest recruitment rates were consistently seen early within trials and declined over the course of studies. Conclusions Trial recruitment projections should plan for fewer than one participant randomized per site per month and consider the number of other AD trials being conducted concurrently.

Abstract INTRODUCTION Alzheimer's disease (AD) trials require enrollment with an informant. METHODS We assessed relationships between informant replacement and Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS‐ADL) scores across four AD trials. Using generalized estimating equations, we examined associations between replacement and change in ADCS‐ADL between successive visits. We used analysis of covariance to estimate the association between replacement and 18‐month change from baseline, and an F‐test to compare the variance of this change. RESULTS Among 1336 participants, 63 (≈5%) experienced replacement. Between‐visit mean change in ADCS‐ADL was 2.44 points lower comparing replacement to stable informants (95% confidence interval [CI]: –3.91, –0.98). The difference in between‐visit mean absolute change was 2.38 points (95% CI: 1.24, 3.52). Replacement was not significantly associated with an 18‐month change from baseline. The ratio of variances (replacement/stable) was 1.80 (95% CI: 1.19, 2.99). DISCUSSION Informant replacement is associated with bias and increased variability between visits and increased variance for overall ADCS‐ADL.

Abstract Background Individuals with Down syndrome (DS) are increasingly eligible for clinical trial intervention, particularly for the treatment or prevention of Alzheimer disease (AD). Yet, little is known about research attitudes that may contribute to decisions regarding clinical trial enrollment for people with DS, a gap which is addressed in the current study. Methods The Research Attitudes Questionnaire (RAQ) is a brief validated instrument that measures cultural and social factors which influence clinical trial enrollment decisions in the general population. Applied herein to a cohort of 1002 families who have an individual with DS, this survey was carried out through a national registry (DS-Connect). In addition to the RAQ, demographic data were collected. Results The response rate to the survey was 49.9%. Respondents were asked to complete demographic information and to respond to the 7 question RAQ. The scores were stratified by a cut point assigned a priori into those more favorable toward research participation vs. those less favorably inclined. Within this sample, nearly 95% self-identified as the primary caretaker for the individual with DS. The RAQ score analyses generally indicated favorable respondent views toward research with particularly high favorability ratings from respondents who had previously participated in research and from those who were older (P = .01 to .001). Conclusions This is one of the first formal studies to evaluate research attitudes among relatives of individuals with DS and shows the feasibility of using this approach to answer important questions that will guide trialists developing treatments for AD in DS. Future research will require broadening the racial and ethnic mix of respondents and the role that a standardized assessment of research attitudes will have for clinical trial participation.

Abstract Objectives Preclinical Alzheimer’s disease (AD) clinical trials screen cognitively unimpaired older adults for biomarker criteria and disclose their results. We examined whether participants in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s disease Study with “elevated” and “not elevated” amyloid differed in scores on the “Views and Perceptions of Amyloid Imaging” questionnaire. We hypothesized that, prior to disclosure, those with elevated amyloid would score higher than those with not elevated amyloid. We also quantified how responses changed after result disclosure. Methods We assessed data from 4327 individuals who completed the questionnaire at screening visit 1 and after amyloid disclosure. We used linear regression models to assess the relationship between questionnaire category scores and amyloid status. We also quantified the relationship between category score changes and amyloid status. Results Overall, participants scored altruism and contribution to research as the strongest motivations for undergoing amyloid imaging. Those with elevated amyloid scored 0.23 points higher in the Perceived Risk category, on average, than those who had not elevated amyloid prior to disclosure; this effect attenuated towards zero after adjusting for Cognitive Function Instrument score. After disclosure, participants with elevated amyloid demonstrated less within‐subject change in Perceived Risk, on average, compared to those with similar pre‐disclosure scores who had not elevated amyloid, while demonstrating greater changes in the altruism and planning categories. Interpretation Altruism and learning disease risk motivated enrollment in this preclinical AD trial. Participants with elevated amyloid differed from their not elevated counterparts in their perceptions of amyloid imaging, even before undergoing the procedure.

Abstract Background Early study exit is detrimental to statistical power and increases the risk for bias in Alzheimer’s disease clinical trials. Previous analyses in early phase academic trials demonstrated associations between rates of trial incompletion and participants’ study partner type, with participants enrolling with non-spouse study partners being at greater risk. Methods We conducted secondary analyses of two multinational phase III trials of semagacestat, an oral gamma secretase inhibitor, for mild-to-moderate AD dementia. Cox’s proportional hazards regression model was used to estimate the relationship between study partner type and the risk of early exit from the trial after adjustment for a priori identified potential confounding factors. Additionally, we used a random forest model to identify top predictors of dropout. Results Among participants with spousal, adult child, and other study partners, respectively, 35%, 38%, and 36% dropped out or died prior to protocol-defined study completion, respectively. In unadjusted models, the risk of trial incompletion differed by study partner type (unadjusted p value = 0.027 for test of differences by partner type), but in models adjusting for potential confounding factors, the differences were not statistically significant (p value = 0.928). In exploratory modeling, participant age was identified as the primary characteristic to explain the relationship between study partner type and the risk of failing to complete the trial. Participant age was also the strongest predictor of trial incompletion in the random forest model. Conclusions After adjustment for age, no differences in the risk of incompletion were observed when comparing participants with different study partner types in these trials. Differences between our findings and the findings of previous studies may be explained by differences in trial phase, size, geographic regions, or the composition of academic and non-academic sites.

Abstract Background Alzheimer’s disease (AD) clinical trials require enrollment of a participant and a study partner, whose role includes assessing participant cognitive and functional performance. AD trials now investigate early stages of the disease, when participants are not cognitively impaired. This gives rise to the question of whether study partners or participants provide more information in these trials. Methods We used data from the AD Cooperative Study Prevention Instrument Project (ADCS-PI) to compare participant and study partner predictions of the participant’s current and future cognitive state. We used the Cognitive Function Instrument (CFI) as a measure of evaluation of the participant’s cognitive status and the modified ADCS Preclinical Alzheimer’s Cognitive Composite (mADCS-PACC) as an objective measure of cognition. Stratifying by cognitive status and study partner type and adjusting for other predictors of the participant’s cognitive state, we used random forests along with estimated mean variable importance (eMVI) to assess how well each member of the dyad can predict cognitive state at current and later visits. We also fit linear regression models at each time point and for each scenario. Results Participants were better at predicting future cognitive status compared to their study partners regardless of study partner type, though the difference between participants and partners was greatest for non-spousal dyads in the lowest-performing quartile. Cross-sectional assessments differed substantially by dyad type. Within the lowest cognitive performance quartile, participants having a non-spousal study partner outperformed their partners in assessing cognition at later times. Spousal partners, in contrast, outperformed participants later in the study in predicting current cognitive performance. Conclusions These results indicate that participants tend to be better at predicting future cognition compared to their study partners regardless of the study partner type. When assessing current cognition, however, spousal study partners perform better at later time points and non-spousal study partners do not provide as much information regarding participant cognitive state.

Abstract Background Preclinical Alzheimer’s disease (AD) clinical trials require participants to enroll with a study partner, a person who can attend visits and report changes in the participant’s cognitive ability. Whether study partners, compared to participants themselves, provide added information about participant cognition in preclinical AD trials is an open question. We tested the hypothesis that study partners provide meaningful information related to participant cognition cross-sectionally and longitudinally, and assessed whether amyloid status modified observed effects. Methods We assessed participant and study partner Everyday Cognition (ECog) scores and participant Alzheimer’s Disease Assessment Scale 13-item cognitive subscale (ADAS13) data from 335 cognitively normal participant-partner dyads in the AD Neuroimaging Initiative. We used random forest and linear mixed effects (LME) models to predict ADAS13 scores as a function of participant and/or study partner ECog scores over time. LME models were adjusted for potential confounding factors, including APOE4 status, amyloid status, baseline age, years of education, and sex. Random forest models were split into the above factors, as well as race/ethnicity and other available neuropsychological battery test scores. Results In random forest models predicting ADAS13 12 months from baseline, we observed no difference in the estimated mean variable importance (eMVI) associated with baseline study partner ECog compared to the baseline participant ECog (eMVI = 0.15, 95%CB 0.13, 0.16 for partner; eMVI = 0.15, 95%CB 0.14, 0.16 for participant). In models predicting ADAS13 48 months after baseline, the eMVI associated with baseline study partner ECog was slightly lower than that associated with baseline participant ECog (eMVI = 0.21, 95%CB 0.20, 0.22 for partner; eMVI = 0.24, 95%CB 0.22, 0.25 for participant). In cross-sectional models, study partner eMVI was twice as large as participant eMVI at 12 months (eMVI = 0.20, 95%CB 0.19, 0.21 for partner; eMVI = 0.09, 95%CB 0.09, 0.10 for participant) and three times as large at 48 months (eMVI = 0.38, 95%CB 0.36, 0.39 for partner; eMVI = 0.13, 95%CB 0.12, 0.14 for participant). We did not observe qualitative differences by amyloid status. Conclusions While baseline participant reports reasonably predict subsequent cognitive change, informants perform better at cross-sectionally recognizing cognitive status as observation time grows. The study partner requirement may be essential to ensure trial data integrity, especially in longer trials.

Abstract Introduction This study elicited Asian Americans and Pacific Islanders’ (AAPI) perspectives about recruitment strategies/messaging for participation in an aging, Alzheimer's disease and related dementias (ADRD), and caregiving research recruitment registry. Methods Using a mixed methods design, CARE (Collaborative Approach for AAPI Research and Education) conducted 14 focus groups (N = 123) with AAPI cultural groups (Asian Indian, Chinese, Filipino, Japanese, Korean, Samoan, Vietnamese) in different languages. Descriptive statistics and thematic qualitative analyses were conducted. Results Mean age of participants was 54 years (median: 61; range 18–80), 66% were female, and 81% were foreign‐born. Themes of consideration for recruitment emerged: (1) culturally/linguistically appropriate outreach in culturally specific spaces, (2) motivations for research participation, and (3) approaches to outreach and recruitment methods. Within each of these themes, there were ethnic differences in specific strategies/approaches reflected as subthemes. Discussion Recruitment and messaging strategies should be tailored uniquely for each targeted AAPI group, with a thorough understanding of the cultural/linguistic factors that facilitate research participation to increase AAPI participation in ADRD, aging, and caregiver‐related research.

Abstract Introduction This study describes practices for disclosing individual research results to participants in Alzheimer's disease research. Methods An online survey of clinical core leaders at National Institutes of Health‐funded Alzheimer's Disease Research Centers in the United States (response rate: 30/31, 97%) examined return of results practices across nine different types of research results. Results Most centers had returned consensus research diagnoses (83%) and neuropsychological test results (73%), with fewer having shared amyloid positron emission tomography (43%), tau imaging (10%), or apolipoprotein E (APOE) genotype (7%) results. Centers reported having disclosed a mean of 3.1 types of results (standard deviation = 2.1; range 0–8). The most commonly cited reason for disclosure was to inform participants’ medical decision‐making (88%). Disclosure involved multiple professionals and modalities, with neurologists (87%) and in‐person visits (85%) most commonplace. Discussion Centers varied widely as to whether and how they disclosed research results. Diagnostic and cognitive test results were more commonly returned than genetic or biomarker results.

Reluctance to undergo lumbar puncture (LP) is a barrier to neurological disease biomarker research. We assessed whether an educational intervention increased willingness to consider research LP and whether message framing modified intervention effectiveness. We randomly assigned 851 recruitment registry enrollees who had previously indicated they were unwilling to be contacted about studies requiring LP to gain or loss framed video educational interventions describing the procedure and the probability of experiencing adverse events. The gain framed intervention emphasized the proportion of individuals free of adverse events; the loss frame emphasized the proportion experiencing adverse events. The primary outcome for the study was the participant's post-intervention agreement to be contacted about studies requiring LP. Participants were mean (SD) age 60.1 years (15.7), 69% female (n = 591), and mostly college educated and white. Among the 699 participants who completed the study, 43% (95% CI: 0.39, 0.47; n = 301) changed their response to agree to be contacted about studies requiring LP. We estimated that participants randomized to the gain framed intervention had 67% higher odds of changing their response compared to those randomized to the loss frame (Odds Ratio = 1.67; 95% CI: 1.24, 2.26; p < 0.001). A classification and regression tree model identified participants' pre-intervention willingness as the strongest predictor of changing response. Education, in particular education that alerts participants to the probability of not experiencing adverse events, may be an effective tool to increase participation rates in research requiring LP.

Abstract Background The experiences of biomarker-ineligible cognitively normal persons can inform trial conduct and the translation of preclinical Alzheimer’s disease (AD) into clinical practice. Methods We interviewed 33 persons whose “not elevated” brain amyloid imaging biomarker result made them ineligible for a preclinical AD trial. Results Most participants (n = 17) reported being informed that they did not demonstrate adequately elevated amyloid to qualify, whereas some (n = 14) reported being told they had no amyloid or plaques. Relief (n = 17) and disappointment related to not being able to participate (n = 12) were the most common reactions to results. Nearly all participants would have made healthy lifestyle changes if they had received an “elevated” result, would have another scan, and would participate in another AD prevention trial. Conclusions Although some participants may misconstrue results, disclosure of a “not elevated” amyloid result in the research setting causes little behavior change; willingness to participate in AD research remains.

Abstract Background Global leaders have set an ambitious goal of developing interventions to effectively treat or prevent Alzheimer’s disease by 2025. Case presentation Achieving this goal will require clinical trials to test promising interventions, yet Alzheimer’s researchers are confronting a clinical trial recruitment crisis. One reason for this is that Alzheimer’s disease trials must enroll “dyads” composed of both a participant and his or her study partner. Conclusions In this article, we argue that it is essential to identify ways to facilitate study partner participation, such as removing logistical barriers, offering payment, and providing paid, protected time off for study visits. Facilitating participation, particularly among non-spousal study partners, should offer a twofold benefit: faster accrual and greater generalizability of results.

Abstract Background In an effort to intervene earlier in Alzheimer’s disease (AD), clinical trials are testing promising candidate therapies in preclinical disease. Preclinical AD trial participants are cognitively normal, functionally independent, and autonomous decision-makers. Yet, like AD dementia trials, preclinical trials require dual enrollment of a participant and a knowledgeable informant, or study partner. Main text The requirement of dyadic enrollment is a barrier to recruitment and may present unique ethical challenges. Despite these limitations, the requirement should continue. Study partners may be essential to ensure participant safety and wellbeing, including overcoming distress related to biomarker disclosure and minimizing risk for catastrophic reactions and suicide. The requirement may maximize participant retention and ensure data integrity, including that study partners are the source of data that will ultimately instruct whether a new treatment has a clinical benefit and meaningful impact on the population health burden associated with AD. Finally, study partners are needed to ensure the scientific and clinical value of trials. Conclusions Preclinical AD will represent a new model of care, in which persons with no symptoms are informed of probable cognitive decline and eventual dementia. The rationale for early diagnosis in symptomatic AD is equally applicable in preclinical AD—to minimize risk, maximize quality of life, and ensure optimal planning and communication. Family members and other sources of support will likely be essential to the goals of this new model of care for preclinical AD patients and trials must instruct this clinical practice.

Abstract Background Research has revealed that manifest Alzheimer’s disease (AD) dementia is preceded by preclinical and prodromal phases during which pathology is accumulating but function remains intact. This understanding and concern that disease-modifying interventions initiated at the dementia stage may come too late in the neurodegenerative process to be successful has led to a paradigm shift in AD clinical trials. AD trials now enroll patients with mild cognitive impairment (MCI) and persons with no cognitive symptoms. Trial designs are similar to those enrolling dementia participants. We set out to test the hypothesis that attitudes towards trial design features differ among different potential AD trial populations. Methods We sent a survey composed of 37 items assessing specific trial elements to 246 cognitively normal, MCI, and AD dementia participants at the University of California Los Angeles (UCLA) Alzheimer’s Disease Research Center (ADRC), from whom we received 91 responses (37 cognitively normal, 32 MCI, and 22 dementia). To quantify willingness to enroll, we created three composite scenarios by summing responses and fitting proportional odds models with a binary outcome variable for whether patients were highly willing to participate in low-, moderate-, or high-risk and burden trials. Results MCI participants less frequently correctly self-identified their diagnoses than those with dementia or normal cognition. Compared to dementia patients, the odds of participating in a low-risk, low-burden trial were 12% lower for MCI patients (odds ratio (OR) = 0.88, 95% confidence interval (CI) 0.23–3.29) and 70% lower (OR = 0.30, 95% CI 0.08–1.09) for cognitively normal participants. With increasing risk and burden, willingness to enroll decreased and the gap in relative willingness between diagnostic groups increased. In the medium-risk, medium-burden scenario, the estimated OR was 0.64 (95% CI 0.17–2.40) for MCI and 0.21 for the cognitively normal (95% CI 0.06–0.77). In the high-risk, high-burden scenario, the estimated OR indicated reduced willingness for MCI (OR = 0.27, 95% CI 0.06–1.15) and cognitively normal respondents (OR = 0.12, 95% CI 0.03–0.54). Conclusions These results suggest that AD trials enrolling predementia populations, especially those requiring frequent visits and implementing biomarker testing procedures, may encounter challenges to enrollment.

Abstract Background Mild cognitive impairment (MCI) has an uncertain etiology and prognosis and may be challenging for clinicians to discuss with patients and families. Amyloid imaging may aid specialists in determining MCI etiology and prognosis, but creates novel challenges related to disease labeling. Methods We convened a workgroup to formulate recommendations for clinicians providing care to MCI patients. Results Clinicians should use the MCI diagnosis to validate patient and family concerns and educate them that the patient’s cognitive impairment is not normal for his or her age and education level. The MCI diagnosis should not be used to avoid delivering a diagnosis of dementia. For patients who meet Appropriate Use Criteria after standard-of-care clinical workup, amyloid imaging may position specialists to offer more information about etiology and prognosis. Clinicians must set appropriate expectations, including ensuring that patients and families understand the limitations of amyloid imaging. Communication of negative results should include that patients remain at elevated risk for dementia and that negative scans do not indicate a specific diagnosis or signify brain health. Positive amyloid imaging results should elicit further monitoring and conversations about appropriate advance planning. Clinicians should offer written summaries, including referral to appropriate social services. Conclusions In patients with MCI, there is a need to devote considerable time and attention to patient education and shared decision-making. Amyloid imaging may be a tool to aid clinicians. Careful management of patient expectations and communication of scan results will be critical to the appropriate use of amyloid imaging information.

Abstract Introduction We sought to examine the association of race/ethnicity with willingness to engage in studies that involve procedures typical of Alzheimer's disease (AD) clinical trials and determine whether any observed differences could be explained by research attitudes. Methods We studied 2749 adults aged ≥50 years who enrolled in a community‐based recruitment registry. Results Compared to non‐Hispanic (NH) whites (n = 2393, 87%), Hispanics (n = 191, 7%), NH Asians (n = 129, 5%) and NH blacks (n = 36, 1%) were 44%, 46%, and 64% less willing, respectively, to be contacted for studies that have requirements typical of AD prevention trials, namely: cognitive testing, brain imaging, blood draws, and investigational medications. Mediation by research attitudes was explored, but did not explain the observed differences. Discussion Our findings suggest that ethnoracial minorities are less willing to engage in studies that are typical of AD prevention trials. Future work should focus on understanding the factors that drive these differences.