Dr. Sander’s Research

Cognitive Disintegration in Delirium

Delirium is a sudden state of confusion, associated with increased morbidity and mortality, impaired long-term cognition and loss of independence. Unfortunately, delirium is bereft of therapies, largely due to the limited understanding of its pathogenesis. The long-term goal of the proposed research program is to develop preventative and therapeutic approaches to delirium. In this application, I seek to identify the neural correlates of delirium, and subsequent cognitive decline, as the first step in a translational research program. The strategy is based on the Cognitive Disintegration model: we hypothesize that delirium results from an acute breakdown in neural network connectivity. In essence, delirium results when “information integration” falls below a critical threshold in vulnerable networks. We use network connectivity as a surrogate of the capacity to integrate information. We will test the hypothesis that impaired preoperative cingulate functional connectivity is associated with increased risk of postoperative delirium following adjustment for confounding variables. The electroencephalogram (EEG) hallmark of delirium is increased slow wave activity however the patients are not asleep. We hypothesize that there is “local” slow wave activity in delirium. If proven, this would provide a mechanism for the breakdown in network connectivity in delirium and highlight specific brain vulnerable regions producing the delirium state. Finally, we will address the role of pre-delirium connectivity in the associations between delirium and long-term cognitive decline, hypothesizing that preoperative connectivity modulates the impact of delirium on long-term cognition. This application will provide insights into the neural network changes predisposing to, and associated with, postoperative delirium and its long-term cognitive sequelae while providing key preliminary data for a future R01 application.