Cholinesterase Activity and DeliriUm During Critical Illness Study

Delirium is a syndrome of acute brain dysfunction involving attention and cognition that
affects up to half of older hospitalized patients and 50%-75% of critically ill ICU patients,
such that millions of patients worldwide experience this acute threat to their health and
well being every year. One-third to half of critical illness survivors struggle with a
dementia-like disorder similar in severity to moderate-to-severe traumatic brain injury or
Alzheimer's Disease, and the only proven risk factor that is potentially modifiable is
delirium in the ICU. Despite the frequency and impact of delirium in the ICU, little is known
regarding the biological mechanisms that lead to this form of organ dysfunction during
critical illness. A widely held hypothesis proposes that inflammation is regulated by the
cholinergic system, and that this interaction plays a pivotal role whether delirium
developments in the setting of acute illness. Acetylcholinesterase (AChE) and
butyrylcholinesterase (BuChE) are enzymes that hydrolyze the neurotransmitter acetylcholine.
Changes in the activity of these enzymes, which can be measured in whole blood, reflect
altered regulation of circulating acetylcholine. AChE and BuChE activities have promise as
both predictors of delirium (when found to be low at admission) and biomarkers of delirium
(when low during serial measurement). Neither of these biomarkers, however, have been studied
in the ICU setting where delirium risk is the highest. The current investigation, therefore
will be the first to determine the validity of circulating AChE and BuChE activities as
biomarkers of delirium during critical illness and subsequent cognitive impairment after
discharge. This study will measure whole blood AChE and butyrylcholinesterase BuChE
activities within the framework of the ICU Delirium and Cognitive Impairment Study Group's
ongoing clinical trials in critically ill patients.