Neural mechanisms of delirium: current hypotheses and evolving concepts

The purpose of this article is to review current knowledge regarding potential neural mechanisms of delirium. A MEDLINE search for relevant English language articles was undertaken using various combinations of delirium (including cognitive disorders, encephalopathy, and confusion) with pathogenesis and pathophysiology. These articles were scanned for content related to hypotheses concerning the neurobiology of delirium. Additional references were obtained from a manual search of the bibliography of these articles. A secondary MEDLINE search of delirium with the mechanism in question (i.e., serotonin, acetylcholine, etc.) was then undertaken. Literature review was last updated as of April 1998. Despite being a common problem among elderly patients, the mechanisms of delirium are poorly understood. Delirium is a syndrome that may occur as the result of multiple complex interacting neurotransmitter systems and pathologic processes. The neurotransmitters acetylcholine and serotonin may play particularly important roles in common medical and surgical delirium. Other neurotransmitters such as dopamine and gamma-aminobutyric acid each may be involved in the development of delirium under special conditions. Other neurobiologic factors such as cytokines, cortisol abnormalities, and oxygen free radicals will require further study to define their role in delirium. Distinct neuropathologic processes leading to delirium are beginning to be defined. Such mechanisms may differ in various clinical settings. There is probably no final common pathway to delirium, but rather, delirium is the final common symptom of multiple neurotransmitter abnormalities. Further situation-specific studies of delirium pathophysiology should lead to more effective prevention and treatment strategies.