The Pathophysiology of Delirium – Neuroinflammatory Pathways


Medical School of Lisbon, University of Lisbon, University clinic of Medical Psychology and Psychiatry, Lisbon, Portugal


Delirium is a neuropsychiatric syndrome, defined as “a transient global disorder of cognition and attention”, being the fluctuations of consciousness the essential signal to a correct diagnosis. It is a condition with a physical etiology, most of the times multifactorial, being sometimes difficult to identify the specific stressors. Delirium is highly prevalent in hospital environments (up to 30% of hospitalized patients) and is associated with prolonged hospital stay and increased morbidity and mortality.

Although the pathophysiology remains poorly understood, recent studies have brought evidences of a relation between cytokine levels and delirium. Increased serum levels of pro-inflammatory cytokines and decreases in anti-inflammatory mediators have been described in medical patients with delirium.

Activation of the inflammatory cascade with acute release of inflammatory mediators is present in several delirium-associated conditions and neuroinflammatory changes, including neuronal and synaptic dysfunction, can be related to behavioural and cognitive symptoms seen in clinical practice.

Consistent with an exaggerated inflammatory response in vulnerable brains, minor inflammatory insult may precipitate significant deterioration in the elderly and those with dementia. Advanced age, infections, medication, alcohol use/withdrawal and prolonged surgeries are all well-known risk factors. Delirium also have a dual relation with dementia, being a precipitating or aggravating factor, associated with adverse outcomes.