Returning AD biomarker Results to Community Dwelling Older Adults: Testing Modalities and Impact

Project Summary This study will develop a process to return Alzheimer Disease (AD) biomarker research results and will evaluate whether the results can be sent directly to participants in a safe and understandable way. The brain changes associated with AD begin decades before symptom onset during a stage called preclinical AD. Until

recently, obtaining a diagnosis of preclinical AD was based on invasive biomarker tests (PET scans and lumbar punctures) only available at specialty research centers and not recommended for clinical use due to the lack of actionability and ethical concerns about the harms of disclosure. This landscape has dramatically

changed with two new developments: a blood-based biomarker test is now available that can identify preclinical AD, and the first drug treatment directly targeting AD brain pathology received FDA approval in July 2023 for those with AD brain pathology and very mild symptoms. Medications targeting AD brain pathology are

now being tested in individuals with preclinical AD because data suggest this is when they are most effective, signaling a future where asymptomatic individuals undergo AD biomarker testing prior to obtaining treatment, dramatically increasing the number of individuals who would be clinically tested and treated. Further, new

regulatory requirements of the 21st Century Cures Act require immediate electronic release of clinical results, bypassing traditional clinician-mediated disclosure of AD biomarker results. Despite a current lack of clinical actionability for returning results related to preclinical AD, a recent participant

Bill of Rights advocates returning AD biomarker research results to respect autonomy and because research results have personal value. Studies suggest that disclosure of AD biomarker results has no major psychosocial harms but have been limited to highly selected research participants in controlled research

settings with in-person disclosure by specialized clinicians. This leaves significant gaps in knowledge and a lack of generalizability – a challenge for AD research more broadly that must be rectified. In a large, community-dwelling cohort of cognitively normal older adults, this study will develop a culturally-

appropriate process for return of AD biomarker research results (Aim 1) and will evaluate whether the results can be sent directly to participants in a safe and understandable way using a randomized non-inferiority trial (Aim 2) with a sequential explanatory qualitative evaluation of experiences (Aim 3). This project responds to

the rapidly evolving landscape where a readily available AD diagnostic blood test followed by a treatment is becoming a reality. The data produced will inform whether sending AD biomarker results directly to older adults can effectively communicate the results in a safe way, which will be necessary for widespread AD diagnostic

testing.