Neuro: 17.7: Dementia and Degenerative Disorders Flashcards
How does memantine work?
an NMDA receptor antagonist –> helps prevent Ca++ mediated excitotoxicity
What alleviates a resting tremor?
intentional movement
Huntington disease is caused by degeneration of GABAergic neurons in the ______ of the basal ganglia.
caudate nucleus
How does Vascular dementia present?
- stepwise decline in cognitive ability
- late-onset memory impairment
How do humans get spongiform encephalopathy?
- sporadic
- inherited
- transmission (infectious)
What is the function of the basal ganglia?
to regulate movement
Binding of dopamine to D2 receptors in the ____ of the ______ will cause decreased inhibition of the cortex.
striatum of the basal ganglia
Normal people have prion proteins in their brains in the _______ conformation.
PRPc alpha-helix
Dx?
- trinucleotide repeat of CAG on chromosome 4
Huntington disease
Dx?
- Tremor (pill-rolling, at rest)
- Rigidity (cogwheel)
- Akinesia (or bradykinesia)
- Postural instability
- Shuffling gait
Parkinsons
What happens when neurons in the cortex degenerate?
dementia occurs
What causes Pick disease?
- round aggregates of tau proteins in cortical neurons
- ubiquitinated TDP-43
What is the tx for normal pressure hydrocephalus?
VP shunt (from the ventricles into the peritoneum)
What will the CT/MRI findings be in Vascular dementia?
multiple cortical and/or subcortical infarcts
Dx?
- increased CSF –> dilated ventricles
- urinary incontinence
- gait instability
- dementia
- normal pressure hydrocephalus
- *** “Wet, Wacky, and Wobbly”
Collectively, what kind of drugs are Tetrabenazine and reserpine? What are they used to treat?
- vesicular monoamine transporter (VMAT) inhibitors –> decrease dopamine
- tx for Huntingtons
What is the neurotransmitter change in Huntingtons?
- decreased GABA
- decreased ACh
- increased dopamine
What is Benztropine used to treat?
- Parkinsons
- acute dystonia
- *** “Park my Benz”
Dx?
- a degenerative disease of the frontal and temporal cortex
Pick disease
These are random muscle movements- sudden, jerky, purposeless.
chorea
What is startle myoclonus?
a sudden, brief, involuntary muscle movement caused by minimal stimuli
What drugs increases L-dopamine availability in Parkinsons?
- Levodopa/carbidopa
- Entacapone
- Tolcapone
Name 4 anticholinesterases used to treat Alzheimers.
- Donezapil
- galantamine
- rivastigmine
- tacrine
What kind of drug is Benztropine?
a muscarinic antagonist
What macroscopic changes are seen in the brain with Pick disease?
- hydrocephalus ex vacuo
- frontotemporal lobe degeneration
How do anticholinesterases work?
they increase ACh by inhibiting its breakdown
This is an acquired prion disease in tribes practicing human cannibalism.
Kuru
Dx?
- rapidly progressive dementia (weeks-months)
- ataxia
- startle myoclonus
- spike-wave complexes on EEG
Creutzfeldt-Jakob disease (CJD)
Dx?
- diffuse cerebral atrophy
- narrowed gyri
- widened sulci
- hydrocephalus ex vacuo (dilated ventricles)
Alzheimers disease
What is normal pressure hydrocephalus?
increased CSF –> dilated ventricles
What does the Epsilon-4 allele of APOE do?
- it increases the conversion of Amyloid precursor protein (APP) to A-beta amyloid protein –> increased deposition –> Alzheimers
What is anticipation?
when the disease occurs earlier or is more severe in subsequent generations
Bromocriptine, pramipexole, and ropiirole are what kind of drugs? What are they used to treat?
- dopamine agonists
- tx for Parkinsons
What is chorea?
random muscle movements- sudden, jerky, purposeless
How can you distinguish Creutzfeldt-Jakob disease (CJD) from variant CJD (vCJD)?
variant = younger pts, consumption of infected cow’s meat
In which layers of the cortex do the pyramidal neurons reside?
3, 5, 6
What is athetosis? What is lesioned in the brain to cause this?
- Slow, writhing, snake-like movements, especially seen in fingers
- the basal ganglia
What is hydrocephalus ex vacuo?
dilated brain ventricles
Which brain pathway helps initiate movement by increasing the overall signal to the cortex?
nigrostriatal pathway
What are neurofibrillary tangles?
- hyperphosphorylated tau proteins
- seen in Alzheimers
What is another name for Pick disease?
Frontotemporal dementia
What are the SEs for memantine?
- dizziness
- confusion
- hallucinations
Dx?
- degenerative loss of dopaminergic neurons in:
- the substantia nigra pars compacta (part of the basal ganglia)
- ventral tegmentum
Parkinson disease
Name 3 dopamine agonists. What are they used to treat?
- Bromocriptine
- pramipexole
- ropiirole
- tx for Parkinsons
What resorbs the CSF?
arachnoid granulations
What 2 major gray matter structures comprise the striatum of the basal ganglia?
- the caudate
- the putamen
If a pt has dementia within the first year of diagnosis of Parkinsons, think ______.
Lewy body dementia
What allele increases the risk of the sporadic form of Alzheimers?
- Epsilon-4 allele of APOE
- *** 4 is bigger than 2, so it has the increased risk
What is the 2nd most common cause of dementia?
vascular dementia
How do Entacapone and tolcapone work?
prevent peripheral L-dopa degradation to 3-O-methyldopa (3‑OMD) by inhibiting COMT
What chromosome encodes Amyloid precursor protein (APP)?
chromosome 21
What, genetically, causes Huntingtons?
- trinucleotide repeats of CAG in the huntingtin gene on chromosome 4
- *** “Caudate loses ACh and GABA”
How does Huntingtons present? What does it progress to? What is the most common cause of death?
- present = chorea
- progress –> dementia, depression
- death by suicide
What are senile plaques associated with?
Alzheimers
What is the cause of normal pressure hydrocephalus? What does it usually cause?
- usually = idiopathic
- can cause dementia
Where is ACh synthesized in the brain?
the basal nucleus of Meynert
What is Haloperidol?
a D2 receptor antagonist
Huntington disease is caused by degeneration of GABAergic neurons in the caudate nucleus of the ______.
basal ganglia
How does Tolcapone work?
blocks conversion of dopamine to 3-OMD by inhibiting central COMT
What are Lewy bodies composed of? What do they look like?
- alpha-synuclein
- intracellular eosinophilic inclusions
What are senile plaques? What are they assoc. with?
- A-beta amyloid + entrapped neuritic processes
- seen in Alzheimers
How does levodopa/carbidopa work?
prevents peripheral (pre-BBB) L-dopa degradation –> increased L-DOPA entering CNS –> increased central L-DOPA available for conversion to dopamine
Dx?
- deposition of A-beta amyloid
Alzheimers
What is Pick disease?
a degenerative disease of the frontal and temporal cortex
Vascular dementia is a consequence of _____ ischemia.
moderate global cerebral
What causes vascular dementia?
- decreased blood flow to the brain from:
- HTN
- atherosclerosis
- vasculitis
This is a contaminant to elicit drugs that can cause Parkinsons.
MPTP
______ is cleaved into A-beta amyloid protein, which deposits in the brain to cause Alzheimers.
Amyloid precursor protein (APP)
What causes most cases of Parkinsons? What causes rare cases?
- most = unknown etiology
- rare = exposure to MPTP (contaminant to elicit drugs)
This increases the conversion of Amyloid precursor protein (APP) to A-beta amyloid protein –> increased deposition –> Alzheimers.
the Epsilon-4 allele of APOE
Dx:
- ubiquitinated TDP-43
Pick disease
Binding of dopamine to ____ receptors in the striatum of the basal ganglia will cause decreased inhibition of the cortex.
D2
What allele decreases the risk of the sporadic form of Alzheimers?
- the Epsilon-2 allele of APOE
- *** 2 is smaller than 4, so it has the decreased risk
What macroscopic changes are seen in the brain with Huntington disease?
- caudate atrophy
- hydrocephalus ex vacuo
What is the most common form of spongiform encephalopathy? How is it transmitted?
- Creutzfeldt-Jakob disease (CJD)
- it’s usually sporadic but can be infectious exposure
What is the problem with hyperphosphorylated tau proteins?
- they’re insoluble cytoskeleton elements
Why do neurons die in Huntingtons disease?
- NMDA-R binding
- glutamate excitotoxicity
What is variant CJD (vCJD)?
encephalopathy from exposure to bovine spongiform encephalopathy (Mad Cow disease)
Dx?
- PRPsc beta-pleated sheets
spongiform encephalopathy
Degenerative disorders are characterized by the loss of neurons in the ______ matter.
gray
When (in the course of the disease) does dementia present in Parkinsons?
late
Dx?
- round aggregates of tau proteins in cortical neurons
- ubiquitinated TDP-43
Pick disease
What is the definition of dementia?
memory loss + cognitive dysfunction WITHOUT loss of consciousness
Anticipation is caused by further expansion of the trinucleotide repeat during _______.
spermatogenesis
What gross findings are seen in the brain in spongiform encephalopathy?
intracellular vacuoles –> white spongy spaces wi the parenchyma
What is the basal gangiia important for?
movement
In general, what causes hydrocephalus ex vacuo?
loss of brain parenchyma –> enlargement of the ventricles
Dx?
- a general name for a degenerative disease due to prion proteins
spongiform encephalopathy
What focal neuro. deficits are seen in Alzheimers?
none
What does the loss of dopaminergic neurons look like histologically?
depigmentation
A-beta amyloid deposition around blood vessels of the brain is called _______.
cerebral amyloid angiopathy
What finding in the eyes is associated with Parkinsons?
Wilsons disease
This is the term for loss of brain parenchyma –> enlargement of the ventricles.
hydrocephalus ex vacuo
What is Kuru?
acquired prion disease in tribes practicing human cannibalism
These are outpouchings of the arachnoid mater that drain into the venous sinuses.
arachnoid granulations
Name the pathologic findings in the brain of an Alzheimers disease pt.
diffuse cerebral atrophy
What is the function of dopamine in the brain?
increase stimulation and decrease inhibition to the cortex –> increase cortical function –> increase movement
This is when the disease occurs earlier or is more severe in subsequent generations.
anticipation
What kind of drugs are donezapil, galantamine, tacrine, and rivastigmine, collectively? What are they used for?
- anticholinesterases
- tx for Alzheimers
What is tau protein? What is its normal function?
- a microtubule-associated protein
- helps the microtubules of the cytoskeleton arrange properly
What are the clinical features of Alzheimers?
- slow-onset memory loss
- progressive disorientation
- loss of learned motor skills and language –> become mute, bedridden
- behavior and personality changes
What is the nigrostriatal pathway?
the major dopaminergic pathway in the brain
_____ is a degenerative disease of the gray matter of the cortex.
Alzheimers
hWhy does normal pressure hydrocephalus cause its triad of symptoms?
bc the corona radiata (nerve fibers) run along the edges of the ventricles, and they get stretched
This is an inherited prion disease characterized by insomnia + exaggerated startle response.
familial fatal insomnia
Binding of dopamine to D2 receptors in the striatum of the basal ganglia will cause ______ of the cortex.
decreased inhibition
Why is carbidopa added to levodopa?
- blocks peripheral conversion of L-DOPA to dopamine by inhibiting DOPA decarboxylase
- reduces SEs of peripheral L-DOPA conversion into dopamine (n/v)
This is composed of A-beta amyloid + entrapped neuritic processes.
senile plaques
What drug increases dopamine availability in Parkinsons?
Amantidine
Binding of dopamine to ____ receptors in the striatum of the basal ganglia will cause increased stimulation to the cortex.
D1
Name a muscarinic antagonist used to treat Parkinsons.
Benztropine
What are the SEs for AChE inhibitors?
- nausea
- dizziness
- insomnia
What is the function of the basal nucleus of Meynert?
ACh synthesis in the brain
Binding of dopamine to D1 receptors in the striatum of the basal ganglia will cause _____ stimulation to the cortex.
increased
What causes Parkinson disease?
- degenerative loss of dopaminergic neurons in the:
- substantia nigra pars compacta (part of the basal ganglia)
- ventral tegmentum
What is the prognosis for Creutzfeldt-Jakob disease (CJD)?
death within 1 year
What is released by the substantia nigra pars compacta?
dopamine
Dx?
- decreased
- decreased ACh
- increased dopamine
Huntington disease
What causes the symptoms seen in Huntington disease?
degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia
This is a sudden, brief, involuntary muscle movement caused by minimal stimuli.
startle myoclonus
What characterizes Lewy body dementia?
- cortical Lewy bodies
- dementia
- hallucinations
- parkinsonian features
What are the 2 kinds of Alzheimers?
- sporadic form
- early onset form
How does Pick disease present?
early behavioral and language (aphasia) symptoms –> dementia
What is spongiform encephalopathy?
a degenerative disease due to prion proteins
What is the problem with cerebral amyloid angiopathy?
it weakens the BV wall –> increased risk of rupture, bleeds
What is familial fatal insomnia?
an inherited prion disease characterized by insomnia + exaggerated startle response
Name 4 causes of hydrocephalus ex vacuo.
- Alzheimers
- advanced HIV
- Pick disease/frontotemporal dementia
- Huntingtons
Dx?
- decreased dopamine
- increased ACh
- increased serotonin
Parkinsons
Huntington disease is caused by degeneration of _____ in the caudate nucleus of the basal ganglia.
GABAergic neurons
These are slow, writhing, snake-like movements, especially seen in fingers.
athetosis
What improves symptoms in normal pressure hydrocephalus?
LP
What nerve fibers line the ventricles?
the corona radiata
What EEG finding is characteristic of Creutzfeldt-Jakob disease (CJD)?
spike-wave complexes
Anticipation is caused by _____ during spermatogenesis.
further expansion of the trinucleotide repeat
What stain can be used to diagnose Pick disease?
silver stain
______ is defined as memory loss + cognitive dysfunction WITHOUT loss of consciousness.
Dementia
How does someone get Huntingtons?
it’s inherited- auto. dominant
What makes Lewy body dementia different from Parkinsons?
- early-onset dementia
- cortical Lewy bodies
Collectively, what drug class are Levodopa/carbidopa, Entacapone, and tolcapone? What are they used to treat?
- drugs that increase L-dopamine availability
- tx for Parkinsons
How is Alzheimers diagnosed?
- clinically, after all other causes of dementia are ruled out
- final confirmation at autopsy
What is another name for frontotemporal dementia?
Pick disease
What is the presentation triad of normal pressure hydrocephalus?
- urinary incontinence
- gait instability
- dementia
- *** “Wet, Wacky, and Wobbly”
Dx?
- slow-onset memory loss
- progressive disorientation
- loss of learned motor skills and language –> mute, bedridden
- behavior and personality changes
Alzheimers
This drug is an NMDA receptor antagonist –> helps prevent Ca++ mediated excitotoxicity. It’s a tx for Alzheimers.
memantine
What is GABA?
an inhibitory neurotransmitter
What parts of the brain does Pick disease affect? What does it spare?
- affects the frontal and temporal cortex
- spares the parietal and occipital
What is the corona radiata?
nerve fibers running along the edges of the brain ventricles
What is memantine?
- an NMDA receptor antagonist
- helps prevent Ca++ mediated excitotoxicity
- Tx for Alzheimers
In the most basic term, where are the language centers of the brain located?
in the temporal lobes
Dx?
- presenilin 1 or presenilin 2 mutations
early onset familial Alzheimers
What correlates to the degree of dementia in Alzheimers?
the number of neurofibrillary tangles
Name 2 vesicular monoamine transporter (VMAT) inhibitors that are tx for Huntingtons.
- Tetrabenazine
- Reserpine
Name 2 mutated genes causing familial early onset Alzheimers disease.
- presenilin 1
- presenilin 2
The caudate + the putamen = _______
the striatum of the basal ganglia
Dx based on these CT/MRI findings?:
- multiple cortical and/or subcortical infarcts
Vascular dementia
What is the neurotransmitter problem in Alzheimers?
- decreased ACh
- increased glutamate
What are the SEs of levodopa?
n/v
What is vascular dementia?
multifocal infarction and injury to the brain from a BV problem
What are the neurotransmitter changes in Parkinson disease?
- decreased dopamine
- increased ACh
- increased serotonin
What form of prion protein causes pathologic spongiform encephalopathy?
PRPsc beta-pleated sheets
If layers 3, 5, and 6 of the cortex are knocked out, what will happen?
dementia (loss of gray matter)
What microscopic lesion is associated with Parkinsons?
Lewy bodies
Dx?
- stepwise decline in cognitive ability
- late-onset memory impairment
Vascular dementia
How does Selegiline work?
blocks conversion of dopamine into DOPAC by selectively inhibiting MAO-B
Amyloid precursor protein (APP) is cleaved into ______, which deposits in the brain to cause Alzheimers.
A-beta amyloid protein
What is MPTP? What can it cause?
- a contaminant to elicit drugs
- Parkinsons
What causes Alzheimers disease?
the deposition of A-beta amyloid
What are hyperphosphorylated tau proteins assoc. with?
Alzheimers
Name 2 places from which the basal ganglia receives input.
- cortex
- substantia nigra pars compacta
What is the major risk factor for the sporadic form of Alzheimers?
age
What is the major risk factor for the early form of Alzheimers?
- presenilin 1 (and 2)
- Down syndrome
Name 2 drugs that prevent dopamine breakdown. What are they used to treat?
- Selegiline
- Tolcapone
- tx for Parkinsons
What is the most common cause of dementia?
Alzheimers
This is a D2 receptor antagonist used to treat Huntington.
Haloperidol
What are arachnoid granulations?
outpouchings of the arachnoid mater that drain into the venous sinuses
Is the ICP increased, decreased, or normal in Alzheimers?
normal
What are the s/s of Parkinsons?
- Parkinsons TRAPS your body:
- Tremor (pill-rolling, at rest)
- Rigidity (cogwheel)
- Akinesia (or bradykinesia)
- Postural instability
- Shuffling gait
What is cerebral amyloid angiopathy?
A-beta amyloid deposition around blood vessels of the brain
This is multifocal infarction and injury to the brain from a BV problem.
vascular dementia
Dx?
- degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia
Huntington disease
What happens when neurons in the brainstem and basal ganglia degenerate?
movement disorders
What causes anticipation?
further expansion of the trinucleotide repeat during spermatogenesis
This is spongiform encephalopathy from exposure to bovine spongiform encephalopathy (Mad Cow disease).
variant CJD (vCJD)
What is the problem with having PRPsc beta-pleated sheets (pathologic prion proteins)?
- they’re not degradable
- they convert normal protein into pathologic ones
- they damage neurons and glia
What kind of tremor is seen in Parkinson?
- resting tremor
- “pill-rolling” tremor
Binding of dopamine to D1 receptors in the ____ of the ______ will cause increased stimulation to the cortex.
striatum of the basal ganglia
