Lesson 2

Topics Dementia, Depression, Delirium

Dementia

A deterioration of intellectual function and other cognitive skills, leading to a decline in the ability to perform activities of daily living.

Dementia is characterized by cognitive decline that occurs with a normal state of consciousness and in the absence of other acute or subacute disorders that may cause reversible cognitive decline (eg, delirium, depression). Dementia is one of the most serious disorders affecting the elderly. The prevalence of dementia increases rapidly with age; it doubles every 5 years after age 60. Dementia affects only 1% of those aged 60 to 64 but 30 to 50% of those > 85. In the USA, about 4 to 5 million persons are affected, and dementia is the leading cause of institutionalization among the elderly. The prevalence among elderly nursing home residents is estimated to be 60 to 80%.

The use of clinician must differentiate dementia from benign senescent forgetfulness (ie, age-related memory loss), which results from the slowing of neural processes with age. Persons with benign senescent forgetfulness learn new information and recall previously learned information more slowly. However, if they are given extra time and encouragement, their intellectual performance is essentially unchanged from their baseline. Daily functioning remains unaffected. Persons with this condition are often more concerned about it than are family members; reassurance and coping strategies are helpful.

Etiology

The causes of dementia are difficult to differentiate because they are imprecise; many cases can be confirmed only by postmortem pathologic examination, which is usually not performed. Moreover, mixed dementias may be common (eg, recent research shows an interplay between Alzheimer's and cerebrovascular diseases).

Alzheimer's disease and vascular dementias are probably the two most common types, accounting for up to 90% of cases of established dementia in about a 2:1 ratio. Lewy body dementia may account for a large number of cases, but this entity is not well understood. Dementias are often divided into those with cortical presentation (ie, primary dementias), of which Alzheimer's disease is the prototype, and those with subcortical presentation, of which vascular dementia is the prototype.

Symptoms and Signs

The natural history varies according to the cause of dementia; however, patients typically experience a steady, inexorable decline in intellectual function over 2 to 10 years, culminating in total dependence and death, often due to infection.

The most common symptom in early dementia is diminished short-term memory. Patients repeatedly ask the same questions, often after only a few minutes, or forget where belongings were placed. The inability to locate belongings may lead to paranoia that they were stolen.

Word-finding becomes difficult; patients may forget a specific word and use elaborate circumlocution to compensate (eg, a necktie may be called "that thing around the collar"). Formerly mastered activities of daily living (eg, driving, handling finances, housekeeping) may also become difficult. A change in the level of functioning is key to diagnosis.

Other symptoms of early dementia include personality changes, emotional lability, and poor judgment. Family members may report that the patient is "not acting like himself" or is doing uncharacteristic things (eg, a miserly widower gives thousands of dollars to a questionable charity). Mood swings, including depression and euphoria, commonly occur. Although early dementia usually does not affect sociability, patients may become increasingly irritable, hostile, and agitated, especially in circumstances in which they are confronted with their cognitive impairment.

Patients with early dementia can usually compensate reasonably well and follow established routines at home. Acute decline often results from disruption of routine or a change in surroundings. For example, an elderly parent who visits a child's home in a distant state may become disoriented or may manifest behavior disorders and functional disability not present in more familiar surroundings.

As patients progress to intermediate dementia, their ability to perform basic activities of daily living (eg, bathing, dressing, toileting) becomes impaired. Patients cannot learn new information. Normal environmental and social cues do not register, thus increasing disorientation to time and place. Patients may become lost even in familiar surroundings (eg, they cannot find their bedroom or bathroom). Patients with intermediate dementia are also at increased risk of falls and accidents due to confusion and poor judgment.

Behavior disorders may develop during early or intermediate dementia and can persist into severe dementia. Significant paranoia (eg, specific delusions, generalized suspicion) occurs in about 25% of patients. One particularly poignant delusion results from the loss of self-recognition in mirrors, leading to a suspicion that strangers have entered the home. Wandering can also be a significant problem, particularly if patients are trying to return to familiar surroundings, which may no longer exist. Physical aggressiveness, inappropriate sexual behavior, and nonspecific agitation may also occur during intermediate dementia.

Patients with severe dementia cannot perform activities of daily living and become totally dependent on others for feeding, toileting, and mobilization. Short-term and long-term memory is completely lost, and patients may be unable to recognize even close family members. The ability to ambulate is variably affected in different dementias but is usually lost in the later stages of illness, particularly in Alzheimer's disease. Loss of other reflex motor tasks (eg, ability to swallow) puts patients at risk of malnutrition and aspiration. The combination of poor mobility and malnutrition increases the risk of pressure sores. Late in the course of dementia, the incidence of seizures increases. Complications such as dehydration, malnutrition, aspiration, and pressure sores are ultimately inevitable but may be delayed by excellent nursing care. Total functional dependence usually requires that the patient be placed in a nursing home or that similar support be implemented in the home. The usual cause of death is infection from respiratory, skin, and urinary tract sources.

Diagnosis

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for dementia include impairment of memory and impairment of at least one other domain of cognition (eg, language, perception, visuospatial function, calculation, judgment, abstraction, problem-solving ability). Often, many or all of these domains are impaired. This impairment must lead to deterioration in usual daily functioning.

The key to diagnosis of dementia is a thorough history; family members should be interviewed whenever possible because they are more aware of cognitive impairment than are patients. The nature of the impairment, time of onset, and pattern of progression should be elicited. Formal mental status examination is also a key component to evaluation of cognitive impairment. Serial assessments can be useful in determining whether cognition is declining.

Patients with cognitive impairment that affects daily functioning require a more thorough evaluation than a mental status examination. Ruling out correctable factors that contribute to cognitive decline (eg, medical disorders, drugs, mood) is most important. With age, persons become more vulnerable to these correctable factors. The older the patient, the more likely that correctable factors are contributing to cognitive impairment.

A thorough review of the patient's known medical disorders and a search for new disorders may hold the key to reversing cognitive deficits. Many acute medical disorders cause acute cognitive decline in the elderly. Rapid onset of cognitive decline is not consistent with dementia and should trigger a prompt evaluation for delirium and correctable medical disorders. Some medical disorders (eg, hypothyroidism, vitamin B₁₂ deficiency) develop slowly and may more closely mimic dementia than delirium, but they are still correctable with treatment.

Drug use may be the most important correctable factor contributing to cognitive impairment. Every patient undergoing evaluation for dementia requires a thorough drug review, including over-the-counter drugs and ophthalmic preparations. A history of alcohol use should also be obtained. Before dementia can be diagnosed, all psychoactive drugs should be eliminated or substituted with less psychoactive drugs. Particularly potent psychoactive drugs include sedative-hypnotics, antidepressants (especially tertiary amine tricyclics), anticholinergics, and opioids. A reasonable strategy is to repeat the mental status examination 6 weeks after optimization of the drug regimen to determine if cognitive impairment persists.

Every elderly patient with a cognitive problem requires a full mood assessment, including a symptom review (using the SIG E CAPS evaluation) and a standardized instrument such as the Geriatric Depression Scale short form. Depression affects up to 40% of patients with dementia, usually in the early to intermediate stage. Cognitive decline resembling dementia in a patient with depression is termed pseudodementia.

A complete physical examination should focus on identifying acute disorders and exacerbations of chronic disorders that may be contributing to cognitive decline. The examination should screen for evidence of a self-care deficit (eg, poor hygiene) that may confirm functional problems described during the history. On neurologic examination, focal neurologic findings may indicate cerebrovascular disease, extrapyramidal signs may indicate parkinsonism or other neurodegenerative diseases, and neuropathies and myopathies may suggest a treatable systemic disorder.

A screening set of laboratory tests (eg, CBC, electrolytes, albumin, renal function, liver function, thyroid function, vitamin B₁₂ levels) is routinely obtained. Other laboratory tests (eg, ESR, arterial blood gas, serologic tests for syphilis, drug levels, cerebrospinal fluid examination) should be performed only in targeted high-risk patients.

Routine use of brain imaging to evaluate the cause of dementia is controversial. Imaging can identify potentially reversible structural abnormalities, such as normal-pressure hydrocephalus, chronic subdural hematomas, and brain tumors. However, these disorders are rare and usually have characteristic presentations. Moreover, whether treatment of these conditions improves cognition is unclear. In practice, the most common use of imaging is to differentiate Alzheimer's disease from vascular dementia. In several studies, the diagnostic yield of imaging patients presenting with classic Alzheimer's disease did not justify the costs of performing the test. However, in practice, most patients evaluated for dementia undergo brain imaging. Unless there is a need to identify small cerebral infarcts affecting the posterior circulation, CT is usually adequate, as opposed to the much more expensive MRI. One imaging study performed after the onset of cognitive decline is sufficient; serial testing is not justified.

Dynamic imaging of cerebral blood flow by single photon emission computed tomography (SPECT) is used in some specialized centers to differentiate Alzheimer's disease from vascular dementia. Alzheimer's disease produces a classic pattern of reduced blood flow to the temporal and parietal lobes, whereas vascular dementia produces a more "patchy" pattern. The expense and limited diagnostic accuracy of SPECT restrict its use to special cases at referral centers. Likewise, electroencephalography may be used to differentiate types of dementia and rule out complex partial seizure disorders, but it has limited diagnostic accuracy and should be reserved for special situations.

Neuropsychologic testing can help in the evaluation of cognitive impairment but is not required in most routine cases. Detailed testing helps primarily in the differentiation between (1) benign senescent forgetfulness and dementia, particularly in borderline cases or those in which the patient or family members are very concerned and desire additional reassurance; (2) dementia and pseudodementia in unusual cases in which depression is particularly hard to diagnose; and (3) dementia and focal syndromes of cognitive impairment (eg, amnesia, aphasia, apraxia, visuospatial difficulties). It is unclear whether neuropsychologic testing differentiates the causes of dementia better than a thorough history and physical examination.

Differential diagnosis: The differential diagnosis of dementia includes normal age-related memory loss, reversible causes of cognitive decline (eg, delirium, depression), milder cognitive impairment that does not meet the criteria for dementia (recently termed CIND--Cognitive Impairment No Dementia), and focal cognitive impairment affecting only one domain (eg, amnesia).

Treatment

Treatment or elimination of all correctable factors that impair cognition may significantly improve daily functioning and quality of life and may delay severe disability and institutionalization. Patients with significant depressive symptoms should be treated, even if they do not fulfill all criteria for major depression. Treatment of depression reverses pseudodementia and may significantly reduce disability in patients with true dementia. The drugs of choice are usually the newer selective serotonin reuptake inhibitors (eg, sertraline, paroxetine) started at a low dose and increased into the therapeutic range as tolerated. After 6 to 12 weeks of treatment, mental status examination should be repeated.

The next step is to create a supportive environment in which patients can function optimally. Patients with early to intermediate dementia usually function best in familiar surroundings. A home safety evaluation and appropriate modifications to improve function should be considered for all patients with dementia who live at home. For example, signs can be posted to cue patients for safety, especially in the kitchen and bathroom.

Homemaking services can provide assistance with instrumental activities of daily living; home health aide services, assistance with basic activities of daily living; and visiting nurses, drug supervision.

The balance between safety and independence is important, and decisions must be individualized. The decision to move into a more supportive living situation is determined by many factors, including patient preference, the home environment, availability of family members and caregivers, financial resources, and clinical factors other than the severity of dementia.

Patients with dementia are susceptible to disuse atrophy and must engage in physical exercise, mental activity, adequate nutrition, and socialization. A regular, supervised exercise program is often as simple as 15 to 20 minutes/day of walking. Continued mental activity usually focuses on the patient's interests before the onset of dementia (eg, current events, reading, art). These activities should be enjoyable and not used as tests of mental function. Adequate nutrition is necessary to maintain body weight. Patients may require prepared meals; monitoring ensures that meals are eaten.

Social isolation should be minimized if possible because it contributes to all of the problems cited above. Special effort may be required to ensure continued socialization. In some cases, adult day care or companion services provide socialization when family members or friends are not available.

Behavior disorders are best treated with individualized behavioral interventions, rather than with drugs. However, frank psychotic symptoms (eg, paranoia, delusions, hallucinations) should be treated with antipsychotic drugs, started at a low dose. Patients must be carefully monitored for adverse effects.

Dementia is also a strong risk factor for other geriatric problems (eg, falls, urinary incontinence; prevention and treatment strategies should be implemented.

Health care practitioners must provide support for family members and caregivers of patients with dementia. Educational materials about dementia in general and the specific type (if known) can be very helpful but are no substitute for the specific advice, listening, and empathy of the clinician. Close monitoring for caregiver burnout is important; the threshold for burnout varies among persons. Various caregiver support groups are available.

End-of-Life Issues

Medical and financial planning is imperative before dementia becomes too severe. Patients should appoint a health care proxy and discuss health care wishes with the proxy and primary physician. As dementia worsens, the risk/benefit ratio becomes less favorable for highly aggressive interventions and hospital care. In severe cases, patient comfort may be more appropriate than attempts to prolong life; the physician and health care proxy must collaborate on the care plan. A time may come when decisions must be made about artificial feeding or treatment of acute illness. These decisions are best discussed before such a situation arises and then discussed again when the situation becomes critical. Unlike cancer and some other conditions, dementia has no good prognostic models. In general, patients with Alzheimer's disease who can no longer walk have about <= 6 months to live.

Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia affecting the elderly, accounting for up to two thirds of cases. AD is increasingly common with age. The typical pathologic findings are a loss of neurons in multiple areas of the brain; senile plaques (composed of neurites, astrocytes, and glial cells surrounding an amyloid core); and neurofibrillary tangles (consisting of paired helical filaments). The specific pathophysiologic mechanism of neuronal cell loss in AD, as well as the role of plaques and tangles, is unknown. Plaques and tangles also occur in normal aging, but to a much lesser degree than in AD.

A protein involved in cholesterol transport, apolipoprotein E (apo E), has been genetically linked with AD. The
4 allele of apo E appears to be a risk factor for the disease, the
2 allele appears protective, and the
3 allele is neither associated nor protective. Persons with the
4 allele develop AD more commonly and at an earlier age than those without the allele. For example,
4 homozygotes have a > 50% risk of developing AD by age 70, whereas
2/
3 persons have only a 12 to 14% risk by age 90. Another important genetic advance has been the localization of the
-amyloid gene to chromosome 21, the same chromosome implicated in some cases of familial AD and AD due to Down syndrome. The finding that
4 binds to
-amyloid may lead to the pathophysiology of the disease. However, none of these findings have yet affected the treatment of AD patients. Moreover, genetic testing for apo E genotype is generally not recommended for most routine cases.

Diagnosis

The diagnosis of AD is based on the clinical features of typical dementia. However, because AD is a common disease, atypical variants, including those with mixed pathophysiology, are also common, and deviations from the classic pattern do not rule out the diagnosis. AD is definitively diagnosed only on postmortem examination of brain tissue.

Treatment

AD is treated the same as dementia of any cause. In addition, treatment involves drugs that improve cognition, given the patient's existing neuronal structure, or drugs that slow progression by reducing the rate of neuronal loss. Of drugs that improve cognition, cholinergic drugs (eg, tacrine, donepezil) are the best studied. Several randomized trials suggest that treatment with these drugs can modestly improve cognitive performance in many patients. This approach "turns the clock back" about 6 to 9 months for the average patient but has no effect on the rate of disease progression. Given the availability of the once-per-day, relatively nontoxic drug donepezil, a closely monitored trial for patients with mild to moderate AD seems reasonable; tacrine is given 4 times per day and is more toxic than donepezil. Donepezil may be started at 5 mg every night and reevaluated after 6 weeks. If improvement does not occur, the drug should be stopped or the dose increased to 10 mg. The 10-mg dose has a much higher incidence of adverse effects than the 5-mg dose. If the dose is increased, the patient should be reevaluated after another 6 weeks. If improvement still does not occur, the drug should be stopped. If mental status improves (by caregiver impression or formal testing) with either dose, the drug may be continued and the patient reevaluated at 3- to 6-month intervals.

Estrogen, nonsteroidal anti-inflammatory drugs, and vitamin E have all been reported to slow the progression of AD, but more research is needed to determine their efficacy. However, cautious use of these drugs in persons with early dementia is appropriate. Ongoing research is also investigating the use of other antioxidants.

Other Cortical Dementias

Pick's disease and frontal lobe dementia syndromes resemble AD. In general, they progress more rapidly than AD and may be associated with more frontal lobe signs and behavioral disturbances earlier in the disease. However, clinical differentiation of these dementias from AD is difficult. The only definitive diagnostic method is pathologic examination of the brain. Because no specific treatments are available for these rare dementias, their diagnosis rarely affects clinical management.

Subcortical Dementias

Vascular Dementia

A clinical syndrome of intellectual decline caused by ischemic insult to brain tissue.

Vascular dementia causes up to one third of cases of dementia and is likely the second most common cause after AD; it is particularly common among patients with many comorbid diseases. Most of these patients have high-risk factors for stroke (eg, hypertension, diabetes, coronary or peripheral vascular occlusive disease, heart disease, hyperlipidemia) and a history of transient ischemic attacks or sudden-onset neurologic deficits (strokes).

Several distinct patterns exist: classic multi-infarct dementia is caused by two or more major cerebral infarcts in the anterior, middle, or posterior cerebral artery territories; strategic infarct dementia is caused by a single infarct in a crucial area of the brain (eg, the angular gyrus, the thalamus); lacunar state or Binswanger's disease is caused by the buildup of multiple small infarcts, most commonly in the periventricular white matter. CT and MRI show periventricular and white matter abnormalities, which include hypodensities and periventricular lucencies without zones of cortical infarction. Mixed vascular dementia has features of two or more of these patterns.

Symptoms and Signs

The symptoms and signs depend somewhat on which pattern is present; the classic presentation is stepwise cognitive decline, with each step characterized by an ischemic insult. In lacunar state dementia, the steps may be so small as to be indistinguishable from a gradual decline.

Cognitive impairment in vascular dementia, unlike that in AD, is more patchy, and some cognitive domains may be entirely unaffected. Focal, often asymmetric neurologic deficits (eg, weakness, sensory loss, exaggerated reflexes, Babinski's sign, visual field defects, pseudobulbar palsy, incontinence) occur earlier in the course of vascular dementia than in AD. Patients with vascular dementia are thought to be more aware of their deficits than patients with AD, and they may have a higher incidence of depression (although depression is also common in AD).

Diagnosis

Vascular dementia is diagnosed on the basis of a typical clinical history, focal findings on neurologic examination, and evidence of strokes (macro or lacunar) on brain imaging. Several assessment tools, such as the modified Hachinski Ischemic Score, may help differentiate vascular dementia from AD. Many patients who present with classic vascular dementia ultimately have AD on postmortem examination of the brain, so the true relationship is likely to be complex.

Treatment

The primary treatment is risk reduction for additional cerebrovascular insults, ie, control of hypertension (including isolated systolic hypertension) and treatment with aspirin to prevent cerebrovascular thrombosis or with warfarin to prevent emboli from a cardiac source. Although these treatments prevent stroke, no trials have demonstrated that they slow the rate of progression of vascular dementia.

Vascular dementia does not have the societal stigma of AD, and many patients and family members find this diagnosis easier to accept. However, the prognosis is somewhat worse than AD, because the dementia is associated with concomitant medical disorders.

Dementia Associated with Lewy Body Disease

Lewy bodies are rounded eosinophilic intracytoplasmic neuronal inclusions classically associated with Parkinson's disease, which they are found in selected subcortical structures, most notably the substantia nigra. Although Parkinson's disease is primarily an extrapyramidal motor disease, up to 40% of patients have Parkinson's-associated dementia. This "subcortical dementia" has clinical features similar to those of vascular dementia. Treatment focuses on the underlying Parkinson's disease, although levodopa and other treatments for Parkinson's disease seem to have little effect on cognition and may even precipitate psychosis. Dementia is also associated with several other primary extrapyramidal motor system degenerative diseases, including progressive supranuclear palsy.

Dementia due to diffuse Lewy body disease has recently been recognized as a distinct entity: Lewy bodies are found throughout the brain, including the cortex. The importance of diffuse Lewy body disease is under debate; some sources suggest it is the second most common cause of dementia after AD, some claim it is a variant of AD, and some state it is only of minor significance.

The clinical presentation is similar to that of AD, but the psychologic symptoms, particularly paranoia, delusions, and visual hallucinations, are more prominent. Mild parkinsonism may be present. Treatment with antipsychotic drugs usually leads to acute deterioration due to adverse extrapyramidal effects. Further clinical and pathologic studies are needed to better define this entity.

Dementia Due to Toxic Ingestion

Acute ingestion of psychoactive drugs may cause acute mental status changes. Rarely, long-term ingestion of these drugs leads to permanent, irreversible cognitive impairment. The most common form, alcohol-associated dementia, is due to heavy ingestion of alcohol for > 10 years. The classic finding is impairment of short-term memory that is disproportionate to the other cognitive domains, although the dementia can be global. Ingestion of other toxic substances (eg, heavy metals) may also cause dementia.

Dementia Due to Infection

Acute central nervous system infections may cause delirium; chronic infections may cause dementia. The most common, HIV-associated dementia, tends to affect a younger population than most other dementias. Although HIV can directly infect and destroy neurons, dementia usually occurs in the later stages of illness and is rarely a presenting symptom of HIV. Early and sustained antiviral treatment usually prevents dementia. Other viruses that infect the brain may cause acute cognitive dysfunction due to encephalitis or chronic cognitive dysfunction due to a postencephalitis syndrome.

Neurosyphilis and Lyme disease, which are spirochetal infections, can cause dementia-like syndromes. These syndromes are treatable and at least partially reversible, but they are better prevented by early recognition and treatment of the primary infection before it affects the central nervous system. Another dementia having an infectious etiology is Creutzfeldt-Jakob disease, which is caused by a prion. It has no specific treatment.

Normal-Pressure Hydrocephalus

Normal-pressure hydrocephalus is thought to be caused by a defect in cerebrospinal fluid resorption in the arachnoid granulations. The classic triad of symptoms is gait disturbance ("magnetic" gait, as though the feet are stuck to the floor), urinary incontinence, and dementia. Brain imaging shows ventricular enlargement disproportionate to cortical atrophy. Patients should undergo lumbar puncture with removal of at least 20 mL of cerebrospinal fluid. Improvement in gait, continence, and cognition after large-volume lumbar puncture may predict the response to ventriculoperitoneal shunting. Several case series (although no randomized trials) report significant improvement after ventriculoperitoneal shunting, although gait and continence are more often improved than cognition.

Dementia Due to Structural Brain Abnormalities

Chronic subdural hematomas rarely cause dementia. Often, no clear history of head trauma or bleeding diathesis is present. Depending on the duration of the hematoma, drainage may only partially improve cognitive function.

Brain tumors (primary or metastatic) also rarely cause dementia. Treatment includes surgery, radiation, or chemotherapy depending on the location and aggressiveness of the tumor.

Depression

A disorder characterized by feelings of sadness and despair and ranging in severity from mild to life threatening.

Depression is one of the most common psychiatric disorders among the elderly. The prevalence of clinically significant depressive symptoms ranges from 8 to 15% among community-dwelling elderly persons and is about 30% among the institutionalized elderly. Major depression occurs less often in later life than at younger ages and affects about 3% of elderly persons in the community, 11% in hospitals, and 12% in long-term care settings. The current cohort between ages 70 and 90 years has had fewer severe depressive episodes in adult life than earlier cohorts. The number of cases is expected to increase substantially over the next 20 to 30 years as younger cohorts, who have a higher prevalence of depression than the current elderly cohort, age.

Depression is one of the most common risk factors for suicide. The highest rates of suicide in the USA occur in persons >= 70. For white men, suicide is 45% more common among those aged 65 to 69 years, > 85% more common among those aged 70 to 74, and more than three and a half times more common among those >= 85 than among white men aged 15 to 19 years. Suicide rates do not increase with age among women. The elderly are less likely than younger patients to seek or respond to offers of help designed to prevent suicide. The elderly make fewer suicide gestures but more often succeed at suicide attempts. As many as 70% of elderly persons who completed suicide visited their primary care physician within the previous 4 weeks.

Etiology

The etiology of depression in the elderly, as in younger persons, is biopsychosocial.

Medical disorders may cause depression in the elderly as may abuse of alcohol, some prescription drugs (especially some antihypertensives), cocaine, or other illicit drugs. Psychologic risk factors are similar across age groups and include guilt and negative thought patterns. Cognitive dysfunction is another major risk factor. Social risk factors (eg, loss of a spouse or partner, decreased social support) appear to cause depression more often in men than in women. Persons with lower incomes are at greater risk for depression.

Heredity plays less of a role in depression with first onset in late life than in that with first onset in midlife. However, persons who first experience depression in early or midlife and have a recurrence in late life are just as likely to report a family history as are persons who experience depression in midlife. Structural brain changes, seen on MRI and thought to be secondary to vascular insufficiency, are associated with depression in late life. Such cases are referred to as vascular depression.

Symptoms and Signs

Chronic and persistent dysphoria (restlessness, malaise) with a mildly depressed mood, common among the elderly, is not severe enough to warrant a diagnosis of depression. The clinical manifestations of depression in the elderly are listed in Table 33-3.

Episodes of brief depression, which are also common among the elderly, include moderately severe depressive symptoms that are consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria except for their duration (2 weeks). The symptoms may have no clear cause and may resolve spontaneously, and episodes may occur in increasingly rapid cycles.

Some elderly persons experience a brief period (usually lasting a few days) of severe depressive symptoms that usually can be explained by obvious difficulties in adjustment or by bereavement. Adjusting to a severe or ultimately fatal chronic illness and losing a spouse or partner are common causes of such symptoms. Affected persons recover with time or when the stressor resolves.

Dysthymic disorder, which may be chronic, persistent, and moderately severe, is defined by DSM-IV as a depressed mood with two or more additional symptoms (eg, sleep problems, decreased appetite, feelings of hopelessness, lethargy). Symptoms must persist for at least 2 years but are not severe enough to constitute a major depressive episode.

Major depression, with or without melancholia, includes a core symptom of dysphoric mood or loss of interest plus at least four of the following symptoms: sleep disturbance (usually decreased sleep), appetite disturbance, weight loss, psychomotor retardation, suicidal ideation, poor concentration, feelings of guilt, and loss of interest in usual activities (if not the core symptom). Melancholia is present if these symptoms are predominated by a lack of interest in the social environment, diurnal variation (ie, feeling significantly worse during one part of the day, usually the morning, compared with the remainder of the day), and psychomotor agitation or retardation.

Sometimes major depression is characterized predominantly by psychotic features, especially delusions of illness or guilt about past actions, thoughts, or events.

Psychotic depression is more prevalent in late life than in midlife. Generally, psychotic symptoms are similar among elderly and younger patients, although elderly patients usually have more of them and are less likely to experience self-deprecation and guilt.

Bipolar I disorder is characterized by one or more manic episodes, with or without episodes of depression. A manic episode is a distinct period (lasting >= 1 week) during which there is an abnormally and persistently elevated, expansive, or irritable mood. Manic episodes may occur for the first time in late life but most often recur from an earlier age. During a manic episode, a person may experience an inflated self-esteem, decreased need for sleep, increased talkativeness, a subjective sense that thoughts are racing, distractibility, psychomotor agitation, and involvement in activities that are perceived to be pleasurable but that can lead to adverse outcomes, such as unrestrained buying. Elderly persons are less likely to experience inflated self-esteem or grandiosity during an episode and are more likely to experience irritability and psychomotor agitation, thus making it somewhat difficult to distinguish a manic episode from agitated depression. A thorough history, including information from the patient and family, can assist in making this distinction. For example, if the elderly person has had previous episodes of depression associated with psychomotor retardation and, over a short period of time, enters an episode of acute agitation, decreased sleep, and increased talkativeness, a manic episode is likely even if the mood is dysphoric.

Some elderly persons may never experience an acute episode of mania but do have clear episodes of major depression. Between the episodes of depression, however, these persons are more elated or more irritable than usual. Such persons are diagnosed as having bipolar II disorder. The periods between episodes of depression may last for days, weeks, or even months. The symptoms, although uncharacteristic of the usual behavior of the elderly person, usually do not significantly interfere with function. Relatives and friends, however, may notice a problem with function.

Diagnosis

A thorough history and physical examination, including complete neurologic and mental status assessment, are necessary. A complete review of drug use (including illicit drugs) and alcohol use is also critical. Interaction with family members is helpful, and if the patient is demented or uncommunicative, obtaining a history from family members or other informants is essential. When the diagnosis is complicated by comorbid conditions or by poor communication with the patient, the physician should focus on the symptoms reported by family members and on change in symptoms over time.

The Geriatric Depression Scale and the Hamilton Depression Rating Scale are useful assessment instruments. However, they are screening devices and should not replace a thorough evaluation and interaction with the patient and family members.

Depressed patients should be asked directly about suicidal thoughts and intentions (eg, "Do you ever feel that life is not worth living? Have you thought of harming yourself?"). Asking about suicide does not increase the risk of suicide. Patients with suicidal thoughts should be asked about plans (eg, "Have you planned how you would do it?"). Those with suicidal plans should be hospitalized immediately.

Sometimes a definitive diagnosis cannot be made on the basis of history and examination alone. Such situations are common when demented patients stop eating or deteriorate in another way that suggests depression. A trial of treatment, usually with an antidepressant, is the best course for these patients.

Laboratory tests have an adjunctive role in the evaluation of depressed patients. However, thyroid function should be assessed for all new cases. A slightly low thyroxine level and an elevated thyroid-stimulating hormone level are common during a depressive episode. Most other tests should be ordered only when clinical findings suggest a concurrent disorder.

An ECG can provide a baseline if concerns arise about the effect of tricyclic antidepressants on cardiac function. Although not diagnostic, the dexamethasone suppression test may help predict prognosis. A positive test result (ie, a postdexamethasone cortisol level of > 5 µg/dL [140 nmol/L]) suggests that a relapse is likely if the level remains high, even when symptoms improve. Polysomnography, when available, can help identify melancholia; decreased sleep time with shortened rapid eye movement latency supports the diagnosis.

The differential diagnosis of major depression includes many medical and psychiatric disorders that may manifest as depression in later life.

Prognosis and Treatment

Patients with dysphoria rarely benefit from traditional modes of therapy. The outcome of major depression in late life, if uncomplicated, follows the "rule of thirds." One third of elderly patients get better and stay better, one third get better but relapse, and one third do not improve or improve only marginally. With time, however, most elderly patients who experience major depression in late life recover. Recovery, however, may take months. The prognosis is worse when depression is complicated by an underlying dysthymic disorder, by a medical disorder, or by cognitive impairment.

The key to the management of depression, especially major depression, in the elderly is early identification and intervention. All caregivers must be alert to the possibility of depression, especially when illness or loss of a loved one occurs. Family members, in particular, must be alert for subtle changes in personality, especially lack of enthusiasm and spontaneity, loss of sense of humor, and new forgetfulness. Loss of interest in sex may be apparent only to a spouse or other sexual partner. Nurses must be alert to loss of appetite, new sleep disturbances, and other signs and symptoms of depression. During treatment, family members and professional caregivers must be trained to monitor for adverse effects of drugs. They must also be alert to warning signs that the depression is worsening or that the patient is considering suicide.

Psychotherapy: Elderly patients with mild, recently established depression may respond to psychotherapy alone and may not need pharmacotherapy. Psychotherapy is often effective in treating depression without significant melancholic symptoms. When combined with antidepressants, it may benefit patients with severe depression. Behavioral and cognitive therapies are considered more effective than nondirected or analytically oriented therapies. Behavioral and cognitive therapies may help reintegrate the patient into a social environment after severe depression and may help prevent relapses, especially for episodic depression. Psychotherapy may be conducted by a psychiatrist, clinical psychologist, or mental health social worker, or it may require an interdisciplinary team.

Pharmacotherapy: Treatment of severe depression with melancholic features is primarily pharmacologic. Choosing a drug depends primarily on which one produces the fewest adverse effects. Although tricyclic antidepressants (eg, nortriptyline, desipramine, amitriptyline) are used often, elderly patients have difficulty tolerating the anticholinergic effects (especially those of amitriptyline) and the postural hypotension these drugs are likely to induce. Monoamine oxidase inhibitors are used less often because they have significant adverse effects and because they are not more effective than other drugs.

Therefore, the drugs of choice are the selective serotonin reuptake inhibitors (SSRIs [eg, fluoxetine, nefazodone, sertraline, paroxetine]), which have relatively few adverse cardiovascular and anticholinergic effects. However, agitation, a common adverse effect with some of these drugs (eg, fluoxetine), can be especially troublesome for elderly depressed patients. Sexual dysfunction is a problem for some persons who take SSRIs. Also, SSRIs can cause akinesthesia and other movement disorders.

Usual starting doses in otherwise healthy elderly patients are typically one half the usual adult doses: eg, fluoxetine 10 mg po daily, nefazodone 100 mg po bid, sertraline 25 mg po daily, or paroxetine 10 mg po daily. A typical starting dose for the tricyclic antidepressant nortriptyline is 10 to 25 mg po at night with gradual increases. Doses should be titrated upward slowly (eg, weekly) and not every 3 to 5 days as for younger adults.

Adjuncts may augment the response to antidepressants. For example, low-dose lithium may augment the effect of tricyclic antidepressants and SSRIs, and carbamazepine may reduce a patient's tendency to cycle in and out of depressive episodes. Methylphenidate has been used independently and as an adjunct to antidepressants, especially for patients in long-term care facilities. Its use may be advantageous for patients who have stopped eating because, if the drug works, it works quickly and also independently stimulates appetite. Methylphenidate may activate the depressed patient, is relatively safe, and rarely leads to dependence.

An acute manic episode may be treated with a mood stabilizer coupled with hospitalization to reduce the likelihood of behavior that can harm the patient or others; lithium carbonate, usually 300 to 600 mg/day, is the treatment of choice. Serum levels for effective therapy in the elderly are usually 0.4 to 0.8 mEq/L; higher levels are often associated with agitation and confusion. Given the toxicity of lithium, many clinicians elect to treat with valproic acid, at an initial dose of 10 to 15 mg/kg/day in 1 to 3 divided doses. Acute symptoms may require that the mood stabilizer be augmented with an antipsychotic drug (eg, olanzapine 2.5 mg daily, haloperidol 0.25 to 0.5 mg daily to bid). In such elderly patients, the doses of both the mood stabilizer and the antipsychotic drug must be increased significantly.

Electroconvulsive therapy (ECT): ECT is used for severely depressed patients, especially those who have previously responded to ECT, those who demonstrate significant psychotic symptoms or self-destructive behavior, and those who do not tolerate or respond to antidepressants. ECT is safest with multiple-channel monitoring (electroencephalography [EEG], ECG, blood pressure, pulse, and respiratory function); it should be administered by a psychiatrist under the supervision of an anesthetist or anesthesiologist. After rehydration, ECT is the treatment of choice for patients with malnutrition and dehydration due to severe depression.

ECT induces improvement in 80% of elderly patients who did not respond to antidepressants--the same rate as for younger patients. Maintenance ECT on an outpatient basis significantly reduces the likelihood of relapse for patients who responded to ECT. If maintenance ECT is impossible, then the risk of relapse can be reduced by the use of antidepressants, even if the patient did not respond to them initially.

Patients who undergo ECT experience acute amnesia, which is often distressing. Some memory loss can persist after ECT, but the nature and extent of this problem have not been determined.

Treatment of Medically Ill and Hospitalized Patients

Some patients respond to an acute or chronic medical disorder by developing a psychiatric disorder (eg, adjustment disorder with depressed mood). Support and psychotherapy (eg, formal intervention with the patient and family members) are often helpful. Small doses of SSRIs (eg, trazodone, 25 mg at night) can help, especially when sleep problems are present. For patients who are dying, similar measures can be used; however, not every dying patient needs psychotherapy or antidepressants. (see page 120)

Pharmacotherapy for major depression in patients with other medical disorders requires special attention. Tricyclic antidepressants and SSRIs (although SSRIs are of less concern) can cause adverse cardiovascular effects in patients with heart disease or unstable blood pressure (eg, a tendency toward orthostatic hypotension). Both classes of drugs are reasonably safe when used properly in patients without serious heart disease.

With longer hospitalization, the inability to respond to rehabilitative efforts and a patient's and family members' fears of chronic invalidism become proportionately greater. Hospitalized patients with depression often view themselves as hopeless; their hopelessness spreads to the staff members, who may pay less attention to them. Modifying the patient's environment may help (eg, involving the patient in group activities), but the depression itself also needs to be treated, usually with pharmacotherapy.

Delirium

• Disturbance of consciousness with reduced ability to focus, sustain, or shift attention

• Cognitive change (memory deficit, disorientation, language disturbance) or development of perceptual disturbance (hallucinations, delusions, illusions) not accounted for by preexisting, established or evolving dementia

• Rapid onset - usually hours to days and course tends to fluctuate during the course of the day

• Evidence that delirium is the direct physiological consequence of a general medical condition, substance intoxication or withdrawal, or medication side effect

Delirium is associated with poor patient outcomes

• Increased morbidity and mortality (several studies estimated 1 and 6 month mortality to be 14% and 22%, respectively - approx. twice that of patients without delirium)

• Threefold increase risk of death after controlling for pre-existing co-morbidities, severity of illness, use of sedatives/analgesics

• In hospital fatality rates estimated 25-33% (rates as high as MI, sepsis)

• Three- to five-fold increase risk of nosocomial complications

Classification based upon psychomotor activity

• Hyperactive delirium - approx. 25% of cases - characterized by increased psychomotor activity and agitation

• Hypoactive delirium - approx. 25% of cases - psychomotor activity is decreased

• Mixed delirium - approx. 35% of cases - psychomotor activity has hyperactive and hypoactive features

• Normal - psychomotor activity normal - approx. 15% of cases

Treatment

Non-pharmacologic

• Provide quiet, well-lit room for patient

• Avoid excessive noise, stimulation

• Encourage familiar faces (family, caregivers) for reassurance

• Provide orientation

• Correct sensory impairment(s)

• Communicate in a succinct, direct style

• Attentive nursing care, observation

• Discontinue non-essential medications

• Avoid restraints (physical, pharmacological, urinary catheters, IVs)

• Geriatric medicine consultation

Pharmacologic

• Haloperidol - use low dose - 0.25-0.50 mg po or 0.125-0.25 mg IV/IM with careful reassessment of patient prior to additonal dosing

• Potential side effects - hypotension, sedation, akathisia (motor restlessness), anticholinergic effects, and extrapyramidal effects

• Atypical antipsychotics - risperidone, olanzapine, queitiapine - fewer side effects with similar efficacy

• Benzodiazepines - reserve for alcohol and BDZ withdrawal delirium

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