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REFERENCES
Hoffenberg EJ, Furuta GT, Kobak G, Walker T, Soden J, Kramer RE, Brumbaugh D. Gastrointestinal
Tract. In: Hay, Jr. WW, Levin MJ, Deterding RR, Abzug MJ. eds. Current Diagnosis & Treatment:
Pediatrics, 24e New York, NY: McGraw Hill. http://accessmedicine.mhmedical.com/content.aspx?
bookid=2390§ionid=189079593. Accessed May 19, 2020.
Maclin J. Acute abdominal pain. In: Rudolph C, Rudolph A, eds. Rudolph’s Pediatrics. New York, NY:
McGraw Hill; 2018: Chap. 378.
Reust CE, William A. Acute abdominal pain in children. Am Fam Physician. 2016;93(10):830-837.
CASE 32
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An 83-year-old woman is brought to the clinic by her husband, who is concerned
with his wife’s memory problems. He noticed some memory decline a few years
ago, but the onset was subtle and did not interfere with her day-to-day activities.
The patient’s husband reports that she has some difficulty remembering
details. She often repeats herself and seems forgetful. The patient’s family
reports these problems have gradually gotten worse over the past year. She is
unable to remember her appointments and relies heavily on written notes and
appointments books. Recently, she got lost while driving and was found by her
family 10 hours later. She was unable to use her cell phone and was unsure about
her home address and phone number. She has also become more reclusive. She
does not enjoy her church activities anymore and prefers to stay at home most
of the time. She does not want to cook and is less attentive to her housework.
She is insistent that she is not having any issues with her memory. Her medical
history is significant for well-controlled hypertension and a history of mastectomy
secondary to breast cancer diagnosed 20 years ago. She has no significant history
of tobacco or alcohol use. She is independent with all activities of daily living but
needs assistance with medication administration, banking, and transportation.
She is up to date with her health maintenance and immunizations. Her vital signs
and general physical examination are normal.
▶ What is the most likely diagnosis?
▶ What office testing can help to determine a diagnosis?
▶ What laboratory testing and imaging studies are indicated at this time?
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ANSWERS TO CASE 32:
Dementia
Summary: An 83-year-old woman presents with
Her family noting that she is having increasing memory difficulties at home
Forgetfulness, repeating questions, and not remembering conversations
A very significant episode of getting lost in her hometown
Being seemingly unaware that there is a problem that is slowly and progressively
worsening
Normal vital signs and general examination
Most likely diagnosis: Dementia of Alzheimer type.
Office-based testing: Folstein Mini-Mental State Examination (MMSE) is the
most widely used instrument. Others available include the clock test, the Short
Portable Mental Status Questionnaire, the Mini-Cog Test, and the Montreal Cognitive Assessment (MoCA). In addition, a screening test for depression should be
performed.
Laboratory testing and imaging studies: Blood count, electrolytes, glucose, calcium,
liver function tests, folate, vitamin B12, and thyroid-stimulating hormone (TSH).
Consider HIV, syphilis, and Lyme disease screening if there is a risk factor or evidence of prior infection or if the patient lives in an area of high incidence. Noncontrast magnetic resonance imaging (MRI) (preferred by expert opinion) or
noncontrast computed tomography (CT) of the head can be used.
ANALYSIS
Objectives
1. Develop a differential diagnosis for dementia. (EPA 1, 2)
2. Describe how to appropriately evaluate a complaint of memory loss. (EPA 1, 3)
3. List treatments for Alzheimer dementia, the most common specific diagnosis
of dementia. (EPA 4)
Considerations
This 83-year-old woman is noted by her family to have a progressive decrease
in cognitive function. She is forgetful and gets lost easily, and her condition has
been slowly but steadily worsening. The most likely diagnosis is dementia; however, other conditions should be considered in the differential diagnosis, such as
medications, stroke, thyroid disorders, chronic syphilis, or other metabolic conditions. Depression can also present as dementia at times. The workup for this
patient includes a careful history and physical examination, imaging of the brain,
and selective laboratory tests such as TSH, vitamin B12 level, complete blood count
(CBC), and comprehensive metabolic panel. Screening for syphilis should also be
considered.
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APPROACH TO:
Dementia
DEFINITIONS
EXECUTIVE FUNCTIONS: High-level cognitive abilities that control other,
more basic, abilities. Executive functions include the ability to start and stop behaviors, alter behaviors to fit circumstances, and adapt behaviors to new situations.
CLINICAL APPROACH TO DEMENTIA
Pathophysiology
The essential features of the diagnosis of dementia are memory loss and impairment
of executive function. Dementia is a clinical diagnosis that can go unrecognized
until it is in an advanced stage. Patients rarely report memory loss; the informants
are usually their family members. However, relatives may fail to recognize signs and
symptoms of dementia because many have a tendency to think that memory loss
can be a part of normal aging. Studies of aging have showed that nonverbal creative
thinking and new problem-solving strategies may decline with age, but information, skills learned with experience, and memory retention remain intact.
Differential Diagnosis. Depression in the elderly can present with symptoms of
memory disturbance. This is known as “pseudodementia.” As depression is common
and treatable, a screening test for depression should be performed when dementia
is evaluated. Similarly, hypothyroidism and vitamin B12 deficiency are common and
treatable conditions that can cause cognitive problems. TSH and vitamin B12 levels
should be performed as a routine part of the workup. Neurosyphilis could present
in this fashion but is such an uncommon diagnosis that routine screening would
not be recommended. Evaluation for neurosyphilis would be warranted if there
were identified high-risk factors or history of the disease, or if the patient lived in
an area with a high prevalence of syphilis. Neuroimaging with either a noncontrast
CT scan or an MRI of the brain is recommended to rule out other confounding
diagnoses. Other testing, such as positron emission tomography, genetic testing,
and spinal fluid analysis, is not routinely recommended. Referral to neurology is
appropriate when a diagnosis is uncertain.
Clinical Presentation
Clinicians should assess cognitive function whenever cognitive impairment or
deterioration is suspected. These concerns may be based upon direct observation, patient report, or concerns raised by family members, friends, or caretakers.
Patients with dementia may have difficulty with one or more of the following:
Learning and retaining new information (rely on lists, calendars)
Handling complex tasks (banking, bills, payments)
Reasoning (adapting to unexpected situations, unfamiliar environments)
Spatial ability and orientation (getting lost driving or walking, wandering)
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Language (word finding, repetition, confabulation)
Behavior (agitation, confusion, paranoia)
Evaluation. The evaluation of a patient with suspected dementia should include
a mental status examination. The Folstein MMSE is one of the most widely used
tool in the screening for dementia. The sensitivity of the MMSE for dementia is as
high as 87%, and the specificity is as high as 82%. The interpretation of the score
depends on the patient’s education level. It is most accurate in those with at least a
high school education.
Another valuable test that can be used in a busy primary care setting is the clock
drawing test. The patient is asked to draw a clock with a specific time. The patient
must then accurately draw the clock face with the “big hand” and “small hand” in
the correct positions. It is quick, easy to administer, and evaluates executive function in multiple cognitive domains. Other brief cognitive screening tests, such as
the Short Portable Mental Status Questionnaire, modified MMSE, MoCA, and
Mini-Cog (three-item recall combined with clock drawing) can be used. In the outpatient setting, the Mini-Cog and the MoCA are widely used.
In the evaluation of dementia, it is necessary to obtain information from people
who know the patient well. Useful information can be obtained from informantbased functional tests, such as the functional activities questionnaire (FAQ), the
instrumental activities of daily living (IADL), and caregiver burden assessments.
This information can be important for providers and families in making plans for
long-term care. See Case 18 for more on functional assessment.
Vascular Dementia
Vascular dementia, or multi-infarct dementia, is the second most common cause
of dementia. In vascular dementia, there is neuronal loss as a consequence of one
or more strokes. The symptoms are related to the amount and location of the neuro-
nal loss. Vascular dementia can exist along with Alzheimer disease or other causes
of dementia, resulting in a mixed-dementia syndrome. Unlike Alzheimer disease,
which is a gradually progressive process, vascular dementia often has a sudden onset
and progresses in a stepwise fashion. Patients tend to function at a certain level and
then show an acute deterioration when the initial, or subsequent, infarcts occur.
The risk factors include those for cerebrovascular disease (hypertension, tobacco
use, diabetes, etc). There are no controlled trials showing medication effectiveness
in vascular dementia, so the treatment is aimed at reducing the risk of further neurologic damage.
Lewy Body Dementia
Lewy body dementia is the third most common form of dementia. This dementia presents early on with vivid hallucinations, fluctuation in cognition, and often
parkinsonian extrapyramidal signs and postural instability. Tremor is less apparent,
and levodopa is not very effective in these patients. Daytime drowsiness and sleeping, staring into space for prolonged periods of time, and episodes of disorganized
speech can further distinguish Lewy body dementia from Alzheimer disease.
Therapies are similar to those for Alzheimer disease.
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Frontotemporal Lobe Dementia
Frontotemporal lobe dementia is the fourth most common form of dementia, and
due to the behavior disturbances associated with this dementia, it can be very distressing for the patient’s family. In this form of dementia, a patient’s personalities
can significantly change, becoming antisocial or disinhibited from social norms
with poor impulse control. Patients can develop apathy; emotional blunting; perseveration behaviors, including echolalia; and stereotypical behaviors, such as toe
tapping and repetitive motor activity. There are few pharmacologic therapies with
significant evidence for efficacy. Counseling and support of the family can mitigate
the stress of caring for these patients.
Other Illnesses Associated With Dementia
Numerous other conditions may present with dementia or have dementia as a
prominent symptom. Parkinson disease commonly has an associated dementia,
especially as the overall disease advances. Huntington disease is an autosomal domi-
nant disorder that presents with progressive dementia, depression, and choreiform
movements. Dementia can be a complication of chronic alcohol abuse, reinforcing the need for a complete history of substance use. Potentially reversible forms
of dementia include normal-pressure hydrocephalus (presents with the triad of
dementia, gait disturbance, and urinary incontinence); chronic subdural hematoma;
repeated head trauma; and depression. Many prescription and over-the-counter
medications can cause memory disturbances. Chief among these are anticholin-
ergic medications, sedatives (benzodiazepines), sleeping pills, and narcotic pain
medications. Metabolic abnormalities, such as hyponatremia or abnormal calcium
levels, and infections, such as HIV, can present with signs and symptoms similar
to dementia.
Delirium
Delirium is an acute change in mental status that is characterized by fluctuations in
levels of consciousness. It is usually caused by an acute medical illness, the use of
a medication, or the withdrawal from a drug or alcohol. Delirium affects 10% to
30% of hospitalized patients, with a higher incidence in the elderly, in those with
an underlying dementia, and in those with multiple underlying medical conditions.
The treatment of delirium consists of addressing the condition that precipitatedit.
Delirium is often reversible if the underlying cause can be found and aggressively managed. Patients with delirium have significantly longer hospital stays and
increased mortality rates.
CLINICAL APPROACH TO ALZHEIMER DISEASE
Pathophysiology
Alzheimer disease is the most common cause of dementia. Although a definitive
diagnosis can only be made by the presence of senile plaques and neurofibrillary tangles detected on autopsy, clinical diagnostic criteria have been developed.
Common diagnostic criteria include the gradual onset and progression of cognitive dysfunction in more than one area of mental functioning that is not caused by
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another disorder. These areas of mental functioning include learning and memory, language, executive function, complex attention, perceptual-motor skills, and
social cognition.
Clinical Presentation
The initial evaluation includes a detailed history from both the patient and another
informant (usually a spouse, child, or other close contact) and complete physical
and neurologic examinations to evaluate for any focal neurologic deficit that may be
suggestive of a focal neurologic lesion. A validated test, such as the MMSE, should
be used to confirm the presence of dementia. The results of this test can also be used
to follow the clinical course, as a reduction in score over time is consistent with
worsening dementia.
A focused evaluation to rule out other causes of dementia must be performed
as well. The physical examination should focus upon neurologic deficits consistent
with prior strokes, signs of Parkinson disease (eg, cogwheel rigidity and/or tremors), gait abnormalities or slowing, and eye movements. Patients with Alzheimer
disease generally have no motor deficits at presentation.
Treatment
When the diagnosis of Alzheimer disease is made, a comprehensive care plan
should be initiated. The management of Alzheimer disease must be directed toward
both the patient and the patient’s family or caregivers. The goals of therapy are to
maximize cognition, delay functional decline, and prevent or improve behavioral
disturbances.
Table 32–1 lists the medications that are primarily used in the treatment of
Alzheimer disease. Family members should understand that the medications may
delay the progression of the disease but may not reverse any decline that has already
Table 32–1 • MEDICATIONS USED IN THE TREATMENT OF
ALZHEIMER DEMENTIA
Medications Indications Side Effects/Comments
Cholinesterase Inhibitors
Donepezil (Aricept) Mild-moderate
Galantamine (Razadyne) Mild-moderate
Rivastigmine (Exelon) Mild-moderate
N-Methyl-d-aspartate (NMDA) antagonist
Memantine (Namenda) Moderate-severe
Alzheimer dementia
Alzheimer dementia
Alzheimer dementia
Alzheimer dementia
Common: nausea, vomiting, diarrhea,
dizziness, headaches
Common: nausea, vomiting
Uncommon and severe: arrhythmias,
dementia bradycardia, urinary
obstruction
Common: nausea, vomiting, diarrhea,
weight loss, tremor, fatigue, falls
Side-effect profile comparable to
placebo; can be used in combination
with cholinesterase inhibitors
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occurred. For that reason, the medications may be more beneficial if started earlier
in the course of the disease.
Antipsychotic medications have also been used to control hallucinations and
agitation in patients with Alzheimer disease. However, this is an “off-label” use of
medication, and data show a higher death rate associated with the use of the newer
antipsychotics. The Food and Drug Administration has placed a black box warning against the use of typical and atypical antipsychotic medications for dementiarelated psychosis due to the increased risk of deaths. Herbal medications such as
gingko biloba and huperzine A have inconsistent evidence for efficacy, but appear
to be safe alternatives. These should not be used with prescription medications due
to potential interactions.
Behavioral interventions also may be beneficial. These can include scheduled toileting in an effort to reduce episodes of incontinence, writing reminder notes, keeping familiar objects around, providing adequate lighting, and making duplicates of
important objects (eg, keys) in case they are lost. Caregivers also need support and
may benefit from appropriate training, support groups, and periodic respite care.
Unfortunately, even with the best of care, Alzheimer disease is relentless and
progressive. Families may have significant difficulties and conflicts regarding issues
surrounding end-of-life care and placement in assisted living or nursing homes.
Resources such as local chapters of the Alzheimer Association (https://www.alz.org)
may provide valuable services, information, and support.
CASE CORRELATION
See Case 18 (Geriatric Health Maintenance and End-of-Life Issues).
COMPREHENSION QUESTIONS
32.1 A 63-year-old man is brought in by his family because of memory loss. They
have noted a worsening of his symptoms over several months. They also
report that he has had multiple falls, hitting his head on one occasion, and
has had frequent urinary incontinence. On examination, a gait apraxia (slow
shuffling steps) is noted. Which of the following is the most likely diagnosis?
A. Alzheimer disease
B. Normal pressure hydrocephalus
C. Dementia with Lewy bodies
D. Delirium
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32.2 An 82-year-old woman is admitted to the hospital for altered mental status.
Her family says that she has been confused, falling asleep frequently, and
hallucinating—talking to people who are not in the room. Her family reports
that prior to this illness, the patient was independent and “sharp as a tack.”
On urine analysis, she is found to have a urinary tract infection. Which of the
following is the most appropriate treatment?
A. Start rivastigmine (Exelon) for worsening of Alzheimer dementia.
B. Start an alerting agent such as modafinil (Provigil) for symptomatic
treatment of her hypersomnia.
C. Start an antibiotic for treatment of her infection and optimize manage-
ment of any other medical conditions.
D. Give her a dose of ziprasidone (Geodon) for her hallucinations.
32.3 A 77-year-old man is brought to your office by his wife, who states that
he has been having mental difficulties in recent months, such as not being
able to balance their checkbook or organize the paperwork for his annual
visit with the accountant. She also tells you that he has reported seeing
animals in the room with him and that he can describe them vividly. He
takes frequent naps and stares blankly for long periods of time. He seems
almost normal at times, but then he randomly appears very confused at
other times. He has also been dreaming a lot and has fallen down more than
once recently. He currently takes aspirin, 81 mg/d. On examination, the
patient walks slowly with a stooped posture and almost falls when turning
around. He has only minimal facial expressiveness. No tremor is noted, and
the remainder of the examination is normal. He is able to recall three words
out of three, but clock drawing is abnormal. Laboratory studies are normal,
and CT of the brain shows changes of aging. What type of dementia does
this patient most likely have?
A. Dementia with Lewy bodies
B. Alzheimer disease
C. Frontotemporal dementia
D. Vascular dementia
E. Dementia of Parkinson disease
32.4 A 66-year-old woman is brought in to the office by her family because of difficulty with memory and being disoriented. These mental status changes have
worsened over the past 6 months. A careful history and physical examination
is performed, which confirms cognitive impairment but no focal neurological
findings. Which of the following tests is most appropriate next diagnostic
step in this patient?
A. Head CT or MRI
B. Lumbar puncture
C. Rapid plasma reagin
D. Electroencephalogram
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ANSWERS
32.1 B. Normal-pressure hydrocephalus classically causes the triad of dementia,
incontinence, and gait disturbance. All of the other listed conditions (answerA,
Alzheimer disease; answer C, dementia with Lewy bodies; and answerD,
delirium) may cause memory disturbance, but the constellation of these three
symptoms is most consistent with normal-pressure hydrocephalus. Also,
delirium is usually of acute onset and not over months.
32.2 C. Treat the underlying infection. This scenario is one that is commonly
seen in elderly patients and is consistent with delirium. The patient is elderly
and has an infection, causing both an acute change in her mental status and
a fluctuating level of consciousness. The main cause of sepsis in an older
patient is urinary tract infection. The treatment is to address the underlying
infection and any associated medical conditions. Dementia (answer A) does
not likely explain the patient’s mental status since this is an abrupt change.
Answer D (ziprasidone) for hallucinations may be indicated, but it is not as
important as addressing a possibly life-threatening condition of urinary tract
infection.
32.3 A. This patient has dementia with Lewy bodies, which is the third most common type after Alzheimer disease and vascular dementia. He demonstrates
typical signs and symptoms, including well-formed hallucinations, fluctuating cognition, sleep disorder with periods of daytime sleeping, frequent falls,
deficits in visuospatial ability (abnormal clock drawing), and REM (rapid eye
movement) sleep disorder (vivid dreams). In Alzheimer disease (answer B),
the predominant early symptom is memory impairment without the other
symptoms found in this patient. In dementia of Parkinson disease (answer
E), extrapyramidal symptoms such as tremor, bradykinesia, and rigidity
precede the onset of memory impairment by more than 1 year. Hallucinations are not as common with Parkinson disease. Frontotemporal dementia
(answer C) presents with behavioral changes, including disinhibition, or language problems, such as aphasia.
32.4 A. This 66-year-old woman has a 6 month history of progressive cognitive decline consistent with dementia. A noncontrast head CT or MRI is
recommended by the American Academy of Neurology for the routine
evaluation of dementia. All of the other tests (answer B, lumbar puncture;
answer C, rapid plasma reagin; and answer D, electroencephalogram) may
be appropriate if there is a finding on the history or examination that calls
for further testing (an exposure to syphilis, episodes suggestive of seizures,
or symptoms of normal-pressure hydrocephalus for which a spinal tap may
be performed).
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