Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

N P Neuro part > 030315 neurodegenerative dis > Flashcards

030315 neurodegenerative dis Flashcards

1
Q

what is crucial for formation of episodic memories?

A

hippocampus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

striatum

A

caudate nucleus and putamen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how does dopamine facilitate movement

A

dopamine releasing cell in substantia nigra pars compact affects 2 different types of output neurons in striatum (neurons w D1 receptors that excite direct pathway, neurons with D2 receptors that inhibit indirect pathway)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

substantia nigra is part of

A

midbrain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

common feature of neurodegnerative dis

A

gray matter dis-progressive loss of neurons, leading to progressive decline in nerv system fxn

misfolded and/or aggregated proteins

sporadic and familial forms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Alzheimer’s affects

A

cerebral cortex (higher order association cortices and limbic system)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

excitotoxicity

A

excessive glutamate can cause persistent activation of NMDA receptors (superoxide can cause this too), leading to excess intracellular Ca, which leads to ATP depletion and cell death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

most powerful risk factor for Alzheimer’s

A

age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

only two conditions that present predominantly with short term memory loss

A

Alzheimer’s

Lewy body dis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

clinical definition of AD

A

gradual decline in cognitive fxn w impairments in SHORT TERM MEMORY and one additional cognitive domain that isn’t due to other medical or pscyhiatric illness and results in a functional impairment socially or occupationally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

cognitive domains for AD

A 
memory
language
abstract thinking and judgment
visuo-spatial or perceptual skills
praxis (practicing a skill)
executive fxn
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

stage I of AD

A

memory (new, and old is mildly impaired)
visuospatial skills-topographic disorientation
language
psychiatric-depression, apathy, delusions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

stage II of AD

A

worse memory
visuospatial skills
calculation-acalculia
pscyhiatric-delusions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

stage III AD

A

intellectual fxn severely impaired
sphincter control-urinary and fecal
motor-limb rigidity, flexion posture

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

gross morphology of AD

A

atrophy of gyri
widening of sulci
increased size of lateral ventricles-hydrocephalus ex vacuo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

diffuse plaque

A

in AD, extracellular accumulation of Abeta protein (from precursor APP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

neuritic plaque

A

in AD, extracellular accumulation of Abeta protein and tau containing neurites (neurites are axons or dendrites)

more closely associated w cognitive decline than diffuse plaque

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

congo red stain

A

can look for amyloid (stains red in cerebral amyloid angiopathy)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

neurofibrillary tangle

A

intraneuronal accumulation of abnormally phosphorylated form of tau, a normal microtubule associated protein

looks like a cone inside cell

not unique to AD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

inherited vs late onset AD

A

inherited-under 60-65 yrs old. often automsomal dominant mutation, highly penetrant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

link btwn Down syndrome and AD

A

APP gene is on chromosome 21

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

most common genetic mutation in AD

A

presenilin 1 (explains 50% of familial AD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

genes involved in familial AD

A 
presenilin 1 (chr 14)
amyloid precurosr protein (APP) (chr 14)
presenilin 2 (chr 1)

mutations in all three of these are autosomal dominant, result in increased Abeta amyloid protein, and result in EARLY ONSET AD under 65

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

genetic risk factor for LATE ONSET AD

A

APO E4 (chr 19)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
cholinergic signaling deficiency occurs in
AD dementia w Lewy bodies vascular dementia
26
second most common form of early dementia
frontotemporal degeneration
27
frontotemporal degeneration
causes focal degernation in frontl and anterior temporal lobes FTLD (lobar degeneration) refers to pathologic entity has different INITIAL symptoms from AD. AD would have memory loss. FTD has dementia later in dis progression
28
mutations involved with frontotemporal dengeration
tau gene (results in accumulation of tau) progranulin (results in accumul of TDP43 protein) C9orf72 (results in accumulation of TDP43) all autosomal dominant
29
clinical subytpes of FTD
behavioral variant-50%-bifrontal lobe atrophy primary progressive aphasia: - progressive nonfluent aphasia (25%)-L peri Sylvian atrophy - semantic variant (25%)-bilateral anterior temporal lobe atrophy. trouble finding the word or comprehending the meaning of a word
30
behavioral variant of FTD
socially inappropriate behavior, loss of manners or impulsive actions early apathy or inertia early loss of sympathy or empathy early compulsive behavior hyperorality and dietary changes
31
microscopic findings for FTLD
vary by subtype tauopathies: -Pick's disease (atrophy of frontal and temporal lobes). Pick bodies (round cytoplasmic inclusions in neurons containing abnormal TAU FILAMENTS) FTLD-TDP43 accumulation: -cytoplasmic protein accumulations in frontal or temporal lobes
32
pick bodies
ROUND cytoplasmic inclusions in neurons containing hyerphosphorylated TAU filaments
33
resting tremor is specific for
PD, not Parkinsonian syndromes
34
Parkinsonism
clinical syndrome: rigidity, bradykinesia, resting tremor, mask facies, stooped posture, festinating gait
35
genes involved w PD
``` Parkin gene (chr 6) alpha synuclein gene (very rare) ```
36
clinical features of PD
resting tremor rigidity bradykinesia gait
37
nonmotor symptoms in premotor phase of PD
REM behavior disorder (kicking and screaming in sleep) olfactory loss dysautonomia (ANS dysfxn)
38
excellent response to levodopa
PD | it's uncharacteristic of any other parkinsonian symptom disease
39
PD pathology
pallor of substantia nigra | neuronal loss and LEWY BODIES in substantia nigra
40
Lewy bodies
eosinophilic cytoplasmic neuronal inclusions, contain alpha synuclein
41
dementia w Lewy body
dementia associated w any 2 of 3 core clinical features - fluctuating cognition or level of sconsioucness - visual hallucinations (pleasant and non-threatening) - Parkinsonian motor signs
42
dementia being early onset in disease
dementia w Lewy body | AD
43
dementia with Lewy body pts have no problems w
episodic memory or language
44
compare and contrast dementia w Lewy body and PD
both have substantia nigra degeneration and Lewy bodies however, CLINIAL PRESENTATIONS are diff
45
clinical presentations of dementia w Lewy body and PD
dementia w Lewy body: -clinical features of dementia at onset PD: - pts present w PARKINSONISM SIGNS - most EVENTUALLY develop dementia - pathological correlate of dementia is Lewy body presence in cortex
46
pathologic findings in dementia w Lewy bodies
neuronal loss and Lewy bodies in substantia nigra AND Lewy bodies in cerebral cortex
47
what cells are vulnerable in PD?
dopaminergic cells of substantia nigra
48
MOA of levodopa
uses amino acid transporters to enter brain (dopamine itself would not be able to cross BBB)
49
levodopa is converted to dopamine by
L-AAAD
50
how do you get levodopa to not affect other tissues outside of brain?
adminiter L-DOPA w CARBIDOPA, an inhibitor of L-AAAD that doesn't cross BBB
51
entacapone
``` COMT inhibitor (COMT metabolizes dopamine) gets into brain and periphery ```
52
best results of L-dopa are obtained when?
in first few years of tx (effectiveness is not as good afterwards) so L-dopa is NOT USED UNTIL symptoms cause functional impairment
53
side effects of L-dopa
due to conversion to dopamine: wearing off effect dyskinesias (too much mvmt) dementia, confusion-can look psychotic
54
what's used more instead of levodopa for PD?
dopamine receptor agonists
55
why are dopamine receptor agonists better than L-DOPA?
no enzymatic conversion needed selectivity for receptor subtypes longer half life less dopamine-dependent oxidative stress possibly
56
dopamine receptor agonists-name them?
pramipexole, ropinerole (selective D2)-most commonly used currently apomorphine (high affinity D4, moderate affinity D2/D3/D5)
57
initial therapy in young pts
direct dopamine agonists (pramipexole, ropinerole)
58
why avoid DA agonists in elderly pts?
confusion side effect is worse than that of L-DOPA
59
side effects of direct DA agonists
``` CNS toxicity nausea fatigue sudden attack of daytime sleep apomorphine-increased QT prolongation ```
60
why are MAO-B inhibitors preferred over MAO-A?
MAO-A is a form found in liver, so would inhibit metabolism of tyramine
61
rationale of MAO-B inhibitors
prolong action of dopamine and may reduce oxidative stress on neurons
62
MAO-B inhibitors-list them
selegiline | rasagiline
63
effectiveness of MAO-B inhibitors
mild usually prescribed as soon as dis is diagnosed also an anti-depressant
64
rationale for COMT inhibitors
COMT metabolizes dopamine so inhibition will prolong the action of dopamine. COMT inhibition also decreases L-DOPA metabolism to non-dopamine metabolites
65
list the COMT inhibitors
tolcapone (signif hepatotoxicity) | entacapone
66
rationale for antimuscarinics
cholinergic interneurons in striatum are normally inhibited by dopamine. loss of dopamine results in overactivity of these excitatory neurons
67
MOA of antimuscarinics
antagonists of striatal muscarinic receptors
68
rationale for amantadine
discovered by serendipity | least effec of the agents
69
MOA of amantadine
increases dopamine release mildly anticholinergic blocks NMDA receptors (to reduce Ca toxicity)
70
Huntington dis
autosomal dominant progressive motor, cognitive, and behavioral domains: - motor symptoms predominant at onset in many cases - cognitive symptoms may occur at or before onset of motor symptoms (as dis progresses, pts become demented eventually) - neuropsychiatric symptoms are exhibited in most pts
71
when do symptoms present for HD?
4-5th decade
72
gene mutation for HD
in huntington gene (chr 4)--expanded CAG repeat
73
what does huntington gene mutation cause
intranuclear inclusions in basal ganglia
74
pathology of HD
loss of medium striatal neurons in the caudate and putamen (these modulate motor activity), resulting in chorea. loss of striatal inhibition of thalamic drive neuronal loss in cerebral cortex-cognitive changes
75
HD-imaging
usually, caudate nucleus makes bump into lateral ventricles. in HD, this is absent
76
gross pathology of HD
atrophy of caudate and putamen, ventricular enlargement mild to moderate atrophy of gyri
77
mechanism of HD
loss of striatal excitation and inhibition of pathways results in thalamus exciting cerebral cortex
78
ALS
widespread degeneration of upper and lower motor neurons lower motor neuron-degeneration of anterior horn cells and axons upper motor neuron-degernation of corticospinal tracts in lateral column of spinal cord bulbar dysfxn (involvement of brainstem motor cranial nerves)-dysarthria, dysphagia
79
most common mutation in ALS
superoxide dismutase 1 gene (SOD1) in subset of ALS, TDP43 gene mutation, causing TDP43 accumulation
80
pathology of ALS
anterior roots of spinal cord are atrophic primary motor cortex (cerebrum) may show atrophy reduced number of anterior horn cells loss of corticospinal tract axons and myelin brainstem motor cranial nerves may be affected
81
drugs for AD
donepezil rivastigmine galantamine memantine
82
riluzole
used for ALS | NMDA channel blocker (increases life span by 2-3 months)
83
neuritic plaques
extracellular Abeta and tau, seen in AD
84
neurofibrillary tangles
intraneuronal phosphorylated tau
85
where do you see neurofibrillary tnagles in AD?
hippocampus and neocortex
86
dementia w Lewy bodies
early dementia, later motor disorder

N P Neuro part (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions