Am Fam Physician. 1998;57(6):1358-1366
Confusion in the elderly patient is usually a symptom of delirium or dementia, but it may also occur in major depression and psychoses. Until another cause is identified, the confused patient should be assumed to have delirium, which is often reversible with treatment of the underlying disorder. Causes of delirium include metabolic disorders, infections and medications. Thyroid dysfunction, vitamin deficiencies and normal-pressure hydrocephalus are some potentially reversible causes of dementia. Major irreversible causes include Alzheimer's disease, central nervous system damage and human immunodeficiency virus infection. All but the rarest causes of confusion can usually be identified based on the complete history, medication review, physical examination, mental status evaluation and laboratory evaluation with longitudinal reevaluation.
Confusion is a common problem in persons over 65 years of age. The decline in normal cognitive ability may be acute, or it may be chronic and progressive. In older persons, confusion is most likely to be a symptom of delirium or dementia, although it can also be associated with psychoses and affective disorders, specifically major depression. This article reviews the common causes of confusion, the diagnostic approach to this problem and the initial management of the confused elderly patient.
Initial Approach
The results of the initial evaluation help to determine whether confusion in an elderly patient is the result of delirium or dementia. Until proved otherwise, the patient should be assumed to have delirium. Only after delirium and psychiatric disorders have been ruled out can dementia be diagnosed in an elderly patient with cognitive impairment. The diagnostic features of delirium, dementia and depression are listed in Table 1.1
| Delirium | |
| Disturbance in consciousness, with a reduced ability to focus, to sustain focus or to shift attention | |
| Change in cognition or the development of a perceptual disturbance that is not better accounted for by preexisting, established or evolving dementia | |
| Disturbance in consciousness that develops over a short period of time and fluctuates during the course of the day | |
| Evidence from the history, physical examination or laboratory tests that the disturbance in consciousness is the direct physiologic consequence of a general medical condition, substance intoxication or withdrawal, medication or toxin exposure, or a combination of these factors | |
| Associated features | |
| Disturbance in sleep-wake cycle | |
| Disturbance in psychomotor behavior | |
| Emotional disturbance | |
| Rapid, unpredictable shifts from one emotional state to another | |
| Dementia | |
| Memory impairment and at least one of the following: | |
| Aphasia | |
| Apraxia | |
| Agnosia | |
| Impaired executive functioning (e.g., planning, organizing, abstracting) | |
| Significant impairment in social or occupational functioning | |
| Significant decline from previous level of functioning | |
| Deficits that do not occur exclusively during the course of delirium | |
| Depression | |
| Occurrence of five or more of the following for at least two weeks (a change from prior function; one symptom must be either depressed mood or loss of interest or pleasure): | |
| Depressed mood | |
| Diminished interest or pleasure in most activities | |
| Weight loss or gain or a marked change in appetite | |
| Insomnia or hypersomnia | |
| Psychomotor agitation or retardation | |
| Fatigue or loss of energy | |
| Feelings of worthlessness or excess guilt | |
| Diminished ability to concentrate or make decisions | |
| Recurrent thoughts of death or suicidal ideation, attempts or plans | |
| Symptoms cause significant distress in function | |
| Symptoms not attributable to substance abuse or general medical condition | |
| Symptoms not better accounted for by bereavement | |
Delirium and Dementia
Definitions
Delirium is a transient global disorder of cognition and consciousness. The delirious patient may also have psychomotor and emotional disturbances. In most patients, delirium due to a medical disease is reversible with treatment of the underlying condition.
Dementia is characterized by a decline in intellectual functioning to the extent that the patient is unable to perform the usual activities of daily living. Memory deficit is a predominant component of dementia, and the deterioration of intellectual functioning may occur over months to years. Dementing diseases in the elderly include Alzheimer's disease (now known as dementia of the Alzheimer's type [DAT]), vascular dementia (previously called multi-infarct dementia) and other disorders. The precise mechanisms of the dementias are generally unclear, and no effective cures are available.
Delirium and dementia may coexist. In this situation, treatment of the delirium often improves the patient's cognitive and/or functional abilities.
Epidemiology
The incidence of delirium increases progressively after the fourth decade of life.2 An estimated 15 to 26 percent of elderly patients with delirium die, usually as a result of the pathologic process responsible for the delirium.3,4 Elderly patients with delirium may have underlying dementia. In fact, dementia is a known risk factor for delirium. As many as 22 percent of community-dwelling elderly persons with dementia have coexisting delirium.5,6 At any one time, 15 percent of hospitalized patients over the age of 70 years are delirious.5,6
Dementia is the most prevalent organic mental syndrome in older persons. An estimated 2 to 4 million Americans have some type of dementing illness.7 The risk of dementing illness increases with age. By the age of 75 years, 10 to 15 percent of elderly persons have a dementing disease; the prevalence of dementia increases to between 25 and 35 percent in persons 85 years of age and older.8 One study7 found Alzheimer's dementia in 47.2 percent of persons who were at least 85 years old. If present population trends continue, the prevalence of severe dementia is expected to triple by the year 2040.9
Etiology
Delirium has a wide variety of potentially reversible causes (Table 2),10 and its pathophysiology depends on the underlying disorder. Because delirium is associated with an increased risk of mortality, it should always be considered first in patients who exhibit cognitive impairment or behavioral changes.
Dementia can be classified as reversible or irreversible. Potentially reversible causes include thyroid dysfunction, deficiencies of vitamins such as B12 and folate, infections such as neurosyphilis, metabolic abnormalities such as uremia, and normal-pressure hydrocephalus. The major irreversible causes of dementia include DAT, vascular dementia, central nervous system (CNS) trauma, Parkinson's disease, Pick's disease and human immunodeficiency virus (HIV) infection. Rarer irreversible causes include Creutzfeldt-Jakob disease and Huntington's disease.
Various theories have been proposed to explain the etiology of DAT. Research efforts are currently focusing on the role of beta-amyloid deposition in the brain,11 as well as the role of apolipoprotein E4, which is produced by the apolipoprotein (apo E) gene. Vascular dementia has been linked to inadequate oxygenation and cell death due to vascular blockage or rupture. Other CNS injuries usually have identifiable events that are responsible for the damage and consequent cognitive decline.
Diagnostic Approach
History
| Age 65 years or older |
| Dementia |
| Hospitalization |
| Acute illness or injury |
| Postoperative status |
| Underlying psychiatric disorder |
| Poor nutrition |
| Acute stress (loss of spouse, change of living environment, etc.) |
| History of substance abuse and/or active substance abuse |
| Family history of mental illness |
| History of serious brain trauma or disease |
| Cancer |
| Impaired ambulation or nonambulatory status |
Are the cognitive or behavioral changes of recent onset or have they been developing over a period of months?
Has the patient had a change in his or her functional activities?
What chronic medical problems exist?
What is the patient's level of alertness?
The family plays a key role in the diagnosis by providing a detailed history of changes in the patient's mental status. However, family members, including the patient's spouse and adult children, will have individual interpretations of the severity and impact of the patient's cognitive symptoms. Family members may minimize subtle but progressive symptoms, such as the patient's inability to balance the family's financial statements, handle psychosocial stressors or manage other situations.
Medication Review
Polypharmacy and adverse drug reactions are major causes of confusion in the elderly. Since many commonly used drugs can cause delirium (Table 6),10 a careful review of medications is essential. When evaluating a complaint of confusion, the physician may find it helpful to have the patient (or caregiver) bring all current over-the-counter and prescription medications to the office visit.
Medications frequently responsible for delirium include anticholinergic agents, benzodiazepines, cardiovascular agents, xanthines and both narcotic and nonnarcotic analgesics.2 Over-the-counter medications such as antihistamines and anticholinergics can also cause delirium.
Physical Examination
The physical examination may be helpful in distinguishing between neurologic and psychiatric disorders in an elderly patient who presents with confusion. Close attention should be given to the patient's underlying illnesses. Unless otherwise indicated by the history, the physician should focus the physical examination on the cardiovascular, neurologic and psychiatric systems. Note that the physical examination is frequently normal in patients with early DAT.
The physical evaluation should include an assessment of the patient's level of arousal and orientation. Patients who lack alertness or have a clouded consciousness are more likely to have delirium than dementia. Focal neurologic changes are signs of an underlying neurologic disorder. Unfortunately, focal changes are not associated exclusively with delirium or dementia.
Mental Status Examination
Standardized mental status questionnaires, diagnostic rating scales and symptom inventories facilitate the evaluation of the elderly patient with confusion. Together with the history and the physical examination, standardized instruments (followed by periodic reevaluation) are usually sufficient to determine the severity, but not the nature, of an elderly patient's cognitive impairment.
The Mini-Mental State Examination (MMSE) is the most widely used method for grading cognitive status (Figure 1).15 This brief test evaluates the cognitive domains of orientation, registration, attention, memory and language. A single summary score can be used to assess the severity of cognitive impairment and to follow the progression of the impairment. A score of less than 24 is considered abnormal, but this score should be adjusted to account for the educational bias associated with the instrument. An abnormal score on the MMSE is not diagnostic of dementia or delirium, but it does reflect the severity of cognitive impairment.
The Short Portable Mental Status Questionnaire (SPMSQ) is also useful for detecting cognitive impairment (Figure 2).16 This test is particularly quick and easy to administer. While the SPMSQ assesses the cognitive domains of orientation, mathematics skill and both short- and long-term memory, it is less useful in assessing other cognitive deficits.
The physician must be able to verify the patient's responses to historical questions. Sources of validation include the patient's spouse and adult children, as well as other caregivers. If the physician is unable to substantiate the patient's responses, other strategies must be used to evaluate that patient, including the sections of the MMSE or SPMSQ that objectively test mathematics skill, immediate and delayed recall, praxis and language.
If the cause of cognitive impairment is unclear, electroencephalography or neuropsychologic testing may be necessary. The electroencephalogram (EEG) can be used to detect patterns characteristic of delirium, especially when a previous EEG is available for comparison. Neuropsychologic testing may be helpful in determining the etiology of unusual presentations of psychiatric disorders such as depression or psychosis.17 If the presentation is unclear, the patient may need to be referred to a neurologist, neuropsychiatrist or psychiatrist.
Laboratory Tests
The initial laboratory studies for evaluating elderly patients thought to have dementia are listed in Table 7.18 When indicated by the history and physical examination, HIV testing and EEG are appropriate. Computed tomographic (CT) scanning or magnetic resonance imaging (MRI) is indicated to rule out normal-pressure hydrocephalus or a tumor. Many physicians, however, recommend that patients have at least one CT or MRI study unless the dementia is advanced or has a characteristic presentation.
Studies conducted for specific indications include regional cerebral blood flow testing, cerebral positron emission tomography, screening tests for heavy metals, carotid ultrasound examination, cerebrospinal fluid analysis, genetic analysis and brain biopsy.19–22 These tests are not needed in most patients.
In the future, apo E genotyping and cerebrospinal fluid analysis for tau protein and beta amyloid levels may have clinical applications.23 In particular, these tests may indicate a person's risk of developing Alzheimer's disease. Currently, however, the recommendation is that apo E genotyping should be limited to use in patients with cognitive deficits who are members of autosomal-dominant families with a history of early-onset DAT.24 Even in these situations, counseling is crucial, since the gene does not cause the disease but, rather, raises the likelihood of a diagnosis of Alzheimer's disease.
At this time, the screening of asymptomatic persons is unwarranted. The identification of persons with a higher risk profile may cause anxiety and increase the risk of discrimination.25
After the Diagnosis
Once the diagnosis of delirium, depression or reversible dementia has been made, the underlying disorder(s) should be treated. If the problem is caused by one or more specific medications, the patient should be switched to other drugs that are less likely to cause confusion in the elderly. Depression should be treated appropriately. Treatment of delirium improves cognitive functioning even in patients with underlying dementia.
If an irreversible dementia is diagnosed, attention is focused on decreasing morbidity during the clinical course of the disease. Tacrine (Cognex) and donepezil (Aricept) are cholinesterase inhibitors that have been approved for use in treating the cognitive effects of DAT. The dosing schedule and side effect profile of tacrine may make it less attractive than donepezil. The risks and benefits of these medications should be discussed with the patient and caregivers.
Metrifonate (not yet available), estrogen, vitamin E, selegiline (Eldepryl), nonsteroidal anti-inflammatory drugs and prednisone may have clinical roles in the prevention and/or treatment of DAT. The family physician should watch the literature for clinical indications for the use of these agents in patients with DAT.
Treatments are available for dementias due to causes other than DAT. For example, ticlopidine (Ticlid) is used to treat vascular dementias.