Demencia y su tratamiento Flashcards
QUESTION ONE
Harold, a 74-year-old patient, is brought to your office by his
daughter, who reports that her father has been exhibiting several
concerning symptoms over the past year. Comprehensive questioning
reveals that his symptoms are: trouble remembering familiar
things, such as telephone numbers commonly dialed; not recognizing
some close family members who visit often; and difficulty
performing writing tasks. The patient’s motor function appears to
be unaffected. Although not definitive, these symptoms are most
likely indicative of which type of dementia?
A. Alzheimer’s disease
B. Frontotemporal dementia
C. Huntington’s disease
Differential diagnosis of dementias can be difficult, as all are characterized
by the core symptom of memory impairment. However, it may
be possible to distinguish dementias clinically through other presenting
symptoms.
A – Correct. In addition to memory impairment, Alzheimer’s disease
consists of deficits in language (aphasia), motor function (apraxia),
recognition (agnosia), or executive functioning, all of which this
patient exhibits. Definitive diagnosis, however, is not possible until
autopsy.
B – Incorrect. In frontotemporal dementia, patients often are disinhibited
and may be extremely talkative, symptoms that are also not
part of this patient’s presentation.
C – Incorrect. Huntington’s disease is associated with spasmodic movements
and incoordination, which are also absent in this patient.
QUESTION TWO
A medical student with a family history of Alzheimer’s disease is
interested in learning more about the brain regions involved in
memory and the development of Alzheimer’s disease. You describe
the pathways of acetylcholine, an important neurotransmitter
involved in dementia. As part of your explanation, you tell him that
major cholinergic projections stemming from the _____ to the
_____ are believed to be involved in memory.
A. Striatum; prefrontal cortex
B. Striatum; hypothalamus
C. Basal forebrain; nucleus accumbens
D. Basal forebrain; hippocampus
A, B, and C – Incorrect.
D – Correct. Acetylcholine is an important neurotransmitter and is
thought to be involved in memory. Major acetylcholine neurotransmitter
projections originating in the basal forebrain project
to the prefrontal cortex, amygdala, and hippocampus, the primary
brain structure involved in short-term memory and most greatly
affected in Alzheimer’s disease.
QUESTION THREE
A middle-aged man brings his 72-year-old mother in for an
appointment because he is concerned that his mother may have
Alzheimer’s disease. The mother does not feel that anything is
wrong, but her son states that she seems somewhat depressed and
forgetful lately. Data have shown that:
A. Depression is often comorbid with Alzheimer’s disease
B. Depression may increase the risk of developing Alzheimer’s
disease
C. Depression may be a prodromal symptom of Alzheimer’s disease
D. All of the above
E. None of the above
A – Partially correct. Mood symptoms can occur as part of Alzheimer’s
disease and in fact are typically the first notable symptom (often
manifested as apathy rather than sadness). In addition, depression is
a common comorbid illness in patients with Alzheimer’s disease.
B – Partially correct. Depression has been hypothesized to be a possible
risk factor for Alzheimer’s disease.
C – Partially correct. Depression has been hypothesized to be a possible
prodromal symptom of Alzheimer’s disease, with some evidence
suggesting that it may exacerbate the progression of Alzheimer’s
pathology.
D – Correct. All of the above.
E – Incorrect (none of the above).
QUESTION FOUR
Thomas is a 60-year-old man with a family history of Alzheimer’s
disease. As a voluntary participant in research studies on Alzheimer’s
disease, Thomas recently had amyloid positron emission tomography
(amyloid PET) neuroimaging done. Although he currently
exhibits no behavioral symptoms of Alzheimer’s disease, Thomas’s
amyloid PET scans reveal accumulation of beta amyloid protein
throughout cortical and limbic areas of his brain. Although much
research is yet to be done, data indicate that the normal physiological
role of amyloid beta protein may include:
A. Blood vessel repair functions
B. Antimicrobial functions
C. Both of the above
D. None of the above
A – Partially correct. One hypothesis posits that amyloid beta may act
as a sealant at sites of injury or leakage on vessel walls. In this
way, amyloid beta may protect from acute brain injury; however,
the accumulation of amyloid is associated with development of
dementia.
B – Partially correct. Evidence indicates that amyloid beta may have
antimicrobial functions. During microbial infection, adhesion
of microbes to the host cell is mediated by carbohydrates found
in the microbial cell wall. Amyloid beta oligomers bind to cell
wall microbial carbohydrates, preventing microbes from adhering
to the host cell. This binding of amyloid beta to the microbial
cell wall also induces fibrillization of amyloid beta, encompassing
microbes and causing agglutination (clumping of microbes so that
they can be more readily removed by phagocytosis).
C – Correct. Both blood vessel repair and antimicrobial actions are
hypothesized to be normal physiological roles for amyloid beta
protein.
D – Incorrect.
QUESTION FIVE
A 68-year-old patient with an early diagnosis of Alzheimer’s disease
is put on a cholinesterase inhibitor in hopes of improving his
cognitive function. This patient has been a chain smoker for over
40 years and refuses to give up the habit. Which of the following
medications would not be appropriate for this patient, given his
smoking habit?
A. Donepezil
B. Galantamine
C. Rivastigmine
D. None of these medications should be prescribed to a patient
who smokes
E. There are no contraindications due to smoking for these
medications
A – Incorrect. Donepezil, a reversible, long-acting selective inhibitor
of acetylcholinesterase (AChE), may be a good choice, resulting in
mainly transient gastrointestinal side effects.
B – Incorrect. Galantamine has a dual mechanism of action: AChE
inhibition and positive allosteric modulation (PAM) of nicotinic
cholinergic receptors. This may be a good choice for this patient.
C – Incorrect. Rivastigmine, delivered both orally and via a transdermal
formulation, has similar safety and efficacy to donepezil. The
oral formulation may result in more gastrointestinal side effects
than donepezil, owing to its pharmacokinetic profile and inhibition
of both AChE and butyrylcholinesterase (BuChE) in the
periphery.
D – Incorrect.
E – Correct. One can potentially choose any cholinesterase inhibitor
as a first-line treatment since specific contraindications due to
smoking do not presently appear in the literature.
QUESTION SIX
Marie, a 70-year-old mid-stage Alzheimer’s patient, has been on
donepezil, 10 mg/day for approximately 8 months to aid in stabilizing
her cognitive functioning. Her daughter has noticed a loss of effectiveness
over the past month, and they present today to determine
a new course of action. You decide to augment Marie’s donepezil
with 5 mg/day of memantine. Which of the following properties of
memantine may be useful in treating Alzheimer’s disease?
A. Sigma antagonism
B. Serotonin 3 (5HT3) antagonism
C. N-methyl-d-aspartate (NMDA) antagonism
A and B – Incorrect. Memantine possesses weak 5HT3 antagonist
properties and sigma antagonist properties, but it is currently
unclear if these contribute to its benefit in Alzheimer’s
disease.
C – Correct. Memantine is an NMDA antagonist that binds to the magnesium
site. It works as an uncompetitive open channel NMDA
receptor antagonist (i.e., low–moderate affinity, voltage dependence,
fast-blocking/unblocking kinetics). Memantine is quickly
reversible if phasic bursts of glutamate occur but is able to block
tonic glutamate release from having negative downstream effects.
This hypothetically stops the excessive glutamate from interfering
with the resting glutamate neuron’s physiological activity,
thus
improving memory.
QUESTION SEVEN
Mildred is a 66-year-old patient. She is currently showing no signs
of Alzheimer’s disease but is considering enrolling in one of the
ongoing Alzheimer’s disease immunotherapy-based clinical trials.
You explain to Mildred that such immunotherapy involves:
A. Antibodies that bind to NMDA receptors
B. Antibodies that bind to amyloid protein
C. Antibodies that bind to tau protein
D. B and C
A – Incorrect. Although the currently available Alzheimer’s drug
memantine acts by antagonizing NMDA receptors, the ongoing
immunotherapy clinical trials do not involve antibodies that bind
to NMDA receptors.
B – Partially correct. Many ongoing immunotherapy clinical trials utilize
various antibodies that bind to different portions or conformations
of the amyloid beta peptide and are thought to remove
amyloid beta from the brain via three hypothesized mechanisms.
These mechanisms include: peripheral sink, disaggregation, and
microglia engagement and phagocytosis.
C – Partially correct. Given that numerous immunotherapy trials utilizing
antibodies that bind to amyloid beta have yielded less than
satisfactory results, there are now several clinical trials involving tau
immunotherapy that are underway.
D – Correct.
QUESTION EIGHT
Diane is a 66-year-old patient with a family history of dementia.
Genotyping of this patient reveals a mutation in her gene for amyloid
precursor protein (APP). Which APP mutation is not associated
with increased development of familial Alzheimer’s disease?
A. Flemish mutation
B. Icelandic mutation
C. London mutation
D. Swedish mutation
A and C – Incorrect. The Flemish and London mutations both affect
processing of APP by gamma-secretase leading to increased
production of beta amyloid. Both mutations are associated
with increased development of familial Alzheimer’s disease.
B – Correct. The Icelandic mutation on the APP gene actually reduces
the cleavage of APP by the beta-secretase enzyme, resulting in
decreased beta amyloid production and decreasing risk of developing
familial Alzheimer’s disease.
D – Incorrect. The Swedish mutation leads to increased cleavage of
APP by the beta-secretase enzyme, leading to increased beta amyloid
production and increased development of familial Alzheimer’s
disease.
QUESTION NINE
A 79-year-old man presents to your office with his wife. She lists
significant medical history, such as chronic renal failure, mild cirrhosis,
arrhythmia, and a recent diagnosis of moderately severe
Alzheimer’s disease by their family physician. Which of the following
medications for Alzheimer’s disease has a “do not use” warning
for patients with renal and hepatic impairment?
A. Rivastigmine
B. Memantine
C. Galantamine
D. Donepezil
A – Incorrect. Rivastigmine, a cholinesterase inhibitor, appears as
though it could be useful in this situation, as it can be used in
patients with renal or hepatic impairment; caution should be exercised
in cardiac patients due to potential syncopal episodes.
B – Incorrect. Memantine, an NMDA receptor antagonist, would be
useful in this case due to its indication of approval for treatment
of moderate to severe dementia, with which this patient has been
diagnosed, although the label indicates a lowered dose for use in
severe renal impairment. However, there is not likely to be a problem
for hepatic or cardiac impaired patients.
C – Correct. Galantamine has a “do not use” warning in patients with
renal and hepatic impairment, as well as a caution warning when
used in cardiac impaired patients. Furthermore, galantamine, a
cholinesterase inhibitor, is often prescribed as one of the firstline
treatments for early-stage Alzheimer’s, rather than moderately
severe cases.
D – Incorrect. Donepezil, a cholinesterase inhibitor, could potentially
be given to this patient to aid in treatment of Alzheimer’s, though
little data has been gathered on its effects regarding renal and
hepatic impairment. Cardiac patients should use this drug with
caution due to reports of syncopal episodes.
QUESTION TEN
Virgil is a 65-year-old man. His daughter reports that he began
forgetting birthdays, grandchildren’s names, and other important
information approximately 1 year ago and that he has become
increasingly unable to perform many activities, such as paying
bills on time. Neuropsychiatric testing shows moderate cognitive
impairment not attributable to any medical or psychiatric condition.
Virgil has never been tested for biomarkers of Alzheimer’s
disease, but genetic testing has revealed that he carries an Alzheimer’s-
associated mutation in the presenilin gene. What would be the
most likely diagnosis for this patient according to the National
Institute on Aging and Alzheimer’s Association 2011 diagnostic
criteria for dementia?
A. Possible Alzheimer’s dementia
B. Probable Alzheimer’s dementia with increased level of certainty
C. Alzheimer’s dementia
A – Incorrect. The diagnosis of “possible Alzheimer’s dementia” is
reserved for individuals who exhibit dementia with an atypical
course and mixed presentation, which is not demonstrated in
this patient’s case. In instances where the dementia is atypical or
mixed in its presentation, and especially without biomarker evidence,
such dementia could be due to Alzheimer’s disease, Lewy
body dementia, vascular dementia, or frontotemporal dementia (or
some combination of the pathologies associated with each of these
dementia types).
B – Correct. This patient is exhibiting the typical symptoms of
Alzheimer’s dementia including an insidious onset, with a history
of worsening cognition, amnesic symptoms, and deficits in
executive function being the most prominent symptoms. Although
biomarker evidence (including positive amyloid PET neuroimaging
and increased cerebrospinal fluid tau levels) would increase
the certainty of the diagnosis, the fact that this patient carries
the Alzheimer’s disease-associated presenilin mutation allows us
to make the diagnosis of “probable Alzheimer’s dementia with
increased level of certainty.”
C – Incorrect. The only way to currently make a confirmed diagnosis
of Alzheimer’s dementia is through postmortem visualization of
Alzheimer’s neuropathology
QUESTION ELEVEN
Ellie is a 59-year-old patient who presents with hypoglycemia.
She also presents with symptoms that could be either dementia or
delirium. One key feature that can help differentiate delirium from
dementia is:
A. Psychosis
B. Memory deficits
C. Disorientation
D. Acute and fluctuating course
A, B, and C – Incorrect. Both dementia and delirium may present
clinically with memory deficits, disorientation, and
psychosis as well as impaired judgment and confusion.
D – Correct. The presentation of delirium is usually acute and fluctuating
whereas dementia is typically a chronic condition that does
not fluctuate. Delirium also typically involves cloudiness of consciousness,
and sleep disturbances compared to dementia.
QUESTION TWELVE
A 75-year-old patient with mild cognitive impairment is suspected of
being in the early, prodromal stage of Alzheimer’s disease. Which biomarker
evidence would support a diagnosis of Alzheimer’s disease?
A. Decreased cerebrospinal fluid (CSF) levels of amyloid beta
B. Increased CSF levels of tau protein
C. Increased levels of brain amyloid beta on PET scans
D. All of the above
A – Partially correct. During the presymptomatic stage of Alzheimer’s
disease, amyloid-beta peptides are slowly and relentlessly deposited
into the brain rather than eliminated via the CSF, plasma, and liver.
Therefore, CSF levels of amyloid beta actually decrease.
B – Partially correct. As Alzheimer’s disease progresses, tau and phosphorylated
tau protein levels in the CSF increase.
C – Partially correct. Levels of brain amyloid beta can be detected with
PET scans using radioactive neuroimaging tracers that bind to the
fibrillar form of amyloid and thus label mature neuritic plaques. In
normal controls, amyloid PET imaging typically shows the absence
of amyloid. However, individuals who are cognitively normal may
have moderate accumulation of amyloid; these individuals may be
in the presymptomatic first stage of Alzheimer’s disease. In the final
stage of Alzheimer’s disease, when full-blown dementia is clinically
evident, a large accumulation of brain amyloid can readily be seen.
D – Correct.
QUESTION THIRTEEN
William is a 77-year-old patient with mid- to late-stage Alzheimer’s
disease. His behavioral impairment has drastically worsened
over the past month. The patient’s family is concerned that William’s
rapidly deteriorating psychiatric and physical functioning
may be due to his medication (donepezil 10 mg/day) no longer
working. The treating clinician feels that Alzheimer’s disease may
not be the primary cause of William’s recent deterioration. Which
comorbid illness most commonly goes undetected in patients with
moderate to severe dementia?
A. Bacteriuria
B. Dehydration
C. Hypothyroidism
A – Correct. Nearly 40% of individuals with dementia may be suffering
from an undetected but modifiable illness. Bacteriuria is
the most common undiagnosed illness in patients suffering from
dementia, and it can lead to incontinence and increased agitation.
B – Incorrect. Although untreated dehydration has been found in
3% of individuals with dementia, it is not the most common
undetected comorbid illness.
C – Incorrect. Although untreated hypothyroidism has been found in
1–3% of individuals with dementia, it is not the most common
undetected comorbid illness.
QUESTION FOURTEEN
Mitchell is a 90-year-old patient with Lewy body dementia. His
daughter, who is his full-time caregiver, reports that her father has
started to exhibit worsening of agitation, wandering, and confusion
in the early evening – also known as sundowning. Which of the
following treatments has actually been shown to worsen sundowning
behavior?
A. Melatonin
B. Cholinesterase inhibitors
C. Bright light therapy
D. Benzodiazepines
A, B, and C – Incorrect. There is some, albeit limited, evidence that
bright light therapy, cholinesterase inhibitors (
specifically
donepezil), and melatonin may improve sundowning
behavior.
D – Correct. The use of benzodiazepines and other hypnotics has been
linked with a paradoxical increase in behavioral issues, such as
sundowning, in patients with dementia. Furthermore, benzodiazepines
are particularly not recommended in elderly patients with
dementia as they may greatly increase the risk of falls, fractures, and
death as well as worsening cognitive impairment.
