Diagnosis
Using the DSM-5 criteria for delirium as framework, the early recognition of signs/symptoms and a careful history, along with any of multiple clinical instruments, can help in making a diagnosis of delirium. A diagnosis of delirium cannot be made without a previous assessment of the patients baseline level of cognitive function. In other words, a mentally-disabled or impaired person might appear to be delirious, but may actually just be operating at their baseline mental ability. General setting
Multiple guidelines recommend that delirium should be diagnosed when it presents to healthcare services. Much evidence reveal, however, that delirium is greatly under-diagnosed. Higher rates of detection of delirium in general settings can be assisted by the use of validated delirium screening tools. Many such tools have been published. They differ in duration, complexity, need for training, etc. Examples of tools in use in clinical practice are:

Richmond Agitation and Sedation Scale (RASS) – highly sensitive and specific for diagnosing delirium in older patients
Observational Scale of Level of Arousal (OSLA) – highly sensitive and specific for diagnosing delirium in older patients
Confusion Assessment Method (CAM)
Delirium Observation Screening Scale (DOS)
Nursing Delirium Screening Scale (Nu-DESC)
Recognizing Acute Delirium As part of your Routine (RADAR)
4AT (4 As Test)
Delirium Diagnostic Tool-Provisional (DDT-Pro), also for subsyndromal delirium

Intensive care unit
People who are in the ICU are at greater risk of delirium and ICU delirium may lead to prolonged ventilation, longer stays in the hospital, increased stress on family and caregivers, and an increased chance of death.
Along with clinical studies using various drugs with anticholinergic activity, these models have contributed to a "cholinergic deficiency hypothesis" of delirium.Profound systemic inflammation occurring during sepsis is also known to cause delirium (often termed sepsis-associated encephalopathy). Animal models used to study the interactions between prior degenerative disease and overlying systemic inflammation have shown that even mild systemic inflammation causes acute and transient deficits in working memory among diseased animals. Prior dementia or age-associated cognitive impairment is the primary predisposing factor for clinical delirium and "prior pathology" as defined by these new animal models may consist of synaptic loss, abnormal network connectivity, and "primed microglia" brain macrophages stimulated by prior neurodegenerative disease and aging to amplify subsequent inflammatory responses in the central nervous system (CNS). Cerebrospinal fluid
Studies of cerebrospinal fluid (CSF) in delirium are difficult to perform. Apart from the general difficulty of recruiting participants who are often unable to give consent, the inherently invasive nature of CSF sampling makes such research particularly challenging. However, a few studies have exploited the opportunity to sample CSF from persons undergoing spinal anesthesia for elective or emergency surgery.A 2018 systematic review showed that, broadly, delirium may be associated with neurotransmitter imbalance (namely serotonin and dopamine signaling), reversible fall in somatostatin, and increased cortisol. The leading "neuroinflammatory hypothesis" (where neurodegenerative disease and aging leads the brain to respond to peripheral inflammation with an exaggerated CNS inflammatory response) has been described, but current evidence is still conflicting and fails to concretely support this hypothesis.