Clinical trials for the prevention of Alzheimer's disease (AD) have been moving to enroll subjects at increasingly early time-points, and are now focusing upon individuals who are cognitively normal, but have biomarkers associated with an increased risk of developing AD. Enriching trials with such biomarkers presents two fundamental concerns that are of critical importance to the future validity and safety of AD trials Will a subject's knowledge of their biomarker status bias the cognitive outcomes of the trial? And will such knowledge cause adverse psychological consequences? In this study, risk communication protocols will be developed and implemented for communicating amyloid PET brain imaging results. Then, 270 cognitively normal individuals (approximately 25% African American), aged 65-80, will be recruited and randomized to receive their amyloid scan results or not, resulting in subjects whose scan results are disclosed or not and subjects whose scans are amyloid positive or not. APOE genotyping with oversampling of e4+ individuals will be used to enrich the enrollment sample, such that roughly half of those scanned will be amyloid positive and half will be amyloid negative. The primary neuropsychological outcome will be the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC) and the primary psychological outcome for psychological distress will be the Impact of Events Scale (IES).
The Specific Aims of this study are 1) to determine whether disclosure of elevated brain amyloid will bias ADCS-Preclinical Alzheimer Cognitive Composite (ADCS-PACC) test results; 2) to determine whether disclosure of elevated brain amyloid will cause psychological distress; and 3) to explore how learning amyloid imaging disclosure will impact preventative health behaviors, advance planning for health (e.g. long-term care insurance decisions) and well-being (e.g. stigma, quality of life and relationships).
As clinical trials for Alzheimer's disease (AD) seek to enroll individuals at the earliest stages of the disease, it will become increasingly important to examine the impact of learning AD risk in cognitively normal individuals. In the near future, researchers are likely to use new amyloid brain imaging methods to identify participants who have Alzheimer's brain pathology but no cognitive impairment ('high-risk' individuals), and enroll them in AD clinical trials. The proposed project will be the first trial to generate data on how to appropriately enroll these individuals and safely disclose risk to them, while measuring performance bias on crucial outcome measures.
| Ridge, Perry G; Wadsworth, Mark E; Miller, Justin B et al. (2018) Assembly of 809 whole mitochondrial genomes with clinical, imaging, and fluid biomarker phenotyping. Alzheimers Dement 14:514-519 |
