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Abstract Introduction Recruitment and retention pose a significant challenge to Alzheimer's disease (AD) research. Returning AD biomarker results to participants has been proposed as a means to improve recruitment and retention. We present findings related to participant satisfaction, utility, and impact on research attitudes from the amyloid positron emission tomography (PET) disclosure sub‐study within the Wisconsin Registry for Alzheimer's Prevention (WRAP). Methods Ninety‐nine cognitively unimpaired WRAP participants learned their amyloid PET results (mean age ± SD = 72.0 ± 4.8). Measures of reasons for wanting to learn results, study comprehension, result utility, visit satisfaction, research attitudes, and future study enrollment willingness were collected. Between‐group, chi‐squared analysis was conducted to determine differences by result type (elevated vs. not elevated amyloid PET result) in study comprehension, result utility, and visit satisfaction. Linear mixed‐effects modeling was used to evaluate changes in research attitudes and enrollment willingness as a function of time, amyloid result type (elevated/not elevated), and their interaction. Results The reasons most frequently endorsed for wanting to learn amyloid PET result was a “desire to contribute to research on Alzheimer's disease dementia” and “to inform preventative measures [one] might take (e.g., change diet, exercise, or other lifestyle changes).” Overall, participants reported understanding the results and found learning them useful. Satisfaction with the study visits was overwhelmingly high, with over 80% agreeing with visit usefulness and their satisfaction. Few differences were found between participants who learned an elevated and not elevated result. Over the course of the study, participants who learned an elevated amyloid PET result reported higher willingness to enroll in drug trials (beta: 0.12, p = 0.01) and lifestyle interventions (beta: 0.10, p = 0.02) compared to participants who learned a not elevated result. Discussion Formal incorporation of disclosure practices may encourage participant recruitment and retention within AD research. Highlights Participants wanted to learn their amyloid results to contribute to research. Satisfaction with disclosure and post‐disclosure visits was high overall. Returning AD biomarkers can increase willingness to participate in research.

Abstract BACKGROUND In the asymptomatic “preclinical” phase of Alzheimer's disease (AD), abnormal biomarkers indicate risk for developing cognitive impairment. Biomarker information is increasingly being disclosed to participants in research settings, and biomarker testing and results disclosure will be implemented in clinical settings in the future. Biomarker disclosure has potential psychosocial benefits and harms, impacting affected individuals and their support person(s). Limited data are available about with whom research participants share their results, information that will be necessary to develop disclosure protocols and post‐disclosure resources. Additionally, existing research has been conducted in largely White cohorts, limiting applicability to future clinical populations. METHODS We enrolled a diverse cohort of 329 adults (184 non‐Hispanic White and 145 Black/African American individuals) who previously participated in AD research. After reviewing a vignette describing a hypothetical biomarker research study, participants indicated their anticipated willingness to share biomarker results with loved ones, and what reactions they anticipated from others. Using mixed‐methods analysis, we identified responses related to willingness to share results. RESULTS A majority (78.7%) were willing to share their results with support persons. Many (59.6%) felt it would not be difficult to share, and most (90.6%) believed their loved ones would be supportive. The most common reasons for sharing were to prepare for possible future AD (41.0% of respondents), while the most common reason for not sharing was to avoid worrying loved ones (4.8% of respondents). A total of 7.3% of respondents related reasons regarding being unsure about sharing. DISCUSSION Participants’ interest in sharing results supports integrating support persons into AD biomarker research, and may help maximize potential benefits for participants. Communicating with this "dyad" of research participant and support person(s) may improve involvement in research, and help prepare for implementation of clinical biomarker testing by clarifying communication preferences and the influence of support persons on psychosocial outcomes.

Abstract Introduction Increased availability of Alzheimer's disease (AD) biomarker tests provides older adults with opportunities to seek out and learn results. We evaluated the feasibility of virtually returning AD biomarker results. Methods Trained study clinicians disclosed amyloid positron emission tomography (PET) results and provided dementia risk‐reduction counseling via televideo to cognitively unimpaired participants already enrolled in AD research (n = 99; mean age ± SD: 72.0 ± 4.8; 67% women; 95% White; 28% amyloid elevated). Results Our study demonstrated acceptable levels of retention (93%), compliance (98%), adherence (98%), clinician competence (97%), education comprehension (quiz scores 14/15), and virtual visit functionality (rating 9.4/10). Depression, anxiety, and suicidality remained low and did not differ by amyloid result. Discussion Virtual return of amyloid PET results to cognitively unimpaired research participants is feasible and does not result in increased psychological symptoms. Technological barriers for some participants highlight the need for flexibility. These findings support the use of televideo in AD biomarker disclosure, although our study sample and design have important limitations for generalizability.

Abstract Introduction This work investigated the relationship between cerebrovascular disease (CVD) markers and Alzheimer's disease (AD) biomarkers of amyloid beta deposition, and neurofibrillary tau tangles in subjects spanning the AD clinical spectrum. Methods A total of 136 subjects participated in this study. Four groups were established based on AD biomarker positivity from positron emission tomography (amyloid [A] and tau [T]) and clinical diagnosis (cognitively normal [CN] and impaired [IM]). CVD markers were derived from structural and quantitative magnetic resonance imaging data. Results Transcapillary pulse wave delay was significantly longer in controls compared to AT biomarker–confirmed groups (A+/T–/CN P

Abstract Disclosure of personal disease‐related information to asymptomatic adults has been debated over the last century in medicine and research. Recently, Alzheimer's disease (AD) has been conceptualized as a continuum that begins with a “preclinical” stage in which biomarkers are present in the absence of cognitive impairment. Studies have begun assessing the safety, psychological, and behavioral effects of disclosing both AD‐related genetic and biomarker information to cognitively unimpaired older adults. Yet, debate continues over the appropriate circumstances and methods for returning such information. This article outlines concerns with and rationale for AD biomarker disclosure and summarizes findings from prior studies. Overall, this article aims to describe and respond to key questions concerning disclosure of amyloid positron emission tomography scan results to asymptomatic adults in a research setting. Moving forward, such conditions are important to consider as interventions target the preclinical phase of AD and normalize disclosing biomarker information to cognitively unimpaired persons.

Abstract Introduction Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods. Methods A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios. Batch differences were assessed using Bland‐Altman plot, paired t test, Pitman‐Morgan test, and linear regression. Generalized linear models were applied to convert CSF values between batches. Results We found statistically significant batch differences for all biomarkers and ratios, except that neurofilament light was comparable between batches 1 and 2. The conversion models generally had high R2 except for converting P‐tau between batches 1 and 3. Discussion Between‐batch conversion allows harmonized CSF values to be used in the same analysis. Such method may be applied to adjust for other sources of variability in measuring CSF or other types of biomarkers.

Abstract Introduction This study applies a novel algorithm to longitudinal amyloid positron emission tomography (PET) imaging to identify age‐heterogeneous amyloid trajectory groups, estimate the age and duration (chronicity) of amyloid positivity, and investigate chronicity in relation to cognitive decline and tau burden. Methods Cognitively unimpaired participants (n = 257) underwent one to four amyloid PET scans (Pittsburgh Compound B, PiB). Group‐based trajectory modeling was applied to participants with longitudinal scans (n = 171) to identify and model amyloid trajectory groups, which were combined with Bayes theorem to estimate age and chronicity of amyloid positivity. Relationships between chronicity, cognition, clinical progression, and tau PET (MK‐6240) were investigated using regression models. Results Chronicity explained more heterogeneity in amyloid burden than age and binary amyloid status. Chronicity was associated with faster cognitive decline, increased risk of abnormal cognition, and higher entorhinal tau. Discussion Amyloid chronicity provides unique information about cognitive decline and neurofibrillary tangle development and may be useful to investigate preclinical Alzheimer's disease.