Diffuse Optical Tomography for Mapping Brain Function in Delirium and Post-Delirium ADRD

About This Grant

PROJECT SUMMARY/ABSTRACT Delirium is a neuropsychiatric syndrome characterized by an acute or subacute onset and fluctuating course, with disruptions in attention, arousal, cognitive domains, psychomotor state, and emotions. More than 75% of critically ill older adults may develop delirium, and approximately 50% of intensive care unit (ICU) survivors will suffer from subsequent mild cognitive impairment (MCI) and Alzheimer’s Disease and Related Dementias (ADRD). Delirium has been strongly linked to post-ICU MCI and ADRD, suggesting a shared neurobiological pathway that underlies these conditions. Identifying biomarkers to capture these early changes could offer critical insights into the mechanisms connecting delirium with long-term cognitive decline. However, the development of a neuroimaging biomarker has been challenging due to the logistical and technical limitations of standard imaging techniques, such as poor portability, limited access, and reduced tolerability in acutely and critically ill patients. The advent of optical imaging techniques offers a potential solution to these challenges. Diffuse optical tomography (DOT) is a modern optical imaging modality that combines high spatiotemporal resolution and bedside capabilities for studying cerebral hemodynamics and functional connectivity. The candidate’s pilot study demonstrated impaired cerebral oxygenation and functional dysconnectivity within the prefrontal cortex during delirium that improved post-delirium resolution but remained significantly lower than matched non-delirious controls. The premise of this K23 proposal is to further validate these results and advance them by conducting a prospective cohort study of older ICU patients to determine whether DOT can be used as a portable imaging biomarker to study longitudinal cognitive decline after ICU delirium. In Aim 1, the candidate will examine differences in DOT imaging metrics between an ICU delirium group and a non-delirium ICU group, with covariate adjustments. In Aim 2, the candidate will determine whether DOT imaging metrics during delirium or post-delirium predict cognitive performance at 12 months, in comparison to the non-delirium ICU group. The support of the K23 award will provide the applicant with the training necessary to achieve these aims. The training objectives will be accomplished with the support of an outstanding mentorship team, Drs. DeKosky, Efron, Oh, Jiang, Marsiske, Vaillancourt, and the world-class resources of the University of Florida. Together, the proposed scientific aims and training objectives will form the foundation for an independent research program that will use advanced optical neuroimaging to understand the relationship between delirium and subsequent dementias.