TABLE 1.
Review of prior literature regarding Aβ disclosure in cognitively unimpaired people
| Publication | Manuscript title | Sample | Study and location | Study design | Data collection protocol | Study findings |
|---|---|---|---|---|---|---|
| Impact of Conducting Disclosure | ||||||
| a Grill et al. (2020) | Short‐term psychological outcomes of disclosing amyloid imaging results to research participants who do not have cognitive impairment | 1705 unimpaired (1167 with elevated Aβ, 538 with not elevated Aβ) | A4 Clinical Trial and LEARN prospective cohort, Multiple sites | Prospective cohort study |
Psychological assessment was completed pre and post‐disclosure (visit 1 and 6, respectively). The Concern About AD assessment was collected pre‐disclosure (visit 1) and within 72 hours of disclosure (visit 3). |
There were no statistically significant differences between participants with and without elevated Aβ in short‐term increases of depression, anxiety, or suicidality. Compared to participants with not‐elevated Aβ, participants with elevated Aβ reported increased concern about AD. |
| a Largent et al. (2020) | Cognitively unimpaired adults' reactions to disclosure of amyloid PET scan results | 80 unimpaired | A4 Clinical Trial and LEARN prospective cohort (SOKRATES), University of Pennsylvania, USA | Prospective cohort study | Post‐disclosure interviews 4–12 weeks and 1 year after disclosure |
Participants with elevated Aβ contemplated making more health changes than not‐elevated participants. Not‐elevated Aβ participants reported relief |
| Wake et al. (2020) |
disclosure of amyloid status for risk of alzheimer disease to cognitively normal research participants with subjective cognitive decline: a longitudinal study |
42 unimpaired with subjective cognitive decline (10 Aβ ‐positive, 32 Aβ‐negative) | Keio University, Japan | Participants recruited from memory clinic | Baseline and 6, 24, and 52 weeks after disclosure. | No significant differences in anxiety or depression between groups. Aβ‐negative participants had significantly higher test‐related distress at 52 weeks than Aβ‐positive participants |
| Largent et al. (2019) | Attitudes toward physician‐assisted death from individuals who learn they have an alzheimer disease biomarker | 77 unimpaired | A4 Clinical Trial and LEARN prospective cohort (SOKRATES), University of Pennsylvania, USA | Prospective cohort study | Semi‐structured interview 4‐12 weeks after disclosure, follow‐up interview at 12 months |
Approximately 1 in 5 interviewees with elevated Aβ stated they would pursue physician assisted death (PAD) if they became cognitively impaired, were suffering, or were burdening others. These interviewees were relatively more likely to report preparing for the future (e.g., financial and legal planning). Baseline attitudes toward PAD do not change after learning Aβ result |
| Mattos et al. (2019) |
Research use of ecological momentary assessment for adverse event monitoring following amyloid‐β results |
24 participants with MCI (12, amyloid positive, 12 amyloid negative) | University of Pittsburgh ADRC, USA | Prospective cohort study | Random phone calls and adverse event monitoring using EMA over 14 days after disclosure | EMA and standard adverse event monitoring can maximize early detection of negative psychological reactions to disclosure in participants with MCI |
| a Grill et al. (2018) | Reactions to learning a "not elevated" amyloid PET result in a preclinical Alzheimer's disease trial | 33 unimpaired | A4 Clinical Trial, University of California Irvine, USA | Prospective cohort study |
Disclosure and post‐disclosure interviews Range of time between PET disclosure and interview was 3–30 months |
Most participants without elevated amyloid stated they would adopt lifestyle changes if they had received an elevated result |
| a Wake et al. (2018) | The psychological impact of disclosing amyloid status to Japanese elderly: a preliminary study on asymptomatic patients with subjective cognitive decline | 42 unimpaired with or without subjective cognitive decline | Keio University, Japan | Participants recruited from memory clinic | Before and after disclosure | State anxiety and depression did not change over time and were not different between elevated and non‐elevated groups. |
| a Burns et al. (2017) | Safety of disclosing amyloid status in cognitively normal older adults | 97 unimpaired | APEX exercise study, University of Kansas Alzheimer's Disease Center, USA | Prospective cohort study | Before and at disclosure, 6 weeks and 6 months post‐disclosure | Low risk of psychological harm upon disclosure of Aβ results to cognitively unimpaired participants |
| a Lim et al. (2016) | Disclosure of positron emission tomography amyloid imaging results: A preliminary study of safety and tolerability | 11 unimpaired | Australian Imaging, Biomarkers and Lifestyle study | Prospective cohort study | Baseline, 9 and 18 months follow‐up | Disclosure of Aβ imaging did not have significant emotional or mood impacts. Those with elevated Aβ were more likely to make positive lifestyle changes |
| Participant and researcher attitudes toward disclosure | ||||||
| a Vanderschaeghe et al. (2019) | Stakeholders’ views on early diagnosis for Alzheimer's disease, clinical trial participation and amyloid PET disclosure: A focus group study | 5 focus groups: informal caregivers (9), researchers (8), healthy elderly (10), nursing staff (6), clinicians (7)) | Katholieke Universiteit Leuven, Belgium | Focus group study | Hypothetical scenarios were presented. Interviews on the focus groups responses were recorded and analyzed | Informal caregivers and researches wanted to know their Aβ PET scan result, healthy elderly, nursing staff and clinicians did not |
| Armstrong et al. (2019) | Patient stakeholder versus physician preferences regarding amyloid PET testing | 221 (107 patient stakeholders, 114 clinicians) | University of Maryland, USA | Focus group study | Surveyed patients, family members, dementia advocates, and clinicians on prospective population, outcomes, and harms of disclosure | Patients and caregivers valued having a dementia diagnosis, testing, and outcomes for asymptomatic populations more than clinicians |
| Grill et al. (2016) | Disclosure of amyloid status is not a barrier to recruitment in preclinical Alzheimer's disease clinical trials | 132 self‐reportedly unimpaired | ADRC, University of California Los Angeles, USA | Hypothetical clinical AD study with two conditions (with and without condition of learning amyloid PET results) | Likelihood of enrollment in the study | No difference between groups in willingness to participate indicating that requirement of biomarker disclosure may not pose a problem for recruitment to preclinical AD trials |
| a Ott et al. (2016) | A survey of knowledge and views concerning genetic and amyloid PET status disclosure | 164 “cognitively intact” | Rhode Island Alzheimer Prevention Registry (RIPR), USA | Survey | 25‐item survey to characterize participant interest in disclosure | 80% of participants reported wanting to learn their APOE and amyloid PET results. |
| a Gooblar et al. (2015) | Attitudes of research participants and the general public regarding disclosure of Alzheimer disease research results | 219 unimpaired | KADRC, Washington University, USA | Randomized control survey (two conditions: education session with and without disclosure specific information) | Pre and post‐education session | Interest in disclosure increases for participants with AD experience. Limitations with result interpretation may decrease interest in disclosure |
| a Shulman et al. (2013) | Using AD biomarker research results for clinical care: a survey of ADNI investigators | 159 ADNI investigators and personnel | ADNI, University of Pennsylvania, USA | Survey | Anonymous online survey on: practices about returning results, attitudes about returning Aβ imaging results, explanations for attitudes, etc. | 73% of ADNI researchers support disclosure to participants with MCI; 58% of ADNI researchers support disclosure to participants with normal cognition |
| Understanding disclosure results | ||||||
| a Mozersky et al. (2018) |
Comprehension of an elevated amyloid positron emission tomography biomarker result by cognitively normal older adults |
50 unimpaired | A4 Clinical Trial (SOKRATES), University of Pennsylvania | Prospective cohort study | Post‐disclosure interviews 4–12 weeks and 1 year after disclosure | Clinicians need to be prepared how to disclose the result of elevated Aβ to cognitively unimpaired individuals. Many want to know their risk for developing AD and how elevated their Aβ is |
| Ethical analysis and disclosure procedure development | ||||||
| Taswell et al. (2019) | Avoiding methodological bias in studies of amyloid imaging results disclosure | N.A. | University of California San Diego, USA | Letter written in response to Grill et al. 2018 | Analyzing studies by Grill et al., Wake et al., and Taswell et al. | Methodological bias can be avoided with multiple examiners/examination tools, multiple comparison groups, including observable life events as outcome measures, and larger sample sizes. There is no evidence of disclosure harming those without neuropsychiatric illness |
| Grill et al. (2019) | Response to "Avoiding methodological bias in studies of amyloid imaging results disclosure" | N.A. | University of California Irvine, USA | Letter written in response to Taswell et al. 2019 | Analyzing Taswell et al. (2019) | Multiple methods and studies are necessary to increase confidence of social science research |
| a Vanderschaeghe et al. (2018) | From information to follow‐up: Ethical recommendations to facilitate the disclosure of amyloid PET scan results in a research setting | 4 studies on amyloid PET disclosure | Katholieke Universiteit Leuven, Belgium | Informal literature review | Empirical evidence from Aβ PET disclosure studies to guide facilitation of Aβ PET disclosure | Developed the six‐step IDT‐CRP method for amyloid PET disclosure. It includes informing the participant on risks and their rights, allowing the participant to make an informed decision about involvement, testing, ensuring the participant still wants to know result, returning the result, and following‐up with the participant over a period of time. |
| Rabinovici et al. (2016) | Testing and disclosures related to amyloid imaging and Alzheimer's disease: Common questions and fact sheet summary | N.A. | Alzheimer's Association and NIA, USA | N.A. | Summary of information to date on Aβ with regards to its role in AD, imaging, and disclosure | This NIA‐AA information sheet does not address disclosure of amyloid PET to cognitively unimpaired research participants, but states “… it is premature to use amyloid imaging to determine whether healthy people who do not have cognitive impairment could be at risk for AD” |
| Molinuevo et al. (2016) | Ethical challenges in preclinical Alzheimer's disease observational studies and trials: Results of the Barcelona summit | N.A. | Barcelona, Spain | Ethical analysis | Analysis of justifications for preclinical AD studies | Developing an accurate risk‐benefit ratio for risk marker status disclosure (including Aβ PET) is a challenge incorporating a variety of considerations including public perception of AD |
| a Harkins et al. (2015) | Development of a process to disclose amyloid imaging results to cognitively normal older adult research participants | Experts in informed consent for genetic testing or human Aβ imaging | University of Pennsylvania, USA | Best practices consensus development | Three rounds of modified Delphi Method | A4 study participants should receive verbal and written information about AD and Aβ imaging. Screening for anxiety and depression is necessary. Disclosure should be in person. Follow‐up to assess impact of disclosure, depression, anxiety, and distress |
| Leuzy et al. (2014) | Use of amyloid PET across the spectrum of Alzheimer's disease: clinical utility and associated ethical issues | N.A. | McGill University, Canada | N.A. | Discussion of the development and use of amyloid PET. | Clinical utility of Aβ PET should be better established before widely disclosing Aβ PET results. Further, assessments of the cost‐effectiveness of Aβ PET are needed |
| Roberts et al. (2013) | Amyloid imaging, risk disclosure and Alzheimer's disease: ethical and practical issues | N.A. | University of Michigan, USA | Ethical analysis | Discussion of key issues in disclosure of Aβ PET to asymptomatic individuals | There are many areas in the field of preclinical PET Aβ disclosure that require investigation, including the development of evidence‐based education and counseling of participants |
| Grill et al. (2013) | Should we disclose amyloid imaging result to cognitively normal individuals? | N.A. | University of California Los Angeles, USA | N.A. | Overview of clinical significance of Aβ, and pros and cons of disclosure | Clinical use of Aβ PET for unimpaired individuals is not yet justified. Studies suggest that disclosure of Aβ PET will have minimal psychological harm |
| Porteri et al. (2010) | Diagnosis disclosure of prodromal Alzheimer disease‐ethical analysis of two cases | 2 with memory symptoms | IRCCS Centro San Giovanni di Dio Fatebenefratelli, Italy | Case study | Ethical analysis of disclosure in two cases. | Disclosure was context specific and personalized to the patient |
| Systematic and literature Reviews | ||||||
| Kim et al. (2019) | Disclosure of amyloid PET scan results: A systematic review | 304 (233 cognitively unimpaired, 38 amnestic MCI, 33 patients/caregivers) | University of Pittsburgh ADRC, USA | Systematic literature review | N.A. | Seven studies were included in the analysis. The three studies collecting measures of depression or anxiety found no significant differences from baseline to follow‐up or between Aβ‐positive and Aβ‐negative participants |
| a de Wilde et al. (2018) | Disclosure of amyloid positron emission tomography results to individuals without dementia: a systematic review | 507 unimpaired | ABIDE, Vrije Universiteit Amsterdam, Netherlands | Systematic literature review | N.A. | Disclosure of Aβ PET result is not harmful regarding anxiety or uncertainty |
| Hughes et al. (2017) | Consent for the diagnosis of preclinical dementia states: A review | N.A. | University of Bristol, England | “Scoping” review | Performed literature review. Identified themes across the 10 papers from the literature review. | Four themes were identified in the 10 papers on issues around preclinical dementia disclosure: stigma, ethical issues, psychological burden, and language/ |
a
Denotes that the study was cited in the Erickson et al. manuscript. Due to restrictions on the number of references allowed, not all of the studies on asymptomatic disclosure from the literature review were expressly discussed and cited. We have included them in this table for transparency in our literature review methods and reader convenience.
Abbreviations: Aβ, amyloid beta; AA, Alzheimer's Association; ADNI, Alzheimer's Disease Neuroimaging Initiative; APOE, apolipoprotein E; EMA, Ecological momentary assessment; IDT‐CRP, information, decision, testing, confirmation, return of result, and postguidance; MCI, mild cognitive impairment; NIA, National Institute on Aging; PET, positron emission tomography.