Predisposing factors
The most important predisposing factors are:
65 or more years of age
Male sex
Cognitive impairment/dementia
Physical comorbidity (biventricular failure, cancer, cerebrovascular disease)
Psychiatric comorbidity (e.g., depression)
Sensory impairment (vision, hearing)
Functional dependence (e.g., requiring assistance for self-care or mobility)
Dehydration/malnutrition
Drugs and drug-dependence
Alcohol dependence

Precipitating factors
Any acute factors that affect neurotransmitter, neuroendocrine, or neuroinflammatory pathways can precipitate an episode of delirium in a vulnerable brain. Clinical environments can also precipitate delirium. Some of the most common precipitating factors are listed below:
Prolonged sleep deprivation
Environmental, physical/psychological stress
Inadequately controlled pain
Admission to an intensive care unit
Immobilization, use of physical restraints
Urinary retention, use of bladder catheter,
Emotional stress
Severe constipation/fecal impaction
MedicationsSedatives (benzodiazepines, opioids), anticholinergics, dopaminergics, corticosteroids, polypharmacy
General anesthetic
Substance intoxication or withdrawal
Primary neurologic diseases
Severe drop in blood pressure, relative to the patients normal blood pressure (orthostatic hypotension) resulting in inadequate blood flow to the brain (cerebral hypoperfusion)
Stroke/Transient ischemic attack(TIA)
Intracranial bleeding
Meningitis, encephalitis
Concurrent illness
Infections – especially respiratory (e.g. pneumonia, COVID-19) and urinary tract infections
Iatrogenic complications
Hypoxia, hypercapnea, anemia
Poor nutritional status, dehydration, electrolyte imbalances, hypoglycemia
Shock, heart attacks, heart failure
Metabolic derangements (e.g. SIADH, Addisons disease, hyperthyroidism, )
Chronic/terminal illness (e.g. cancer)
Post-traumatic event (e.g. fall, fracture)
Mercury poisoning (e.g. Erethism)
Surgery
Cardiac, orthopedic, prolonged cardiopulmonary bypass, thoracic surgeries

Pathophysiology
The pathophysiology of delirium is still not well understood, despite extensive research. Animal models
The lack of animal models that are relevant to delirium has left many key questions in delirium pathophysiology unanswered. Earliest rodent models of delirium used atropine (a muscarinic acetylcholine receptor blocker) to induce cognitive and electroencephalography (EEG) changes similar to delirium, and other anticholinergic drugs, such as biperiden and hyoscine, have produced similar effects.
Neuroimaging
Neuroimaging provides an important avenue to explore the mechanisms that are responsible for delirium. Despite progress in the development of magnetic resonance imaging (MRI), the large variety in imaging-based findings has limited our understanding of the changes in the brain that may be linked to delirium. Some challenges associated with imaging people diagnosed with delirium include participant recruitment and inadequate consideration of important confounding factors such as history of dementia and/or depression, which are known to be associated with overlapping changes in the brain also observed on MRI.Evidence for changes in structural and functional markers include: changes in white-matter integrity (white matter lesions), decreases in brain volume (likely as a result of tissue atrophy), abnormal functional connectivity of brain regions responsible for normal processing of executive function, sensory processing, attention, emotional regulation, memory, and orientation, differences in autoregulation of the vascular vessels in the brain, reduction in cerebral blood flow and possible changes in brain metabolism (including cerebral tissue oxygenation and glucose hypometabolism). Altogether, these changes in MRI-based measurements invite further investigation of the mechanisms that may underlie delirium, as a potential avenue to improve clinical management of people with this condition. Neurophysiology
Electroencephalography (EEG) allows for continuous capture of global brain function and brain connectivity, and is useful in understanding real-time physiologic changes during delirium.