Delirium, Dementia, and Amnesia in Emergency Medicine

Updated: Aug 29, 2022
Author: Richard D Shin, MD, FACEP; Chief Editor: Gil Z Shlamovitz, MD, FACEP 



Delirium, dementia, amnesia (and certain other alterations in cognition, judgment, and/or memory) are grouped together in this article as organically based disruptions of brain functioning. While psychiatric illnesses can at times mimic some features of these conditions or complicate their presentation in the emergency department, the primary etiologies are physiological rather than psychiatric. Causes of these conditions include metabolic disruptions, endocrine dysfunction, drug toxicity, structural injury (eg, trauma, stroke, chronic dementing process), brain ischemia, severe physiologic/psychological stressors (including prolonged sensory deprivation, "ICU psychosis", sleep deprivation), encephalitis and sepsis.


Altered mental status can be divided into 2 major subgroups: acute (delirium or acute confusional state) and chronic (dementia). A third entity, encephalopathy (subacute organically based brain dysfunction), denotes a gray zone between these extremes; its early course may fluctuate and/or resolve, but it is often persistent and progressive.

The final common pathway of all forms of organically based mental status change is an alteration in cortical brain function, at times in concert with abnormalities of deep brain structures. These conditions result from (1) an exogenous insult or an intrinsic process that affects cerebral neurochemical functioning and/or (2) physical or structural damage to the cortex, subcortex, or to deeper structures involved with memory. Some of the etiologies include trauma, mass lesions, hydrocephalus, strokes (ie, multi-infarct dementia), atrophy, infection, toxins, or dementing processes.

The end result of these disruptions of brain function and/or structure is impairment of cognition that affects some or all of the following: alertness, orientation, emotion, behavior, memory, perception, language, praxis, problem solving, judgment, and psychomotor activity. Knowledge of which areas of this spectrum are affected or spared guides both the workup and the diagnosis.



Delirium accounts for or develops during 10–15% of all admissions to acute-care hospitals but is seen much more frequently in elderly persons (up to 75% of seriously ill and hospitalized), particularly following major surgery, trauma or prolonged ICU care. ICU delirium, with a prevalence estimated at 31.8%, is associated with increased ICU length of stay, longer mechanical ventilation duration, and increased mortality.[1]  Delirium is usually transient, but it can be persistent leading to a chronically dementing process in elderly patients.

The prevalence of dementia doubles every 5 years between ages 60 to about 90 years: 1% of persons aged 60–64 years up to 30–50% of those older than 85 years. Approximately 60% of nursing home beds are occupied by patients with dementia. In the ED, patients in nursing homes are more likely to present with delirium than other patients, even after adjusting for delirium risk factors.[2]  Alzheimer disease (AD) accounts for most patients with dementia who are older than 55 years (50–90% of all cases). It is estimated that over 4 million people in the United States suffer from AD.

Although slowing of memory and word-finding are normal features of brain aging, approximately 10–15% of patients with mild cognitive impairment, a transitional state between normal functioning and dementia, progress to AD yearly.

For as yet unknown reasons, dementia rates in the United States have been declining over the past several years.

Alzheimer disease is less common and has an older age of onset in Japan, China, and parts of Scandinavia. In these countries, vascular causes of dementia may outnumber Alzheimer disease.


Some causes of delirium (eg, delirium tremens, severe hypoglycemia, CNS infection, heatstroke, thyroid storm) may be fatal or result in severe morbidity if unrecognized and untreated. With some exceptions (such as overdose with tricyclic antidepressants), drug intoxications generally resolve fully with supportive care alone. Failure to provide thiamine when administering glucose may rarely lead to acute Wernicke syndrome (ataxia, confusion, oculomotor palsies in the setting of malnutrition). If unrecognized, Wernicke syndrome may also result in chronic dementia.

Certain withdrawal syndromes can present with delirium (eg, alcohol, benzodiazepines, barbiturates and naloxone-induced acute opiate withdrawal). Some of these withdrawal states can be fatal if if not aggressively treated.

Patients with primary dementia have a significantly reduced life expectancy, depending on the cause of the dementia and its severity and rapidity of progression.[3]


There is no specific data collected to detect specific rates of delirium between races in the Emergency Department. In the United States, dementia is more prevalent in African American, American Indian/Alaska Native, intermediate in Latinos, Pacific Islanders and Whites, and lowest among Asian Americans.[4]


Delirium is seen more commonly in males,[5]  while Alzheimer disease and dementia is more prevalent among women because of their longer life expectancy. Lifetime risk in women is estimated to be 32%, whereas the lifetime risk in men is 18%. However, the age-specific risk is equal in both sexes.


Delirium due to physical illness is more frequent among the very young and those in advanced age. Delirium due to drug and alcohol intoxication or withdrawal is most frequent in persons aged mid-teens to late thirties.

Dementia, particularly Alzheimer disease, is seen predominantly in elderly persons; however, certain types of dementia are seen in younger patients (eg, AIDS-related dementia, certain familial forms of Alzheimer disease), and some cases of variant Creutzfeldt-Jakob disease (ie, bovine spongiform encephalopathy or mad cow disease). 


Smoking, obstructive sleep apnea, alcohol excess, atrial fibrillation, renal dysfunction, obesity, and heart failure have been reported as risk factors for developing delirium.[6]  Of all causes of dementia, these are the most modifiable in order to reduce dementia risk.

Genetic Factors

Early-onset familial Alzheimer's disease, a rare subtype occurring in patients 30–60 years of age, is typically caused by an inherited mutation in one of three genes: chromosomes 21, 14 and 1. Transmission is autosomal dominant with a high degree of penetration. Other types of early-onset dementia have no known specific causes. Typical late-onset AD, first manifesting around the mid-sixties and older, may have some genetically inheritable risk, particularly involving the apolipoprotein E gene on chromosome 19. Researchers have now identified many other areas of interest in the Alzheimer's genome that may prove to increase risk of developing the disease to varying degrees.[7]


One prospective cohort study of acutely ill hospitalized older adults observed that delirium occurred in 47% of admissions. One in three of these admissions resulted in death during hospitalization, with a cumulative mortality of 52% in 12 months. Although hypoactive delirium is usually described as potentially more severe than other forms, results presented in the literature on prognostic differences among the subtypes of delirium are sparse and conflicting.[8]

Delirium is fully reversible in most cases with proper recognition and treatment of the etiology. However, some cases of delirium can last weeks or months and can become chronic.

Dementia is usually insidious and relentlessly progressive. However, about 20–30% of cases are due to reversible causes. On average, patients with Alzheimer disease die within 8 years of onset, with a range of 2–15 years. Younger patients usually have a more fulminant course. Pick disease has a similar course.

Subacute encephalopathy may be reversible, persistent, or progressive.




Altered Mental Status (AMS) can evolve acutely with a rapidly fluctuating and usually transient course (delirium); or insidiously and inexorably over months or years with an intermittently or gradually worsening course chiefly involving loss of short-term memory (dementia).


Delirium presents with acute onset of impaired awareness, easy distractability, confusion, and disturbances of perception (eg, illusions, misinterpretations or visual hallucinations). Recent memory is usually deficient, and the patient is typically disoriented to time and place. Level of awareness may range from hypervigilant and agitated to obtunded, and abnormalities of congition and behavior may fluctuate dramatically over brief periods. Speech may be incoherent, pressured, nonsensical, perseverating, or rambling. Obtaining a reliable history from a delirious patient may be difficult or impossible. Patients with delirium have difficulty maintaining attention and/or shifting the focus of their attention.

For patients with delirium, attempt to obtain a current and past history from other sources, including prehospital workers, family or friends, and past medical records. Look specifically for street drug, alcohol, over-the-counter or prescribed medication use. Consider preexisting endocrine disorders. Inquire about recent activities that may have resulted in exposure to toxins or environmental injury. Ask about prior psychiatric illness, history of overdose and similar episodes of confusion in the past.

Delirium typically manifests with either of two patterns of psychomotor activity: hypoactive or hyperactive. Hypoactive delirium is characterized by stupor, psychomotor lentification and lethargy, and is the most frequent pattern in older adults. Conversely, hyperactive delirium is characterized by agitation, hypervigilance and hallucinations.[8]  


Dementia presents with a history of chronic, steady decline in short and, later, long-term memory and is associated with difficulties in social relationships, work, and activities of daily life. In contrast to delirium, the sensorium is usually clear. However, acute confusional states can be superimposed on an underlying dementing process. The diagnosis is usually known previously in a patient who presents to the ED with moderate-to-severe symptoms.

Earlier stages of dementia may present subtly, and patients may minimize or attempt to hide their impairments. Patients at this stage often have an associated depression. In addition, major depression alone can present as a dementia-like condition in elderly patients but is treatable and reversible. Dementia of relatively recent onset has a higher likelihood of a potentially reversible etiology. Take a careful history, looking for past or present drug or alcohol abuse, current medications, chronic or acute medical illnesses and psychiatric disorders to uncover a treatable or modifiable cause for the cognitive impairment.

Elderly patients with depressed mood, hopelessness, and suicidality may be suffering from "pseudodementia" (false dementia). When the depression is alleviated with treatment, the dementia-like condition resolves.

A history of a stuttering course of chronic memory loss may point to multi-infarct dementia, which is caused by repeated lacunar strokes. Treatment aimed at preventing future strokes may arrest further progression of the dementia. However, small strokes in specific areas of the brain may trigger the onset of progressive Alzheimer-type dementia


Any patient who presents with altered mental status (AMS) needs a complete physical examination, with particular attention to general appearance, vital signs, hydration status, evidence of physical trauma, and neurologic signs. The delirious or obtunded patient should be evaluated for pupillary, funduscopic, and extraocular abnormalities; nuchal rigidity; thyroid enlargement; and heart murmurs or rhythm disturbances. Other clues include a pulmonary examination that reveals wheezing, rales, or absent breath sounds; an abdominal examination that reveals hepatic or splenic enlargement; or a cutaneous examination that shows rashes, icterus, petechiae, ecchymoses, track marks, or cellulitis. Cellulitis in elderly persons often is hidden under clothing, particularly pants and socks. Checking these areas in patients with diabetes is critical. Any serious infection can lead to acute mental status changes.

General appearance (eg, unkempt and/or malnourished) may suggest the possibility of drug or alcohol abuse.

Look for track marks indicative of IV drug use.

Smell for alcohol, the musty odor of fetor hepaticus, or the fruity smell of ketoacidosis.

Icterus and asterixis point to liver failure with an elevation of the serum ammonia level.

Agitation and tremulousness suggest sedative drug or alcohol withdrawal.

Close attention to vital signs is essential and easy to overlook in the setting of extreme behavioral difficulties in a delirious patient. It is unusual for a patient with acute delirium to present to the ED with normal vital signs.

Fever may point to infection, heat illness, thyroid storm, aspirin toxicity, or the extreme adrenergic overflow of certain drug overdoses and withdrawal syndromes (in particular, delirium tremens). Extreme hyperthermia (with pinpoint pupils) may be seen in pontine strokes. In patients with a rapid respiratory rate, consider diabetic ketoacidosis (ie, Kussmaul respiration), sepsis, stimulant drug intoxication, and aspirin overdose. In patients with a slow respiratory rate, consider narcotic overdose, CNS insult, or various sedative intoxications.

A rapid pulse rate is seen in patients with fever, sepsis, dehydration, thyroid storm, and various cardiac dysrhythmias and in overdoses of stimulants, anticholinergics, quinidine, theophylline, tricyclic antidepressants, or aspirin. Patients with a slow pulse rate may have elevated intracranial pressure, asphyxia, or complete heart block. Calcium channel blockers, digoxin, and beta-blockers also may produce altered mental status and bradycardia.

Blood pressure elevation is common in delirium because of resulting adrenergic overload.

In patients with acute altered mental status and severely elevated blood pressure, check the ocular fundi for arteriolar spasm, disc pallor, papilledema, flame hemorrhages, and exudates. These are all signs of malignant hypertension. Even with these changes, the patient may be alert and minimally symptomatic.

In pregnant or recently post-partum patients with a systolic blood pressure greater than 160 or a diastolic blood pressure greater than 90 mm Hg consider preeclampsia or eclampsia. 

In patients with hypertension and bradycardia, consider an elevated intracranial pressure.

With delirium and hypotension, the differential diagnosis includes dehydration, diabetic coma, hemorrhage due to trauma, aneurysmal rupture, gastrointestinal bleeding or sepsis. Consider adrenergic depletion secondary to cocaine; amphetamine; or tricyclic overdose, which usually responds to norepinephrine. Acute adrenal insufficieny, causing hypotension refractory to IV fluid challenge, should be considered in patients on long-term steroid therapy.

Pupillary dilation can be seen in anticholinergic overdose, stimulant use, and hallucinogen use. A common feature of diphenhydramine and other antihistamine overdoses is the behavior of picking at imaginary objects in the air. Early in the course, mydriasis may be absent but other signs of anti-cholinergic poisoning may be evident: dry mucous membranes, flushing, tachycardia, elevated body temperature, urinary retention and delirium.

Pupillary constriction can be seen in narcotic intoxication. Delirium can be associated with both acute intoxication and withdrawal, the latter of which can be precipitated with naloxone.

Serious head trauma is usually obvious. However, occult trauma may be discovered by findings of basilar skull fracture, such as hemotympanum, Battle sign (ie, mastoid area ecchymoses), raccoon eyes, or otorhinorrhea. The latter condition may be tested for by placing a drop of the draining blood on filter paper and then looking for a clear ring of cerebrospinal fluid (CSF). A funduscopic examination may show loss of venous pulsations in cases of early intracranial pressure (ICP) elevation or papilledema in severe ICP elevation. Pupillary inequality may be a late sign of uncal herniation.

At times, it may be difficult to distinguish between acute delirium, psychiatric crisis, or a chronic process with exacerbation such as dementia. It is safest to presume delirium until an alternative process can be proven through testing and/or clinical observation.

A brief bedside neurologic examination, including mental status testing, is an essential part of the workup of AMS when a rapidly treatable cause is not immediately apparent.

The Mini-Mental Status Examination (MMSE) is a formalized way of documenting the severity and nature of mental status changes.[9] The MMSE, as modified from Folstein, is outlined here. The maximum score per item is indicated in parentheses.

  • Orientation (5): What are the year, season, date, day, and month?

  • Orientation (5): Where are we (ie, state, county, town, hospital, and floor)?

  • Registration (3): Name 3 objects (ask the patient to repeat these 3 objects).

  • Attention and calculation (5): The serial 7 test awards 1 point for each correct answer. Stop after 5 answers. Spelling "world" backwards is optional.

  • Recall (3): Ask for the 3 objects (from Registration) to be repeated. One point is scored for each correctly recalled object.

  • Language (2): Name a pencil and a watch.

  • Repetition (1): Repeat the following: "No ifs, ands, or buts."

  • Complex commands (6): Follow a 3-stage command, such as "Take a paper in your right hand, fold it in half, and put it on the floor" (3 points). Next, read and follow these printed commands: "Close your eyes" (1 point); "Write a sentence" (1 point); and "Copy design" (1 point)

Instructions for administering the MMSE are as follows:

  • Orientation: Ask for the date. Specifically, ask for any omitted information. Give 1 point for each correct response.

  • Registration: Ask permission to test memory. Name 3 unrelated objects clearly and slowly about 1 second apart. After all 3 objects have been named, ask the patient to repeat them. The first repetition determines the score. Keep repeating the items, as many as 6 times, until the patient can repeat all 3 of them. (This step is also required for the Recall test.)

  • Attention and calculation: Ask the patient to begin with 100 and count backwards by 7s. Stop after 5 subtractions and score correct answers. If the patient cannot calculate, ask him or her to spell "world" backwards. The score is the number of letters in correct order.

  • Recall: Ask the patient to recall the 3 objects previously asked to remember (from Registration). Zero to 3 points may be scored.

  • Language: To test skills in naming objects, show a wristwatch and a pencil to the patient, and ask the patient to name each item. Zero to 2 points may be scored.

  • Repetition: Ask the patient to repeat a sentence. Allow 1 trial. Zero to 1 point may be scored.

  • Complex 3-stage command: Give the patient a piece of paper and repeat the command. Score 1 point for each portion of the command that is performed correctly.

  • Reading: Print clearly on a piece of paper in large letters the command "Close your eyes." Ask the patient to read and perform the command. Score 1 point if the eyes are closed.

  • Writing: Provide a blank piece of paper and ask the patient to write a sentence of his/her own choosing. It must contain a subject and a verb to be scored 1 point. Punctuation does not matter for the purpose of scoring.

  • Copying: On a clean piece of paper, draw intersecting pentagons, each side measuring 1 inch, and ask the patient to copy the figures exactly. All 10 angles must be present, and the 2 figures must intersect to score 1 point. Any rotation of the figures or tremor is ignored.

A score of less than 24 suggests the presence of delirium, dementia, or another problem affecting the patient's mental status and may indicate the need for further evaluation.

In addition, or as an alternative to the MMSE, correctly drawing the face of a clock (to include the circle, numbers, and hands) is a sensitive test of cognitive function. To perform this test, ask the patient to draw a clock with the hands at 8:20. Two or more errors significantly correlate with dementia. No errors rule against dementia.

The "Sweet 16" cognitive assessment tool offers a faster, simpler, and reasonably accurate alternative to the MMSE.[10] Advantages include the absence of a requirement for frail patients to manipulate pen and paper, freedom from props, and better accuracy across varying educational levels. The "Sweet 16" test is less selective (72% vs 89%) than the MMSE but is more sensitive (99% vs 87%). Therefore, a negative test result is highly accurate in ruling out dementia.

Other simple screening tests include asking the patient to spell "world" backwards or performing "serial 7's," which involves starting at the number 100 and subtracting 7 repeatedly in series (ie, 100, 93, 86, 79).


Delirium or acute altered mental status may be caused by the following:

  • Intoxication with a substance (eg, hallucinogens, alcohol, medications, toxins)

  • Polypharmacy, most often with psychoactive medications

  • Major surgery, orthopedic trauma, prolonged immobility, and “ICU psychosis”

  • Occult infection (eg, UTI, meningitis, encephalitis, neurosyphilis, sepsis)

  • Head trauma

  • Seizure disorder

  • Acute mania or other psychiatric etiology

  • Endocrine crisis (eg, thyroid, adrenal, diabetic)

  • High fever seen with infection or heat stroke

  • Renal failure

  • Liver failure

  • Neoplasia

  • Inflammation (eg, systemic lupus erythematosus)

  • Cerebral vascular accident (CVA)

  • Respiratory dysfunction (eg, hypoxia, hypercarbia)

  • Shock

  • Chronic neurological disorders such as dementia and Parkinson disease

  • “Sundowning” (see below)

In the elderly, the combined effects of visual and auditory impairments, dementia or other chronic brain dysfunction, medication side effects (particularly polypharmacy), and/or unfamiliar environment or nighttime darkness can lead to acute confusion or psychosis, which is known as sundowning. As the name implies, this condition usually occurs in the evening hours. Vitamin B-12 deficiency is a potential cause of sundowning as well as progressive but reversible dementia.

Head trauma, Korsakoff syndrome, transient global amnesia, and various dementing processes can cause amnesia. Head trauma can lead to transient amnesia with retrograde (events prior to injury) and anterograde (events following injury) features.

Postconcussive syndrome is a constellation of mental dullness, poor memory, depressed mood, and headaches that may follow head trauma, often lasting days to weeks, with full resolution in most cases. This may involve confusional state, but frank delirium is rare.

Transient global amnesia (TGA) is seen in previously well, usually middle-aged patients who present with a sudden onset of confusion, amnesia, and anxious perseveration.[11] TGA can occur spontaneously or following minor trauma, exertion, or emotional stress. The amnesia usually lasts a few hours, with full recovery and rare recurrence.

Various causes have been proposed for TGA: most recently, transient ischemia-like attacks or perhaps ministrokes in the hippocampal or thalamic memory areas of the brain. Although the incidence of cerebrovascular risk factors in TGA is low, those patients with such risk factors (eg, hypertension, smoking, diabetes mellitus, hypercholesterolemia) should be considered for antiplatelet therapy. Although TGA may involve a transient ischemia to brain areas involved with memory (hippocampus, thalamus, mediobasilar temporal lobe), symptoms typically resolve more slowly than TIA. In addition, future risk of stroke and death are lower than in TIA. All patients with TGA should be admitted for monitoring and further workup.

Traveler’s amnesia is typically seen following a nap on an airplane after taking a short-acting hypnotic, such as alprazolam, triazolam, or zolpidem.

Korsakoff syndrome is caused by neuronal damage that results from thiamine deficiency in association with chronic alcohol abuse. It is usually preceded by an episode of Wernicke encephalitis (eg, ataxia, confusion, oculomotor palsy), typically precipitated by administration of glucose to a malnourished alcoholic without concomitant parenteral thiamine. Confabulation is a hallmark finding of Korsakoff syndrome (also called Korsakoff psychosis).

Dementia can occur primarily, or can be secondary to cerebrovascular disease, chronic CNS infection, CNS trauma, increased ICP (eg, neoplasia, mass effect, hydrocephalus), toxins, avitaminosis, autoimmune disease, and psychiatric illness.

Primary dementias include Alzheimer disease and frontotemporal dementia (FTD). AD accounts for up to 90% of all primary dementias and more than 50% of all dementing illnesses.

FTD is highly familial, presents at a younger age than Alzheimer disease, and is associated with profound personality changes, social incompetence, and stereotypical behaviors, yet with preserved visuospatial skills. The brain invariably shows a severe and asymmetric atrophy of the frontal and temporal lobes with only rare involvement of the parietal or occipital lobes associated with sparing of the posterior two thirds of the superior temporal gyrus. A thin, knife-edge appearance of the gyri is often seen secondary to the severe atrophy present in Pick disease, a subtype of FTD. The typical pattern of atrophy is often prominent enough to distinguish Pick disease from Alzheimer disease macroscopically.

Some forms of Alzheimer disease are thought to have a genetic or familial basis. This is particularly true of Alzheimer disease that begins at a relatively young age and follows a fulminant course.

Alzheimer-like dementia is seen in 40% of patients with Parkinson disease and in a very high percentage of patients with Down syndrome who live long enough to develop Alzheimer disease.

Cerebrovascular causes include lacunar stroke syndrome (multi-infarct dementia), thalamic stroke, and vasculitides as seen in systemic lupus erythematosus and other rheumatologic disorders.

Infectious causes of dementia include HIV, Creutzfeldt-Jakob disease, neurosyphilis, and the end stages of some cases of meningitis and encephalitis.

Traumatic causes of chronic dementia include anoxia, diffuse axonal injury (following a severe blow to the head), and dementia pugilistica ("punch drunk"), which results from repeated concussive trauma. A chronic subdural hematoma may present with a dementia-like syndrome.

Dementia, often in association with hostility and severe mood disorders can result from repeated sub-clinical head trauma or "mild concussions" over an extended period. Called chronic traumatic encephalopathy (CTE), the condition is only confirmed after death via brain autopsy.[12, 13] Athletes involved in a variety of contact sports, most notably football and soccer (heading the ball), are at increased risk for CTE.[14] This is true even in the absence of any severe blows to the head. CTE has been diagnosed in young athletes playing contact sports for a relatively short period and dying of other causes (allowing for brain autopsy). This has led to reconsideration of the safety of football and soccer in children and teenagers. 

Toxins causing chronic organic brain syndrome include heavy metals (eg, lead in solder, ceramic glazes), organic chemical exposures, severe carbon monoxide poisoning, and chronic substance abuse.

Deficiencies of vitamin B-12 and folate can cause organic brain syndrome.

Autoimmune causes include systemic lupus erythematosus, giant cell arteritis, and sarcoidosis. Delirium has been associated with treatment or withdrawal of treatment of autoimmune diseases with high-dose steroids.

Psychiatric illnesses mimicking dementia include the pseudodementia of major depression in elderly persons and chronic schizophrenia (originally termed "dementia praecox"). Mania and hypomania as seen in bipolar disorder can be confused with delirium. In its severe form, “excited delirium” can be exacerbated by physical restraining and can lead to sudden cardiac death.

Other causes to consider include chronic endocrinopathies, Wilson disease (copper storage disease), and lipid storage diseases.


Delirium is a true medical emergency. Failure to recognize and aggressively treat the underlying cause can be catastrophic.

Delayed recognition of dementia can result in trauma secondary to cognitively impaired driving or the use of other hazardous equipment, including cooking stoves.

Patients with dementia are at increased risk of victimization by predatory business practices, Internet scams, and other fraudulent or criminal attacks.





Approach Considerations

Workup for most cases of newly recognized dementia can be completed in an outpatient setting. In some cases, admission is needed until an appropriate living situation or a nursing home placement is arranged.


Laboratory Studies

Laboratory studies may be helpful for ruling in or excluding specific diagnoses that cause delirium or a dementia-like presentation. Many of these tests may not be immediately available to the ED physician including vitamin levels, Venereal Disease Research Laboratory (VDRL) test, and certain thyroid function studies.

Oxygen saturation, or ABG with carbon monoxide level, may be diagnostic. CBC, electrolytes, blood glucose, BUN and creatinine should be checked. In older patients, consider vitamin B-12 and folate levels. Consider calcium level, magnesium level, liver function tests (LFTs), serum ammonia, and prothrombin time (PT). Consider VDRL and/or fluorescent treponemal antibody absorption (FTA-ABS) test to help rule out neurosyphilis (see cerebrospinal fluid [CSF] studies below). Urinalysis is also indicated.

When alcohol, drugs, and/or toxins are suspected, consider the following:

  • Serum ethanol, salicylate, acetaminophen, carbon monoxide, and other specific drug or toxin levels as indicated

  • Comprehensive drug analysis of urine

In a suspected endocrine emergency, the following are required:

  • A bedside fingerstick blood glucose determination followed by serum glucose and serum acetone

  • Thyroid-stimulation hormone (TSH), possibly thyroid panel

  • Serum cortisol

  • Serum calcium, phosphorus, and parathyroid levels

In suspected CNS infection, the following may be ordered:

  • Lumbar puncture may be done for CSF studies, including cryptococcal antigen, Lyme disease and VDRL.

  • CT scan of head should be done before lumbar puncture to rule out toxoplasmosis or abscess, especially in patients with HIV who present with headache.

Imaging Studies

A head CT scan without intravenous (IV) contrast should be obtained if CNS infection, trauma, or a cerebral vascular accident (CVA) is suspected. A CT scan is excellent for detecting acute hematomas and most subarachnoid hemorrhages (SAH) but is most accurate early in the course. Follow-up lumbar puncture may be needed to rule out SAH.

One study found a high prevalence (41%) of abnormal CT scan findings in patients with acute mental status changes in the ED. Eight clinical predictors were significantly associated with an abnormal scan, including diastolic blood pressure of more than 80 mm Hg, focal weakness, a Glasgow Coma Score of less than 15, antiplatelet use, upgoing plantar response, headache, anticoagulant use, and dilated pupils.[15]

Although not typically part of the workup in the ED, a brain MRI may be considered if readily available and the need confirmed by neurologist and/or radiologist. MRI helps distinguish between Alzheimer disease and vascular causes of dementia. The MRI may show subtle signs of stroke missed on CT and is the imaging modality of choice for multiple sclerosis. An example of MRI in a patient with moderate Alzheimer disease is shown in the image below.

Coronal T1-weighted MRI scan in a patient with mod Coronal T1-weighted MRI scan in a patient with moderate Alzheimer disease. Brain image reveals hippocampal atrophy, especially on the right side.

Plain abdominal radiographs may reveal swallowed bags that contain drugs of abuse ("body packing") or radiodense substances such as iron tablets.

Other Tests

An ECG may be performed to search for myocardial infarction or atrial fibrillation with rapid ventricular response. Low voltages, as seen in hypothyroidism and pericardial effusion, may give a clue to the etiology. Look for tachycardia, widened QRS, or prolonged QT interval, which suggest tricyclic overdose.

A postmortem examination of the brain is currently the only way to positively diagnose the various dementing illnesses.

A blood test for apolipoprotein E (ApoE) subtype e4 is still under study, but it promises to greatly enhance diagnostic accuracy for AD.

Researchers at the Stanford University School of Medicine developed a blood test that may someday be a step toward predicting AD 2-6 years in advance of onset. The test identifies changes in certain blood proteins that cells use to convey messages to one another and has a 90% positive predictive value.[16]

Testing vitamin B-12 levels and thyrotropin is useful as part of a dementia workup.


Lumbar puncture to obtain CSF for analysis should be considered in certain circumstances, including the following:

  • To rule out SAH not seen on CT scan

  • To diagnose CNS infections such as encephalitis or meningitis



Approach Considerations

All patients with unresolved delirium require admission and often require telemetry or ICU care.

Prehospital Care

Prehospital care workers involved in the transport of an acutely confused, combative, or delirious patient must ensure the safety of the patient and staff.

Prior to transport, consider sedation with a benzodiazepine with or without an antipsychotic if unable to easily control an agitated patient without physical restraints. Keep in mind that excess sedation may obscure the Mini-Mental Status Examination (MMSE) in the ED.

Use the least restrictive physical restraints if necessary for safe transport.

Provide supplemental oxygen.

Intubate when the airway is at risk or when the patient is comatose or has a poor gag reflex. Protect the cervical spine in the setting of trauma.

Emergency Department Care

ED physicians caring for the patient with agitation, confusion, delirium, combativeness, or obtundation must ensure the safety of both the patient and the staff while attending to issues of airway protection and immediate recognition and treatment of rapidly reversible problems (eg, hypoxia, hypoglycemia, narcotic overdose).

Provide supplemental oxygen unless oxygen saturation is above 93% on room air.

When carbon monoxide poisoning is suspected, ignore the oxygen saturation, obtain a carboxyhemoglobin level, and provide 100% oxygen.

In cases of airway compromise, coma, or poor gag reflex, the ED physician should have a low threshold for intubation. Use rapid sequence intubation (RSI), particularly in the settings of possible head trauma, elevated ICP, or a combative patient. RSI/intubation may be necessary to facilitate imaging studies.

Treat suspected overdose-induced delirium based on ingestion history and/or toxidromes. Such treatment may range from simple observation and supportive care, activated charcoal, gastrointestinal lavage (rarely performed), sedation, specific antidotes to intoxication and life support.

The treatment of delirium is dependent on the identification of the underlying cause, which may not be elucidated during an ED stay. If patients remain delirious they should be admitted for further observation. 

Behavioral control of a patient with delirium who is agitated and combative should be primarily medication-based with physical restraining kept at a minimum and for protection of both the patient and staff (see Medication).

Conversely, inpatient and ICU prevention and management of delirium should strive to avoid or minimize use of sedating medications. These medications increase confusion, reduce attentiveness, impair orientation and thereby cause or exacerbate delirium. A prospective study of ICU patients, for example, found that lorazepam sedation increased the risk of delirium by 20%.[17] Most cases of delirium are helped by reassuring, compassionate human contact—particularly by those with whom the patient is familiar.


Specific cases may require consultation with neurosurgery, neurology, or medicine subspecialists (eg, infectious disease, endocrinology, nephrology, gastroenterology, toxicology, psychiatry).

In the setting of trauma or neurosurgical emergency, notify surgeons early in the workup for surgical emergencies that are contributing to the patient's delirium. 

The patient's private physician and/or family members are often the best sources of information regarding baseline functioning, prior medical history, and current medications.

Consult social services for home evaluation and placement issues for patients with dementia.

Medical Care

Outpatient medications for primary dementia are coordinated best by healthcare providers who have continuing contact with the patient. Medications may include the following:

  • Anticholinesterase inhibitors, such as donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon): These medications are useful early in the disease course, but they lose their effectiveness or may worsen mental status in advanced stages of the disease.

  • N -methyl D -aspartate (NMDA) receptor antagonists, including memantine (Namenda)

  • Antidepressants, especially the selective serotonin reuptake inhibitors or bupropion. Avoid tricyclic antidepressants because of their anticholinergic properties which can worsen dementia.

  • Benzodiazepines for sedation or sleep. However, these drugs may worsen cognitive deficits, increase the risk of falls and are best avoided if possible.

  • Antipsychotics for psychotic ideation or aggressive behavior: High-potency agents are preferred. Risperidone (Risperdal), a newer atypical antipsychotic, is well tolerated and useful for sundowning. However, the atypical antipsychotics as a group have been associated with a slightly higher death rate in patients with dementia (3.5% vs. 2.3% for placebo). Despite a US Food and Drug Administration (FDA) black box warning, experts warn against abandoning this class of medications in the treatment of dementia-related psychosis and aggression.



To date, few clinical studies have been published on preventing delirium; nevertheless, they have already indicated that around 30% to 40% of delirium episodes are preventable. Immobility, using physical constraints, using bowl catheter, malnutrition, psychadelics, some types of drugs, associated diseases, and dehydration in the individual can cause delirium symptoms. Old age, severe illness, dementia, physical frailty, infection and/or dehydration, vision impairments, drug interference caused by polypharmacy, surgery, and excessive use of alcohol are among other risk factors for delirium.

Yale Clinical Trial was the first controlled clinical trial that showed there are other non-pharmacological ways to prevent delirium in geriatric patients. This intervention included employing a standardized protocol on taking medical measures to eliminate or reduce the 6 risk factors of delirium in individuals older than 70 years. The 6 delirium risk factors in this study were cognitive impairment, sleep deprivation, immobility, visual impairments, hearing impairment and dehydration. The results of this study showed that delirium symptoms were 9.9% in intervention group in comparison with 15% in the usual-care group. The total number of delirium and the total number of its episodes showed a significant decrease in the intervention group. This intervention was associated with considerable improvement in the degree of cognitive impairment manifested in patients with cognitive impairment at admission as well as significant reduction in the rate of use of sleep medications in all patients in the intervention group.[18]


Various substances to prevent or retard the onset of dementia have been proposed and/or studied. Prevention mechanisms have included preservation of CNS supporting cells, prevention of CNS inflammation, or free-radical inhibition. Unfortunately, no supplement or medication has been conclusively shown to prevent or retard the progression of dementia.

  • Nonsteroidal anti-inflammatory drugs (NSAIDs): The mechanism of action is thought to involve prevention of CNS inflammation.[20]  More recent studies suggest that heavy NSAID intake is a risk factor for dementia; however, moderate intake may delay but not prevent dementia onset.[21]

  • Vitamin E: The suggested dose for prevention is 200-400 IU/d; much higher doses are sometimes given for treatment. The mechanism of action may be antioxidant, free-radical inhibition. Efficacy is controversial and vitamin E can increase mortality risk. Therefore, should only be considered for patients with AD or at high risk for AD.

  • Vitamin B-6, vitamin B-12, and folate: These reduce levels of homocysteine, a potential brain neurotoxin. Efficacy is controversial and recent studies show no benefit.

  • Statin cholesterol-lowering medications: Reports suggest that these drugs substantially protect against dementia via an effect not related directly to blood levels of cholesterol. Mechanisms of action may be reduction of insulin levels in the brain and/or C-reactive protein (CRP) levels in the blood (indicative of inflammation). A study of more than 17,000 adults older than 60 years in Finland concluded that statins appeared to reduce risk by 58%.[22]  Other studies have found no benefit to statins in delaying dementia progression in patients with AD.

  • Estrogen replacement: This is being studied, but no evidence of benefit has been found at present.

  • Ginko biloba: This is a medicinal herb considered safe but of questionable efficacy. Preparations are of uncertain purity and dose consistency.

  • High caloric intake in concert with obesity and sedentariness is associated with an increased risk of Alzheimer disease.

Undertreated depression, hypertension, diabetes mellitus, hypercholesterolemia and obesity have all been associated with higher risk of Alzheimer disease.

Excessive amounts of alcohol act as a neurotoxin and can increase Alzheimer disease risk. In moderate doses, alcohol inhibits cerebrovascular disease although it may still enhance brain atrophy. However, recent studies suggest that moderate drinking is protective against dementia as compared with abstinence. Antioxidants in wine (bioflavonoids) may be additionally beneficial (over spirits and beer).

Sedentary lifestyle is an independent risk factor for dementia. Regular exercise is protective.




Guidelines Summary

In 2016, the American Psychiatric Association released a practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia.[19] The guideline is intended to apply to individuals with dementia in all settings of care as well as to care delivered by generalist and specialist clinicians.

The 15 statement guidelines are as follows:

  • Statement 1. Assess patients with dementia for the type, frequency, severity, pattern, and timing of symptoms. (1C)
  • Statement 2. Assess patients with dementia for pain and other potentially modifiable contributors to symptoms as well as for factors, such as the subtype of dementia, that may influence choices of treatment. (1C)

  • Statement 3. In patients with dementia with agitation or psychosis, assess response to treatment with a quantitative measure. (1C)

  • Statement 4. Develop a documented comprehensive treatment plan that includes appropriate person-centered nonpharmacological and pharmacological interventions, as indicated. (1C)

  • Statement 5. Only use nonemergency antipsychotic medication for the treatment of agitation or psychosis in patients with dementia when symptoms are severe, are dangerous, and/or cause significant distress to the patient. (1B)

  • Statement 6. Review the clinical response to nonpharmacological interventions prior to non-emergency use of an antipsychotic medication to treat agitation or psychosis in patients with dementia. (1C)

  • Statement 7. Before starting nonemergency treatment with an antipsychotic, assess the potential risks and benefits of the medication and discuss with the patient and the patient's caregiver/family. (1C)

  • Statement 8. If antipsychotic treatment is indicated, initiate treatment at a low dose and titrate up to the minimum effective dose as tolerated. (1B)

  • Statement 9. If a clinically significant side effect of antipsychotic treatment emerges, review the potential risks and benefits of antipsychotic medication to determine whether tapering and discontinuance of the medication are indicated. (1C)

  • Statement 10. If there is no clinically significant response after a 4-week trial of an adequate dose of an antipsychotic drug, taper or withdraw the medication. (1B)

  • Statement 11. In a patient who has shown a positive response to an antipsychotic, decisions about possible tapering of the medication should be made with input from the patient (if feasible) or surrogate decision maker, family, or other caregiver.  (1C)

  • Statement 12. In patients with dementia who show adequate response of behavioral/psychological symptoms to treatment with an antipsychotic drug, an attempt to taper and withdraw the drug should be made within 4 months of initiation, unless the patient experienced a recurrence of symptoms with prior attempts at tapering of antipsychotic medication. (1C)

  • Statement 13. In patients with dementia whose antipsychotic medication is being tapered, assessment of symptoms should occur at least monthly during the taper and for at least 4 months after medication discontinuation to identify signs of recurrence and trigger a reassessment of the benefits and risks of antipsychotic treatment. (1C)

  • Statement 14. In the absence of delirium, if nonemergency antipsychotic medication treatment is indicated, haloperidol should not be used as a first-line agent. (1B)

  • Statement 15. A long-acting injectable antipsychotic medication should not be utilized unless it is otherwise indicated for a co-occurring chronic psychotic disorder. (1B)



Medication Summary

Medications typically used in the ED treatment of delirium or acute mental status changes include sedatives, neuroleptics and specific antidotes. Other drugs may be useful in treating specific etiologies uncovered in the workup. The medications outlined here are used for acute behavioral changes.


Class Summary

These agents are used to calm acute agitation, to control the behavior of combative patients, and to facilitate procedures.

Lorazepam (Ativan)

Commonly used Benzodiazepine in ED. Safe for a wide variety of acute behavioral disturbances. Can be given PO/SL (for rapid effect in panic attack)/IV/IM and can be mixed in syringe with neuroleptic agent. Sedative hypnotic with short onset of effects and relatively long duration of action. By increasing action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. When patient needs to be sedated for longer than 24-h period, this medication is excellent. Has longer CNS effect than diazepam and is preferred for seizure control. Easily titrated for acute withdrawal syndromes (eg, alcohol, benzodiazepines, barbiturates) and status seizures when given IV (10 mg or more may be needed in status epilepticus). Two mg of lorazepam approximately equivalent to 5 mg of diazepam. Preferred over neuroleptics for treating toxic effects of hallucinogens, cocaine, stimulants, or PCP.


Benzodiazepine with rapid onset of action, effective for acute agitation. Excellent choice to calm a combative/agitated patient with rapid onset and relatively short duration of action.

Onset of action: IM: Sedation: Children: Within 5 minutes; Adults: ~15 minutes; IV: 3 to 5 minutes

A prospective observational study demonstrated intramuscular midazolam achieved more effective sedation in agitated ED patients at 15 minutes than haloperidol, ziprasidone, and perhaps olanzapine.

Glucose supplements

Class Summary

Monosaccharides absorbed from intestine after PO absorption of dextrose results in rapid increase of blood glucose concentrations.


Should be given to any obtunded patient in whom hypoglycemia cannot be rapidly ruled out via bedside testing. Monosaccharide, absorbed from intestine and distributed, stored, and used by tissues. Parenterally injected dextrose is used in patients unable to obtain adequate PO intake; direct PO absorption results in rapid increase of blood glucose concentrations.

Serves to restore blood glucose levels. Each 100 mL of 5% dextrose contains 5 g of dextrose while each 100 mL of 10% dextrose contains 10 g of dextrose.

Effective in small doses; no evidence indicates that it may cause toxicity; concentrated infusions provide higher amounts of glucose and increased caloric intake with minimum fluid volume.


Class Summary

These agents have more robust calming effects than benzodiazepines in acutely agitated patients. They act fast when given IV. They can be mixed in the same syringe with lorazepam for rapid chemical restraint (IM/IV). They are easily titrated and long acting.

Haloperidol and droperidol are of the butyrophenone class, which is noted for high potency and low potential for orthostasis. However, they have great potential for extrapyramidal symptoms (EPS)/dystonia.

Caveat: Neuroleptics can mask the signs of withdrawal from alcohol, benzodiazepines, and barbiturates while failing to treat adrenergic and GABA-nergic dysregulation. They do not prevent seizures.

Haloperidol (Haldol)

DOC for severe agitation, acute psychosis, and severe delirium when no contraindications exist. Parenteral dosage form may be admixed in same syringe with 2 mg lorazepam for better anxiolytic effects.


Some clinicians believe droperidol is DOC for control of severely disturbed and/or violent patient. Somewhat faster acting and more sedating than haloperidol, but more likely to cause hypotension. May exert antipsychotic activity through dopaminergic system. May alter dopamine action in CNS. Parenteral dosage form may be admixed in same syringe with 2 mg lorazepam for better anxiolytic effects.

Now has black-box warning regarding life-threatening torsade de pointes (TdP) (a rhythmic pattern of sinusoidal ventricular complexes that leads to ventricular fibrillation and cardiac arrest), especially in the setting of prolonged QT syndrome. Assessing QT interval via ECG or rhythm strip advised before administering droperidol.

Atypical antipsychotics

Class Summary

These are newer neuroleptics with a lowered risk of extrapyramidal syndrome (EPS) and improved efficacy for the negative symptoms (eg, withdrawal, apathy) of psychosis because of their enhanced serotonergic activity as compared to older-style neuroleptics. These medications have largely supplanted older neuroleptics for sedation and treatment of psychosis in elderly patients with dementia.


Indicated for acute behavioral control in setting of acute psychosis, delirium, and as "chemical restraint." Less likely to cause severe dystonic reactions in younger patients than haloperidol and droperidol.

Risperidone (Risperdal)

Often used for sundowning in elderly patients but can increase mortality rate in dementia. Binds to dopamine D2 receptor with 20 times lower affinity than for serotonin 5-HT2 receptor. Improves negative symptoms of psychoses and reduces incidence of EPS. Also may have antidepressant effects, probably because of its serotonin activity.

Olanzapine (Zyprexa, Zyprexa Relprevv, Zyprexa Zydis)

Atypical antipsychotic that can be used for acute agitation. A prospective observational study revealed IM Olanzapine resulted in a greater proportion of patients adequately sedated at 15 minutes compared with IM haloperidol 5 mg, IM haloperidol 10 mg, and IM ziprasidone.


Class Summary

These agents are used when the toxic agent is known and has an antidote or as a coma cocktail in patients who are stuporous or comatose. Includes oxygen, thiamine (100 mg IV/IM), glucose (50 mL of D50W IV push), and naloxone (Narcan; 2-10 mg SC/IM/IV or via ETT). The use of flumazenil (Romazicon) for suspected or known benzodiazepine overdose is controversial. Flumazenil may precipitate refractory seizures in the setting of long-term use or mixed overdose with seizure-inducing agents (eg, TCAs). It may be useful in diagnosis and in avoiding the need for intubation.


In setting of suspected antihistaminic/anticholinergic overdose, increased concentration of acetylcholine can improve patient's delirium dramatically; for reasons that are not entirely clear, appears to have less effect if administered within 4 h postexposure. May be useful diagnostically. Avoid in suspected TCA OD.

Naloxone (Narcan, Evzio)

Prevents or reverses opioid effects (hypotension, respiratory depression, sedation), possibly by displacing opiates from their receptors.


Questions & Answers


What are delirium, dementia, and amnesia?

What is the pathophysiology of delirium, dementia, and amnesia?

What is the prevalence of delirium, dementia, and amnesia in the US?

What is the global prevalence of delirium, dementia, and amnesia?

What is the mortality and morbidity associated with delirium, dementia, and amnesia?

What are the racial predilections of delirium, dementia, and amnesia?

What are the sexual predilections of delirium, dementia, and amnesia?

Which age groups have the highest prevalence of delirium, dementia, and amnesia?

What are the risk factors for delirium, dementia, and amnesia?

What is the role of genetics in the etiology of delirium, dementia, and amnesia?

What is the prognosis of delirium, dementia, and amnesia?


How is mental status altered in delirium and dementia?

What are the signs and symptoms of delirium?

What should be the focus of the clinical history for delirium?

What are the types of delirium?

Which clinical history findings are characteristic of dementia?

What is included in the physical exam to evaluate for delirium, dementia, and amnesia?

Which physical findings are characteristic of delirium, dementia, and amnesia?

Which conditions should be included in the differential diagnoses of delirium, dementia, and amnesia?

How is an anticholinergic overdose differentiated from delirium?

How is head trauma differentiated from delirium?

What is the role of the Mini-Mental Status Exam (MMSE) in the diagnosis of delirium, dementia, and amnesia?

How is the Mini-Mental Status Exam (MMSE) administered in the diagnosis of delirium, dementia, and amnesia?

What are alternative assessments to the Mini-Mental Status Exam (MMSE) for the diagnosis of delirium, dementia, and amnesia?

What causes of delirium?

What are causes of delirium, dementia, and amnesia in the elderly?

What is the role of head trauma in the etiology of delirium, dementia, and amnesia?

What causes amnesia?

What causes dementia?


What are the differential diagnoses for Delirium, Dementia, and Amnesia in Emergency Medicine?


What is the role of lab testing in the workup of delirium, dementia, and amnesia?

Which lab tests are performed when alcohol, drugs, and/or toxins are the suspected cause of delirium, dementia, and amnesia?

Which lab tests are performed when an endocrine emergency is the suspected cause of delirium, dementia, and amnesia?

Which lab tests are performed when a CNS infection is the suspected cause of delirium, dementia, and amnesia?

What is the role of imaging studies in the workup of delirium, dementia, and amnesia?

What is the role of an ECG in the workup of delirium, dementia, and amnesia?

How is a diagnosis of dementia confirmed?

Which vitamin testing may be helpful in the diagnosis of dementia?

What is the role of lumbar puncture in the workup of delirium, dementia, and amnesia?


What is included in prehospital care for delirium, dementia, and amnesia?

What is included in emergency department (ED) care of delirium, dementia, and amnesia?

What is included in inpatient care for delirium?

Which specialist consultations may be helpful to patients with delirium, dementia, and amnesia?

How is delirium prevented?


What are the APA guidelines for the use of antipsychotics to manage agitation or psychosis in dementia?


What is the role of medications in the emergency department (ED) treatment of delirium, dementia, and amnesia?

Which medications in the drug class Antidotes are used in the treatment of Delirium, Dementia, and Amnesia in Emergency Medicine?

Which medications in the drug class Atypical antipsychotics are used in the treatment of Delirium, Dementia, and Amnesia in Emergency Medicine?

Which medications in the drug class Neuroleptics are used in the treatment of Delirium, Dementia, and Amnesia in Emergency Medicine?

Which medications in the drug class Glucose supplements are used in the treatment of Delirium, Dementia, and Amnesia in Emergency Medicine?

Which medications in the drug class Sedatives are used in the treatment of Delirium, Dementia, and Amnesia in Emergency Medicine?