Comprehension of an Elevated Amyloid Positron Emission Tomography Biomarker Result by Cognitively Normal Older Adults

Abstract

IMPORTANCEThe goal of Alzheimer disease (AD) prevention together with advances in understanding the pathophysiology of AD have led to clinical trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Data are needed to inform the processes of describing AD biomarkers to cognitively normal adults and assessing their understanding of this knowledge.OBJECTIVE To determine the comprehension of an elevated amyloid positron emission tomographic (PET) biomarker result by cognitively unimpaired adults. DESIGN, SETTING, AND PARTICIPANTSThe Study of Knowledge and Reactions to Amyloid Testing, a substudy of an AD prevention trial, involved 2 semistructured telephone interviews with 80 participants recruited from 9 study sites: 50 received elevated and 30 received not elevated amyloid PET scan results. Interviews were conducted 4 to 12 weeks after result disclosure and again 1 year later. Data presented here were collected from November 5, 2014, through December 10, 2015. The 50 participants included in this study were cognitively normal, aged 65 to 85 years, evenly distributed by gender, and had elevated amyloid PET results. Subsequent reports will examine persons with "not elevated" results and compare the influence of the different results. MAIN OUTCOMES AND MEASURES Participant comprehension of an elevated amyloid resultwas assessed by analyzing their responses to the following questions: "What was the result of your amyloid PET scan?" (followed by "Can you tell me in your own words what that means?" or "How would you explain it to a friend?"), "Was it the result you expected?" and "Did the result teach you anything or clarify anything for you?" RESULTS Of the 50 participants aged 65 to 85 years, 49 (98%) were white, 40 (80%) reported a family history of AD, and 30 (60%) had a postgraduate educational level. Most participants (31 [62%]) understood that elevated amyloid conferred an increased but uncertain risk of developing AD. Some desired understanding of the term elevated other than its being a categorical result enabling trial entry eligibility; they wanted information regarding how elevated their amyloid was, how close to the study threshold they were, or percentages, numbers, or a scale to help them make sense of the result.CONCLUSIONS AND RELEVANCE Including an explanation of how and why a dimensional biomarker is converted to a categorical classification would enhance future AD biomarker clinical trials and educational materials.

Cognitively unimpaired adults’ reactions to disclosure of amyloid PET scan results

“…Most participants who received an "elevated" amyloid PET scan result (31 of 50 [62%]) understood that the result described an increased but uncertain risk of developing AD dementia. [18] Some (20 of 50 [40%]) felt it was ambiguous, and many of these participants wanted quantitative information about the amount of amyloid detected.…”

“…The methods have previously been reported. [18] Briefly, the research team reviewed all transcripts to develop a coding scheme to reflect the four aforementioned domains and to capture themes that emerged during coding and analysis. This iterative process involved multiple consensus meetings to resolve coding discrepancies, regular checks on agreement using the Cohen coefficient for inter-coder reliability, and adjustments to the codebook with an audit trail of coding rules and decisions made.…”

“…SOKRATES participants generally understood the key point of the A4 amyloid imaging disclosure process: an "elevated" amyloid PET scan result means a person has an increased but presently unquantifiable risk of developing AD dementia. [18] Notably, participants differed in their interest in further details about the amyloid PET scan result. Participants who received an "elevated" result often wanted more information, whereas those who received a "not-elevated" result were generally satisfied with detail they received.…”

Perspectives on Communicating Biomarker-Based Assessments of Alzheimer’s Disease to Cognitively Healthy Individuals

“…However, currently, this limitation should be addressed through the development within these studies of information or education materials to accompany disclosure processes [ 33, 40 ]. In line with the findings from qualitative work following amyloid disclosure, these may need to address how classifications of amyloid ‘positive’ or ‘negative’ are produced [ 32 ], and should also be transparent about the scientific uncertainties associated with biomarkers [ 52 ]. However, more work is also needed to inform the communication of scientific ambiguity or epistemic uncertainty [ 53 ] related to Alzheimer’s disease, as well as in our understanding of the concept of Alzheimer’s disease itself, given that the majority of individuals die with these pathologies in their brains and that, among the oldest old—the age of greatest risk for dementia—the risk of Alzheimer’s dementia associated with these pathologies is attenuated [ 54, 55 ].…”

“…Importantly, the impact of disclosure is also likely to be affected by the manner in which information about amyloid biomarkers is presented to the research participant. Careful attention is needed to determine whether people want to learn information about biomarkers for Alzheimer’s dementia, what this information should include, and when and how it should be communicated [ 32 ].…”