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Editors: Kane, Robert L.; Ouslander, Joseph G.; Abrass, Itamar B.

Title: Essentials of Clinical Geriatrics, 5th Edition

> Table of Contents > Part II - Differential Diagnosis and Management > Chapter 6 - Confusion: Delirium and Dementia

Chapter 6

Confusion: Delirium and Dementia

The appropriate diagnosis and management of geriatric patients exhibiting symptoms and signs of confusion can make a critical difference to their overall health and ability to function independently. Confusion can be acute in onset, or it can be manifest by slowly progressive cognitive impairment. The major causes of confusion in the geriatric population are delirium and dementia. As more people live into the tenth decade of life, the chance that they will develop some form of dementia increases substantially. Community-based studies report a prevalence of dementia as high as 47 percent among those 85 years of age and older. Prevalence rates are, however, highly dependent on the criteria used to define dementia (Erkinjuntti et al., 1997). Between 25 and 50 percent of older patients admitted to acute care medical and surgical services are delirious on admission, or develop delirium during their hospital stay. In nursing homes, 50 to 80 percent of those older than age 65 years have some degree of cognitive impairment.

Misdiagnosis and inappropriate management of syndromes causing confusion in geriatric patients can cause substantial morbidity among the patients, hardship to their families, and millions of dollars in health care expenditure. This chapter provides a practical framework for diagnosing and managing geriatric patients who demonstrate confusion. We focus on the most common causes of confusion in the geriatric population delirium and dementia although a variety of other disorders can cause confusion.

DEFINING CONFUSION

Imprecise definition of the abnormalities of cognitive function in older patients labeled as confused has led to problems in the diagnosis and management of these patients. Confusion has been defined as a mental state in which reactions to environmental stimuli are inappropriate because the person is bewildered, perplexed, or unable to orientate himself (Stedman's Medical Dictionary, 2000). This type of definition, although descriptive, is too broad and imprecise to be clinically

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useful. Terms such as confused or confused at times are also imprecise. Descriptions such as impairment of mental function or cognitive impairment coupled with careful documentation of the timing and nature of specific abnormalities provide more precise and clinically useful information. Such documentation is best accomplished by means of a thorough mental status examination.

A thorough mental status examination has several basic components that are essential in diagnosing dementia, delirium, or other syndromes (Table 6-1). In evaluating older patients who appear confused, attention should focus on each of these components in a systematic manner. Recording observations in each area is critical to recognizing and evaluating changes over time. Standardized and validated measures of cognitive function such as the Mini-Mental State Examination (see Appendix), and the Time and Change Test (Inouye et al., 1998a) can be helpful screening tools in these assessments, as well as in subsequent monitoring. Several factors may influence performance and interpretation of standard mental status tests, such as prior educational level, primary language other than English, severely impaired hearing, or poor baseline intellectual function. Thus, scores on one or more of these tests should not be used to replace a more comprehensive examination that includes all the components listed in Table 6-1.

TABLE 6-1 KEY ASPECTS OF MENTAL STATUS EXAMINATIONS

State of consciousness

General appearance and behavior

Orientation

Memory (short- and long-term)

Language

Visuospatial functions

Executive control functions (planning and sequencing of tasks)

Other cognitive functions (e.g., calculations, proverb interpretation)

Insight and judgment

Thought content

Mood and affect

Important information can be gleaned unobtrusively from simply observing and interacting with the patient during the history. Is the patient alert and attentive? Does the patient respond appropriately to questions? How is the patient dressed and groomed? Does the patient repeat himself or herself or give an imprecise medical history, suggesting memory impairment? Orientation, insight, and judgment can sometimes be assessed during the history as well.

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Questions relating to specific areas of cognitive functioning should be introduced in a nonthreatening manner, because many patients with early deficits respond defensively. Each of the three basic components of memory should be tested: immediate recall (e.g., repeating digits), recent memory (e.g., recalling three objects after a few minutes), and remote memory (e.g., ability to give details of early life). Language and other cognitive functions should be carefully evaluated. Is the patient's speech clear? Can the patient read (and understand) and write? Does there seem to be a good general fund of knowledge (e.g., current events)? Other cognitive functions that can be tested easily include the ability to perform simple calculations (one that relates to making change while shopping, for example) and to copy diagrams. The ability to interpret proverbs abstractly and to list the names of animals (12 names in 1 minute is normal) are sensitive indicators of cognitive function and are easy to test.

Judgment and insight can usually be assessed during the examination without asking specific questions, though input from family members or other caregivers can be helpful and sometimes necessary. Any abnormal thought content should also be noted during the examination; bizarre ideas, mood-incongruent thoughts, and delusions (especially paranoid delusions) may be prominent in older patients with cognitive impairment and are important both diagnostically and therapeutically. Observations during the examination may also detect abnormalities of executive control. Executive function involves the planning, sequencing, and executing of goal-directed activities. These functions are critical to the ability to perform instrumental activities of daily living. Screening tests for executive dysfunction, including the EXIT and a Clock-Drawing Test, have been developed and validated (Roman and Royall, 1999). The Clock-Drawing Test can be especially helpful in clinical practice and is performed by asking the patient to draw a clock face with a specific time. Inability to perform this test may be unsuspected and indicate a need for further evaluation.

Throughout the examination, the patient's mood and affect should be assessed. Depression, apathy, emotional liability, agitation, and aggression are common in older patients with cognitive impairment (Lyketsos et al., 2002), and failure to recognize these abnormalities can lead to improper diagnosis and management. In some patients such as those who are very intelligent or poorly educated, or have low intelligence, as well as those in whom depression is suspected more detailed neuropsychological testing by an experienced psychologist is helpful in more precisely defining abnormalities in cognitive function and in differentiating between the many and often interacting underlying causes.

DIFFERENTIAL DIAGNOSIS OF CONFUSION

The causes of confusion in the geriatric population are myriad. The differential diagnosis in an older patient who presents with confusion includes disorders

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of the brain (e.g., stroke, dementia), a systemic illness presenting atypically (e.g., infection, metabolic disturbance, myocardial infarction, congestive heart failure), sensory impairment (e.g., hearing loss), and adverse effects of a variety of drugs or alcohol.

Similar to many other disorders in geriatric patients, confusion often results from multiple interacting processes rather than a single causative factor. Accurate diagnosis depends on specifically defining abnormalities in mental status and cognitive function and on consistent definitions for clinical syndromes. Disorders causing confusion in the geriatric population can be broadly categorized into three groups:

Acute disorders, usually associated with acute illness, drugs, and environmental factors (i.e., delirium).
More slowly progressive impairment of cognitive function as seen in most dementia syndromes.
Impaired cognitive function associated with affective disorders and psychoses.

Old age alone does not cause impairment of cognitive function of sufficient severity to render an individual dysfunctional. Mild, recent memory loss and slowed thinking and reaction time are common. The prognostic and therapeutic implications of mild cognitive impairment are subjects of intensive research. Older patients are often labeled senile because they are unable to answer a question or because they are not given adequate time to respond. Other age-associated disorders such as impaired hearing can also lead to mislabeling an older patient as confused or senile.

Three questions are helpful in making an accurate diagnosis of the underlying cause(s) of confusion:

Has the onset of abnormalities been acute (i.e., over a few hours or a few days)?
Are there physical factors (i.e., medical illness, sensory deprivation, drugs) that may contribute to the abnormalities?
Are psychological factors (i.e., depression and/or psychosis) contributing to or complicating the impairments in cognitive function?

These questions focus on identifying treatable conditions, which, when diagnosed and treated, might result in substantially improved cognitive function.

DELIRIUM

Delirium is an acute or subacute alteration in mental status especially common in the geriatric population. The prevalence of delirium in hospitalized geriatric patients is approximately 15 percent on admission (Francis, 1992), and the

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incidence in this setting may be up to one-third (Inouye et al., 1996; Schor et al., 1992). In the past, a variety of labels have been used to describe delirious patients (including acute confusional state, acute brain syndrome, metabolic encephalopathy, and toxic psychosis). The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) (American Psychiatric Association, 2000) defines diagnostic criteria for delirium (Table 6-2). The key features of this disorder include the following:

TABLE 6-2 DIAGNOSTIC CRITERIA FOR DELIRIUM

Disturbance of consciousness (that is, reduced clarity of awareness of the environment) in conjunction with reduced ability to focus, sustain, or shift attention
A change in cognition (such as memory deficit, disorientation, or language disturbance) or the development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia
Development of the disturbance during a brief period (usually hours to days) and a tendency for fluctuation during the course of the day
Evidence from the history, physical examination, or laboratory findings that the disturbance is caused by:
1. A general medical condition
2. A substance intoxication, side effect, or withdrawal

Source: From the American Psychiatric Association, 2000, with permission.

Disturbance of consciousness
Change in cognition not better accounted for by dementia
Symptoms and signs developing over a short period of time (hours to days)
Fluctuation of the symptoms and signs
Evidence that the disturbances are caused by the physiological consequences of a medical condition

The disturbances of consciousness and attention, with the suddenness of onset and the fluctuating cognitive status, are the major features that distinguish delirium from other causes of impaired cognitive function. Delirium is characterized by difficulty in sustaining attention to external and internal stimuli, sensory misperceptions (e.g., illusions), and a fragmented or disordered stream of thought. Disturbances of psychomotor activity (such as restlessness, picking at bedclothes, attempting to get out of bed, sluggishness, drowsiness, and generally decreased psychomotor activity) and emotional disturbances (anxiety, fear, irritability, anger, apathy) are very common in delirious patients. Neurological signs (except

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asterixis) are uncommon in delirium. Many hospitalized patients have delirium on only a single day, but the severity and time course of delirium varies considerably. Many factors predispose geriatric patients to the development of delirium, including impaired sensory functioning and sensory deprivation, sleep deprivation, immobilization, transfer to an unfamiliar environment, and psychosocial stresses such as bereavement.

Among hospitalized geriatric patients, several factors are associated with the development of delirium (Schor et al., 1992; Inouye and Charpentier, 1996), including:

Age greater than 80 years
Male sex
Preexisting dementia
Fracture
Symptomatic infection
Malnutrition
Addition of three or more medications
Use of neuroleptics and narcotics
Use of restraints
Bladder catheters

Rapid recognition of delirium is critical because it is often related to other reversible conditions and its development may be a poor prognostic sign for adverse outcomes including nursing home placement and death (Inouye et al., 1998b). Inouye and colleagues described a strategy to identify delirium, termed the Confusion Assessment Method (CAM) (Inouye et al., 1990). The diagnosis of delirium by the CAM requires the presence of:

Acute onset and fluctuating course and
Inattention and
Disorganized thinking or
Altered level of consciousness

It is also important to differentiate delirium from dementia, because the latter is not immediately life-threatening, and inappropriately labeling a delirious patient as demented may delay the diagnosis of serious and treatable conditions. It is not possible to make the diagnosis of dementia when delirium is present in a patient with previously normal or unknown cognitive function. The diagnosis of dementia must await the treatment of all of the potentially reversible causes of delirium, as discussed below. Table 6-3 shows some of the key clinical features that are helpful in differentiating delirium from dementia. Sundowning is a term that describes an increase in confusion which commonly occurs in geriatric patients, especially those with preexisting dementia, at night. This condition is probably related to sensory deprivation in unfamiliar surroundings (such as the acute care hospital) and patients who sundown may actually meet the criteria for delirium.

TABLE 6-3 KEY FEATURES DIFFERENTIATING DELIRIUM FROM DEMENTIA

FEATURE	DELIRIUM	DEMENTIA
Onset	Acute, often at night	Insidious
Course	Fluctuating, with lucid intervals, during day; worse at night	Generally stable over course of day
Duration	Hours to weeks	Months to yearsy
Awareness	Reduced	Clear
Alertness	Abnormally low or high	Usually normal
Attention	Hypoalert or hyperalert, distractible; fluctuates over course of day	Usually normal
Orientation	Usually impaired for time, tendency to mistake unfamiliar for familiar place and persons	Often impaired
Memory	Immediate and recent impaired	Recent and remote impaired
Thinking	Disorganized	Impoverished
Perception	Illusions and hallucinations (usually visual) relatively common	Usually normal
Speech	Incoherent, hesitant, slow or rapid	Difficulty in finding words
Sleep wake cycle	Always disrupted	Often fragmented sleep
Physical illness or drug toxicity	Either or both present	Often absent, especially in Alzheimer's disease
Source: From Lipkowski, 1987, with permission.

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A complete list of conditions that can cause delirium in the geriatric population would be too long to be useful in a clinical setting. Table 6-4 lists some of the common causes of this disorder. Several of them deserve further attention. Each geriatric patient who becomes acutely confused should be evaluated to rule out treatable conditions such as metabolic disorders, infections, and causes for decreased cardiac output (i.e., dehydration, acute blood loss, heart failure). Sometimes this workup is unrevealing. Small cortical strokes, which do not produce focal symptoms or signs, can cause delirium. These events may be difficult or impossible to diagnose with certainty, but there should be a high index of suspicion for this diagnosis in certain subgroups of patients especially those with a history of hypertension, previous strokes, transient ischemic attacks, or cardiac arrhythmias. If delirium recurs, a source of emboli should be sought and associated conditions (such as hypertension) should be treated optimally. Fecal impaction and urinary retention, common in geriatric patients (especially those in acute care hospitals),

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can have dramatic effects on cognitive function and may be causes of acute confusion. The response to relief from these conditions can be just as impressive.

TABLE 6-4 COMMON CAUSES OF DELIRIUM IN GERIATRIC PATIENTS

Metabolic disorders
   Hypoxia
   Hypercarbia
   Hypo- or hyperglycemia
   Hyponatremia
   Azotemia
Infections
Decreased cardiac output
   Dehydration
   Acute blood loss
   Acute myocardial infarction
   Congestive heart failure
Stroke (small cortical)
Drugs (see Table 6-5)
Intoxication (alcohol, other)
Hypo- or hyperthermia
Acute psychoses
Transfer to unfamiliar surroundings (especially when sensory input is diminished)
Other
   Fecal impaction
   Urinary retention

Drugs are a major cause of acute as well as chronic impairment of cognitive function in older patients (Medical Letter, 2002). Table 6-5 lists commonly prescribed drugs that can cause or contribute to delirium. Every attempt should be made to avoid or discontinue any medication that may be worsening cognitive function in a delirious geriatric patient. Environmental factors, especially rapid changes in location (such as being hospitalized, going on vacation, or entering a nursing home) and sensory deprivation, can precipitate delirium. This is especially true of those with early forms of dementia (see below). Measures such as preparing older patients for changes in location, placing familiar objects in the surroundings, and maximizing sensory input with lighting, clocks, and calendars may help prevent or manage delirium in some patients. A Hospital Elder Life Program has been described that may help prevent delirium, and cognitive and functional decline among high risk older patients in acute hospitals (Inouye et al., 2000). This program incorporates several strategies for identifying potentially reversible causes of delirium and medical behavioral and environmental interventions for patients who develop delirium.

TABLE 6-5 DRUGS THAT CAN CAUSE OR CONTRIBUTE TO DELIRIUM AND DEMENTIA*

Analgesics Narcotic Nonnarcotic Nonsteroidal antiinflammatory agents Anticholinergics/antihistamines Anticonvulsants Antihypertensives Antimicrobials Antiparkinsonism drugs	Cardiovascular Antiarrhythmics Digoxin H₂ receptor antagonists Psychotropic drugs Antianxiety drugs Antidepressant drugs Antipsychotics Sedative/hypnotics Skeletal muscle relaxants Steroids
* See AHCPR guidelines (Costa et al., 1996) and Medical Letter, 2002, for a more complete list.

DEMENTIA

Dementia is a clinical syndrome involving a sustained loss of intellectual functions and memory of sufficient severity to cause dysfunction in daily living. Its key features include:

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A gradually progressing course (usually over months to years)
No disturbance of consciousness

Dementia in the geriatric population can be grouped into two broad categories:

Reversible or partially reversible dementias
Nonreversible dementias

Reversible Dementias

While it is especially important to rule out treatable and potentially reversible causes of dementia in individual patients, these dementias account for fewer than 20 percent of all causes of dementia in most series (Costa et al., 1996; Clarfield, 1988). Moreover, finding a reversible cause does not guarantee that the dementia will improve after the putative cause has been treated.

Table 6-6 lists causes of reversible dementia. These disorders can be detected by careful history, physical examination, and selected laboratory studies. Drugs known to cause abnormalities in cognitive function (see Table 6-5) should be discontinued whenever feasible. There should be a high index of suspicion regarding excessive alcohol intake in older patients. The incidence of alcohol consumption varies considerably in different populations but is easily missed and can cause dementia as well as delirium, depression, falls, and other medical complications.

TABLE 6-6 CAUSES OF POTENTIALLY REVERSIBLE DEMENTIAS

Neoplasms Metabolic disorders Trauma Toxins Alcoholism Heavy metals Organic poisons Infections	Autoimmune disorders Central nervous system vasculitis, temporal arteritis Disseminated lupus erythematosus Multiple sclerosis Drugs (see Table 6-5) Nutritional disorders Psychiatric disorders Depression Other disorders (e.g., normal-pressure hydrocephalus)
Sources: From Costa et al., 1996, and Katzman et al., 1988, with permission.

One particular disorder, depressive pseudodementia, deserves special emphasis. This term has been used to refer to patients who have reversible or partially

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reversible impairments of cognitive function caused by depression. Depression may coexist with dementia in more than one-third of outpatients with dementia, and in an even greater proportion in nursing homes. The interrelationship between depression and dementia is complex. Many patients with early forms of dementia become depressed. Sorting out how much of the cognitive impairment is caused by depression and how much by an organic factor(s) can be difficult. Some clinical characteristics can be helpful in diagnosing depressive pseudodementia, including prominent complaints of memory loss, patchy and inconsistent cognitive deficits on exam, and frequent don't know answers. Detailed neuropsychological testing, performed by a psychologist or other health care professional skilled in the use of these tools, can be helpful in many patients. At times, even after a complete assessment, uncertainty still exists regarding the role of depression in producing intellectual deficits. Under these circumstances, a careful trial of antidepressants (in rare instances, electroconvulsive therapy) is justified to facilitate the diagnosis and may help improve overall (but not cognitive) functioning. Older patients who develop reversible cognitive impairment while depressed appear at relatively high risk for developing dementia over the following few years, and their cognitive function should be followed closely over time.

Nonreversible Dementias

Several different classifications have been recommended for the nonreversible dementias. The Agency for Health Care Policy and Research (AHCPR) guideline on Alzheimer's and related dementias (Costa et al., 1996) lists four basic categories, based on the work of Katzman et al. (1988) (Table 6-7):

TABLE 6-7 CAUSES OF NONREVERSIBLE DEMENTIAS

Degenerative diseases
   Alzheimer's disease
   Dementia associated with Lewy bodies
   Parkinson's disease
   Pick's disease
   Huntington's disease
   Progressive supranuclear palsy
   Others
Vascular dementias
   Occlusive cerebrovascular disease (multiinfarct dementia)
   Binswanger's disease
   Cerebral embolism(s)
   Arteritis
   Anoxia secondary to cardiac arrest, cardiac failure of carbon monoxide intoxication
Traumatic dementia
   Craniocerebral injury
   Dementia pugilistica
Infections
   Acquired immunodeficiency syndrome
   Opportunistic infections
   Creutzfeldt-Jakob disease
   Progressive multifocal leukoencephalopathy
   Postencephalitic dementia

Sources: From Costa et al., 1996, and Katzman et al., 1988, with permission.

Degenerative diseases of the central nervous system
Vascular disorders
Trauma
Infections

Alzheimer's disease, other degenerative disorders, and vascular dementias account for a vast majority of dementias in the geriatric population, and are the focus of discussion in this chapter.

Alzheimer's and Other Degenerative Diseases Alzheimer's disease accounts for close to two-thirds of dementias in the geriatric population. Dementia with Lewy bodies (DLB) accounts for up to 25 percent of dementias in some series, and may overlap with Alzheimer's and Parkinson's dementia (Small et al., 1997; McKeith et al., 1996). In addition to the characteristic pathological findings, DLB is characterized by

Detailed visual hallucinations

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Parkinsonian signs
Alterations of alertness and attention

Table 6-8 lists the diagnostic criteria for Alzheimer's disease (AD). Family history and increasing age are the primary risk factors for AD. Approximately 6 to 8 percent of persons older than age 65 have AD. The prevalence doubles every 5 years, so that nearly 30 percent of the population older than age 85 has AD. By the age of 90, almost 50 percent of persons with a first-degree relative suffering from AD might develop the disease themselves. Rare genetic mutations on chromosomes 1, 14, and 21 cause early onset familial forms of AD, and some forms of late-onset AD are linked to chromosome 12 (Small et al., 1997). The strongest genetic linkage with late-onset AD identified thus far is the apolipoprotein E epsilon-4 (APOE-E4) allele on chromosome 19.

TABLE 6-8 DIAGNOSTIC CRITERIA FOR ALZHEIMER'S DEMENTIA

The development of multiple cognitive deficits manifested by both:
1. Memory impairment (impaired ability to learn new information or to recall previously learned information)
2. One (or more) of the following cognitive disturbances:
  1. Aphasia (language disturbance)
  2. Apraxia (impaired ability to perform motor activities despite intact motor function)
  3. Agnosia (failure to recognize or identify objects despite intact sensory function)
  4. Disturbance in executive functioning (that is, planning, organizing, sequencing, abstracting)
The cognitive deficits cause severe impairment in social or occupational functioning and represent a major decline from a previous level of functioning
The course is characterized by gradual onset and continuing cognitive decline
The cognitive deficits are not due to any of the following:
1. Other central nervous system conditions that cause progressive deficits in memory and cognition (e.g., cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor)
2. Systemic conditions known to cause dementia (for example, hypothyroidism, vitamin deficiencies, hypercalcemia, neurosyphilis, HIV infection)
The deficits do not occur exclusively during the course of a delirium
The disturbance is not better accounted for by another axis I disorder (for example, major depressive disorder, schizophrenia)

Source: From the American Psychiatric Association, 2000, with permission.

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The relative risk of AD associated with one or more copies of this allele in whites is approximately 2.5. However, APOE-E4 does not appear to confer increased risk for AD among African Americans or Hispanics. One study suggests, however, that the cumulative risks of AD to age 90 in the general population, adjusted for education and sex, are four times higher for African Americans and two times higher for Hispanics than for whites (Tang et al., 1998). Because the presence of one or more APOE-E4 alleles is neither sensitive nor specific, there is disagreement on recommending it as a screening test for AD (Small et al., 1997; Mayeux et al., 1998). Until more sensitive and specific tests become available, routine screening, even among high-risk populations, is generally not recommended.

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Other possible risk factors for AD include previous head injury, female sex, lower education level, and other yet-to-be-identified susceptibility genes. Possible protective factors include the use of estrogen, antioxidants, and nonsteroidal antiinflammatory drugs. The clinical significance of these possible protective effects, however, remains to be proven.

Vascular Dementias Vascular dementias, predominately caused by multiple infarcts (multiinfarct dementia), account for approximately 15 percent of dementia in the geriatric population. Multiinfarct dementia can occur alone or in combination with other disorders that cause dementia. Autopsy studies suggest that cerebrovascular disease may play an important role in the presence and severity of symptoms of AD (Snowdon et al., 1997). Multiinfarct dementia results when a patient has sustained recurrent cortical or subcortical strokes. Many of these strokes are too small to cause permanent or residual focal neurological deficits or evidence of strokes on computed tomography (CT). Magnetic resonance imaging (MRI) may be more sensitive in detecting small infarcts, but there has been a tendency to overinterpret some of these findings as more MRI scans are being done. Table 6-9 identifies characteristics of patients likely to have multiinfarct dementia and compares the clinical characteristics of primary degenerative and multiinfarct dementias. A key feature of multiinfarct dementia is the stepwise deterioration in cognitive functioning, as illustrated in Fig. 6-1. Another form of vascular form of dementia has been described, termed senile dementia of the Binswanger type, which may be impossible to differentiate clinically from multiinfarct dementia. It has become increasingly important to differentiate vascular from other dementias because patients with the former may benefit from more aggressive treatment of hypertension and other cardiovascular risk factors (Forette et al., 2002; Murray et al., 2002), whereas new pharmacological treatments for AD may not help patients with vascular forms of dementias.

TABLE 6-9 ALZHEIMER'S DISEASE VERSUS MULTIINFARCT DEMENTIA: COMPARISON OF CLINICAL CHARACTERISTICS

CHARACTERISTICS	ALZHEIMER'S DISEASE	MULTIINFARCT DEMENTIA
Demographic
Sex	Women more commonly affected	Men more commonly affected
Age	Generally over age 75 years	Generally over age 60 years
History
Time course of deficits	Gradually progressive	Stuttering or episodic, with stepwise deterioration
History of hypertension	Less common	Common
History of stroke(s), transient ischemic attack(s), or other focal neurological symptoms	Less common	Common
Examination
Hypertension	Less common	Common
Focal neurological signs	Uncommon	Common
Signs of atherosclerotic cardiovascular disease	Less common	Common
Emotional lability	Less common	More common

FIGURE 6-1 Primary degenerative dementia versus multiinfarct dementia: comparison of time courses. ¹ Recognized by patient, but only detectable on detailed testing. ² Deficits recognized by family and friends. ³ See text for explanation. ⁴ Exact time courses are variable; see text.

EVALUATION

The AHCPR practice guideline (Costa et al., 1996) and a consensus statement of the American Association of Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society (Small et al., 1997) have updated recommendations for the evaluation of patients suspected of having a dementia syndrome. The first step is to recognize clues that dementia may be present. Table 6-10 lists symptoms that should suggest further evaluation. Patients suspected of having dementia should undergo the following:

TABLE 6-10 SYMPTOMS THAT MAY INDICATE DEMENTIA

Learning and retaining new information
Is repetitious; has trouble remembering recent conversations, events, appointments; frequently misplaces objects.
Handling complex tasks
Has trouble following a complex train of thought or performing tasks that require many steps, such as balancing a checkbook or cooking a meal.
Reasoning ability
Is unable to respond with a reasonable plan to problems at work or home, such as knowing what to do if the bathroom is flooded; shows uncharacteristic disregard for rules of social conduct.
Spatial ability and orientation
Has trouble driving, organizing objects around the house, finding his or her way around familiar places.
Language
Has increasing difficulty with finding the words to express what he or she wants to say and with following conversations.
Behavior
Appears more passive and less responsive, is more irritable than usual, is more suspicious than usual, misinterprets visual or auditory stimuli.

Source: From Costa et al., 1996, with permission.

Focused history and physical examination, including assessment for delirium and depression and identification of comorbid conditions (e.g., sensory impairment, physical disability)

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A functional status assessment (see Chap. 3)
A mental status examination (see above and Table 6-1)
Selected laboratory studies to rule out reversible dementia and delirium

Table 6-11 outlines key aspects of the history. Because many physical illnesses and drugs can cause cognitive dysfunction, active medical problems and use of prescription and nonprescription drugs (including alcohol) should be reviewed. The nature and severity of the symptoms should be characterized. What are the deficits? Does the patient admit to them or is the family member describing them? How is the patient reacting to the problems? The responses to these questions can be helpful in differentiating between dementia and depressive pseudodementia. The onset of symptoms and the rate of progression are particularly important. The sudden onset of cognitive impairment (over a few days) should prompt a search for one of the underlying causes of delirium listed in Table 6-4. Irregular, stepwise decrements in cognitive function (as opposed to a more even and gradual loss) favor a diagnosis of multiinfarct dementia (see Table 6-9 and Fig. 6-1). Patients with dementia are often brought for evaluation at a time of sudden worsening of cognitive function (as illustrated by the broken line in Fig. 6-1) and may even meet the criteria for delirium. These sudden changes may be triggered by a number of acute events (a small stroke without focal signs, acute physical illness, drugs, changes in environment, or personal loss such as the death or departure of a relative). Only a careful history (or familiarity with the patient) will

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help to determine when an acute event has been superimposed on a preexisting dementia. Appropriate management of the acute event will, in many instances, result in improvement in cognitive function (see Fig. 6-1, broken line).

TABLE 6-11 EVALUATING DEMENTIA: THE HISTORY

Summarize active medical problems and current physical complaints
List drugs (including over-the-counter preparations and alcohol)
Cardiovascular and neurological history
Characterize the symptoms
   Nature of deficits (memory versus other cognitive functions)
   Onset and rate of progression
   Impaired function (e.g., managing money or medications)
   Associated psychological symptoms
    Depression
    Anxiety or agitation
    Paranoid ideation
    Psychotic thought processes (delusions and/or hallucinations)
Ask about special problems
   Wandering (and getting lost)
   Dangerous driving and car crashes
   Disruptive or self-endangering behaviors
   Verbal agitation
   Physical aggression
   Insomnia
   Poor hygiene
   Malnutrition
   Incontinence
Assess the social situation
   Living arrangements
   Social supports
   Availability of relatives and other caregivers
   Employment and health of caregivers

The history should also include specific questions about common problems requiring special attention in patients with dementia. These problems may include wandering, dangerous driving and car crashes, disruptive behavior (e.g., verbal agitation, physical aggression, and nighttime agitation), delusions or hallucinations, insomnia, poor hygiene, malnutrition, and incontinence. They require careful management and most often substantial involvement of family or other caregivers.

A social history is especially important in patients with dementia. Living arrangements and social supports should be assessed. Along with functional status, these factors play a major role in the management of patients with dementia and are of critical importance in determining the necessity for institutionalization. A patient with dementia and weak social supports may require institutionalization at a higher level of function than will a patient with strong social supports. In addition to the lack of availability of a spouse, child, or other relative who can

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serve as a caregiver, the caregiver's employment and/or poor health can play an important role in determining the need for institutional care.

A general physical examination should focus particularly on cardiovascular and neurological assessment. Hypertension and other cardiovascular findings and focal neurological signs (such as unilateral weakness or sensory deficit, hemianopsia, Babinski reflex) favor a diagnosis of multiinfarct dementia. Pathological reflexes (such as the glabellar sign and grasp, snout, and palmomental reflexes) are nonspecific and occur in many forms of dementia as well as in a small proportion of normal aged persons. These frontal lobe release signs as well as impaired stereognosis or graphesthesia, gait disorder, and abnormalities on cerebellar

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testing are significantly more common in patients with Alzheimer's disease than in age-matched controls. Parkinsonian signs (tremor, bradykinesia, muscle rigidity) should be sought because they may indicate either dementia associated with Lewy bodies or frank Parkinson's disease.

A careful mental status examination (see Table 6-1) and a standardized mental status test should be performed. Although practice guidelines indicate that no single test is clearly superior, the Mini-Mental State Examination and the Time and Change Test are rapid tests that can be used in clinical practice (see Appendix). Neuropsychological testing can be helpful when there is a normal mental status score but also functional and/or behavioral changes (this can occur in patients with high baseline intelligence) or when there is a low score without functional deficits (this can occur in patients with lower educational levels). Neuropsychological testing can also be helpful in differentiating depression and dementia and in pinpointing specific cognitive strengths and weaknesses for patients, families, and health providers.

Selected diagnostic studies are useful in ruling out reversible forms of dementia (Table 6-12). Although CT and MRI scans of the head are expensive, many clinicians and experts order one of these tests for patients with dementia of recent onset in whom no other clinical findings explain the dementia and in those with focal neurological signs or symptoms. Cerebral atrophy on one of these scans

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does not establish the diagnosis of Alzheimer's disease; it can occur with normal aging as well as with several specific disease processes. The scan is thus recommended to rule out treatable causes (e.g., subdural hematoma, tumors, normal-pressure hydrocephalus). CT and MRI each have advantages and disadvantages. They are roughly equivalent in the detection of most remediable structural lesions. MRI will demonstrate more lesions than CT in patients with multiinfarct dementia, but will also demonstrate white matter changes of uncertain clinical significance (Small et al., 1997). Position emission tomography (PET) scanning is increasingly available, but remains largely a research tool. PET scanning quantitates glucose metabolism and reveals decreases in specific areas (e.g., frontotemporal) that are highly associated with Alzheimer's disease. PET scan abnormalities can precede the development of clinical deficits by several years in patients at risk for Alzheimer's disease.

TABLE 6-12 EVALUATING DEMENTIA: RECOMMENDED DIAGNOSTIC STUDIES

Blood studies
   Complete blood count
   Glucose
   Urea nitrogen
   Electrolytes
   Calcium and phosphorous
   Liver function tests
   Thyroid stimulating hormone
   Vitamin B₁₂ and folate
   Serologic test for syphilis
   Human immunodeficiency virus antibodies (if suspected)
Radiographic studies
   Computed tomography (or magnetic resonance imaging) of the head
Other studies
   Neuropsychological testing (selected patients; see text)

MANAGEMENT OF DEMENTIA

General Principles

Although complete cure is not available for the vast majority of dementias, optimal management can provide improvements in the ability of these patients to function, as well as in their overall well-being and that of their families and other caregivers. Table 6-13 outlines key principles for the management of dementia.

TABLE 6-13 KEY PRINCIPLES IN THE MANAGEMENT OF DEMENTIA

Optimize the patient's function
   Treatment underlying medical conditions (e.g., hypertension, Parkinson's disease)
   Avoid use of drugs with central nervous system side effects (unless required for management of psychological or behavioral disturbances see Chap. 14)
   Assess the environment and suggest alterations if necessary
   Encourage physical and mental activity
   Avoid situations stressing intellectual capabilities; use memory aids whenever possible
   Prepare the patient for changes in location
   Emphasize good nutrition
Identify and manage complications
   Wandering
   Dangerous driving
   Behavioral disorders
   Depression (see Chap. 7)
   Agitation or aggressiveness
   Psychosis (delusions, hallucinations)
   Malnutrition
   Incontinence (see Chap. 8)
Provide ongoing care
   Reassessment of cognitive and physical function
   Treatment of medical conditions
Provide medical information to patient and family
   Nature of the disease
   Extent of impairment
   Prognosis
Provide social service information to patient and family
   Local Alzheimer's Association
   Community health care resources (day centers, homemakers, home health aides)
   Legal and financial counseling
   Use of advance directives
Provide family counseling for
   Identification and resolution of family conflicts
   Handling anger and guilt
   Decisions on respite or institutional care
   Legal concerns
   Ethical concerns (see Chap. 17)

If causes of reversible or partially reversible forms of dementia are identified (see Table 6-6), they should be specifically treated. Small strokes (lacunar infarcts), which can cause further deterioration of cognitive function in patients with AD, as well as those with vascular dementia, may be prevented by controlling hypertension; thus hypertension should be aggressively treated in patients with dementia as long as side effects can be avoided. Other specific diseases such as Parkinson's disease should be optimally managed. The treatment of these and other medical conditions is especially challenging because treatment (usually drugs) may have adverse effects on cognitive function.

Pharmacological Treatment of Dementia

There are three basic approaches to the pharmacological treatment of dementia:

Agents that enhance cognition and function
Drug treatment of coexisting depression

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Pharmacological treatment of complications such as paranoia, delusions, psychoses, and agitation (verbal and physical)

Drug treatment of depression is discussed in detail in Chap. 7. Pharmacological treatments including antipsychotics and sedatives are discussed in Chap. 14.

The primary pharmacological approach to the treatment of AD has been the use of cholinesterase inhibitors. Some evidence suggests that these drugs are also effective for DLB and multiinfarct dementia. There are four approved drugs of this class on the market (tacrine, donepezil, rivastigmine, and galantamine). Randomized, placebo-controlled clinical trials suggest that these drugs can have clinically important positive effects on cognitive function, and may improve or prevent decline in overall function and potentially delay nursing home admission. Tacrine is potentially hepatotoxic, and is generally not prescribed for this reason. No studies have compared the other three drugs in this class to each other. Gastrointestinal side effects can be problematic and include nausea, vomiting, and diarrhea. On the other hand, the benefits of these drugs include slight improvements in cognitive function (e.g., generally less than 3 points on a Mini-Mental State Exam), improvements in behavior, and a substantial several month delay in the progression of cognitive impairment and the development of related behavioral symptoms.

Other drugs, including estrogen (in women), vitamin E, ginkgo biloba, and nonsteroidal antiinflammatory agents, are commonly used to prevent dementia. There is, however, no evidence that these drugs are effective in preventing or treating dementia (most evidence suggests they are not). The role of these agents in preventing dementia is under active investigation. Many geropsychiatrists and geroneurologists do prescribe vitamin E in addition to a cholinesterase inhibitor for patients with new onset and early dementia.

Nonpharmacological Management

A variety of supportive measures and other nonpharmacological management techniques are useful in improving the overall function and well-being of patients with dementia and their families (see Table 6-13). These interventions range from specific recommendations for caregivers, such as alterations in the physical environment, the use of memory aids, the avoidance of stressful tasks, and preparation for the patient's move to another living setting with a higher level of care, to more general techniques, such as providing information and counseling services. Many nursing homes have developed special care units for dementia patients. With few exceptions, however (Rovner et al., 1996), there is little evidence that such units improve outcomes (Phillips et al., 1997). Assisted-living facilities are now establishing specialized dementia units, with optimally designed environments, trained staff, and intensive activities programming, and without the more hospital-like environment typical of many nursing homes.

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The provision of ongoing care is especially important in the management of dementia patients. Reassessment of the patient's cognitive abilities can be helpful in identifying potentially reversible causes for deteriorating function and in making specific recommendations to family and other caregivers. The family is the primary target of strategies to help manage dementia patients in noninstitutional settings. Caring for relatives with dementia is physically, emotionally, and financially stressful. Information on the disease itself and the extent of impairment and on community resources helpful in managing these patients can be of critical importance to family and caregivers. The local chapter of the Alzheimer's Association and the Area Agency on Aging are examples of community resources that can provide education and linkages with appropriate services. Anticipating and teaching family members strategies to cope with common behavioral problems associated with dementia such as wandering, incontinence, day night reversal, and nighttime agitation can be of critical importance. Hazardous driving that can result in car crashes is an especially troublesome problem. Several states now require reporting patients with dementia who maintain drivers' licenses. There remain, however, no validated methods of assessing driving capabilities and safety among individuals with early dementia. Wandering may be especially hazardous for the dementia patient's safety and is associated with falls. Incontinence is common and often very difficult for families to manage (see Chap. 8). Books providing information and suggestions for family management techniques are very useful (see Suggested Readings). Support groups for families of patients with Alzheimer's disease through the Alzheimer's Association are available in most large cities. Family counseling can be helpful in dealing with a variety of issues such as anger, guilt, decisions on institutionalization, handling the patient's assets, and terminal care. Dementia patients and their families should also be encouraged to discuss and document their wishes, using a durable power of attorney for health care or an equivalent mechanism early in the course of the illness (see Chap. 17). Family members should be encouraged to seek respite care periodically to provide time for themselves. Some communities have formal respite care programs available. In the absence of such programs, informal arrangements can often be made to relieve the primary family caregivers for short periods of time at regular intervals. Such relief will help the caregiver to cope with what is generally a very stressful situation. Often a multidisciplinary group of health professionals made up of a physician, a nurse, a social worker, and, when needed, rehabilitation therapists, a lawyer, and a clergy member must coordinate efforts to manage these patients and provide support to family and caregivers.

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