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Delirium, Dementia, and Amnesia
Updated: Jan 17, 2008
Introduction
Background
Delirium, dementia, amnesia, and certain other alterations in cognition are subsumed under more general terms such as mental status change (MSC), acute confusional state (ACS), or organic brain syndrome (OBS). Acute alterations in brain function are commonly referred to as MSC or ACS; chronic alterations and any MSC specifically due to nonpsychiatric causes are generally referred to as OBS.
In this article, OBS is used to distinguish changes in cognitive/behavioral functions due to physical (organic) causes from those due to psychiatric (functional) causes. However, with the growing recognition of the organic bases of many psychiatric disorders, the distinction between organic and functional has become blurred. As a result, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), no longer recognizes OBS as a diagnostic entity.
Nevertheless, the term OBS is useful to the practicing emergency physician by highlighting a sizable list of diagnoses to be considered before a patient with abnormal mentation and behavior is presumed to have a psychiatric illness. If a more precise diagnosis of a change in mental status can be determined, the nebulous term OBS should be abandoned.
Pathophysiology
OBS can be divided into 2 major subgroups: acute (delirium or ACS) and chronic (dementia). A third entity, encephalopathy (subacute OBS), denotes a gray zone between delirium and dementia; its early course may fluctuate, but it is often persistent and progressive.
The final common pathway of all forms of OBS is an alteration in cortical brain function. This condition results from (1) an exogenous insult or an intrinsic process that affects cerebral neurochemical functioning or (2) physical or structural damage to the cortex. 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 function 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.
Frequency
United States
Delirium accounts for 10-15% of admissions to acute-care hospitals (but usually is not the primary diagnosis).
The prevalence of dementia doubles every 5 years between ages 60 to about 90: 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. Alzheimer disease (AD) accounts for most patients with dementia who are older than 55 years (50-90%).
While slowing of memory/word-finding are a normal feature of brain aging, 50% of patients with mild cognitive impairment whose day-to-day functioning is as yet unaffected will develop the onset of dementia within 3 years. Currently, no accurate way exists to predict which patients will go on to develop progressive dementia.
International
AD 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 AD.
Mortality/Morbidity
- 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 of tricyclic antidepressants, drug intoxications generally resolve fully with supportive care. Failure to provide thiamine when administering glucose rarely may lead to acute Wernicke syndrome (ataxia, confusion, oculomotor palsies in the setting of malnutrition). If unrecognized, Wernicke syndrome may also result in chronic OBS.
- Certain withdrawal syndromes (eg, alcohol, benzodiazepines, barbiturates) can be deadly if untreated.
- Patients with primary dementias have a significantly reduced life expectancy depending upon the cause of the dementia and its severity and rapidity of progression.
Race
Delirium is seen more commonly in whites than in other races.
Sex
- Delirium is seen more commonly in females than in males.
- AD is more prevalent among women because of their longer life expectancy. Lifetime risk in women is estimated to be 32%, while that in men is 18%. However, the age-specific risk is equal in both sexes.
Age
- Delirium due to physical illness is more frequent among the very young and those older than 60 years.
- Delirium due to drug and alcohol intoxication or withdrawal is most frequent in persons aged mid teens to the late 30s.
- Dementia, particularly AD, is seen predominantly in elderly persons; however, certain types of dementia are seen in younger patients (eg, AIDS-related dementia, certain familial forms of AD), and some cases of variant Creutzfeldt-Jakob disease (ie, bovine spongiform encephalopathy or mad cow disease). AIDS-related dementia is the most common nontraumatic dementia seen in younger persons.
Clinical
History
- Mental status changes can evolve acutely with a rapidly fluctuating, usually transient course (delirium) or insidiously and inexorably over months or years with a gradually worsening or stuttering course (dementia).
- Delirium presents with acute onset of impaired awareness, easy distraction, confusion, and disturbances of perception (eg, illusions, misinterpretations, visual hallucinations).
- Recent memory is usually deficient, and the patient is typically disoriented to time and place.
- The patient may be agitated or obtunded, and the level of awareness may fluctuate over brief periods.
- Speech may be incoherent, pressured, nonsensical, perseverating, or rambling, which may make the taking of an accurate history from the patient impossible.
- 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, and medication use; preexisting endocrine disorders; and recent activities that may have resulted in exposure to toxins or environmental injury.
- Ask about prior psychiatric illness and similar episodes of confusion in the past.
- 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 clear. However, acute confusional states can be superimposed on an underlying dementing process.
- The diagnosis usually is 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. Depression alone can present as a dementialike condition in elderly patients.
- Dementia of relatively recent onset has a higher likelihood of a potentially reversible etiology (5-47%).
- 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 dementialike condition fully resolves.
- A history of a stuttering course 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 Alzheimer-type dementia.
Physical
Any patient who presents with altered mental status 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: 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 mental status changes.
- General appearance (eg, unkempt, tattooed, and/or malnourished) may suggest the possibility of drug or alcohol abuse.
- Look for track marks.
- Smell for alcohol, the musty odor of fetor hepaticus, or the fruity smell of ketoacidosis.
- Icterus and/or 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.
- 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 MSC and bradycardia.
- Blood pressure elevation is common in delirium because of resulting adrenergic overload.
- In patients with acute MSC 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 patients with a diastolic pressure greater than 75 mm Hg in the second trimester or greater than 85 mm Hg in the third trimester, consider preeclampsia (ie, hyperreflexia, edema, proteinuria).
- In patients with hypertension and bradycardia, consider an elevated intracranial pressure (Cushing reflex).
- With delirium and hypotension, the differential diagnosis includes dehydration, diabetic coma, hemorrhage due to trauma, aneurysmal rupture, or GI bleeding. Also, consider adrenergic depletion secondary to cocaine; amphetamine; or tricyclic overdose, which usually responds only to norepinephrine, not dopamine. Addisonian crisis, particularly in those who are steroid dependent, should be considered.
- A brief bedside neurologic examination, to include mental status testing, is an essential part of the workup of OBS when a rapidly treatable cause, such as hypoglycemia or narcotic overdose, is not immediately apparent.
- The Mini-Mental Status Examination (MMSE) is a formalized way of documenting the severity and nature of mental status changes. 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: 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; 1 point for each correct answer. Stop after 5 answers. Optional: Spell "world" backwards.
- 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: "Take a paper in your right hand, fold it in half, and put it on the floor." (3 points) Then, 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, up to 6 times, until the patient can repeat all 3 of them. (This step also is 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.
- Overall scoring: A score of less than 24 suggests the presence of delirium, dementia, or another problem affecting the patient's mental status, and it 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 correlate significantly with dementia. No errors rule against 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…).
- The Mini-Mental Status Examination (MMSE) is a formalized way of documenting the severity and nature of mental status changes. The MMSE, as modified from Folstein, is outlined here. The maximum score per item is indicated in parentheses.
- Pupillary dilation may be secondary to intoxication with a hallucinogen, amphetamine, cocaine, or anticholinergic medication.
- Pupillary constriction may be secondary to narcotic intoxication.
- 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.
Causes
- Delirium or acute MCS may be caused by the following:
- Intoxication with a substance (eg, hallucinogens, alcohol, medications, toxins)
- Occult infection (eg, meningitis, encephalitis, neurosyphilis, sepsis)
- Head trauma
- Seizure disorder
- Acute mania or other psychiatric etiology
- Endocrine crisis (eg, thyroid, adrenal, diabetic)
- Renal failure
- Liver failure
- Neoplasia
- Inflammation (eg, systemic lupus erythematosus)
- Cerebral vascular accident (CVA)
- Respiratory dysfunction (eg, hypoxia, hypercarbia)
- Shock
- 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 and progressive, reversible dementia.
- Amnesia: 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.
- 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. 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, TIA-like ischemia 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, DM, hypercholesterolemia) should be considered for antiplatelet therapy. All patients with TGA should be admitted for further workup.
- Traveler amnesia typically is 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 usually is 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 causes include AD 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 AD; and is associated with profound personality changes, social incompetence, and stereotypical behaviors, yet with preserved visuospatial skills. Pick disease is a subtype of FTD. 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. The typical pattern of atrophy is often prominent enough to distinguish Pick disease from AD macroscopically.
- Some forms of AD are thought to have a genetic or familial basis. This is particularly true of AD 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 AD.
- Cerebrovascular causes include lacunar stroke syndrome (multi-infarct dementia), thalamic stroke, and vasculitides as seen in systemic lupus erythematosus (SLE) 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 OBS include anoxia, diffuse axonal injury (following a severe blow to the head), and dementia pugilistica (punch drunk). A chronic subdural hematoma may present with a dementialike syndrome.
- Primary causes include AD and frontotemporal dementia (FTD). AD accounts for up to 90% of all primary dementias and more than 50% of all dementing illnesses.
- Toxins causing chronic OBS include heavy metals (eg, lead in solder, ceramic glazes), organic chemical exposures, severe carbon monoxide poisoning, and chronic substance abuse.
- Avitaminoses, including deficiencies of vitamin B-12 and folate, can cause OBS.
- Autoimmune causes include SLE, giant cell arteritis, and sarcoidosis. Dementia has followed a corticosteroid-treated episode of polymyalgia rheumatica.
- Psychiatric illnesses mimicking dementia include the pseudodementia of major depression in elderly persons and chronic schizophrenia.
- Other causes to consider include chronic endocrinopathies, Wilson disease (copper storage disease), and lipid storage diseases.
More on Delirium, Dementia, and Amnesia |
 Overview: Delirium, Dementia, and Amnesia |
| Differential Diagnoses & Workup: Delirium, Dementia, and Amnesia |
| Treatment & Medication: Delirium, Dementia, and Amnesia |
| Follow-up: Delirium, Dementia, and Amnesia |
| References |
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Further Reading
Keywords
acute confusional state, ACS, mental status change, MSC, organic brain syndrome, OBS, altered mental status, confusion, amnesia, long-term memory disturbance, Alzheimer dementia, Alzheimer's dementia, Alzheimer's disease, Alzheimer disease, AD, senility, transient global amnesia, TGA, encephalopathy, subacute OBS, head trauma, mass lesions, hydrocephalus, multi-infarct dementia, atrophy, dementing processes, delirium tremens, severe hypoglycemia, CNS infection, heat stroke, thyroid storm, Wernicke syndrome, Wernicke's syndrome, drug intoxication, alcohol intoxication, drug withdrawal, alcohol withdrawal, AIDS-related dementia, Creutzfeldt-Jakob disease, pseudodementia, repeated lacunarstrokes, aspirin toxicity, heat illness, hyperthermia, diabetic ketoacidosis, sepsis, narcotic overdose, dehydration, asphyxia, complete heart block, seizure disorder, acute mania, endocrine crisis, renal failure, liver failure, neoplasia, cerebral vascular accident, CVA, respiratory dysfunction, shock, sundowning, Korsakoff syndrome, Korsakoff's syndrome, Korsakoff psychosis, postconcussive syndrome, frontotemporal dementia, FTD, Pick disease, Pick's disease, thalamic stroke, neurosyphilis, meningitis, encephalitis, anoxia, dementia pugilistica, punch drunk, avitaminosis, systemic lupus erythematosus, SLE, giant cell arteritis, sarcoidosis, schizophrenia, Wilson disease, copper storagedisease, lipid storage diseases
