EPIDEMIOLOGY AND SOCIETAL IMPACT
DIFFERENTIAL DIAGNOSIS OF DEMENTIA
Dementia is a general term used to describe a series of disorders that cause significant decline in two or more areas of cognitive functioning. One of these areas must be severe enough to cause functional decline. Of those who suffer from dementia, most have Alzheimer’s disease (AD), which affects an estimated 4 million people in the United States. The pain and anguish of the disorder also afflicts millions more caregivers and relatives, who must cope with the patient’s progressive and irreversible decline in cognition, functioning, and behavior. Both caregivers and patients may misinterpret the initial symptoms of dementia as normal age-related cognitive losses, and physicians may not recognize early signs or may misdiagnose them. However, dementia and aging are not synonymous. As people age, they usually experience such memory changes as slowing in information processing, but these kinds of changes are benign. By contrast, dementia is progressive and disabling and not an inherent aspect of aging.
Diagnostic and treatment advances have benefited many patients. Early and accurate diagnosis of dementia and its cause may minimize costly use of medical resources and give patients and their relatives time to anticipate future medical, financial, and legal needs. Sustained reversal of the progressive cognitive decline of dementia is not currently possible, but psychosocial and pharmacologic treatments may improve such associated conditions as depression, psychosis, and agitation. (See also Psychosocial Issues, Legal and Ethical Issues, Financing, Coverage, and Costs of Health Care.)
Dementia is a disease of late life, generally beginning after age 60 years. AD represents the most common type of dementia, accounting for approximately two thirds of all cases and affecting 6% to 8% of those aged 65 and over. The disease prevalence doubles every 5 years after age 60; an estimated 30% or more of those who are aged 85 or older have AD. Vascular dementia is thought to be the second most common, causing an estimated 15% to 25% of cases. In recent years, dementia associated with Lewy bodies has received increased attention, and although the exact prevalence is not known, estimates suggest that it may be as common as vascular dementia. Frontotemporal dementia is also a more recent diagnostic category of dementia and represents a smaller percentage of cases, with a younger age of onset than other dementias. Neurodegenerative diseases such as Huntington’s disease, Parkinson’s disease, or other metabolic causes such as head injury and alcoholism account for other dementia syndromes.
Dementia has a major impact on society. The total costs approach $100 billion annually if the costs of medical and long-term care, home care, and lost productivity for caregivers are included. Medicare, Medicaid, and private insurance pay much of the direct cost, but families caring for patients with dementia must bear the greatest burden of expense.
The financial costs of dementia are only one aspect of the total burden. The emotional toll is immense for both patients and their families. Nearly half of primary caregivers of patients with dementia experience psychologic distress, particularly depression. An accurate economic assessment of the problem underestimates the true cost of the disease to society unless the quality of life of both patients and caregivers is included in the analysis.
The two greatest risk factors for AD are age and family history. Studies that account for death from other causes suggest that by age 90 years, nearly half of persons with first-degree relatives (ie, parents, siblings) with AD develop the disease themselves. Rare forms of familial AD beginning before age 60 have been associated with genetic mutations on chromosomes 1, 14, and 21. Most commonly, AD begins late in life; for such late-onset cases, the apolipoprotein E gene (APOE) on chromosome 19 influences risk.
The APOE gene has three alleles, APOE*2, APOE*3, and APOE*4. Everyone inherits one allele from each parent, so that six common genotypes are possible (2/2, 2/3, 3/3, 2/4, 3/4, and 4/4). Approximately 3% of the general population has the 4/4 genotype, 20% has the 3/4 genotype, and most persons have the 3/3 genotype. The APOE*4 allele increases risk and decreases age of onset in a dose-related fashion, whereas the APOE*2 allele may have a protective effect. Thus, the 2/3 genotype has a lower risk for AD than the 3/4 genotype; the AD risk is higher for the 3/4 genotype, and highest for the 4/4 genotype. The APOE*4 allele may be less common in black Americans.
Using APOE genotyping as a prognostic test for asymptomatic persons is not recommended until results from further studies are available. APOE*4 is neither necessary nor sufficient to cause AD, and cognitively normal centenarians who are homozygous for APOE*4 have been reported. The asymptomatic person who learns that his or her genotype is 3/3 or 2/3 may be falsely reassured, whereas the person who learns that his or her genotype is 3/4 may be falsely alarmed. APOE genotyping may be useful only in increasing the diagnostic confidence for AD if a patient already has dementia.
Other possible risk factors include a previous head injury, female sex, and fewer years of educational achievement. Head trauma is thought to disrupt neuronal synapses. Research suggests that education may delay the onset of dementia, which may represent a confounding variable of socioeconomic status or a factor that truly provides protection by supplying a cognitive “reserve.” Risk factors for vascular dementia include hypertension, hyperlipidemia, diabetes mellitus, smoking, age, male sex, and perhaps homocysteine levels. These factors are thought to increase risk by predisposing individuals to impairment in cognition through ischemic mechanisms, although there is new evidence linking some vascular risk factors to Alzheimer’s pathology.
The prevention of dementia, especially AD, has been the subject of recent research. Drugs associated with reduced risk in epidemiologic studies include nonsteroidal anti-inflammatory drugs, statins, and possibly antioxidants. Research in normal elderly persons shows a possible protective effect of physical and intellectual activity on the risk for cognitive decline. The onset of dementia may also be delayed by the treatment of hypertension. Table 30.1 lists both risk and protective factors for dementia.
Most cases of dementia can be diagnosed on the basis of a general medical and psychiatric evaluation. It is important for primary care physicians to be alert to the early symptoms, as dementia is often undetected until severe symptoms or an adverse event flags its presence. If a patient or family member expresses concerns about cognitive decline, a mental status assessment and probably a dementia evaluation are indicated. There are now consensus guidelines available for the clinical diagnosis and treatment of most types of dementia.
The informant interview and office-based clinical assessment are the most important diagnostic tools for dementia. Both the patient and a reliable informant should be interviewed to determine the patient’s current condition, medical and medication history, patterns of alcohol use, and living arrangements. Useful informant-based instruments, such as the Functional Activities Questionnaire, can help determine whether lapses in memory or language use have occurred and assess the patient’s ability to learn and retain new information, handle complex tasks, and demonstrate sound judgment. Any changes are best determined by comparing present with previous performance, since functional decline and multiple cognitive deficits confirm the diagnosis.
A comprehensive physical examination includes a brief neurologic and mental status evaluation. Brief quantified screening tests of cognitive function, such as the Folstein Mini-Mental State Examination or the Mini–Cog Assessment Instrument for Dementia, may be useful, particularly if they demonstrate change over a 6-month or 1-year follow-up period. A laboratory evaluation, generally including a complete blood cell count, blood chemistries, liver function test, rapid plasma reagent test, and thyrotropin stimulating hormone and vitamin B12 levels, is also recommended. In addition, the history or physical examination may indicate the need for other laboratory tests. It is important to conduct cognitive and functional assessments in the patient’s native language, if at all possible. In the face of cognitive decline, it is common for dementia patients to retain the greatest fluency in their language of origin.
Although brain imaging studies are optional, specialists may recommend them. They may be considered if:
In general, a noncontrast computed tomography head scan is adequate to exclude intracranial bleeding, space-occupying lesions, and hydrocephalus. If vascular dementia is suspected, magnetic resonance imaging (MRI) is often performed, but white matter changes revealed by T2 weighted MRI images generally are not related to dementia and should not be overinterpreted. In cases of unclear diagnosis, a repeat assessment in 6 months will confirm the presence or absence of progressive cognitive decline. Functional brain imaging studies such as positron emission tomography often show the characteristic parietal and temporal deficits in AD or the widespread irregular deficits in vascular dementia and may be useful when the diagnosis is uncertain after routine testing.
Cognitive tests are influenced by educational level. Affected patients with more years of education may have normal scores while patients with less education may have low scores and no decline in function. In addition, it has been shown that tests that are most sensitive to language performance may have cultural differences that lead to an overinterpretation of dementia in minority patients. Poor performance on cognitive tests may result in an increased rate of dementia diagnoses among patients in ethnic minority groups, even though the actual rate of dementia determined in systematic cross-cultural studies does not appear to be different across populations. One way to improve the accuracy of assessment is to evaluate changes in everyday memory function by evaluating a person’s performance of daily living skills, either by direct observation or obtaining information from reliable family members.
The practical utility of cognitive measures is that they provide a quantitative baseline against which to compare future assessments. Neuropsychologic testing is helpful in distinguishing normal aging from dementia, as well as identifying deficits that point to a specific diagnosis, and it is recommended when the diagnosis is unclear. In general, the diagnosis of dementia is a clinical one, and laboratory assessment is used to identify uncommon treatable causes and common treatable comorbid conditions.
Dementia can be defined as an acquired syndrome of decline in memory and other cognitive functions sufficient to affect daily life in an alert patient. Diagnosis then requires further investigation to identify the cause of the dementia by determining chronology of symptoms along with the pattern and extent of deficits. A general discussion of the most common dementias is provided below, and an overview of diagnostic features is provided in Table 30.2.
Cognition in aging is now understood to be a continuum ranging from mild changes in normal aging to the significant impairments that define dementia. Although studies are not conclusive, it appears that normal aging involves some mild decline in memory, usually requiring more effort and time to recall new information. However, this decline does not impair functioning and is usually well compensated with lists, calendars, and other memory supports.
With early identification of cognitive deficits, a disorder now referred to as mild cognitive impairment has been identified. These patients do not have dementia but do have significant impairment in memory without deficits in other cognitive domains and no overt functional impairment. Some research suggests that these individuals convert to AD at a rate of about 12% per year. There is disagreement among experts if this is a unique disorder or merely an early prodrome to AD that has been identified with earlier diagnosis of memory impairments. Studies are under way to determine what if any interventions may be beneficial in this condition.
AD is characterized by gradual onset and progressive decline in cognitive functioning; motor and sensory functions are spared until late stages. Memory impairment is a core symptom of any dementia, and in AD it is present in the earliest stages. Typically, AD patients demonstrate difficulty learning new information and retaining it for more than a few minutes. In later disease stages their ability to learn shows even greater compromise, and patients are unable to access older, more distant memories. Aphasia, apraxia, disorientation, visuospatial dysfunction, and impaired judgment and executive functioning are also present. The initial stages of AD are characterized by normal motor, sensory, and cerebellar functioning. If focal motor or sensory signs, except fluent aphasia and apraxia, are present, a diagnosis of vascular dementia or mixed vascular dementia with AD is likely.
Vascular dementia refers to cognitive deficits most often associated with vascular damage in the brain. Cognitive and neurologic impairments should correlate anatomically with the areas of ischemia, although the often diffuse nature of vascular disease may make this correlation difficult to identify. A history of “small strokes,” unless accompanied by a clear demonstration of focal signs of motor or sensory impairment, may not necessarily constitute vascular dementia. Cerebrovascular disease, however, does appear to contribute to the severity of cognitive symptoms in AD.
In recent years dementia with Lewy bodies has received increased attention. For a diagnosis of dementia with Lewy bodies, both dementia and at least one of the following must be present: detailed visual hallucinations, parkinsonian signs, and alterations of alertness or attention. The diagnosis may overlap with AD and the dementia associated with Parkinson’s disease. Poor visuospatial abilities are also often out of proportion to other cognitive deficits. The chronology of symptoms and pattern of cognitive deficits allow differentiation between dementia with Lewy bodies and AD or the dementia associated with Parkinson’s disease. Parkinsonian signs, particularly a “pill rolling” tremor that develops prior to cognitive impairment, generally indicate Parkinson’s disease rather than AD. When parkinsonian rigidity and bradykinesia are present during the onset of dementia, a diagnosis of dementia with Lewy bodies should be considered.
Frontotemporal dementia is a disease often seen in patients with younger onset of cognitive symptoms; these patients present most often with executive and language dysfunction and significant behavioral changes. These include disinhibition and hyperorality, and they often have had a profound effect on the patient’s social functioning. Memory deficits are often not as pronounced in these patients in the early stages as they are in patients with other dementias. The language impairments in frontotemporal dementia may be detected in neuropsychologic tests such as the Boston Naming Test and may progress even early in the course of illness in excess of other cognitive impairments. It is important to recognize the difference between frontotemporal dementia and AD with “frontal” symptoms. The latter refers to social disinhibition and behavioral impulsivity that may occur with AD. In these patients the behavioral problems occur much later in the course of illness, after a memory problem is already clearly evident. In contrast, the patient with frontotemporal dementia will display social disinhibition prior to prominent memory decline.
Common to all types of dementia, cognitive impairment eventually has a profound effect on the patient’s daily life. Difficulties in planning meals, managing finances or medications, using a telephone, and driving without getting lost are not uncommon. Such functional impairments may first alert others that a problem is emerging. Numerous functions are maintained in patients with dementia of mild to moderate severity, including such activities of daily living as eating, bathing, and grooming. Many patients remain socially appropriate during the early disease stages.
Behavior and mood changes are common, including personality alterations, irritability, anxiety, or depression. During the middle and late stages of the disease, delusions, hallucinations, aggression, and wandering may develop. These behaviors are extremely troubling to caregivers and often result in family distress and nursing-home placement. Although the course of dementia is variable, the progression of dementia often follows a sequential clinical and functional pattern of decline (see Table 30.3).
Dementia recognition may be complicated by the presence of either delirium or depression. Delirium has been defined as an acquired impairment of attention, alertness, and perception. Delirium and dementia are in some ways similar: both are characterized by global cognitive impairment. Delirium can be distinguished by an acute onset, cognitive fluctuations throughout the course of a day, impaired consciousness and attention, and altered sleep cycles. In hospitalized patients, delirium and dementia often occur together. The presence of dementia increases the risk for delirium and accounts in part for the high rate of delirium in elderly patients. A delirium episode in an older person, therefore, should alert the clinician to search for dementia once the delirium clears. (See also Delirium.)
Symptoms of depression and dementia often overlap, presenting additional diagnostic challenges. Patients with primary dementia commonly experience symptoms of depression, and such patients may minimize cognitive losses. By contrast, patients with primary depression may demonstrate decreased motivation during the cognitive examination and express cognitive complaints that exceed objectively measured deficits. Patients with primary depression, moreover, usually have intact language and motor skills, whereas patients with primary dementia may show impairment in these domains. As many as half of elderly patients who present with reversible dementia and depression become progressively demented within 5 years. (See also Depression and Other Mood Disorders.)
The primary treatment goals for patients with dementia are to enhance quality of life and maximize functional performance by improving cognition, mood, and behavior. Both pharmacologic and nonpharmacologic treatments are available, and the latter should be emphasized. Patients with dementia often develop significant behavioral symptoms that are a challenge to both family and professional caregivers. Any acute change requires an evaluation for undiagnosed medical problems, pain, depression, anxiety, sleep loss, or delirium. Other factors that may contribute to behavioral symptoms include interpersonal or emotional issues. Addressing such issues, treating underlying medical conditions, providing reassurance, and attending to the possible need for changes in the patient’s environment may reduce agitation. (See Behavioral Problems in Dementia.) The use of pharmacologic treatments for behavioral problems is recommended only after nonpharmacologic ones prove ineffective, or there is an emergent need for them (eg, risk of danger, extreme patient distress).
Reality orientation and memory retraining have been proposed as possible psychotherapeutic techniques to restore cognitive impairment. Although memory retraining may provide modest, transient benefit, it can also cause frustration for both patients and caregivers. Given that new learning is a skill lost very early in the course of AD, an overemphasis on quizzing or retraining may lead to anxiety and self-depreciation. In general, a preferred approach is to provide support to accommodate lost skills.
Emotion-oriented psychotherapy, such as “pleasant events” and “reminiscence” therapy, and stimulation-oriented treatment, including art and other expressive recreational or social therapies, exercise, and dance, are examples of psychosocial treatments that may influence depressive symptoms. Patient support groups may be helpful, but only when patients are mildly impaired. Well-controlled trials have not demonstrated efficacy for these approaches, but preliminary studies and clinical experience suggest their usefulness for some behavioral and mood symptoms in patients and family members.
One approach to ensuring optimal health care for patients with dementia is to schedule regular patient surveillance and health maintenance visits every 3 to 6 months. During such visits the physician should address and treat comorbid conditions, evaluate ongoing medications, and consider initiating drug-free periods. In addition, it is useful to check for sleep and behavioral disturbances and provide guidance on proper sleep hygiene. Caregiver well-being should also be regularly assessed.
Working closely with family members and caregivers will help establish a therapeutic alliance. Education of family and caregivers about diagnosis, clinical course, treatment options, and management strategies is critical. Information about community resources as well as strategies for managing challenging behavioral symptoms can allow families to cope more effectively. Relatives are often helpful sources of information about cognitive and behavioral changes, and generally they take the primary responsibility for implementing and monitoring treatment. Often they are responsible for medical and legal assistance as well. However, early identification of dementia can allow the affected individual to participate in treatment decision and future planning. Subjects to pursue with family include medical and legal advance directives (also called advance care plans in some contexts). It is often best for a trusted relative to cosign important financial transactions and attend to paying bills. (See Legal and Ethical Issues.)
Discussion about long-term-care placement options should be initiated early rather than late, to provide the individual or family members time to complete the arrangements and begin to adjust emotionally. Eventually, almost 75% of patients with dementia need admission to a long-term-care facility and remain for a long time. Caregivers often express concern about their own memory lapses, which should be addressed with counseling or neuropsychologic assessment. Caregiver distress is often reduced with support-group participation, which may relieve common feelings of anger, frustration, and guilt. Respite care is another community resource that offers caregivers relief. Psychosocial support may enhance quality of life for patients and family and even delay nursing-home placement. (See the resources section in the Appendix.)
Patients with dementia can be extremely sensitive to their environment; in general, a moderate level of stimulation is best. When they experience overstimulation, increased confusion or agitation may result, whereas too little stimulation may cause withdrawal. Familiar surroundings will maximize existing cognitive functions, and predictability through daily routines is often reassuring. Other helpful orientation and memory measures include conspicuous displays of clocks, calendars, and to-do lists. Links to the outside world through newspapers, radios, and televisions may benefit some mildly impaired patients. Simple sentence structure and repeated reminders about conversation content also may enhance communication.
Door locks or electronic guards prevent wandering, and many families benefit from registering with Safe Return through the Alzheimer’s Association. (See the resources section in the Appendix.) Patient name tags and medical-alert bracelets will assist in locating lost patients.
Cognitive impairment affects driving skills, and the visuospatial and planning disabilities of many even mildly demented patients may make them unsafe drivers. Discussions about driving are best initiated early in treatment. In California and some other states, physicians must report patients with dementia to the health department, which forwards the information to the motor vehicle department for further assessment. Patients with advanced dementia definitely should not drive, but clinicians disagree about driving by mildly demented patients. Referral for an independent driving assessment is recommended if there is any concern regarding safety. Certainly, when a patient has a history of traffic accidents or significant spatial and executive dysfunction, driving abilities should be carefully scrutinized. (See also the section on the elderly driver in Assessment.)
When prescribing medications for older patients with dementia, the clinician should consider several factors. Patients in the upper age groups vary in their response, so that treatments need to be individualized. In addition, age is associated with decreased renal clearance and slowed hepatic metabolism. Older patients often take several medications simultaneously, so drug interactions and side effects are likely. Drugs with anticholinergic effects present a particular problem for patients with dementia because they may worsen cognitive impairment and lead to delirium. Another group of problem drugs that may worsen cognition include those causing central nervous system sedation. The best strategy, in light of such factors, is to start with low doses and increase dosing gradually (“start low and go slow”). The goal is to identify the lowest effective dose, thus minimizing side effects, and still avoid subtherapeutic dosing. Before initiating any treatment, conduct a thorough medical examination to identify and treat any underlying medical conditions that might impair cognition.
The primary treatments available for stabilizing cognitive function in AD are cholinesterase inhibitors. Currently, four cholinesterase inhibitors approved by the U.S. Food and Drug Administration (FDA) are available: tacrine (rarely prescribed because of its side effects), donepezil, rivastigmine, and galantamine. By slowing the breakdown of the neurotransmitter acetylcholine, these medications are thought to facilitate memory function because of the association of acetylcholine and memory. Clinical trials show that these drugs may modestly improve cognition and activities of daily living in patients with AD of mild to moderate severity. Studies of patients with dementing disorders other than AD are also becoming available. Data indicate that cholinesterase inhibitors may be helpful in managing the hallucinations associated with dementia with Lewy bodies, and preliminary data indicates a potential role in vascular dementia as well. There appears to be no role for cholinesterase inhibitors in treating frontotemporal dementia.
Donepezil is the most widely prescribed cholinesterase inhibitor. The recommended starting dosage is 5 mg per day; after 4 to 6 weeks of treatment, an increase to 10 mg daily is recommended. For patients experiencing gastrointestinal side effects such as nausea and diarrhea, a slower titration may reduce side effects. Rivastigmine is started at 1.5 mg by mouth twice daily for 2 weeks and then doubled no faster than every 2 weeks, to a maximum of 6 mg twice daily. Galantamine is prescribed in initial doses of 4 mg by mouth twice daily for at least 4 weeks, then 8 mg twice daily for at least 4 weeks, and then increased to a maximum of 12 mg twice daily. An extended-release formulation is also now available that permits the option of once-daily dosing. Although the higher doses are more efficacious for all agents, they are more likely to cause such cholinergic effects as nausea, diarrhea, and insomnia, especially if the dose is increased too rapidly. Such adverse effects also may worsen the patient’s behavior. Other cholinesterase inhibitors and cholinergic receptor antagonists are currently under development. Direct comparisons among them have not been conducted.
Memantine, an N-methyl-d-aspartate antagonist, has been used in Europe for many years. This drug is thought to have neuroprotective effects by reducing glutamate-mediated excitotoxicity. Recently completed clinical trials in the United States support the efficacy of this medication in moderate to severe stages of AD. Memantine now has FDA approval for the treatment of moderate to severe AD. The recommended dosing for memantine in the management of Alzheimer’s type dementia involves 5 mg by mouth once daily, which may then be increased on a weekly basis in 5-mg increments to 10 mg per day, dosed as 5 mg by mouth twice daily, then up to 15 mg per day dosed as 5 mg by mouth in the morning then 10 mg by mouth in the evening, and finally arriving at a target dose of 20 mg per day dosed as 10 mg twice daily after a 4-week titration period. The most common side effects noted with memantine are constipation, dizziness, and headache. Memantine has been used safely in conjunction with cholinesterase inhibitors, and one study in 2004 has suggested additional benefits, but this area awaits further research.
Ongoing studies are assessing a variety of other agents in AD, including antioxidants and Ginkgo biloba extract. In a trial including over 300 patients with moderately severe AD, treatment with vitamin E (α-tocopherol) or the selective monoamine oxidase-B inhibitor selegiline (approved for Parkinson’s disease treatment) was found to lower rates of functional decline. The use of these agents, however, was not associated with evidence of cognitive improvement, but this study involved patients with moderate to severe dementia, so effects on cognition earlier in the illness remain unknown. Results from a randomized placebo-controlled trial of the use of vitamin E and donepezil in mild cognitive impairment showed some short-term benefit from donepezil in delaying conversion to AD but no effect of vitamin E. High-dose vitamin E supplementation was associated with increased mortality in a meta-analysis and should be prescribed with caution.
Extract from the leaf of the ginkgo tree has been promoted primarily in Europe for peripheral vascular disease as well as “cerebral insufficiency.” Other studies in Europe and the United States have explored its use in AD. One 52-week double-blind, placebo-controlled study of ginkgo leaf extract in treating AD seemed to show small but statistically significant improvement in some cognitive measures. However, global measures did not improve in the small, limited study. Uncommonly, G. biloba has been linked to an increase of bleeding. More research is needed before ginkgo can be recommended.
Many patients also use over-the-counter preparations for cognitive enhancement. A complete review of medications includes questions about over-the-counter medications being used.
Antidepressant drug treatment is generally considered for AD patients with depressive symptoms, including depressed mood, appetite loss, insomnia, fatigue, irritability, and agitation. (See Depression and Other Mood Disorders.) Anecdotal evidence exists that selective serotonin-reuptake inhibitors may be helpful in managing the disinhibitions and compulsive behaviors associated with frontotemporal dementia.
Behavioral symptoms of dementia—paranoia, agitation, and irritability—are best managed by nonpharmacologic strategies, such as reducing overstimulation. However, when medications are required, identify the target symptoms and select therapy accordingly. Cholinesterase inhibitors have been demonstrated to have modest effects on controlling behavioral symptoms. Antipsychotics can be used to manage delusions, hallucinations, and paranoia as well as some of the irritability associated with dementia. The antipsychotics have been associated with extrapyramidal (eg, rigidity, tremor) symptoms in dementia with Lewy bodies, and only very small doses of atypical antipsychotic medications should be considered for treating these patients. However, the FDA recently issued a “black box” warning that atypical antipsychotics have been associated with an increase in mortality among elderly patients with dementia who are being treated for behavioral disorders. This warning arose from an analysis of placebo-controlled trials performed with olanzapine, aripiprazole, risperidone, or quetiapine in elderly dementia patients with behavioral disorders. These trials showed a 1.6- to 1.7-fold increase in mortality in the drug-treated groups over that in the placebo-treated patients. Specific causes of death revealed that most were due either to heart-related events (eg, heart failure, sudden death) or infections (mostly pneumonia). More information is available at: http://www.fda.gov/cder/drug/infopage/antipsychotics/default.htm. Data on the use of drugs such as carbamazapine and valproic acid in managing irritability and agitation suggest that they may be included as options for drug therapy. Avoid the use of benzodiazepines and medications with anticholinergic effects. Finally, antidepressants with sedating effects such as mirtazapine and trazodone can be considered in the management of insomnia.
Most primary care physicians successfully treat and manage most patients with dementia, but referral to a specialist is sometimes necessary. When the presentation or history is atypical or complex, particularly when the onset begins before age 60, consultation with a specialist in treating dementia patients (eg, geriatric psychiatrist, neurologist) can be useful. Geriatric specialists with psychology or psychiatry training can assist with behavioral management, particularly when patients are agitated, psychotic, or violent. They are also helpful when patients are suicidal or suffer from major depression or when individual or family therapy is indicated for patients or caregivers.
A neurologist can be helpful for patients with parkinsonism, focal neurologic signs, unusually rapid progression, or abnormal neuroimaging findings. Neuropsychologic consultation may clarify diagnostically complex cases, and clinical psychologists can provide psychotherapy, especially for caregivers. Social workers may provide counseling and contact with community resources. Guidance on physical and group activity can be sought from physical therapists, and occupational therapists can assess the patient’s functional level and suggest approaches to maximize functioning. Nurses can make management suggestions and guide behavior management, feeding, and other care issues. Wills, conservatorships, estate planning, and other legal matters are best addressed with the assistance of an attorney. Because most dementias are progressive, patients with early dementia should be offered an opportunity to plan for future incapacity and illness. (See Legal and Ethical Issues.)
Community support can be informal, when neighbors or friends help out, or formal, such as home-care or family service agencies, the aging or mental health networks, or adult day care centers. Available specialized services include adult day care and respite care, home-health agencies that can provide skilled nursing, help lines of the Alzheimer’s Association, and outreach services offered by Area Agencies on Aging and Councils on Aging, which are mandated and funded under the federal Older Americans Act. Food services for the homebound are available from meals-on-wheels, and many senior citizens’ centers, church and community groups, and hospitals offer transportation options.
Organizations providing information and referral for dementia patients and families are listed in the resources section of the Appendix.
■ Borson S, Scanlan J, Brush M, et al. The mini-cog: a cognitive 'vital signs' measure for dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry. 2000;15(11):1021–1027.
The Mini-Cog is a 3-minute instrument to screen for cognitive impairment in older adults in the primary care setting. It consists of a three-item recall task to assess memory as well as a clock-drawing task to help clarify when the memory score is equivocal. The Mini-Cog was designed as a brief test for distinguishing dementia in a community sample of older adults. The Mini-Cog has been shown to be an effective and useful screening test for dementia particularly for the busy clinical practice, as it may be conducted more expediently than the Mini–Mental State Examination and can detect a variety of different dementias.
■ Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1154–66.
This is a review of studies to make literature-based treatment recommendations about pharmacotherapy for cognitive and noncognitive symptoms of dementia, education interventions for patients and caregivers, and other nonpharmacologic interventions. Cholinesterase inhibitors may benefit patients with Alzheimer’s disease, and vitamin E may delay time to clinical worsening; however, further study is needed of antioxidants, selegiline, and nonsteroidal anti-inflammatory drugs. Educational programs should be offered and may improve caregiver satisfaction and delay nursing-home placement. Nonpharmacologic therapies such as scheduled toileting and behavior modification are also recommended.
■ Geldmacher DS, ed. Dementia update: overview from the first annual dementia congress. J Am Geriatr Soc. 2003;51(5 Suppl):S281–S326.
This overview provides information on the pathophysiology and current approaches to the management of Alzheimer’s disease and other dementias. It includes review articles about early diagnosis of Alzheimer’s disease, current pharmacotherapy for Alzheimer’s disease, diagnosis and management of vascular dementia, medical management of advanced dementia, and an update on new developments in treating Alzheimer’s disease.
■ Knopman DS, Dekosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1143–1153.
This is a review of studies to determine criteria for the diagnosis of dementia and appropriate work-up. Results were an update to the 1994 practice guidelines developed by the American Academy of Neurology. Diagnostic criteria for Alzheimer’s disease and Creutzfeldt-Jakob disease were found to be reliable and valid, whereas those for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use, though their reliability and validity are not well established.
■ Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal assessment of neurocognitive function after coronary artery bypass surgery. N Engl J Med. 2001:344(6):395–402.
This article describes changes in neurocognitive function among 261 patients undergoing coronary artery bypass graft surgery. A detailed neurocognitive battery was administered prior to surgery, at the time of hospital discharge, 6 weeks, 6 months, and 5 years after discharge. Decline was defined as a one–standard deviation drop (approximately 20%) in the scores of tests in any one or more of four cognitive domains. Delirium itself was not assessed. Among the patients studied, the incidence of cognitive decline was 53% at discharge, 36% at 6 weeks, 24% at 6 months, and 42% at 5 years. Cognitive dysfunction at discharge was a significant predictor of long-term dysfunction (P < .001). This article brings attention to the magnitude of cognitive dysfunction after cardiac surgery and raises provocative questions as to the nature of the “late decline” following surgery.
■ Peterson RC, Stevens JC, Ganguli M, et al. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1133–1142.
This is a review of epidemiologic studies of aging and dementia to determine whether screening elderly persons in a general or specialty practice would be beneficial in detecting dementia. There were sufficient data to recommend the evaluation and clinical monitoring of persons with mild cognitive impairment. Screening instruments, neuropsychologic batteries, brief focused cognitive instruments, and structured interview were found to be useful.
■ Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA. 2005;293(5):596–607.
This article describes a systematic review of 29 articles published between 1966 and 2004 describing randomized controlled trials or meta-analyses of any drug therapy for patients with dementia that included neuropsychiatric outcomes. Results indicated that pharmacologic therapies were not very effective for managing neuropsychiatric symptoms of dementia. Of agents reviewed, atypical antipsychotics had the best evidence for efficacy; however, effects were modest and complicated by increased risk of stroke.
■ Trinh NH, Hoblyn J, Mohanty S, et al. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer’s disease: a meta-analysis. JAMA. 2003;289(2):210–216.
This is a review of trials of cholinesterase inhibitors published between 1966 and 2002 for effects on neuropsychiatric and functional outcomes in patients with mild to moderate Alzheimer’s disease. Results indicated that cholinesterase inhibitors have a modest beneficial impact on neuropsychiatric and functional outcomes for patients with Alzheimer’s.
Cynthia Barton, RN, MSN
Gary W. Small, MD
Kristine Yaffe, MD