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Pathoma LAH > Neuro: 17.7: Dementia and Degenerative Disorders > Flashcards

Neuro: 17.7: Dementia and Degenerative Disorders Flashcards

1
Q

How does memantine work?

A

an NMDA receptor antagonist –> helps prevent Ca++ mediated excitotoxicity

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2
Q

What alleviates a resting tremor?

A

intentional movement

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3
Q

Huntington disease is caused by degeneration of GABAergic neurons in the ______ of the basal ganglia.

A

caudate nucleus

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4
Q

How does Vascular dementia present?

A
  • stepwise decline in cognitive ability
  • late-onset memory impairment
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5
Q

How do humans get spongiform encephalopathy?

A
  • sporadic
  • inherited
  • transmission (infectious)
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6
Q

What is the function of the basal ganglia?

A

to regulate movement

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7
Q

Binding of dopamine to D2 receptors in the ____ of the ______ will cause decreased inhibition of the cortex.

A

striatum of the basal ganglia

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8
Q

Normal people have prion proteins in their brains in the _______ conformation.

A

PRPc alpha-helix

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9
Q

Dx?

  • trinucleotide repeat of CAG on chromosome 4
A

Huntington disease

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10
Q

Dx?

  • Tremor (pill-rolling, at rest)
  • Rigidity (cogwheel)
  • Akinesia (or bradykinesia)
  • Postural instability
  • Shuffling gait
A

Parkinsons

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11
Q

What happens when neurons in the cortex degenerate?

A

dementia occurs

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12
Q

What causes Pick disease?

A
  • round aggregates of tau proteins in cortical neurons
  • ubiquitinated TDP-43
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13
Q

What is the tx for normal pressure hydrocephalus?

A

VP shunt (from the ventricles into the peritoneum)

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14
Q

What will the CT/MRI findings be in Vascular dementia?

A

multiple cortical and/or subcortical infarcts

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15
Q

Dx?

  • increased CSF –> dilated ventricles
  • urinary incontinence
  • gait instability
  • dementia
A
  • normal pressure hydrocephalus
  • *** “Wet, Wacky, and Wobbly”
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16
Q

Collectively, what kind of drugs are Tetrabenazine and reserpine? What are they used to treat?

A
  • vesicular monoamine transporter (VMAT) inhibitors –> decrease dopamine
  • tx for Huntingtons
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17
Q

What is the neurotransmitter change in Huntingtons?

A
  • decreased GABA
  • decreased ACh
  • increased dopamine
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18
Q

What is Benztropine used to treat?

A
  • Parkinsons
  • acute dystonia
  • *** “Park my Benz”
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19
Q

Dx?

  • a degenerative disease of the frontal and temporal cortex
A

Pick disease

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20
Q

These are random muscle movements- sudden, jerky, purposeless.

A

chorea

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21
Q

What is startle myoclonus?

A

a sudden, brief, involuntary muscle movement caused by minimal stimuli

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22
Q

What drugs increases L-dopamine availability in Parkinsons?

A
  • Levodopa/carbidopa
  • Entacapone
  • Tolcapone
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23
Q

Name 4 anticholinesterases used to treat Alzheimers.

A
  1. Donezapil
  2. galantamine
  3. rivastigmine
  4. tacrine
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24
Q

What kind of drug is Benztropine?

A

a muscarinic antagonist

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25
Q

What macroscopic changes are seen in the brain with Pick disease?

A
  • hydrocephalus ex vacuo
  • frontotemporal lobe degeneration
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26
Q

How do anticholinesterases work?

A

they increase ACh by inhibiting its breakdown

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27
Q

This is an acquired prion disease in tribes practicing human cannibalism.

A

Kuru

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28
Q

Dx?

  • rapidly progressive dementia (weeks-months)
  • ataxia
  • startle myoclonus
  • spike-wave complexes on EEG
A

Creutzfeldt-Jakob disease (CJD)

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29
Q

Dx?

  • diffuse cerebral atrophy
  • narrowed gyri
  • widened sulci
  • hydrocephalus ex vacuo (dilated ventricles)
A

Alzheimers disease

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30
Q

What is normal pressure hydrocephalus?

A

increased CSF –> dilated ventricles

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31
Q

What does the Epsilon-4 allele of APOE do?

A
  • it increases the conversion of Amyloid precursor protein (APP) to A-beta amyloid protein –> increased deposition –> Alzheimers
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32
Q

What is anticipation?

A

when the disease occurs earlier or is more severe in subsequent generations

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33
Q

Bromocriptine, pramipexole, and ropiirole are what kind of drugs? What are they used to treat?

A
  • dopamine agonists
  • tx for Parkinsons
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34
Q

What is chorea?

A

random muscle movements- sudden, jerky, purposeless

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35
Q

How can you distinguish Creutzfeldt-Jakob disease (CJD) from variant CJD (vCJD)?

A

variant = younger pts, consumption of infected cow’s meat

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36
Q

In which layers of the cortex do the pyramidal neurons reside?

A

3, 5, 6

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37
Q

What is athetosis? What is lesioned in the brain to cause this?

A
  • Slow, writhing, snake-like movements, especially seen in fingers
  • the basal ganglia
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38
Q

What is hydrocephalus ex vacuo?

A

dilated brain ventricles

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39
Q

Which brain pathway helps initiate movement by increasing the overall signal to the cortex?

A

nigrostriatal pathway

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40
Q

What are neurofibrillary tangles?

A
  • hyperphosphorylated tau proteins
  • seen in Alzheimers
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41
Q

What is another name for Pick disease?

A

Frontotemporal dementia

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42
Q

What are the SEs for memantine?

A
  • dizziness
  • confusion
  • hallucinations
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43
Q

Dx?

  • degenerative loss of dopaminergic neurons in:
    • the substantia nigra pars compacta (part of the basal ganglia)
    • ventral tegmentum
A

Parkinson disease

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44
Q

Name 3 dopamine agonists. What are they used to treat?

A
  1. Bromocriptine
  2. pramipexole
  3. ropiirole
  • tx for Parkinsons
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45
Q

What resorbs the CSF?

A

arachnoid granulations

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46
Q

What 2 major gray matter structures comprise the striatum of the basal ganglia?

A
  1. the caudate
  2. the putamen
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47
Q

If a pt has dementia within the first year of diagnosis of Parkinsons, think ______.

A

Lewy body dementia

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48
Q

What allele increases the risk of the sporadic form of Alzheimers?

A
  • Epsilon-4 allele of APOE
  • *** 4 is bigger than 2, so it has the increased risk
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49
Q

What is the 2nd most common cause of dementia?

A

vascular dementia

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50
Q

How do Entacapone and tolcapone work?

A

prevent peripheral L-dopa degradation to 3-O-methyldopa (3‑OMD) by inhibiting COMT

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51
Q

What chromosome encodes Amyloid precursor protein (APP)?

A

chromosome 21

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52
Q

What, genetically, causes Huntingtons?

A
  • trinucleotide repeats of CAG in the huntingtin gene on chromosome 4
  • *** “Caudate loses ACh and GABA”
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53
Q

How does Huntingtons present? What does it progress to? What is the most common cause of death?

A
  • present = chorea
  • progress –> dementia, depression
  • death by suicide
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54
Q

What are senile plaques associated with?

A

Alzheimers

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55
Q

What is the cause of normal pressure hydrocephalus? What does it usually cause?

A
  • usually = idiopathic
  • can cause dementia
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56
Q

Where is ACh synthesized in the brain?

A

the basal nucleus of Meynert

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57
Q

What is Haloperidol?

A

a D2 receptor antagonist

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58
Q

Huntington disease is caused by degeneration of GABAergic neurons in the caudate nucleus of the ______.

A

basal ganglia

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59
Q

How does Tolcapone work?

A

blocks conversion of dopamine to 3-OMD by inhibiting central COMT

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60
Q

What are Lewy bodies composed of? What do they look like?

A
  • alpha-synuclein
  • intracellular eosinophilic inclusions
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61
Q

What are senile plaques? What are they assoc. with?

A
  • A-beta amyloid + entrapped neuritic processes
  • seen in Alzheimers
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62
Q

How does levodopa/carbidopa work?

A

prevents peripheral (pre-BBB) L-dopa degradation Ž–> increased L-DOPA entering CNS Ž–> increased central L-DOPA available for conversion to dopamine

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63
Q

Dx?

  • deposition of A-beta amyloid
A

Alzheimers

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64
Q

What is Pick disease?

A

a degenerative disease of the frontal and temporal cortex

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65
Q

Vascular dementia is a consequence of _____ ischemia.

A

moderate global cerebral

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66
Q

What causes vascular dementia?

A
  • decreased blood flow to the brain from:
    • HTN
    • atherosclerosis
    • vasculitis
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67
Q

This is a contaminant to elicit drugs that can cause Parkinsons.

A

MPTP

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68
Q

______ is cleaved into A-beta amyloid protein, which deposits in the brain to cause Alzheimers.

A

Amyloid precursor protein (APP)

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69
Q

What causes most cases of Parkinsons? What causes rare cases?

A
  • most = unknown etiology
  • rare = exposure to MPTP (contaminant to elicit drugs)
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70
Q

This increases the conversion of Amyloid precursor protein (APP) to A-beta amyloid protein –> increased deposition –> Alzheimers.

A

the Epsilon-4 allele of APOE

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71
Q

Dx:

  • ubiquitinated TDP-43
A

Pick disease

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72
Q

Binding of dopamine to ____ receptors in the striatum of the basal ganglia will cause decreased inhibition of the cortex.

A

D2

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73
Q

What allele decreases the risk of the sporadic form of Alzheimers?

A
  • the Epsilon-2 allele of APOE
  • *** 2 is smaller than 4, so it has the decreased risk
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74
Q

What macroscopic changes are seen in the brain with Huntington disease?

A
  • caudate atrophy
  • hydrocephalus ex vacuo
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75
Q

What is the most common form of spongiform encephalopathy? How is it transmitted?

A
  • Creutzfeldt-Jakob disease (CJD)
  • it’s usually sporadic but can be infectious exposure
76
Q

What is the problem with hyperphosphorylated tau proteins?

A
  • they’re insoluble cytoskeleton elements
77
Q

Why do neurons die in Huntingtons disease?

A
  • NMDA-R binding
  • glutamate excitotoxicity
78
Q

What is variant CJD (vCJD)?

A

encephalopathy from exposure to bovine spongiform encephalopathy (Mad Cow disease)

79
Q

Dx?

  • PRPsc beta-pleated sheets
A

spongiform encephalopathy

80
Q

Degenerative disorders are characterized by the loss of neurons in the ______ matter.

A

gray

81
Q

When (in the course of the disease) does dementia present in Parkinsons?

A

late

82
Q

Dx?

  • round aggregates of tau proteins in cortical neurons
  • ubiquitinated TDP-43
A

Pick disease

83
Q

What is the definition of dementia?

A

memory loss + cognitive dysfunction WITHOUT loss of consciousness

84
Q

Anticipation is caused by further expansion of the trinucleotide repeat during _______.

A

spermatogenesis

85
Q

What gross findings are seen in the brain in spongiform encephalopathy?

A

intracellular vacuoles –> white spongy spaces wi the parenchyma

86
Q

What is the basal gangiia important for?

A

movement

87
Q

In general, what causes hydrocephalus ex vacuo?

A

loss of brain parenchyma –> enlargement of the ventricles

88
Q

Dx?

  • a general name for a degenerative disease due to prion proteins
A

spongiform encephalopathy

89
Q

What focal neuro. deficits are seen in Alzheimers?

A

none

90
Q

What does the loss of dopaminergic neurons look like histologically?

A

depigmentation

91
Q

A-beta amyloid deposition around blood vessels of the brain is called _______.

A

cerebral amyloid angiopathy

92
Q

What finding in the eyes is associated with Parkinsons?

A

Wilsons disease

93
Q

This is the term for loss of brain parenchyma –> enlargement of the ventricles.

A

hydrocephalus ex vacuo

94
Q

What is Kuru?

A

acquired prion disease in tribes practicing human cannibalism

95
Q

These are outpouchings of the arachnoid mater that drain into the venous sinuses.

A

arachnoid granulations

96
Q

Name the pathologic findings in the brain of an Alzheimers disease pt.

A

diffuse cerebral atrophy

97
Q

What is the function of dopamine in the brain?

A

increase stimulation and decrease inhibition to the cortex –> increase cortical function –> increase movement

98
Q

This is when the disease occurs earlier or is more severe in subsequent generations.

A

anticipation

99
Q

What kind of drugs are donezapil, galantamine, tacrine, and rivastigmine, collectively? What are they used for?

A
  • anticholinesterases
  • tx for Alzheimers
100
Q

What is tau protein? What is its normal function?

A
  • a microtubule-associated protein
  • helps the microtubules of the cytoskeleton arrange properly
101
Q

What are the clinical features of Alzheimers?

A
  • slow-onset memory loss
  • progressive disorientation
  • loss of learned motor skills and language –> become mute, bedridden
  • behavior and personality changes
102
Q

What is the nigrostriatal pathway?

A

the major dopaminergic pathway in the brain

103
Q

_____ is a degenerative disease of the gray matter of the cortex.

A

Alzheimers

104
Q

hWhy does normal pressure hydrocephalus cause its triad of symptoms?

A

bc the corona radiata (nerve fibers) run along the edges of the ventricles, and they get stretched

105
Q

This is an inherited prion disease characterized by insomnia + exaggerated startle response.

A

familial fatal insomnia

106
Q

Binding of dopamine to D2 receptors in the striatum of the basal ganglia will cause ______ of the cortex.

A

decreased inhibition

107
Q

Why is carbidopa added to levodopa?

A
  • blocks peripheral conversion of L-DOPA to dopamine by inhibiting DOPA decarboxylase
  • reduces SEs of peripheral L-DOPA conversion into dopamine (n/v)
108
Q

This is composed of A-beta amyloid + entrapped neuritic processes.

A

senile plaques

109
Q

What drug increases dopamine availability in Parkinsons?

A

Amantidine

110
Q

Binding of dopamine to ____ receptors in the striatum of the basal ganglia will cause increased stimulation to the cortex.

A

D1

111
Q

Name a muscarinic antagonist used to treat Parkinsons.

A

Benztropine

112
Q

What are the SEs for AChE inhibitors?

A
  • nausea
  • dizziness
  • insomnia
113
Q

What is the function of the basal nucleus of Meynert?

A

ACh synthesis in the brain

114
Q

Binding of dopamine to D1 receptors in the striatum of the basal ganglia will cause _____ stimulation to the cortex.

A

increased

115
Q

What causes Parkinson disease?

A
  • degenerative loss of dopaminergic neurons in the:
    • substantia nigra pars compacta (part of the basal ganglia)
    • ventral tegmentum
116
Q

What is the prognosis for Creutzfeldt-Jakob disease (CJD)?

A

death within 1 year

117
Q

What is released by the substantia nigra pars compacta?

A

dopamine

118
Q

Dx?

  • decreased
  • decreased ACh
  • increased dopamine
A

Huntington disease

119
Q

What causes the symptoms seen in Huntington disease?

A

degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia

120
Q

This is a sudden, brief, involuntary muscle movement caused by minimal stimuli.

A

startle myoclonus

121
Q

What characterizes Lewy body dementia?

A
  • cortical Lewy bodies
  • dementia
  • hallucinations
  • parkinsonian features
122
Q

What are the 2 kinds of Alzheimers?

A
  1. sporadic form
  2. early onset form
123
Q

How does Pick disease present?

A

early behavioral and language (aphasia) symptoms –> dementia

124
Q

What is spongiform encephalopathy?

A

a degenerative disease due to prion proteins

125
Q

What is the problem with cerebral amyloid angiopathy?

A

it weakens the BV wall –> increased risk of rupture, bleeds

126
Q

What is familial fatal insomnia?

A

an inherited prion disease characterized by insomnia + exaggerated startle response

127
Q

Name 4 causes of hydrocephalus ex vacuo.

A
  1. Alzheimers
  2. advanced HIV
  3. Pick disease/frontotemporal dementia
  4. Huntingtons
128
Q

Dx?

  • decreased dopamine
  • increased ACh
  • increased serotonin
A

Parkinsons

129
Q

Huntington disease is caused by degeneration of _____ in the caudate nucleus of the basal ganglia.

A

GABAergic neurons

130
Q

These are slow, writhing, snake-like movements, especially seen in fingers.

A

athetosis

131
Q

What improves symptoms in normal pressure hydrocephalus?

A

LP

132
Q

What nerve fibers line the ventricles?

A

the corona radiata

133
Q

What EEG finding is characteristic of Creutzfeldt-Jakob disease (CJD)?

A

spike-wave complexes

134
Q

Anticipation is caused by _____ during spermatogenesis.

A

further expansion of the trinucleotide repeat

135
Q

What stain can be used to diagnose Pick disease?

A

silver stain

136
Q

______ is defined as memory loss + cognitive dysfunction WITHOUT loss of consciousness.

A

Dementia

137
Q

How does someone get Huntingtons?

A

it’s inherited- auto. dominant

138
Q

What makes Lewy body dementia different from Parkinsons?

A
  • early-onset dementia
  • cortical Lewy bodies
139
Q

Collectively, what drug class are Levodopa/carbidopa, Entacapone, and tolcapone? What are they used to treat?

A
  • drugs that increase L-dopamine availability
  • tx for Parkinsons
140
Q

How is Alzheimers diagnosed?

A
  • clinically, after all other causes of dementia are ruled out
  • final confirmation at autopsy
141
Q

What is another name for frontotemporal dementia?

A

Pick disease

142
Q

What is the presentation triad of normal pressure hydrocephalus?

A
  1. urinary incontinence
  2. gait instability
  3. dementia
  • *** “Wet, Wacky, and Wobbly”
143
Q

Dx?

  • slow-onset memory loss
  • progressive disorientation
  • loss of learned motor skills and language –> mute, bedridden
  • behavior and personality changes
A

Alzheimers

144
Q

This drug is an NMDA receptor antagonist –> helps prevent Ca++ mediated excitotoxicity. It’s a tx for Alzheimers.

A

memantine

145
Q

What is GABA?

A

an inhibitory neurotransmitter

146
Q

What parts of the brain does Pick disease affect? What does it spare?

A
  • affects the frontal and temporal cortex
  • spares the parietal and occipital
147
Q

What is the corona radiata?

A

nerve fibers running along the edges of the brain ventricles

148
Q

What is memantine?

A
  • an NMDA receptor antagonist
  • helps prevent Ca++ mediated excitotoxicity
  • Tx for Alzheimers
149
Q

In the most basic term, where are the language centers of the brain located?

A

in the temporal lobes

150
Q

Dx?

  • presenilin 1 or presenilin 2 mutations
A

early onset familial Alzheimers

151
Q

What correlates to the degree of dementia in Alzheimers?

A

the number of neurofibrillary tangles

152
Q

Name 2 vesicular monoamine transporter (VMAT) inhibitors that are tx for Huntingtons.

A
  1. Tetrabenazine
  2. Reserpine
153
Q

Name 2 mutated genes causing familial early onset Alzheimers disease.

A
  1. presenilin 1
  2. presenilin 2
154
Q

The caudate + the putamen = _______

A

the striatum of the basal ganglia

155
Q

Dx based on these CT/MRI findings?:

  • multiple cortical and/or subcortical infarcts
A

Vascular dementia

156
Q

What is the neurotransmitter problem in Alzheimers?

A
  • decreased ACh
  • increased glutamate
157
Q

What are the SEs of levodopa?

A

n/v

158
Q

What is vascular dementia?

A

multifocal infarction and injury to the brain from a BV problem

159
Q

What are the neurotransmitter changes in Parkinson disease?

A
  • decreased dopamine
  • increased ACh
  • increased serotonin
160
Q

What form of prion protein causes pathologic spongiform encephalopathy?

A

PRPsc beta-pleated sheets

161
Q

If layers 3, 5, and 6 of the cortex are knocked out, what will happen?

A

dementia (loss of gray matter)

162
Q

What microscopic lesion is associated with Parkinsons?

A

Lewy bodies

163
Q

Dx?

  • stepwise decline in cognitive ability
  • late-onset memory impairment
A

Vascular dementia

164
Q

How does Selegiline work?

A

blocks conversion of dopamine into DOPAC by selectively inhibiting MAO-B

165
Q

Amyloid precursor protein (APP) is cleaved into ______, which deposits in the brain to cause Alzheimers.

A

A-beta amyloid protein

166
Q

What is MPTP? What can it cause?

A
  • a contaminant to elicit drugs
  • Parkinsons
167
Q

What causes Alzheimers disease?

A

the deposition of A-beta amyloid

168
Q

What are hyperphosphorylated tau proteins assoc. with?

A

Alzheimers

169
Q

Name 2 places from which the basal ganglia receives input.

A
  1. cortex
  2. substantia nigra pars compacta
170
Q

What is the major risk factor for the sporadic form of Alzheimers?

A

age

171
Q

What is the major risk factor for the early form of Alzheimers?

A
  • presenilin 1 (and 2)
  • Down syndrome
172
Q

Name 2 drugs that prevent dopamine breakdown. What are they used to treat?

A
  1. Selegiline
  2. Tolcapone
  • tx for Parkinsons
173
Q

What is the most common cause of dementia?

A

Alzheimers

174
Q

This is a D2 receptor antagonist used to treat Huntington.

A

Haloperidol

175
Q

What are arachnoid granulations?

A

outpouchings of the arachnoid mater that drain into the venous sinuses

176
Q

Is the ICP increased, decreased, or normal in Alzheimers?

A

normal

177
Q

What are the s/s of Parkinsons?

A
  • Parkinsons TRAPS your body:
    • Tremor (pill-rolling, at rest)
    • Rigidity (cogwheel)
    • Akinesia (or bradykinesia)
    • Postural instability
    • Shuffling gait
178
Q

What is cerebral amyloid angiopathy?

A

A-beta amyloid deposition around blood vessels of the brain

179
Q

This is multifocal infarction and injury to the brain from a BV problem.

A

vascular dementia

180
Q

Dx?

  • degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia
A

Huntington disease

181
Q

What happens when neurons in the brainstem and basal ganglia degenerate?

A

movement disorders

182
Q

What causes anticipation?

A

further expansion of the trinucleotide repeat during spermatogenesis

183
Q

This is spongiform encephalopathy from exposure to bovine spongiform encephalopathy (Mad Cow disease).

A

variant CJD (vCJD)

184
Q

What is the problem with having PRPsc beta-pleated sheets (pathologic prion proteins)?

A
  • they’re not degradable
  • they convert normal protein into pathologic ones
  • they damage neurons and glia
185
Q

What kind of tremor is seen in Parkinson?

A
  • resting tremor
  • “pill-rolling” tremor
186
Q

Binding of dopamine to D1 receptors in the ____ of the ______ will cause increased stimulation to the cortex.

A

striatum of the basal ganglia

Pathoma LAH (77 decks)

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