ESSENTIALS OF DIAGNOSIS
Progressive decline of intellectual function.
Acquired deficits in one or more cognitive domains severe enough to cause impairment of function.
Not due to delirium or another mental disorder.
Dementia is an acquired, persistent, and progressive impairment in intellectual function, with compromise of one or more cognitive domains. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition, identifies these domains (with example deficits) as: (1) complex attention (easily distracted, difficulty performing calculations), (2) executive function (poor abstraction, mental flexibility, planning, and judgment), (3) learning and memory (difficulty recalling items from a list, forgetting recent events), (4) language (word finding and object naming difficulty), (5) perceptual-motor function (difficulty navigating in known environments, copying a drawing), and (6) social cognition (change in personality, trouble reading social cues). The diagnosis of dementia requires a significant decline in function that is severe enough to result in the loss of independence in IADLs.
While dementia prevalence doubles every 5 years in the older population, reaching 30–50% at age 85, the prevalence among US adults 65 years or older has been declining. This improvement has been attributed to higher education levels and better control of cardiovascular risk factors. Women suffer disproportionately, both as patients and as caregivers. Alzheimer disease accounts for roughly two-thirds of dementia cases in the United States, with vascular dementia (either alone or combined with Alzheimer disease) and dementia with Lewy bodies accounting for much of the rest. Some risk factors for Alzheimer disease are older age, hyperlipidemia, hypertension, family history, lower education level, and female sex. Education, physical exercise, heart healthy diets, and social connectivity may be protective. Risk factors for vascular dementia are those for stroke, ie, older age, hypertension, cigarette use, atrial fibrillation, diabetes mellitus, and hyperlipidemia.
Depression and delirium are also common in elders, may coexist with dementia, and may also present with cognitive impairment. Depression is a common concomitant of early dementia. A patient with depression and cognitive impairment whose intellectual function improves with treatment of the mood disorder has an almost fivefold greater risk of suffering irreversible dementia later in life. Delirium, characterized by acute confusion, occurs much more commonly in patients with underlying dementia.
According to the US Preventive Services Task Force (USPSTF), there is insufficient evidence to recommend for or against screening all older adults for cognitive impairment. While there is logic in the argument that early detection may improve future planning and patient outcomes, empiric evidence that demonstrates a clear benefit for either patients or caregivers is lacking. It is important to note, however, that the Medicare Annual Wellness Visit mandates that clinicians assess patients for cognitive impairment based on the clinician’s observations and reports from others.
At-home genetic testing for a susceptibility gene that is associated with late-onset Alzheimer disease (APOE-e4) has US Food and Drug Administration approval. While the presence of the APOE-e4 allele increases the risk of developing Alzheimer disease, quantifying such risk for an individual is difficult. Because it is possible to have one or two copies of the APOE-e4 allele and not develop Alzheimer disease or to have no copies and yet still become stricken, genetic testing is not widely recommended and, if considered, should not proceed without genetic counseling.
When there is suspicion of cognitive impairment, several cognitive tests have been validated for clinical use. The mini-cog is a combination of a three-item word recall with a clock drawing task, and it can be completed in 3 minutes. The clinician asks the patient to repeat three items followed by instructions to draw the face of a clock, or pre-draws a four-inch circle on a sheet of paper and instructs the patient to “draw a clock” with the time set at 10 minutes after 11. If the patient recalls all three items after 3 minutes, the test is considered normal, and there is no need to score the clock. Conversely, if the patient recalls zero items, the test is considered abnormal, and there is no need to score the clock. When the patient recalls one or two items, the test is normal when the clock is drawn correctly (numbers in the proper position and the time accurately portrayed). When a patient fails this simple test, further cognitive evaluation with a standardized instrument is warranted. The Montreal Cognitive Assessment (MoCA©) is a 30-point test that takes about 10 minutes to administer and examines several areas of cognitive function. A score below 26 has a sensitivity of 0.94 or more and a specificity of 0.60 or less. Accuracy of results is improved when the instructions are followed as precisely as possible. Free downloadable versions in multiple languages are available at http://www.mocatest.org. Completion of a training and certification program is required to gain access to the test.
2. Decision-making capacity
Older adults with cognitive impairment commonly face serious medical decisions, and the clinicians involved in their care must ascertain whether the capacity exists to make medical decisions. While no single test of capacity exists, the following five elements should be considered in a thorough assessment: (1) ability to express a choice; (2) understanding relevant information about the risks and benefits of planned therapy and the alternatives (including no treatment), in the context of one’s values; (3) comprehension of the problem and its consequences; (4) ability to reason; and (5) consistency of choice. A patient’s choice should follow from an understanding of the consequences.
Sensitivity must be used in applying these five components to people of various cultural backgrounds. Decision-making capacity varies over time; a delirious patient may regain his capacity after an infection is treated, and so reassessments are often appropriate. Furthermore, the capacity to make a decision is a function of the decision in question. A woman with mild dementia may lack the capacity to consent to coronary artery bypass grafting yet retain the capacity to designate a surrogate decision maker.
The clinician can gather important information about the type of dementia by asking about (1) the rate of progression of the deficits as well as their nature (including any personality or behavioral change); (2) the presence of other neurologic and psychiatric symptoms, particularly motor problems and psychotic symptoms; (3) risk factors for HIV; (4) family history of dementia; and (5) medications, with particular attention to recent changes.
Workup is directed at identifying any potentially reversible causes of dementia. However, such cases are rare. For a detailed description of the symptoms and signs of different forms of dementia, see Chapter 24.
Alzheimer disease typically presents with early problems in memory and visuospatial abilities (eg, becoming lost in familiar surroundings, inability to copy a geometric design on paper), yet social graces may be retained despite advanced cognitive decline. Personality changes and behavioral difficulties (wandering, inappropriate sexual behavior, and aggression) may develop as the disease progresses. Hallucinations, delusions, and symptoms of depression often occur as the dementia worsens. End-stage disease is characterized by near-mutism; inability to sit up, hold up the head, or track objects with the eyes; difficulty with eating and swallowing; weight loss; bowel or bladder incontinence; and recurrent respiratory or urinary infections.
Vascular dementias are characterized by psychomotor slowing, deficits in complex attention, early loss of executive function, and personality changes. The onset of symptoms is often related to a cerebrovascular event and the progression may be step-wise or gradual.
Dementia with Lewy bodies may be confused with delirium, as fluctuating cognitive impairment is frequently observed. Rigidity and bradykinesia are the primary signs, and tremor is rare. Response to dopaminergic agonist therapy is poor. Complex visual hallucinations—typically of people or animals—may be an early feature that can help distinguish dementia with Lewy bodies from Alzheimer disease. These patients demonstrate a hypersensitivity to neuroleptic therapy, and attempts to treat the hallucinations may lead to marked worsening of extrapyramidal symptoms.
Frontotemporal dementias are a group of diseases that include Pick disease, dementia associated with amyotrophic lateral sclerosis, and others. Patients manifest personality change (euphoria, disinhibition, apathy) and compulsive behaviors (often peculiar eating habits or hyperorality). In contrast to Alzheimer disease, visuospatial function and memory are relatively preserved.
Dementia in association with motor findings, such as extrapyramidal features or ataxia, may represent a less common disorder (eg, progressive supranuclear palsy, corticobasal ganglionic degeneration, olivopontocerebellar atrophy).
The neurologic examination emphasizes assessment of mental status but should also include evaluation for sensory deficits, previous strokes, parkinsonism, or peripheral neuropathy. The remainder of the physical examination should focus on identifying comorbid conditions that may aggravate the individual’s disability. For a detailed description of the neuropsychological assessment, see Chapter 24.
Laboratory studies should include a complete blood count and serum electrolytes, calcium, creatinine, glucose, thyroid-stimulating hormone (TSH), and vitamin B12 levels. While hypothyroidism or vitamin B12 deficiency may contribute to the cognitive impairment, treating these conditions typically does not completely reverse the dementia. HIV and rapid plasma reagin (RPR) tests, a heavy metal screen, and liver biochemical tests may be informative in selected patients but are not part of routine testing. For a detailed description of laboratory findings, see Chapter 24.
Most patients should receive neuroimaging as part of the workup to rule out subdural hematoma, tumor, previous stroke, and hydrocephalus (usually normal pressure). Those who are younger; those who have focal neurologic symptoms or signs, seizures, or gait abnormalities; and those with an acute or subacute onset are most likely to have positive findings and most likely to benefit from MRI scanning. In older patients with a more classic picture of Alzheimer disease for whom neuroimaging is desired, a noncontrast CT scan is sufficient. For a detailed description of imaging, see Chapter 24.
Older individuals experience occasional difficulty retrieving items from memory (usually word-finding difficulty) and experience a slowing in their rate of information processing. In the amnestic type of mild cognitive impairment, a patient complains of memory problems, demonstrates mild deficits (most commonly in short-term memory) on formal testing, but the impairment does not significantly impact function. Annual dementia conversion rates vary from less than 5% to 20%. No medications have been demonstrated to delay the progression of mild cognitive impairment to Alzheimer disease. An elderly patient with intact cognition but with severe impairments in vision or hearing commonly becomes confused in an unfamiliar medical setting and consequently may be falsely labeled as demented. Cognitive testing is best performed after optimal correction of the sensory deficits.
Delirium can be distinguished from dementia by its acute onset, fluctuating course, and deficits in attention rather than memory. Because delirium and dementia often coexist, it may not be possible to determine how much impairment is attributable to each condition until the patient has resolved the delirium and is back in his or her usual setting. Many medications have been associated with delirium and other types of cognitive impairment in older patients. Anticholinergic agents, hypnotics, neuroleptics, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines (both H1- and H2-antagonists), and corticosteroids are just some of the medications that have been associated with cognitive impairment in elders.
Patients and families should be made aware of the Alzheimer’s Association (http://www.alz.org) as well as the wealth of helpful community and online resources and publications available. Caregiver support, education, and counseling may prevent or delay nursing home placement. Education should include the manifestations and natural history of dementia as well as the availability of local support services, such as respite care. Even under the best of circumstances, caregiver stress can be substantial. Collaborative care models and disease management programs appear to improve the quality of care for patients with dementia. Exercise should be a component of treatment as evidence suggests physical activity may have beneficial effects on cognition and physical function.
Because demented patients have greatly diminished cognitive reserve, they are at high risk for experiencing acute cognitive or functional decline in the setting of new medical illness. Consequently, fragile cognitive status may be best maintained by ensuring that comorbid diseases such as heart failure and infections are detected and treated.
1. Acetylcholinesterase inhibitors
Donepezil, galantamine, and rivastigmine are acetylcholinesterase inhibitors approved for the treatment of Alzheimer disease. These medications produce a modest improvement in cognitive function that is not likely to be detected in routine clinical encounters, and they have not convincingly been shown to delay functional decline or institutionalization. Compared to patients with Alzheimer disease, acetylcholinesterase inhibitors may have similarly modest cognitive benefits in patients with vascular dementia or dementia with Lewy bodies. There is insufficient evidence to recommend their use in mild cognitive impairment to slow the progression toward dementia or to improve cognitive test scores.
Starting (and maximum) doses are donepezil, 5 mg orally once daily (maximum 10 mg once daily); galantamine, 4 mg orally twice daily (maximum 12 mg twice daily); and rivastigmine, 1.5 mg orally twice daily (maximum 6 mg twice daily). Dosages are increased gradually as tolerated. Donepezil is also available in a 23-mg tablet, but this higher dose is associated with greater frequency of side effects without appreciable increase in benefit. The most bothersome side effects of acetylcholinesterase inhibitors include diarrhea, nausea, anorexia, weight loss, and syncope. As dementia progresses, some patients with moderate to severe cognitive impairment may continue to experience subjective benefits from acetylcholinesterase inhibitors, but the medication should be discontinued in those patients who have had no apparent benefit, who experience side effects, or for whom the financial outlay is a burden. While there are no published guidelines that describe what constitutes an adequate treatment trial, evaluation after 2 months at the highest tolerated dose is reasonable.
In clinical trials, patients with more advanced disease have been shown to have statistical benefit from the use of memantine (5 mg orally daily to 10 mg twice daily), an N-methyl-D-aspartate (NMDA) antagonist. Long-term and meaningful functional outcomes have yet to be demonstrated, and evidence suggests there is no clinically meaningful benefit to giving memantine in combination with an acetylcholinesterase inhibitor.
1. Nonpharmacologic approaches
Behavioral problems in patients with dementia are often best managed nonpharmacologically. Initially, it should be established that the problem is not unrecognized delirium, pain, urinary obstruction, or fecal impaction. Determining whether the caregiver or institutional staff can tolerate the behavior is also helpful, since it is often easier to find ways to accommodate the behavior than to modify it. If not, the caregiver should keep a brief log in which the behavior is described along with antecedent events and consequences. This may uncover patterns that delineate precipitants of the behavior or perhaps that the behavior is being rewarded. Caregivers are taught to use simple language when communicating with the patient, to break down activities into simple component tasks, and to use a “distract, not confront” approach when the patient seems disturbed by a troublesome issue. Additional steps to address behavioral problems include providing structure and routine, discontinuing all medications except those considered absolutely necessary, and correcting, if possible, sensory deficits.
2. Pharmacologic approaches
There is no clear consensus about pharmacologic approaches to the treatment of behavioral problems in patients who have not benefited from nonpharmacologic therapies. Pharmacologic treatment should be reserved for those patients who pose an imminent danger to others or themselves or when symptoms are substantially distressing to the patient.
Despite evidence of harm and recommendations against their use, antipsychotic medications have remained a mainstay for the treatment of behavioral disturbances, particularly agitation and aggression, largely because of the lack of alternatives. The atypical antipsychotic agents (eg, risperidone, olanzapine, quetiapine, aripiprazole) are increasingly becoming the first choice because of an overall better side-effect profile compared to typical agents (eg, haloperidol) but should be used with caution in patients with vascular risk factors due to an increased risk of stroke; they can also cause weight gain and are also associated with hyperglycemia in diabetic patients and are considerably more expensive. Both typical and atypical antipsychotics increase mortality compared with placebo when used to treat elderly patients with dementia and behavioral disturbances. When the choice is made to use these agents, patients and caregivers should be carefully warned of the risks. Starting and target dosages should be much lower than those used in schizophrenia (eg, haloperidol, 0.5–2 mg orally; risperidone, 0.25–2 mg orally). Federal regulations require that if antipsychotic agents are used in treatment of a nursing home patient, medication reduction efforts must be made at least every 6 months. However, relapses of problem behaviors are common after discontinuation of antipsychotics.
Citalopram at a dose of 30 mg daily may improve symptoms of agitation; however, according to the US Food and Drug Administration, the maximum recommended dose is 20 mg daily (a dose not specifically evaluated in the study) for patients older than 60 years because of the risk of QT prolongation and associated dysrhythmia. In addition, while no serious cardiac events were observed, QT prolongation did occur, as did a small but measurable decline in cognitive function. Thus, while citalopram may be used to treat agitation, safe and effective dosing for patients older than age 60 has not been established. In the specific instance of patients with dementia with Lewy bodies, treatment with acetylcholinesterase inhibitors has been shown to improve behavioral symptoms. Valproate medications have been used in the treatment of agitated and physically aggressive behavior, but evidence demonstrates no identifiable benefit.
A common yet vexing problem that providers are regularly asked to assess is whether a patient with dementia can continue driving. The consequences of a decision to either stop or continue driving can be far-reaching for the patient, family, and the general public, and therefore, every case requires careful consideration. Although drivers with dementia are at an increased risk for motor vehicle accidents, many patients continue to drive safely well beyond the time of initial diagnosis, making the timing of when to recommend that a patient stop driving particularly challenging.
There is no clear-cut evidence to suggest a single best approach to determining an individual patient’s capability, and there is no accepted “gold-standard” test. The result is that clinicians must consider several factors upon which to base their judgment. For example, determining the severity of dementia can be useful. Patients with very mild or mild dementia according to the Clinical Dementia Rating Scale were able to pass formal road tests at rates of 88% and 69%, respectively. Experts agree that patients with moderately severe or more advanced dementia should be counseled to stop driving. Although not well studied, clinicians should also consider the effects of comorbid conditions and medications and the role each may play in contributing to the risk of driving by a patient with dementia. Assessment of the ability to carry out IADLs may also assist in the determination of risk. Caregivers of patients with at least a 30% decline in their IADL score were more likely to rate them as unable to drive safely compared to other, less impaired patients. Finally, in some cases of mild dementia, referral may be needed to a driver rehabilitation specialist for evaluation. Although not standardized, this evaluation often consists of both off- and on-road testing. The cost for this assessment can be substantial, and it is typically not covered by health insurance. Experts recommend such an evaluation for patients with mild dementia, for those with dementia for whom new impairment in driving skills is observed, and for those with significant deficits in cognitive domains, such as attention, executive function, and visuospatial skills. At present, there is no convincing evidence to support the use of interventions to improve driving skills and driver safety.
Clinicians must also be aware of the reporting requirements in their individual jurisdictions. Some states have mandatory reporting laws for clinicians, but in other states, the decision to report an unsafe driver with dementia is voluntary. When a clinician has made the decision to report an unsafe driver to the Department of Motor Vehicles, he or she must consider the impact of a potential breach in confidentiality and must weigh and address, in advance when possible, the consequences of the loss of driving independence.
D. Advance Financial Planning
Difficulty in managing financial affairs often develops early in the course of dementia. The patient’s caregiver may seek advice from the patient’s primary care clinician. Although expertise is not expected, clinicians should have some proficiency to address financial concerns. Just as clinicians counsel patients and families about advance care planning, the same should be done to educate about the need for advance financial planning and to recommend that patients complete a durable power of attorney for finance matters (DPOAF) when the capacity to do so still exists. In most states, the DPOAF can be executed with or without the aid of an attorney. Other options to assist in managing and monitoring finances include online banking, automatic bill payments, direct deposits, and joint bank accounts. A potential risk of the joint account is that the joint account holder has no obligation to act in the best interest of the patient.
No gold-standard test is available to identify when a patient with dementia no longer has financial capacity. However, the clinician should be on the lookout for signs that a patient is either at risk for or actually experiencing financial incapacity. Because financial impairment can occur when dementia is mild, making that diagnosis should alone be enough to warrant further investigation. Questioning patients and caregivers about late, missed, or repeated bill payments, unusual or uncharacteristic purchases or gifts, overdrawn bank accounts, or reports of missing funds can provide evidence of suspected financial impairment. Patients with dementia are also at increased risk for becoming victims of financial abuse, and some answers to these same questions might also be signs of potential exploitation. When financial abuse is suspected, clinicians should be aware of the reporting requirements in their local jurisdictions. Social workers can aid with this reporting.
Life expectancy after a diagnosis of Alzheimer disease is typically 3–15 years; it may be shorter than previously reported. Other neurodegenerative dementias, such as dementia with Lewy bodies, show more rapid decline. Hospice care is often appropriate for patients with end-stage dementia. For patients with Alzheimer disease, the Centers for Medicare and Medicaid Services has published guidelines to determine hospice eligibility. To be considered in the terminal stage of dementia, patients should demonstrate all the following characteristics: (1) Stage 7 or beyond according to the Functional Assessment Staging Scale (FAST); (2–4) unable to ambulate, dress, and bathe without assistance; (5) urinary and fecal incontinence, intermittent or constant; and (6) no consistently meaningful verbal communication (stereotypical phrases only or the ability to speak is limited to six or fewer intelligible words). In addition, during the prior 12 months the patient should have had one of the following: (1) aspiration pneumonia; (2) pyelonephritis or other upper urinary tract infection; (3) septicemia; (4) pressure injuries, multiple, stage 3–4; (5) fever, recurrent after antibiotics; or (6) inability to maintain sufficient fluid and calorie intake with 10% weight loss during the previous 6 months or serum albumin less than 2.5 g/dL.
Referral for neuropsychological testing may be helpful to distinguish dementia from depression, to diagnose dementia in persons of very poor education or very high premorbid intellect, and to aid diagnosis when impairment is mild.
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