Date Published: December 22, 2018
Publisher: BioMed Central
Author(s): Joshua D. Grill, Chelsea G. Cox, Kristin Harkins, Jason Karlawish.
The experiences of biomarker-ineligible cognitively normal persons can inform trial conduct and the translation of preclinical Alzheimer’s disease (AD) into clinical practice.
We interviewed 33 persons whose “not elevated” brain amyloid imaging biomarker result made them ineligible for a preclinical AD trial.
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.
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.
Increasing evidence supports a hypothesis that dementia due to Alzheimer’s disease (AD) is the end result of a long pathophysiological process that begins years before symptoms . This asymptomatic or preclinical stage offers an opportunity to test disease-modifying therapies to delay the onset of cognitive and behavioral symptoms due to AD [2, 3].
Clinical trials frequently disclose AD biomarker results to cognitively normal individuals. Disclosure processes focus on educating potential subjects about what is known and not known about amyloid imaging, minimizing negative reactions, and ensuring the safety of those who are informed that AD biomarkers are present [16, 22]. Better understanding of the impact of learning a “negative” result is needed, given that this will be the most common type of information disclosed in future trials and ultimately in large public health screening campaigns when effective therapies are developed. This study of individuals who learned they did not have an elevated amyloid result shows how trial participants understood, reacted to, and used this information as well as whether they would participate in another study.
These results suggest that the disclosure process in the A4 study was effective and safe in ineligible participants, though important opportunities to improve the process may exist. Disclosure did not result in adoption of unhealthy behaviors among participants; however, most indicated that there were risk-reducing strategies that they would have implemented had they received an elevated result. Communicating the need to adopt such strategies to all participants will be important in future preclinical AD trials, as well as in future public health campaigns that aim to identify appropriate candidates for disease-delaying therapies.