Transcript Alzheimer`s Disease

HPI
• A 73-year-old woman is brought to your practice by her
husband who is concerned for his wife’s well-being. He
explains that for the past few months he has noticed a
severe decline in his wife’s short term memory. At first
he attributed this to “normal aging”, but has recently
noticed that has become less involved in her bridge
club and rarely leaves the house. Of most concern,
however, is a recent episode in which his wife had been
preparing a meal for their son’s visit and had left the
gas stove on for several hours unattended.
What other questions would you like to ask?
HPI
• Medical Hx: Tonsilectomy (1948), Hysterectomy (1989)
• Family Hx: Mother suffered from dementia and HTN,
Father had HTN and CAD
• Social Hx: Married 55 years, 2 children, works as a
substitute teacher
What is your differential diagnosis?
Differential Diagnosis
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MCI
Dementia
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– Alzheimer’s disease
– Vascular dementia
– Mixed dementia
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– Dementia with Lewy bodies (DLB)
– Frontotemporal dementia (FTD) •
Depression (“Pseudodementia”)
Hypothyroidism
Normal pressure hydrocephalus (NPH)
Infection
– Neurosyphilis
Head trauma
– Chronic subdural hematoma
Side effect of medication
Vitamin deficiency
– B12
What is your next step in
assessing the patient?
Physical Exam
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Vitals:
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BP 115/48
T 37.3
RR 22
Gen: The patient is calm and cooperative
CV, Resp, abdominal exams: all wnl
Psych: negative depression screen
Neuro:
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alert and oriented to person and place, unable to name the day of the week.
Registration 3/3, recall 0/3 at 5 minutes
Unable to recall what the patient ate for breakfast this AM
MMSE: 21/30
Speech is fluent and appropriate in content
CN II-XII grossly intact
Motor: Strength 5/5 proximal and distal bilateral upper and lower extremeties
Sensory: intact to light touch, pinprick, and vibration throughout
MSRs 2+ and equal in upper and lower extremeties
Downgoing plantar response bilaterally
No resting or intention tremor
Tone normal (no rigidity)
Gait is smooth; not wide-based
Laboratory tests
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CBC: normal
WBC: 6,000
TSH: 2.7 uU/mL (normal)
Free T4: normal
B12: 816 pg/mL (normal)
VDRL/RPR: negative
What would you like to do next?
MRI
MRI can detect patterns of cerebral atrophy
suggestive of various neurodegenerative diseases.
In AD, cortical atrophy is seen as accentuation of
the sulci and is localized most commonly to the
frontal, temporal, and parietal lobes. Commonly,
hippocampal atrophy is seen.
What does this pattern of atrophy suggest?
What further testing can we perform?
Neuropsychological Tests
• Tests were preformed in order to identify lapses in cognitive
function and abilities. Patient was found to be profoundly affected
by short-term memory loss, testing in the 3rd percentile.
• The patient was asked to draw a clock face displaying a time of
2:45. The patient scored a four based on the following scale:
Alzheimer’s Disease
• AD is the most common cause of dementia (~50%)
• Alzheimer disease (AD) is a neurodegenerative disorder of
uncertain cause and pathogenesis that primarily affects older
adults.
• The main clinical manifestations of AD are selective memory
impairment and dementia.
• AD symptoms are likely a result of the accumulation of neuritic
(senile) plaques as well as neurofibrillary tangles.
How would you like to proceed with this patient?
Histological interpretations
Light micrograph of human brain tissue in
Alzheimer's disease, showing a senile plaque
(pale area in center), a characteristic histological
feature of the disease. Alzheimer's disease is a
form of progressive dementia; the brain is
smaller than normal, with degenerative changes
affecting the frontal and temporal lobes.
Senile plaques are extracellular tangled masses
of filaments & granules, often centered around
an area of amyloid beta. Amyloid beta is
derived from the larger protein amyloid
precursor protein (APP) located on
chromosome 21. Other genes associated with
AD are presenilin 1 and 2. The main other
feature of Alzheimer's disease is the formation
of neurofibrillary tangles, masses of thickened
filaments in the cytoplasm of neurons (nerve
cells).
Histological features cont’d
Neurofibrillary tangles are
bundles of filaments in the
cytoplasm of the neurons that
displace the nucleus.
They are composed of abnormal
tau protein (tauopathy), which
normally acts as a microtubule
stabilizing protein.
In pyramidal neurons, they often
have an elongated flame shape,
as demonstrated in this slide.
Treatment
• While treatments are available that can modulate the course of the
disease and/or ameliorate some symptoms, there is no cure, and
the disease inevitably progresses in all patients.
• Most treatments are designed to augment the neurotransmitter
acetylcholine.
• Acetylcholinesterase inhibitors (Aricept) are the only drugs that are
known to slow the progress of AD-related memory loss.
• NMDA glutamate receptor antagonists (memantine/Namenda) are
also commonly used to slow the progression of AD.
• Antidepressants and antipsychotics are frequently employed to
treat behavioral disturbances.
Summary
• The patient and her husband were given
information on the disease and some symptoms
that might manifest as its progression continues.
• Language deficits, loss of mathematical skills and
eventual loss of learned motor skills are
commonly found in late-stage AD.
• In final stages, patients may become incontinent,
mute, or unable to walk.
Neuropsychological Testing Role in
Diagnosis
• Helpful in the evaluation of individuals with cognitive
impairment and dementia.
• Cognitive testing under standardized conditions using
demographically appropriate norms is more sensitive to the
presence of impairments, especially impairments of
executive function.
• Can establish a baseline in order to follow the patient over
time.
• Neuropsychological assessment can also help differentiate
between dementia and depression.
• Can assess competencies and guide recommendations
pertaining to driving, financial decisions, and need for
increasing supervision