A 55-year-old man, who is under emotional stress but other-
wise healthy, suddenly begins to repeatedly ask his wife,
“Where am I?” and “What is happening?” He is attentive, and
his speech and language are normal. After 4 hours of difficulty,
his wife brings him to the emergency department. On mental
status testing, he cannot recall 3 items after 5 minutes. He does
not have motor, sensory, or cranial nerve abnormalities.
Computed tomography of the head and electroencephalogra-
phy do not show any abnormalities. What is the best treatment
of this condition?
a. Verapamil
b. Levetiracetam
c. Topiramate
d. Sumatriptan
e. Reassurance
VII.1. Answer e.
Sudden-onset anterograde amnesia (more than retrograde
amnesia) that lasts for hours is likely transient global amne-
sia (TGA). The differential diagnosis for amnesia is broad,
and select diagnoses should be ruled out. These include
metabolic disorders such as those affecting glucose and elec-
trolyte levels, medications and toxins or withdrawal from
them, structural abnormality, or seizure. Unusual for seizure
is the length of the episode; however, transient epileptic
amnesia would be in the differential diagnosis. TGA is self-
limited and generally lasts less than 24 hours.
Which of the following characteristics is the main distinction
between mild neurocognitive impairment and major neurocog-
nitive impairment according to the Diagnostic and Statistical
Manual of Mental Disorders (Fifth Edition) (DSM-5)?
a. Language is abnormal in major but not mild neurocognitive
impairment
b. Social cognition is abnormal in major but not mild neurocogni-
tive impairment
c. The Mini-Mental State Examination (MMSE) score must be less
than 24 for major neurocognitive impairment
d. The deficits result in functional impairment in major but not
mild neurocognitive impairment
e. Secondary causes do not have to be ruled out for mild neuro-
cognitive impairment
VII.2. Answer d.
DSM-5 renames dementia as major neurocognitive disorder
and de-emphasizes memory as the main area of cognitive
dysfunction. With these criteria, the main difference
between major neurocognitive disorder and mild neurocog-
nitive disorder is the interference with functional activities.
While the MMSE score is helpful for assessing for dementia,
it is not part of the DSM-5 criteria.
Three days after an emergent appendectomy, a 55-year-old,
frail-appearing man is less attentive and has agitation, tachycar-
dia, and hyperhidrosis. No family member is available to assist
with past medical history. Oxygen saturation and electrolyte,
glucose, and creatinine levels are normal. Results of liver func-
tion tests (alanine aminotransferase and aspartate aminotrans-
ferase) are 1.5 times the upper limit of the reference range.
What might be the cause of hyperactive delirium in this man?
a. Delirium tremens
b. Postoperative opioids
c. Hepatic encephalopathy
d. Blood loss
e. Antiemetic use
VII.3. Answer a.
While alcohol withdrawal symptoms may occur within 12 to
24 hours of the last drink, delirium tremens typically occurs
72 to 96 hours after the last drink. Delirium tremens is char-
acterized usually by a hyperactive delirium, whereas opioid
use and hepatic encephalopathy generally cause a hypoac-
tive delirium. Characteristics of delirium tremens include
agitation, poor attention, and autonomic symptoms such as
hypertension, tachycardia, and excessive sweating.
Which of the following tests should be performed for every
patient who has major neurocognitive impairment?
a. Electroencephalography
b. Positron emission tomography
c. Liver function tests
d. Serum copper and ceruloplasmin levels
e. Thyroid function testing
VII.4. Answer e.
The American Academy of Neurology guidelines recom-
mend that initial testing include vitamin B12 and thyroid
laboratory testing and imaging of the head. However, select
patients may require more in-depth testing, including some
of the tests listed, depending on their age at onset, other
comorbidities, and neurologic findings.
What is the annual conversion rate from mild cognitive impair-
ment (MCI) to dementia in the general population?
a. 1% to 2%
b. 3% to 5%
c. 6% to 10%
d. 10% to 15%
e. 15% to 25%
VII.5. Answer c.
The annual conversion rate of MCI is 6% to 10% in the gen-
eral population. Within specialty clinics, the conversion rate
is 10% to 15%.
What is the expected effect of acetylcholinesterase inhibitors
on symptoms in patients with Alzheimer disease?
a. Donepezil, galantamine, and rivastigmine have been associated
with cognitive improvements
b. Only donepezil has been shown to improve cognitive symptoms
c. All cholinesterase inhibitors have been shown to reduce the rate
of progression from mild cognitive impairment (MCI) to dementia
d. No cholinesterase inhibitors have been shown to reduce the
rate of progression from MCI to dementia
e. Only donepezil has been shown to reduce the rate of progres-
sion from MCI to dementia
VII.6. Answer e.
In 1 study, donepezil reduced progression to Alzheimer dis-
ease in the first 12 months but not for the duration of the
36-month study.
Mutations in which of the following genes are associated with
autosomal dominant inheritance of Alzheimer disease?
a. Amyloid precursor protein gene (APP) on chromosome 1
b. Presenilin 1 gene (PSEN1) on chromosome 14
c. α-Synuclein gene (SNCA) on chromosome 4
d. Presenilin 2 gene (PSEN2) on chromosome 2
e. Microtubule-associated protein tau gene (MAPT) on chromo-
some 17
VII.7. Answer b.
Autosomal-dominant early-onset forms of Alzheimer dis-
ease are caused by mendelian mutations in the following
genes: APP on chromosome 21, PSEN1 on chromosome 14,
and PSEN2 on chromosome 1.
A 59-year-old man has progressive decline in self-care, and his
family reports that he has an online gambling problem. He
appears disheveled and has poor attention, reduced verbal flu-
ency, reduced ability to plan, and poor working memory. His
father had been institutionalized in his 60s for similar issues.
What is the most likely diagnosis?
a. Alzheimer disease
b. Lewy body dementia
c. Corticobasal degeneration (CBD)
d. Frontotemporal dementia (FTD)
e. HIV dementia
VII.8. Answer d.
In the early stage of FTD, patients may show disinhibition,
apathy, inertia, loss of empathy, perseveration, stereotyped
or compulsive behavior, and lack of initiation. Patients with
FTD are more likely than patients with Alzheimer disease to
have a relevant family history and to present when they are
50 to 60 years old. Lewy body dementia and CBD generally
have associated motor findings. HIV dementia is a subcorti-
cal dementia characterized by slow mental processing, apa-
thy, and extrapyramidal symptoms, and the patient would
not have a relevant family history.
Which of the following genes is most commonly associated with
frontotemporal dementia (FTD)?
a. MAPT gene (microtubule-associated protein tau)
b. APOE gene (apolipoprotein E) ε4 allele
c. NOTCH3 gene (Notch3 receptor) mutation
d. SNCA gene (α-synuclein)
e. FUS gene (fused in sarcoma)
VII.9. Answer a.
Mutations in the MAPT, C9orf72, and GRN genes account for
the majority of known spontaneous or inherited cases of FTD
(see also Table 78.1). Mutations in the FUS, TARDBP, CHMP2B,
and VCP genes are rare. The APOE ε4 allele is a risk marker for Alzheimer disease. NOTCH3 mutations are associated
with cerebral autosomal dominant arteriopathy with sub-
cortical infarcts and leukoencephalopathy (CADASIL).
The SNCA gene may relate to Lewy body dementia.
VII.10. Which of the following describes treatment of frontotemporal
dementia (FTD)?
a. Aggressive behavior in patients with FTD responds favorably to
cholinesterase inhibitors
b. Antipsychotic medications are contraindicated because of neu-
roleptic hypersensitivity
c. Patients may continue to drive until their memory is
impaired
d. Amantidine may help aphasia
e. Selective serotonin reuptake inhibitors (SSRIs) may be used to
improve behavioral symptoms
VII.10. Answer e.
SSRIs are commonly used to improve behavioral and psy-
chiatric symptoms. Atypical antipsychotic drugs may be
used to manage severe behavioral problems, including dis-
inhibition and aggressive behavior. Cholinesterase inhibi-
tors are not typically helpful in FTD, and they may worsen
behavioral symptoms. Home safety evaluations and future
planning are important. Most patients with FTD should be
counseled about discontinuing driving.
VII.11. The criteria for the clinical diagnosis of dementia with Lewy
bodies (DLB) include dementia and 2 or more of the 4 core
features. Which of the following is not a core feature?
a. Fully formed visual hallucinations
b. Rapid eye movement (REM) sleep disorder
c. Fluctuations in arousal or cognition
d. Bilateral hippocampal atrophy
e. Spontaneous parkinsonism
VII.11. Answer d.
The criteria for the clinical diagnosis of DLB include
dementia and 2 or more of the 4 core features: 1) fully
formed visual hallucinations, 2) fluctuations in cognition
or arousal, 3) spontaneous parkinsonism, and 4) REM
sleep behavior disorder.
VII.12. Answer a.
Cholinesterase inhibitors have been shown to be reason-
ably well tolerated and often beneficial in DLB, most likely
because of the relatively mild neocortical and limbic neu-
ronal loss but considerable cholinergic deficit.
VII.13. Which of the following statements is true about Parkinson dis-
ease with dementia (PDD)?
a. Symptoms of dementia and parkinsonism generally begin at the
same time
b. PDD affects women more often than men
c. Bifrontal hypometabolism on 18F-fludeoxyglucose–positron emis-
sion tomography (FDG-PET) is common
d. Cholinesterase inhibitors may help in the treatment of both
parkinsonian and neuropsychiatric symptoms
e. Levodopa can be used for parkinsonian symptoms
VII.13. Answer e.
There are no gender differences in PDD. The criteria for diag-
nosis of PDD require dementia and an established diagnosis of
Parkinson disease. FDG-PET may show occipital hypometab-
olism. Magnetic resonance imaging generally shows minimal
hippocampal atrophy. Levodopa is the main therapy for par-
kinsonian symptoms. Cholinesterase inhibitors may improve
neuropsychiatric and cognitive symptoms.
VII.14. A 69-year-old man presents with progressive walking difficul-
ties over the past year. He feels as if his feet are stuck to the
ground. He also reports some recent urinary incontinence and
has cognitive decline. On neurologic examination, he has a
magnetic gait with a shortened stride, and he takes 8 steps to
turn; bedside cognitive testing shows mild deficits. Magnetic
resonance imaging of the head shows enlarged ventricles and
loss of sulci superiorly. What is the best next step?
a. Cisternography
b. Large-volume lumbar puncture and comparison of videos
before and after the procedure
c. Magnetic resonance angiography of the head
d. Insertion of an external ventricular drain
e. Insertion of a lumbar drain
VII.14. Answer b.
The triad of progressive gait decline, urinary incontinence,
and cognitive difficulties is characteristic of normal-pres-
sure hydrocephalus. Large-volume lumbar puncture and
comparison of videos before and after the procedure are use-
ful for evaluating the gait, which improves in patients who
are most likely to respond to ventriculoperitoneal shunting.
VII.15. Which protein is pathologically associated with repetitive head
injuries that result in chronic traumatic encephalopathy?
a. Amyloid
b. α-Synuclein
c. Transactive response DNA-binding protein 43 (TDP-43)
d. Tau
e. Prion
VII.15. Answer d.
Chronic traumatic encephalopathy is associated with tau
deposition and is considered a progressive tauopathy.
Amyloid is found in Alzheimer disease. α-Synuclein is
found in Parkinson disease and Lewy body disease. TDP-
43 is found in certain types of frontotemporal dementia
and amyotrophic lateral sclerosis. Prion proteins are found
in Creutzfeldt-Jakob disease.
VII.16. A 55-year-old woman with alcoholism had multiple episodes of
vomiting from gastroenteritis and then a progressive decline in
neurologic status, including imbalance, confusion, and double
vision. On neurologic examination, she had truncal ataxia, enceph-
alopathy, and ophthalmoplegia. Computed tomography of the
head did not show any abnormalities. What is the best next step?
a. Measure the serum thiamine level and administer parenteral
thiamine
b. Perform magnetic resonance imaging (MRI) of the head
c. Give intravenous dextrose
d. Measure the GQ1b antibody titers
e. Measure the serum ethanol level
VII.16. Answer a.
The presentation of confusion, ataxia, and ophthalmople-
gia in a patient with alcoholism and a history of recent
vomiting is highly suggestive of Wernicke encephalopathy
from thiamine deficiency. Although MRI can be useful
diagnostically if it shows mammillary body hemorrhages
and thalamic and periaquaductal gray T2-signal abnormal-
ities, measuring the serum thiamine level and administer-
ing parenteral thiamine should take precedence in this
neurologic emergency. Thiamine should be administered
before glucose because glucose can precipitate or worsen
Wernicke encephalopathy. GQ1b antibody titers are useful
diagnostically if the patient has sensory ataxia and oph-
thalmoplegia because the test results can be used to con-
firm Miller Fisher syndrome, but the patient in this
question is more likely to have Wernicke encephalopathy.
Measuring the serum ethanol level can be useful in patients
with alcoholism, but the clinical syndrome described in
this question is consistent with Wernicke encephalopathy.
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