Amyloid PET and blood biomarker supplement to the Delirium Program Project

摘要

Abstract Delirium is a common, costly, life-threatening, and potentially preventable problem for older persons. The development of delirium is considered to be a marker of brain vulnerability; however, its relationship to dementia and Alzheimer’s disease and related dementias (AD/ADRD) remains unclear. In the parent Program Project renewal grant, we are now conducting a series of 5 interlinked projects applying innovative approaches to deepen our exploration of pathophysiologic pathways potentially contributing to delirium and its associated cognitive decline. We are examining the role of amyloid markers in primary aims of Projects 1, 3, and 5, and in cross-linking aims across all projects. In our original proposal, we proposed using cerebrospinal fluid (CSF) biomarkers to quantify amyloid status in a subsample (n=128) of the SAGES I cohort, and in all of the new SAGES II cohort (n=350-400); however, about 25-30% of the participants are either medically ineligible or will not receive CSF sampling (due to their own or their surgeon’s preference). We will be completing SAGES II cohort enrollment in the next year, and anticipate about 80-90 participants where CSF amyloid status will not have been determined. In this supplement, we request support for 2 Sub-Projects: (1) addition of 30 [F18] Florbetapir (“Amyloid”) Positron Emission Tomography (PET) scans to measure amyloid status in SAGES II participants who did not receive CSF sampling; (2) measurement of novel biomarkers for neurodegeneration (p-tau 181 and GFAP) in stored plasma from the entire SAGES I cohort (n=560). This supplement will enhance the impact of the Program Project in several ways. First, amyloid-PET will allow us to assure we can assess amyloid status for most high-risk participants who do not receive CSF sampling, and to achieve the original aims. Second, PET imaging allows abnormally elevated cerebral amyloid to be localized, which will offer opportunities to relate amyloid imaging measures to the variety of MRI and electrophysiological measures we are obtaining. Third, the biomarker assays would allow us to validate additional potential blood-based predictors of delirium, delirium severity, and post-operative cognitive decline (aligned with our original aims), which would provide risk markers to stratify future patients for clinical trials and to monitor response to treatment. Thus, obtaining the additional scans and assays will ensure the achievement of our original aims and will also magnify the overall impact of the Program Project, through modifications that are well-aligned with the original aims. This supplement will truly bolster the Program Project, and allow it to achieve its goals of advancing our understanding of delirium and its relationship to AD/ADRD, and ultimately, to develop more effective strategies for prevention and treatment.