The Pathophysiology and Biomarkers of Delirium

Delirium is a major disturbance in the mental state characterized by fluctuations in arousal, deficits in attention, distorted perception, and disruptions in memory and cognitive processing. Delirium affects approximately 18% to 25% of hospital inpatients, with even higher rates observed during critical illness. To develop therapies to shorten the duration and limit the adverse effects of delirium, it is important to understand the mechanisms underlying its presentation. Neuroimaging modalities such as magnetic resonance imaging (MRI), positron emission tomography, functional MRI, and near-infrared spectroscopy point to global atrophy, white matter changes, and disruptions in cerebral blood flow, oxygenation, metabolism, and connectivity as key correlates of delirium pathogenesis. Electroencephalography demonstrates generalized slowing of normal background activity, with pathologic decreases in variability of oscillatory patterns and disruptions in functional connectivity among specific brain regions. Elevated serum biomarkers of inflammation, including interleukin-6, C-reactive protein, and S100B, suggest a role of dysregulated inflammatory processes and cellular metabolism, particularly in perioperative and sepsis-related delirium. Emerging animal models that can mimic delirium-like clinical states will reveal further insights into delirium pathophysiology. The combination of clinical and basic science methods of exploring delirium shows great promise in elucidating its underlying mechanisms and revealing potential therapeutic targets.