A 69-year-old female with no complaints presents to your office with her two daughters. Further history from her daughters reveals that the patient was widowed 4 years ago, now lives alone, and has experienced memory loss over the last 2 years. One daughter has taken over the patient's checkbook and is responsible for paying the bills. She has noticed that her mother often wears the same clothes and bathes infrequently—new and unfortunate habits for her. The past medical history includes hypothyroidism and hypertension. Family history is significant for depression and memory problems in the patient's mother prior to her death from "old age." The patient takes chlorthalidone, levothyroxine, and acetaminophen as needed.
Physical examination reveals a thin, elderly female in no distress. She is alert but does not correctly identify the year. She describes her mood as "happy" most of the time. The remainder of the examination is unremarkable. You suspect dementia.
Question 21.5.1 Which of the following is true regarding the diagnosis of dementia?
A) The diagnosis is rarely missed in the primary-care setting
B) To diagnose dementia, impairment in executive function must be present
C) To diagnose dementia, impairment in memory must be present
D) Alzheimer disease (AD) is a diagnosis of exclusion
E) Neuroimaging is essential in the diagnosis of dementia
Answer 21.5.1 The correct answer is "C." One of the necessary components in order to make a diagnosis of dementia is memory impairment. "A" is incorrect. In contrast to delirium and depression, the onset of dementia is insidious. Symptoms often go unrecognized for months to years prior to diagnosis. Although the patient may complain of confusion or memory loss, family members are more likely to provide the chief complaint and history. During the initial phases of a dementing illness, patients and family members may attribute cognitive changes to normal aging. In early cognitive impairment, memory symptoms may wax and wane. However, symptoms of dementia can be differentiated from occasional normal lapses based on their increasing severity. For example, it is normal to forget an acquaintance's name, but clearly abnormal to forget a spouse's name. "B" is incorrect. Many patients with dementia have impaired executive functioning (e.g., judgment, reasoning, and planning), but the presence of impaired executive functioning is not a requirement. "D" is incorrect, as AD is diagnosed by a specific set of clinical criteria. DSM-V provides diagnostic criteria for dementia and AD, making AD a diagnosis of inclusion rather than exclusion. "E" is incorrect. Dementia is a clinical diagnosis and does not require neuroimaging for confirmation. Experts and professional medical associations differ in their recommendations regarding the use of neuroimaging in dementia. In general, neuroimaging is recommended if dementia occurs in the following scenarios: onset before age 65, sudden onset, presence of focal neurologic signs, and suspicion of normal pressure hydrocephalus (NPH), which includes urinary incontinence, gait disturbance, and cognitive impairment.
You use several office assessment tools to further characterize the memory loss. She scores 23/30 on the Folstein Mini-Mental State Exam, missing orientation and recall items. Clock drawing is grossly abnormal. Her geriatric depression scale is 3 positive responses out of 15 (positive screen is 5/15 or greater). She performs all basic activities of daily living (ADLs) independently, but has voluntarily given up driving and control of her finances.
Question 21.5.2 Regarding assessment tools used in the evaluation of memory loss, which of the following statements is most accurate?
A) The Mini-Mental State Exam (MMSE) evaluates executive function and visual-spatial skills
B) Formal neuropsychological testing offers no benefit over the MMSE for detecting dementia
C) The use of a screening tool for depression is not helpful in the evaluation of memory loss
D) Clock drawing evaluates executive function and visual-spatial skills
E) The MoCA evaluates the ability to discern a chocolate coffee beverage from regular coffee
Answer 21.5.2 The correct answer is "D." Clock drawing can be used to evaluate executive function as well as visual-spatial skills. Clock drawing is a simple test that takes 1 minute or less to perform. The patient is asked to draw a clock face and set the hands to 2:50 or 11:10. This test requires planning and visual-spatial ability on the part of the patient—two areas that are incompletely evaluated by the MMSE. A normal clock does not rule out dementia, but an abnormal clock is suggestive of cognitive impairment. There are several scoring systems, and the sensitivity and specificity for dementia are as high as 87% and 82%, respectively.
"A" and "B" are incorrect. The MMSE is a 30-point scale, with the cutoff for dementia between 24 and 26. The MMSE can be performed in a few minutes and tests memory, orientation, language, construction, and concentration. The MMSE does not test prosody (expressive and receptive inflection of vocalization) or executive function and, as a result, has poor sensitivity for early cognitive impairment in some individuals. Performance on the MMSE is strongly correlated with education; therefore, there may be false-positives in undereducated patients and false-negatives in highly educated individuals. Compared with the MMSE, formal neuropsychological testing assesses a broader array of cognitive functions, and it identifies behavioral abnormalities and assesses mood disorders. It can also help to differentiate between types of dementia. In general, neuropsychological testing is the most sensitive and specific cognitive assessment tool, but it is time-consuming and requires a high level of expertise to administer and interpret.
"C" is incorrect because depression may cause memory problems, especially in the elderly, and depression screening should be included in the workup of memory concerns. Depression often coexists with dementia, and treatment of depression may improve memory problems. It is also important to keep in mind that depression commonly is the first presenting sign for memory problems. "E" is incorrect. See the related Helpful Tip for more on the MoCA.
The Montreal Cognitive Assessment (MoCA) is a cognitive assessment tool freely available online, published in multiple languages, and validated in the diagnosis of dementia. Like the MMSE, it is a 30-point scale, but the MoCA tests a wider range of cognitive domains with less emphasis on orientation. Compared to the MMSE, the MoCA has greater sensitivity for detecting dementia but takes a few minutes longer to administer.
So far, you have collected the following information on this patient: MMSE score 23/30, impairment in driving and managing finances, disorientation to time, but intact abilities to cook, clean, and care for herself.
Question 21.5.3 Using conventional staging for AD, how would you categorize this patient's dementia?
E) Insufficient information to determine the stage
Answer 21.5.3 The correct answer is "A."
Mild AD symptoms include impaired memory, mild personality changes, and mild disorientation (MMSE 19–24)
Moderate AD symptoms include aphasia, apraxia, insomnia, and increasing confusion (MMSE 10–19)
Severe AD symptoms include severe memory loss, motor impairment, and loss of some basic ADLs (e.g., urinary incontinence and feeding difficulties) (MMSE <10)
Symptoms of terminal AD include immobility, dysphagia, and increasing susceptibility to infections
Question 21.5.4 Which of the following findings would most likely cause you to search for a diagnosis other than AD in a patient presenting with memory impairment?
D) Aphasia and personality changes
E) Bradykinesia and rigidity
Answer 21.5.4 The correct answer is "E." Bradykinesia and rigidity are features of parkinsonism, which, in the setting of memory loss, should prompt consideration of Lewy body dementia or Parkinson disease. Paranoid behavior, delusions, and hallucinations can all occur with more severe AD. Aphasia, apraxia, and personality changes typically occur later in AD but can be initial complaints in atypical presentations of AD. In order to diagnose dementia, impairment in memory must be present along with at least one of the following:
Aphasia (language disturbance)
Apraxia (impaired motor abilities despite intact motor function)
Agnosia (impaired ability to identify objects despite intact sensation)
Disturbance in executive function (e.g., planning, judgment, and insight)
The diagnostic criteria for dementia require that these cognitive disturbances result in functional impairments that represent a significant change from a previous level of functioning.
Although you strongly suspect AD in this patient, you consider other types of dementia as well. Suppose this patient presented with urinary incontinence and ataxia in addition to her current findings.
Question 21.5.5 Which of the following diagnoses would be most likely?
A) Creutzfeldt–Jakob disease
C) Normal pressure hydrocephalus (NPH)
E) Walking corpse syndrome
Answer 21.5.5 The correct answer is "C." NPH classically presents with dementia, gait ataxia, and urinary incontinence. When detected early, it responds to ventriculoperitoneal shunting and is thus a reversible cause of dementia. However, the dementia is rarely fully reversible. Gait abnormalities typically occur first and are the most likely to improve with removal of cerebrospinal fluid (CSF). The diagnosis of NPH is supported by findings on brain MRI, and it is confirmed by symptom improvement after CSF removal. Incidentally, NPH is a misnomer since intermittent CSF pressure elevations have a pathophysiologic role in the disease. "E" is a real thing, but not the right answer. Walking corpse syndrome is a rare psychiatric illness in which the patient is under the delusion that he is dead. Keep reading to learn why the other foils are wrong.
You've got this patient stuck in your head (perhaps with superglue?). On morning rounds in the hospital, your colleague asks your opinion on a patient with frontotemporal dementia (FTD).
Question 21.5.6 You think it is unlikely that your patient has FTD because she does not have:
D) Rapidly progressing dementia
E) Tremors and hallucinations
Answer 21.5.6 The correct answer is "B." FTDs (including Pick disease) constitute a heterogeneous group of neurodegenerative disorders that have the common pathologic finding of cortical degeneration in frontal areas of the brain. Typical features of these dementias include an insidious onset and a slowly progressive course. Patients have impairments in judgment and insight. They are disinhibited and socially inappropriate. Patients may present with anxiety, depression, delusions, or emotional indifference. "A" is incorrect. Depression frequently coexists with many types of dementia but does not define one particular type. "C" is incorrect; the presence of hemiplegia in a patient with dementia should bring to mind vascular causes. "D" is incorrect because rapidly progressing dementia is the hallmark of prion disease, such as Creutzfeldt–Jakob disease. "E" is incorrect as tremors, hallucinations, and memory loss are consistent with Lewy body dementia (named for its characteristic pathological finding—the presence of Lewy bodies in the brain stem and cortex). Clinical features consist of cognitive impairment, detailed visual hallucinations, fluctuation in alertness, and motor symptoms of parkinsonism.
AD is the most common form of dementia, encompassing about 60% of patients with dementia. Vascular and Lewy body dementias account for about 15% to 30%. In many cases, dementia has more than a single cause. AD and vascular dementias frequently coexist—an entity commonly referred to as "mixed dementia."
The elevator is stuck on your way back from making your rounds, giving you more time to consider dementia.
Question 21.5.7 Which of the following is NOT consistent with the diagnosis of vascular dementia?
C) Diffuse slowing or normal electroencephalogram (EEG)
E) History of carotid endarterectomy
Answer 21.5.7 The correct answer is "D." A normal MRI essentially rules out vascular dementia. Features suggestive of vascular dementia include a stepwise deterioration in cognitive function, onset of cognitive impairment with stroke, infarcts and white matter changes on neuroimaging, and focal neurologic findings on examination. There are no well-defined criteria for clinically diagnosing vascular dementia, and available rating scales have poor predictive value when compared with autopsy as the diagnostic standard. Known vascular disease (like carotid artery disease) and vascular risk factors, such as diabetes, hypertension, and smoking, support the diagnosis.
Finally back in your office with coffee in hand, you decide to evaluate for reversible causes for this patient's dementia, and you consider ordering laboratory tests.
Question 21.5.8 Which of the following laboratory tests is NOT indicated in the initial evaluation for reversible causes of dementia?
A) Cyanocobalamin (vitamin B12)
E) Thyroid function tests
Answer 21.5.8 The correct answer is "D." When evaluating a newly diagnosed case of dementia, one must consider infectious, metabolic, toxic, and inflammatory etiologies. Therefore, the minimal required laboratory tests should include CBC, serum glucose and electrolytes, vitamin B12, and renal, liver, and thyroid function tests. Further laboratory tests should be obtained as clinical suspicion indicates. In the appropriate patient, one might obtain urinalysis, urine toxicology screen, HIV antibody assay, and CSF analysis. Because of the extremely low incidence of neurosyphilis in modern times, routine testing for syphilis is no longer required but should be considered in the appropriate setting. Neuroimaging is not a required part of every workup but may be helpful in some patients. See Table 21-3.
TABLE 21-3LABORATORY EVALUATION OF DEMENTIA ||Download (.pdf) TABLE 21-3 LABORATORY EVALUATION OF DEMENTIA
Required Minimum Testing
Testing Based on Clinical Suspicion
Blood chemistries, blood counts, thyroid hormone levels, vitamin B12 level, and liver enzymes are in the normal range. A noncontrast CT scan of the brain shows nonspecific "age-related" changes (that was helpful!). The patient and her family return to discuss the test results. You begin to educate them about AD and dementia in general. The two daughters are concerned that other family members may be at risk for developing AD.
Question 21.5.9 Which of the following is the strongest risk factor for developing AD?
B) Apolipoprotein E 4 (APOE 4) allele
Answer 21.5.9 The correct answer is "A." As with many diseases, age is the greatest risk factor for developing AD. Among persons 65 to 69 years old, the incidence of AD is 1%. In persons 85 years and older, the incidence rises to 8%. All of the other answer options are associated with an increased risk of AD but not to the same degree as age.
Family history is another factor strongly associated with developing AD. By age 90, almost half of persons with first-degree relatives with AD develop the disease. There are genetic risk factors as well. Mutations on chromosomes 1, 14, and 21 are known risk factors for AD. Trisomy 21 is a risk factor for developing AD at an earlier age (often by age 50). APOE 4 allele increases risk and decreases age-of-onset of AD in a dose-related fashion, with the greatest risk present in persons homozygous for APOE 4.
Other potential risk factors include a history of head trauma, lower educational achievement, female gender, and depression. Postmenopausal estrogens may actually increase the risk of dementia. Hypertension, diabetes, and hyperlipidemia are associated with dementia, and controlling these diseases might reduce the risk of developing dementia in the future, but the evidence is not strong. Increased physical, mental, and social activities may reduce cognitive decline in later years.
Question 21.5.10 The patient and family ask about medications to treat AD. Which of the following statements is TRUE?
A) All studies show that vitamin E supplementation improves cognition and prevents further neuron loss in AD.
B) Ginkgo biloba and cholinesterase inhibitors have a synergistic effect, improving cognition in AD.
C) Cholinesterase inhibitors do not prevent neuron loss in AD.
D) Cholinesterase inhibitors maintain cognition at baseline levels for 2 years after initiation of therapy; after that time, patients decline slowly.
E) Memantine is considered first-line therapy for mild cognitive impairment and early dementia.
Answer 21.5.10 The correct answer is "C." Cholinesterase inhibitors do not prevent neuron loss. Results with vitamin E have been inconsistent, and some studies have found a slightly higher risk of death in those on high-dose vitamin E (400 IU/day), primarily in those with coronary artery disease. Given the low cost and potential benefits of vitamin E, it may still be reasonable to use in combination with a cholinesterase inhibitor in AD at a dose of <400 IU/day if the patient or family is so inclined. There is no evidence to support the use of ginkgo biloba in AD. As of 2015, there are just two classes of drugs FDA approved for AD. Cholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine, and tacrine) represent the larger class of available pharmacotherapy used to treat mild-to-moderate AD. Studies suggest that cognitive decline may stabilize for 3 to 6 months after which there is steady loss of cognition. By 9 to 12 months, there is no difference in decline between those on therapy and those on placebo. The other class has only one medication, memantine, which is an N-methyl D-aspartate (NMDA) antagonist used to treat moderate-to-severe AD. NMDA antagonists and cholinesterase inhibitors are often prescribed in combination; however, there seems to be no benefit to combining these drugs. Memantine appears to do nothing for mild dementia and has shown very minimal (some might say clinically insignificant) difference in moderate-to-severe dementia.
All of the cholinesterase inhibitors have similar efficacy. Tacrine is known to cause hepatotoxicity and is rarely used. The choice of cholinesterase inhibitor depends on cost, patient acceptance, and physician experience.
Using your favorite clinical decision aid, the Ouija board, you decide to start the patient on a cholinesterase inhibitor.
Question 21.5.11 In your discussion about the medication, you tell the patient and her family:
A) "These drugs are indicated for treating all types of dementia"
B) "These drugs offer no benefit in moderate Alzheimer dementia"
C) "These drugs are proven to reverse memory loss"
D) "These drugs are proven to reduce mortality"
E) "Gastrointestinal intolerance is one of the most common side effects of these drugs"
Answer 21.5.11 The correct answer is "E." There is no shortage of controversy when it comes to medications for dementia. However, the side effects are indisputable. Gastrointestinal intolerance—with nausea, anorexia, and diarrhea—is the most common. Also, cholinesterase inhibitors have a "vagotonic" action, which can cause bradycardia and syncope and worsen cardiac conduction abnormalities. To minimize adverse events, the dose of cholinesterase inhibitor should be increased only after the patient has been on a stable dose for 4 to 6 weeks.
There are statistical differences in the outcomes measured for AD patients on cholinesterase inhibitors, but are these changes clinically significant? There is no difference in performance of ADLs, time to nursing home placement, etc. "A" is incorrect. Mostly, these drugs are used in AD. Their use in Lewy body and vascular dementia is off-label but may be worth a try; there is some data to support cholinesterase inhibitors for these patients. However, there is no evidence to support their use in FTDs (e.g., Pick disease). "B" is not true. Most studies of cognitive effects of cholinesterase inhibitors have occurred in mild-to-moderate AD (MMSE 10–24). "C" and "D" are incorrect. Compared with placebo, cholinesterase inhibitors delay further cognitive and functional decline but neither reverse dementia nor affect mortality. In cholinesterase inhibitor studies of mild-to-moderate dementia, there is typically a 3-point difference on the MMSE between treatment and placebo groups at 6 months. This finding is due to a loss of thinking abilities in the placebo group and a delay in that loss in the treatment group.
Not every confused elderly person should be put on a cholinesterase inhibitor. Consider the diagnosis, severity of disease, and the goals for the patient and family. Determine why you are starting the drug and be clear on the goals you hope to achieve. Then be willing to discontinue it if your patient is not reaching those goals. The side effects of cholinesterase inhibitors are symptoms often seen in nursing home patients (e.g., falls due to bradycardia and weight loss from anorexia). If your patient is losing weight and/or falling, consider discontinuing the cholinesterase inhibitor.
One year later, the patient returns with her daughter, with whom she now lives. The daughter reports disturbing symptoms that occur nightly. The patient wakes up in the middle of the night and wanders the house, becoming confused and agitated. With a subtle nod toward her mother, the daughter states, "I just can't take much more of this."
Question 21.5.12 After inquiring about pain and any changes in health status and finding none, your initial recommendation is to:
A) Employ soft restraints only during the night
B) Consider environmental changes including more daytime structured activities through an adult day care center
C) Initiate an antipsychotic before bedtime
D) Initiate a sedative–hypnotic before bedtime
Answer 21.5.12 The correct answer is "B." Treating behavioral issues in patients with AD can be very challenging. Further history must explore the possibility of pain-related agitation, decline in comorbid conditions or new health conditions, such as occult infection, and any medication changes that may be playing a role. If a treatable cause is not identified, then environmental change is the best initial recommendation. Adding structured daytime activities may facilitate a better sleep–wake cycle. Adult day care programs exist that specialize in day care for elderly people including patients with dementia. Adult day care can provide structured activities during the day, along with respite for the daughter who is obviously asking for extra support. Although medications are sometimes needed, "C" and "D" are incorrect for initial treatment in this case. Once environmental changes have failed or there are other immediate health risks involved, then medications may be necessary. Antipsychotics currently offer the only drug treatment for behavioral symptoms in dementia; however, there are no great choices. Haloperidol, risperidone, and olanzapine are used most often. See Table 21-4 for selected medications used to treat behavioral symptoms in dementia. Sedatives, such as benzodiazepines, often result in paradoxical agitation in elderly patients with dementia. "A" is incorrect. Restraints should be avoided in most cases, even soft restraints. Although they are sometimes required to prevent harm to the patient or caretakers, restraints are known to result in worsened agitation and an increased risk of fall, injury, and rhabdomyolysis.
TABLE 21-4MEDICATION MANAGEMENT FOR BEHAVIORAL SYMPTOMS OF DEMENTIA ||Download (.pdf) TABLE 21-4 MEDICATION MANAGEMENT FOR BEHAVIORAL SYMPTOMS OF DEMENTIA
|Behavioral Subtype ||Acute Management ||Long-Term Management |
|Psychosis ||Conventional high potency Antipsychotic (CHAP)a ||Risperidone, CHAP |
|Anxiety ||Benzodiazepines ||Buspirone |
|Insomnia ||Trazodone ||Trazodone |
|Sundowning ||Trazodone; consider CHAP, risperidone, olanzapine ||Trazodone; consider CHAP, risperidone, olanzapine |
|Aggression, severe ||CHAP, risperidone ||Divalproex, risperidone, CHAP |
|Aggression, mild ||Trazodone ||Divalproex, SSRIs, trazodone, buspirone |
When patients with Lewy body dementia receive antipsychotic medication for hallucinations, parkinsonian features become much more pronounced. If possible, avoid antipsychotics in these patients.
Despite the addition of adult day programming, medication became necessary. Haloperidol, or "vitamin H," nightly has resolved the agitation. Although you may have increased your patient's risk of dying (as seems to occur when antipsychotics are used in dementia), her daughter is thrilled with the result. Three months later she returns with concerns about depression. The patient spontaneously cries several times per day, her appetite is poor, and she has no desire to leave the house or even get dressed most days.
Question 21.5.13 Since a pill worked last time, her daughter wants to know what antidepressant is most effective for depression in patients with dementia?
Answer 21.5.13 The correct answer is "D." There are very few quality studies available to guide treatment of depression in patients with dementia. The available evidence shows no difference between antidepressant therapy and placebo. The diagnosis of depression in a patient with dementia is complicated, since dementia causes apathy, sleep disturbance, appetite loss, and social withdrawal. If depression is suspected in a patient with dementia, a prudent approach would be to employ nonpharmacologic therapy and then provide an empiric trial of an antidepressant.
Over time, as the patient's dementia progresses, you reevaluate end-of-life issues and advance directives. With the support of her family, the patient decides not to have cardiopulmonary resuscitation.
Question 21.5.14 In end-stage AD, which of the following is correct?
A) Malnutrition is the most common cause of death in patients with severe dementia
B) Hospitalization for pneumonia in patients with severe dementia improves morbidity and mortality
C) In severe dementia, gastrostomy tube feeding prevents aspiration
D) To increase comfort, dehydrated patients with severe dementia should receive IV hydration
E) In advanced AD, treatment of infections with oral and IV antibiotics is equally efficacious
Answer 21.5.14 The correct answer is "E." Hospitalization for demented patients with pneumonia is a wash. The number of patients saved by the use of IV antibiotics is offset by an increase in death and functional deterioration as a result of the hospitalization. Thus, on balance, oral and IV antibiotics are equally efficacious in the treatment of infections in these patients; therefore, severely homebound patients with dementia or nursing home residents should be treated in their usual environment rather than hospitalized if the family agrees. "A" is incorrect. The majority of patients with dementia die of infection, not malnutrition. "B" is incorrect as noted above. "C" is incorrect. Even in moderate-to-severe AD, feeding tubes can be useful in the acute setting. But the tube should be removed and natural feeding resumed as soon as the acute event passes. Permanent gastrostomy tube feeding is not recommended in patients with severe or terminal dementia. Tube feeding does not prolong life, prevent aspiration, or promote weight gain in advanced dementia. Although many patients with advanced dementia are malnourished and dehydrated, these conditions do not appear to cause discomfort. Hand feeding is as effective as any other means for providing nutrition and can lead to rewarding interactions for both the patient and the caregiver.
Remember the caregivers! Ask about their health and mood. Twenty-five percent of caregivers to the elderly are depressed, while older people caring for their disabled spouses have a 63% higher chance of dying than noncaregivers of the same age.
Objectives: Did you learn to…
Identify symptoms, signs, and diagnostic criteria for dementia?
Describe different types of dementia and how they are diagnosed?
Evaluate the patient with dementia, considering the potential causes of dementia?
Describe potential benefits and limitations of current pharmacologic therapy for AD?
Describe the natural course of AD?
Manage a patient with end-stage AD?