Communicating Alzheimer's biomarker results to cognitively unimpaired research participants: Satisfaction, utility, and impact on research attitudes.

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.

Longitudinal normative standards for cognitive tests and composites using harmonized data from two Wisconsin AD-risk-enriched cohorts.

INTRODUCTION: Published norms are typically cross-sectional and often are not sensitive to preclinical cognitive changes due to dementia. We developed and validated demographically adjusted cross-sectional and longitudinal normative standards using harmonized outcomes from two Alzheimer's disease (AD) risk-enriched cohorts. METHODS: Data from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were combined. Quantile regression was used to develop unconditional (cross-sectional) and conditional (longitudinal) normative standards for 18 outcomes using data from cognitively unimpaired participants (N = 1390; mean follow-up = 9.25 years). Validity analyses (N = 2456) examined relationships between percentile scores (centiles), consensus-based cognitive statuses, and AD biomarker levels. RESULTS: Unconditional and conditional centiles were lower in those with consensus-based impairment or biomarker positivity. Similarly, quantitative biomarker levels were higher in those whose centiles suggested decline. DISCUSSION: This study presents normative standards for cognitive measures sensitive to pre-clinical changes. Future directions will investigate potential clinical applications of longitudinal normative standards. HIGHLIGHTS: Quantile regression was used to construct longitudinal norms for cognitive tests. Poorer percentile scores were related to concurrent diagnosis and Alzheimer's disease biomarkers. A ShinyApp was built to display test scores and norms and flag low performance.

Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in late-onset dementia due to Alzheimer's disease.

INTRODUCTION: DNA microarray-based studies report differentially methylated positions (DMPs) in blood between late-onset dementia due to Alzheimer's disease (AD) and cognitively unimpaired individuals, but interrogate < 4% of the genome. METHODS: We used whole genome methylation sequencing (WGMS) to quantify DNA methylation levels at 25,409,826 CpG loci in 281 blood samples from 108 AD and 173 cognitively unimpaired individuals. RESULTS: WGMS identified 28,038 DMPs throughout the human methylome, including 2707 differentially methylated genes (e.g., SORCS3, GABA, and PICALM) encoding proteins in biological pathways relevant to AD such as synaptic membrane, cation channel complex, and glutamatergic synapse. One hundred seventy-three differentially methylated blood-specific enhancers interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD. DISCUSSION: WGMS identifies differentially methylated CpGs in known and newly detected genes and enhancers in blood from persons with and without AD. HIGHLIGHTS: Whole genome DNA methylation levels were quantified in blood from persons with and without Alzheimer's disease (AD). Twenty-eight thousand thirty-eight differentially methylated positions (DMPs) were identified. Two thousand seven hundred seven genes comprise DMPs. Forty-eight of 75 independent genetic risk loci for AD have DMPs. One thousand five hundred sixty-eight blood-specific enhancers comprise DMPs, 173 of which interact with the promoters of 95 genes that are differentially expressed in blood from persons with and without AD.

Anticipated Psychological or Behavioral Reactions to Learning Alzheimer Biomarker Results: Associations With Contextual Factors.

BACKGROUND: As Alzheimer disease (AD) biomarker testing becomes more widely available, adults may opt to learn results. Considering potential reactions to learning biomarker results can guide prebiomarker and postbiomarker testing education and counseling programs. METHODS: Cognitively healthy adults enrolled in observational Alzheimer research responded to a telephone survey about learning AD risk information (n=334; 44% Black or African American; mean age=64.9±7.0). Multiple linear regression models tested if contextual factors predicted anticipated psychological impact (distress, stigma, and cognitive symptoms) or behavior change (planning and risk-reduction). Secondary analyses tested for differences in relationships by racial identity. RESULTS: Internal health locus of control, concern about AD, self-identified sex, education, family dementia history, and belief in AD modifiability predicted anticipated psychological impact. Concern about AD, age, racial identity, belief in AD modifiability, research attitudes, and exposure to brain health-related social norms predicted anticipated behavior change. For Black respondents, there were no sex differences in anticipated distress, whereas there were stronger relationships between health locus of control, brain health social norms, and education on outcomes compared with White respondents. CONCLUSIONS: Results may inform personalized and culturally tailored biomarker testing education and counseling to minimize psychological impacts and increase behavior change related to learning AD risk information.

Informing Disclosure: Efficacy of a Brief Educational Intervention on Research Participants' Knowledge about Alzheimer's Disease Biomarkers.

Recommendations for communicating Alzheimer's disease (AD) biomarkers include pre-disclosure participant education and counseling, to allow individuals to make an informed decision. In a cohort of largely non-Hispanic White, cognitively unimpaired older adults from the Wisconsin Registry for Alzheimer's Prevention, we conducted a structured amyloid PET disclosure process that included knowledge assessment and education. Baseline participant knowledge about AD biomarkers and research was high, but information needs existed around dementia causes, early AD symptoms, genetic information, and psychosocial consequences of disclosure. Knowledge scores increased after education, highlighting the potential of brief educational interventions to improve informed decision-making about biomarker disclosure.

Feasibility of virtual Alzheimer's biomarker disclosure: Findings from an observational cohort.

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.

Associations of the Lifestyle for Brain Health index with longitudinal cognition and brain amyloid beta in clinically unimpaired older adults: Findings from the Wisconsin Registry for Alzheimer's Prevention.

Introduction: Modifiable health and lifestyle factors increase risk of dementia, but whether modifiable factors, when measured in late-midlife, impact the emergence or progression of Alzheimer's disease (AD) pathophysiologic or cognitive changes remains unresolved. Methods: In initially cognitively unimpaired, late middle-aged participants (N = 1215; baseline age, M [standard deviation] = 59.3 [6.7] years) from the Wisconsin Registry for Alzheimer's Prevention (WRAP), we investigated the influence of the Lifestyle for Brain Health (LIBRA) index, a lifestyle-based dementia risk score, on AD-related cognitive trajectories and amyloid beta (Aß) plaque accumulation. Results: Overall, lower baseline LIBRA, denoting healthier lifestyle and lower dementia risk, was related to better overall cognitive performance, but did not moderate apolipoprotein E ε4 or Aß-related longitudinal cognitive trajectories. LIBRA was not significantly associated with Aß accumulation or estimated age of Aß onset. Discussion: In WRAP, late-midlife LIBRA scores were related to overall cognitive performance, but not AD-related cognitive decline or Aß accumulation in the preclinical timeframe. Highlights: The Lifestyle for Brain Health (LIBRA) index was associated with cognitive performance in late-midlife.LIBRA did not moderate apolipoprotein E ε4 or amyloid-related cognitive decline.LIBRA was not associated with the onset or accumulation of amyloid plaques.

Implications of preclinical Alzheimer's disease biomarker disclosure for US policy and society.

Disclosure of Alzheimer's disease (AD) biomarkers to cognitively unimpaired adults are currently conducted only in research settings. Yet, US Food and Drug Administration approval of a disease-modifying treatment for symptomatic individuals, improved understanding of the "preclinical" phase of disease, and advancements toward more accessible biomarker tests suggest such disclosure will increase in frequency, eventually becoming routine in clinical practice. The changing landscape in AD research to focus on biomarkers has generated debate on the validity and clinical utility of disclosure to cognitively unimpaired adults. This article explores the broader social implications of more widespread AD biomarker disclosure-that is, of individuals learning their risk for developing dementia caused by AD. We identify 10 challenges and offer preliminary solutions. As the field continues to evolve, it is essential to anticipate and address these broader ethical, legal, and social implications of disclosure.

Anticipated reactions to learning Alzheimer's disease biomarker results.

INTRODUCTION: We developed the Alzheimer's Biomarker Survey to assess willingness to enroll in biomarker studies that disclose results and anticipated reactions to an elevated biomarker result. METHODS: Participants included cognitively unimpaired adults enrolled in longitudinal AD studies (n = 334, mean age = 64.8 ± 7.7, 44% non-Hispanic Black or African American). Exploratory and confirmatory factor analyses determined the latent structure comprising anticipated reactions to learning AD biomarker results. Measurement invariance was tested across racial groups. RESULTS: Two models comprising behavior change and psychological impact fit well for the total sample and the two racial groups. The 2-factor behavior change model assessed constructs of planning and dementia risk-reduction. The 3-factor psychological impact model assessed constructs of distress, cognitive symptoms, and stigma. Both models exhibited measurement invariance across racial groups. DISCUSSION: The 28-item Anticipated Reactions to AD Biomarker Disclosure scale is a reliable and valid measure of anticipated reactions when communicating AD biomarker results to research participants.

Comparing emergency department use among individuals with varying levels of cognitive impairment.

INTRODUCTION: As the population ages, Alzheimer's disease and related dementias (ADRD) are becoming increasingly common in patients presenting to the emergency department (ED). This study compares the frequency of ED use among a cohort of individuals with well-defined cognitive performance (cognitively intact, mild cognitive impairment (MCI), and ADRD). METHODS: We performed a retrospective cohort study of English-speaking, community-dwelling individuals evaluated at four health system-based multidisciplinary memory clinics from 2014-2016. We obtained demographic and clinical data, including neuropsychological testing results, through chart review and linkage to electronic health record data. We characterized the frequency and quantity of ED use within one year (6 months before and after) of cognitive evaluation and compared ED use between the three groups using bivariate and multivariate approaches. RESULTS: Of the 779 eligible patients, 89 were diagnosed as cognitively intact, 372 as MCI, and 318 as ADRD. The proportion of subjects with any annual ED use did not increase significantly with greater cognitive impairment: cognitively intact (16.9%), MCI (26.1%), and ADRD (28.9%) (p = 0.072). Average number of ED visits increased similarly: cognitively intact (0.27, SD 0.72), MCI (0.41, SD 0.91), and ADRD (0.55, SD 1.25) (p = 0.059). Multivariate logistic regression results showed that patients with MCI (odds ratio (OR) 1.62; CI = 0.87-3.00) and ADRD (OR 1.84; CI = 0.98-3.46) did not significantly differ from cognitively intact adults in any ED use. Multivariate negative binomial regression found patients with MCI (incidence rate ratio (IRR) 1.38; CI = 0.79-2.41) and ADRD (IRR 1.76, CI = 1.00-3.10) had elevated but non-significant risk of an ED visit compared to cognitively intact individuals. CONCLUSION: Though there was no significant difference in ED use in this small sample from one health system, our estimates are comparable to other published work. Results suggested a trend towards higher utilization among adults with MCI or ADRD compared to those who were cognitively intact. We must confirm our findings in other settings to better understand how to optimize systems of acute illness care for individuals with MCI and ADRD.

What Influences the Willingness of Blacks and African Americans to Enroll in Preclinical Alzheimer's Disease Biomarker Research? A Qualitative Vignette Analysis.

BACKGROUND: Alzheimer's disease (AD) begins with an asymptomatic "preclinical" phase, in which abnormal biomarkers indicate risk for developing cognitive impairment. Research is increasingly focused on validating biomarkers to improve reliable diagnosis and timely clinical treatment of AD. Most preclinical biomarker research lacks adequate representation of Black/African American and other racially and ethnically minoritized individuals, limiting the applicability of data to these groups. This may exacerbate existing disparities by hindering diagnosis and treatment among racially and ethnically minoritized individuals. OBJECTIVE: Understand the factors influencing willingness of Blacks/African Americans to participate in AD biomarker research and identify opportunities to improve enrollment. METHODS: We enrolled Blacks/African Americans (N = 145) between 46-85 years of age who had previously participated in AD research. Participants gave open-ended responses to a vignette describing a hypothetical biomarker research study. Using qualitative content analysis, we identified themes that motivated and discouraged enrollment in AD biomarker research. RESULTS: Participant responses were categorized into several themes. Themes motivating participation included a desire to know their biomarker results and to support research. Major themes discouraging participation included concerns about potential negative psychological outcomes to learning one's increased risk for AD, doubt about the usefulness of testing, and worry about the potential physical harms of testing. CONCLUSION: Understanding themes motivating and discouraging AD preclinical biomarker research participation may inform research material development, approach to community engagement, and/or trial design to increase enrollment of Blacks/African Americans.

Cardiology clinic patient attitudes toward and potential personal utility of genetic testing: Findings from a unique multiracial clinical sample.

As more is understood about the hereditary nature of disease risk, the utility of genetic testing within cardiovascular medicine is increasingly being explored. Although testing may afford more personalized risk stratification, there is a paucity of information regarding patient knowledge, attitudes, and beliefs toward genetic testing among cardiology patients. Participants (n = 530) recruited primarily from a cardiology clinic filled out a 41-item written questionnaire assessing knowledge, beliefs, and attitudes toward genetic testing, motivators and detractors for considering genetic testing, and perceived likelihood for behavior change after hypothetical genetic testing risk stratification. Path analysis was used to test the hypothetical models predicting the likelihood of getting a genetic test and making behavior changes following genetic testing. The patient population was late-middle-aged (59.0 ± 14.5 years), majority women (61.5%), and about half reported having a bachelor's degree. 58.1% of participants self-identified as White, 25.7% as African American or Black, 6.8% as Spanish, Latino, or Hispanic, 3.0% as Asian or Pacific Islander, and 0.5% as Native American. Gender (being a woman) and more years of education were related to greater knowledge about genetic testing. Racial identity and years of education were related to beliefs about genetic testing. Beliefs, but not knowledge, were related to more positive attitudes and a higher likelihood of pursuing genetic testing. Positive attitudes were related to greater perceived personal control (PPC). Furthermore, attitudes and PPC were related to higher likelihood of lifestyle change after genetic testing. These results highlight the need to integrate the experiences of racialized communities into education/counseling efforts. Most educational counseling efforts lack a nuanced discussion of social determinants of health or beliefs. In addition to factual information, educational counseling must also address people's beliefs, concerns, and the intersecting experiences and identities, which shape patients' relationships with the evolving landscape of healthcare and personalized medicine.

The Wisconsin Alzheimer's Institute Dementia Diagnostic Clinic Network: A community of practice to improve dementia care.

BACKGROUND: The Wisconsin Alzheimer's Institute (WAI) Dementia Diagnostic Clinic Network is a community of practice formed in 1998 as a collaboration of community-based clinics from various healthcare systems throughout the state. Its purpose is to promote the use of evidence-based strategies to provide high quality care throughout Wisconsin for people with dementia. The purpose of this study is to describe the use of a community of practice to facilitate education of healthcare providers on best practices in dementia care, and the implementation of an interprofessional approach to diagnose and manage dementia and related disorders. METHODS: Cross-sectional study of the members of the WAI's Dementia Diagnosis Clinic Network. Characteristics of clinics and healthcare teams, learners' participation in educational events and educational outcomes were collected from evaluation forms. Number and characteristics of patients seen in the memory clinics were collected from de-identified data forms submitted by members to a centralized location for data analysis. RESULTS: The clinic network currently has 38 clinics affiliated with 26 different healthcare systems or independent medical groups in 21 of 72 Wisconsin counties. Most (56%) are based in primary care, 15% in psychiatry, and 29% in neurology. Between 2018 and 2021, we received data on 4710 patients; 92% were ≥65 years old, 60% were female, and 92% were white. Network members meet in-person twice a year to learn about innovations in the field of dementia care and to share best practices. Educational events associated with the network are shown to be relevant, useful, and improve knowledge and skills of participants. CONCLUSION: Communities of practice provide added value via shared best practices and educational resources, continuing education of the health workforce, continuous quality improvement of clinical practices, and adoption of new diagnostic and management approaches in dementia care.

Predictors of Willingness to Enroll in Hypothetical Alzheimer Disease Biomarker Studies that Disclose Personal Results.

INTRODUCTION: We examined factors related to willingness to enroll in hypothetical Alzheimer disease (AD) biomarker studies. METHODS: Using linear regression, we assessed the relationship among enrollment willingness and demographics, family dementia history, research attitudes, concern about AD, experiences of discrimination, and belief in AD risk modifiability. Inductive coding was used to assess qualitative data. RESULTS: In middle-aged and older adult AD research participants (n=334), willingness to enroll in biomarker studies was driven by biomarker collection method, research attitudes, and disclosure of personal results. Predictors of willingness were similar for Black and White participants. Themes associated with increased willingness included a desire to learn biomarker results and support research. DISCUSSION: Research attitudes were an important predictor of biomarker study willingness regardless of race. As seen elsewhere, Black participants were more hesitant to participate in biomarker research. Disclosure of biomarker results/risk can bolster willingness to enroll in biomarker studies, particularly for Black participants.

Moving beyond disclosure: Stages of care in preclinical Alzheimer's disease biomarker testing.

Alzheimer's disease (AD) begins with an asymptomatic "preclinical" phase, in which abnormal biomarkers indicate risk for developing cognitive impairment. Biomarker information is increasingly being disclosed in research settings, and is moving toward clinical settings with the development of cheaper and non-invasive testing. Limited research has focused on the safety and psychological effects of disclosing biomarker results to cognitively unimpaired adults. However, less is known about how to ensure equitable access and robust counseling for decision-making before testing, and how to effectively provide long-term follow-up and risk management after testing. Using the framework of Huntington's disease, which is based on extensive experience with disclosing and managing risk for a progressive neurodegenerative condition, this article proposes a conceptual model of pre-disclosure, disclosure, and post-disclosure phases for AD biomarker testing. Addressing research questions in each phase will facilitate the transition of biomarker testing into clinical practice.

Validity Evidence for the Research Category, "Cognitively Unimpaired - Declining," as a Risk Marker for Mild Cognitive Impairment and Alzheimer's Disease.

While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer's disease (AD) continuum, subtle cognitive decline is now known to occur years before a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to AD is made. The primary aim of this study was to examine criterion validity evidence for an operational definition of "cognitively unimpaired-declining" (CU-D) in the Wisconsin Registry for Alzheimer's Prevention (WRAP), a longitudinal cohort study following cognition and risk factors from mid-life and on. Cognitive status was determined for each visit using a consensus review process that incorporated internal norms and published norms; a multi-disciplinary panel reviewed cases first to determine whether MCI or dementia was present, and subsequently whether CU-D was present, The CU-D group differed from CU-stable (CU-S) and MCI on concurrent measures of cognition, demonstrating concurrent validity. Participants who changed from CU-S to CU-D at the next study visit demonstrated greater declines than those who stayed CU-S. In addition, those who were CU-D were more likely to progress to MCI or dementia than those who were CU-S (predictive validity). In a subsample with positron emission tomography (PET) imaging, the CU-D group also differed from the CU-S and MCI/Dementia groups on measures of amyloid and tau burden, indicating that biomarker evidence of AD was elevated in those showing sub-clinical (CU-D) decline. Together, the results corroborate other studies showing that cognitive decline begins long before a dementia diagnosis and indicate that operational criteria can detect subclinical decline that may signal AD or other dementia risk.

Measurement batch differences and between-batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values.

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 R 2 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.

Association of Neighborhood Context, Cognitive Decline, and Cortical Change in an Unimpaired Cohort.

OBJECTIVE: To test the hypothesis that neighborhood-level disadvantage is associated with longitudinal measures of neurodegeneration and cognitive decline in an unimpaired cohort. METHODS: Longitudinal MRI and cognitive testing data were collected from 601 cognitively unimpaired participants in the Wisconsin Registry for Alzheimer's Prevention Study and the Wisconsin Alzheimer's Disease Research Center clinical cohort. Area Deprivation Index was geospatially determined based on participant residence geocode and ranked relative to state of residence. Linear regression models were fitted to test associations between neighborhood-level disadvantage and longitudinal change in cortical thickness and cognitive test performance. Mediation tests were used to assess whether neurodegeneration and cognitive decline were associated with neighborhood-level disadvantage along the same theoretical causal path. RESULTS: In our middle- to older-aged study population (mean baseline age 59 years), living in the 20% most disadvantaged neighborhoods (n = 19) relative to state of residence was associated with cortical thinning in Alzheimer signature regions (p = 0.002) and decline in the Preclinical Alzheimer's Disease Cognitive Composite (p = 0.04), particularly the Trail-Making Test, part B (p < 0.001), but not Rey Auditory Verbal Learning Test (p = 0.77) or Story Memory Delayed Recall (p = 0.49) subtests. Associations were attenuated but remained significant after controlling for racial and demographic differences between neighborhood-level disadvantage groups. Cortical thinning partially mediated the association between neighborhood-level disadvantage and cognitive decline. CONCLUSIONS: In this longitudinal study of cognitively unimpaired adults, living in the most highly disadvantaged neighborhoods was associated with accelerated degeneration in Alzheimer signature regions and cognitive decline. This study provides further evidence for neighborhood-level disadvantage as a risk factor for preclinical neurodegeneration and cognitive decline in certain populations. Limitations of the present study, including a small number of participants from highly disadvantaged neighborhoods and a circumscribed geographic setting, should be explored in larger and more diverse study cohorts.

Disclosure of preclinical Alzheimer's disease biomarker results in research and clinical settings: Why, how, and what we still need to know.

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.