DEMENTIA

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DEMENTIA

• JEON, JOON-SEOK M.D.

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What is Dementia?

• Dementia is a term used to describe a cluster of
  symptoms including
• Forgetfulness (progressive)
• Difficulty doing familiar tasks
• Confusion
• Poor judgment
• Decline in intellectual functioning
• Dementia is not the name of an actual disease
• Dementia is not a part of normal aging

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Causes of Dementia

• Alzheimers disease (approximately 70)
• Vascular dementia (Strokes and TIAs)
• Parkinsons disease
• Frontotemporal dementia (FTD)
• Normal-Pressure hydrocephalus (NPH)
• Dementia with Lewy Bodies
• Delirium/Depression
• Other, less common causes

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Clinical course
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ALZHEIMER DISEASE 

• progressive neurologic disorder that results in
  memory loss, personality changes, global
  cognitive dysfunction, and functional
  impairments.
• Loss of short-term memory is most prominent
  early.
• In the late stages of disease, patients are
  totally dependent upon others for ADLS
• the most common form of dementia in the elderly,
  accounting for 60 to 80 of cases
• estimated to affect more than 4 million Americans

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Diagnosis

• Clinical diagnosis
• History, mental status evaluation, physical
  examination, limited laboratory testing, and in
  many cases, neuroimaging, more extensive
  neuropsychological testing and a depression
  screen.
• An MRI finding of bilateral hippocampal atrophy
  suggests AD, but is not specific or sensitive
• The laboratory testing includes a CBC,
  electrolytes, glucose, BUN and creatinine, serum
  B12, TSH and liver function tests.

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Pathology of AD

• There are 3 consistent neuropathologicalhallmarks
  
• Amyloid-rich senile plaques
• Neurofibrillarytangles
• Neuronal degeneration
• These changes eventually lead to clinical
  symptoms, but they begin years before the onset
  of symptoms

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Acetylcholinesterase Inhibitors

• Drugs used to treat Alzheimers disease act by
  inhibiting acetylcholinesterase activity
• These drugs block the esterase-mediated
  metabolism of acetylcholine to choline and
  acetate. This results in
• Increased acetylcholine in the synaptic cleft
• Increased availability of acetylcholine for
  postsynaptic and presynaptic nicotinic (and
  muscarinic) acetylcholine receptors

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VASCULAR DEMENTIA 

• The onset of cognitive deficits associated with a
  stroke
• Abrupt onset of symptoms followed by stepwise
  deterioration
• Findings on neurologic examination consistent
  with prior stroke(s)
• Infarcts on cerebral imaging

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criteria for probable vascular dementia 

• Cerebrovascular disease evident on history,
  examination or imaging
• Two disorders must be related by
• onset of dementia within 3 months or
• abrupt, fluctuating or stepwise progression

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Features that make vascular dementia uncertain or
unlikely

• Early memory loss and progressive deterioration
  in the absence of corresponding focal lesions on
  imaging
• Absence of focal neurological signs
• Absence of cerebrovascular lesions on CT or MRI

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Clinical features supportive of vascular dementia

• Early gait disorder
• Frequent falls
• Urinary incontinence or frequency early in
  disorder
• Pseudobulbar palsy
• Personality and mood changes

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FRONTOTEMPORAL DEMENTIA 

• characterized by focal atrophy of the frontal and
  temporal lobes in the absence of Alzheimer
  pathology
• Pick's disease was the first recognized subtype
  of FTD, one that is characterized pathologically
  by the presence of Pick bodies (silver staining
  intracytoplasmic inclusions) in the neocortex and
  hippocampus.
• Clinically, presents with language abnormalities
  and behavioral disturbances.

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FRONTOTEMPORAL DEMENTIA

• occurs between the ages of 35 and 75 years, and
  only rarely after age 75 the mean age of onset
  is the sixth decade
• Both sexes are equally affected.
• Familial occurrence occurs in 20 to 40 percent of
  cases and may be associated with a variety of
  identified mutations in the tau gene on
  chromosome 17

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Normal-Pressure Hydrocephalus

• a condition of pathologically enlarged
  ventricular size with normal opening pressures on
  lumbar puncture
• triad of dementia, gait disturbance, and urinary
  incontinence
• reversible by the placement of a
  ventriculoperitoneal shunt

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Dementia with Lewy Bodies

• the most common dementia syndrome associated with
  parkinsonism
• the second most common form of neurodegenerative
  dementia after Alzheimer disease (AD).
• characterized by dementia accompanied by
  delirium, visual hallucinations, and
  parkinsonism. Other common symptoms include
  syncope, falls, sleep disorders, and depression.
• The presence of both Lewy bodies and amyloid
  plaques with deficiencies in both acetylcholine
  and dopamine neurotransmitters suggests that
  dementia with Lewy bodies represents the middle
  of a disease spectrum ranging from Alzheimers
  disease to Parkinsons disease

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Parkinsons disease

• Cardinal motor features
• Brady- and akinesia
• Rigidity
• Resting tremor
• Postural instability
• Dementia typically occurs in the last half of the
  clinical course of PD, whereas it is often one of
  the presenting features of DLB.

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Progressive supranuclear palsy 

• also known as Steele Richardson Olszewski
  syndrome
• a rare syndrome that can mimic PD in its early
  phase
• Characteristic features of PSP
• vertical supranuclear palsy with downward gaze
  abnormalities
• postural instability with unexplained falls
• Bradykinesia and rigidity are typically
  symmetrical in onset
• Apathy, disinhibition, dysphoria, and anxiety are
  common

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classic neuropathologic features of PSP

• globose neurofibrillary tangles (NFT) consisting
  of hyperphosphorylated tau proteins.
• These lesions and accompanying neuronal loss are
  seen primarily in the substantia nigra,
  subthalamic nucleus, globus pallidus, superior
  colliculus and midbrain, and pontine reticular
  formation.
• Cortical involvement is more variable but
  predominately affects the frontal lobes.

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1. What criterion is required for the diagnosis
of Alzheimers disease? A) Disturbances in
consciousness B) Static loss of memory
function C) Impairment of two areas of
cognition D) Changes in personality E) Myoclonus
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1. (C) Impairment of two areas of cognition. The
diagnosis of Alzheimers disease requires
impairment of two areas of cognition, no
disturbance in consciousness, progressive loss of
memory function, and no systemic disease or
disorder to account for dementia. Although
changes in personality and myoclonus mayoccur in
patients with Alzheimers disease, these changes
are not required for the diagnosis.
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A 72-year-old woman is admitted to the hospital
with agitation and visual hallucinations. The
patients symptoms started 1 year ago, and 6
months later, the patient started to have
fluctuating cognitive impairments. Physical
examination reveals tremor and rigidity.
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2. Which of the following is this patients most
likely diagnosis? (A) Alzheimers disease (B)
Corticobasal degeneration (C) Dementia with Lewy
bodies (D) Multi-infarct dementia (E) Progressive
supranuclear palsy
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3. Which of the following medications is the most
appropriate for the long-term management of the
patients visual hallucinations and
agitation? (A) Amitriptyline (B)
Chlorpromazine (C) Haloperidol (D) Quetiapine (E)
Thioridazine
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2. (C) Dementia with Lewy bodies. This patient
has dementia with Lewy bodies, which is a
Parkinson plus syndrome. The central feature of
dementia with Lewy bodies is progressive
cognitive decline in addition to 3 defining
features pronounced fluctuations in alertness
and attention, recurrent visual hallucinations,
and parkinsonian motor symptoms. 3. (D)
Quetiapine. Typical antipsychotics, such
as haloperidol, and newer agents with dopamine D2
receptor affinity are avoided in the long-term
treatment of visual hallucinations and agitation
because of potential worsening of motor symptoms,
cognitive decline, delirium, and features of
neuroleptic malignant syndrome associated with
dopamine receptor blockage. Amitriptyline is not
indicated for psychosis.
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4. A 72-year-old man presents to the emergency
department after a fall. He states that he has
fallen frequently over the past 8 months. On
examination, he has no tremor, but he has
generalized rigidity (mostly axial),
bradykinesia, increased gag reflex, and
difficulty with vertical gaze. What is this
patients most likely diagnosis? (A) Corticobasal
degeneration (B) Multiple system atrophy (C)
Parkinsons disease (D) Parkinsonism-dementia-amyo
trophic lateral sclerosis (E) Progressive
supranuclear palsy
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4. (E) Progressive supranuclear palsy.
Progressive supranuclear palsy is a
neurodegenerative disease that presents with
primarily vertical gaze dysfunction accompanied
by extrapyramidal symptoms and cognitive
dysfunction. The disease usually develops after
the fourth decade of life, and the diagnosis is
purely clinical.
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5. Which of the following studies should be
included in the laboratory work-up for
Alzheimers disease? A) Imaging studies of the
brain B) Assessment of thyroid hormone levels C)
Liver function tests D) Imaging studies of the
brain and assessment of thyroid hormone levels E)
Imaging studies of the brain, assessment of
thyroid hormone levels, and liver function tests
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5. (E) Imaging studies of the brain, assessment
of thyroid hormone levels, and liver function
tests. A laboratory work-up for Alzheimers
disease should include imaging studies of the
brain, assessment of thyroid hormone levels, and
liver function tests, as well as assessment of
vitamin B12 levels, urinalysis, VDRL/fluorescent
treponemal antibody absorbed, cerebrospinal fluid
analysis, and electroencephalography.