Neurodegenerative disorders Flashcards
(111 cards)
1
Q
If only one cognitive domain is affected without functional impairment, it is more likely to be _ rather than dementia
A
If only one cognitive domain is affected without functional impairment, it is more likely to be mild cognitive impairment rather than dementia
2
Q
Dementia is an acquired, persistent, progressive impairment in intellectual function that affects _ cognitive domain(s)
A
Dementia is an acquired, persistent, progressive impairment in intellectual function that affects multiple cognitive domain(s)
* One of which is usually memory
* Also see a decline in function
* Interference with work or social life
3
Q
By definition, neurodegenerative disorders are _
A
By definition, neurodegenerative disorders are loss of neurological function (dementia, loss of movement control, paralysis) due to loss of neurons
* The most common is Alzheimer disease
* All neuronal death is linked to the deposition of abnormal proteins
4
Q
Lewy body dementia is often associated with [symptoms]
A
Lewy body dementia is often associated with visual hallucinations, parkinson-like symptoms
* Tremor, shuffling gait, mask-like facies
5
Q
CJD is associated with [neuro exam finding] and [neuro exam finding]
A
CJD is associated with myoclonus and ataxia
6
Q
Progressive supranuclear palsy is sometimes referred to as _
A
Progressive supranuclear palsy is sometimes referred to as Parkinson plus
* Postural instability, bradykinesia, oculomotor findings
7
Q
Supranuclear palsy is distinguished from parkinson disease by the presence of _
A
Supranuclear palsy is distinguished from parkinson disease by the presence of oculomotor findings (impaired downward gaze, loss of vertical saccades)
* They often fall backwards
8
Q
Progressive supranuclear palsy is associated with accumulation of [protein] and formation of [structure]
A
Progressive supranuclear palsy is associated with accumulation of tau and formation of neurofibrillary tangles
* It is another “tauopathy”
9
Q
The three most important proteinopathies associated with neurodegenerative dementias are:
A
The three most important proteinopathies associated with neurodegenerative dementias are:
1. Tau
2. Amyloid
3. Alpha synuclein
10
Q
Alzheimer disease specifically affects [locations]
A
Alzheimer disease specifically affects cerebral cortex, hippocampus, amygdala
11
Q
Plaques seen in Alzheimer disease are composed of [protein]
A
Plaques seen in Alzheimer disease are composed of beta-amyloid
12
Q
Neurofibrillary tangles seen in Alzheimer disease are composed of [protein]
A
Neurofibrillary tangles seen in Alzheimer disease are composed of hyperphosphorylated tau
13
Q
Lewy bodies are composed of [protein]
A
Lewy bodies are composed of alpha-synuclein
* Seen in Lewy body dementia and Parkinson disease
* “Lew” “Synu”
14
Q
Diffuse lewy bodies is suggestive of _
A
Diffuse lewy bodies is suggestive of lewy body dementia
* Parkinson disease has lewy bodies in the basal ganglia
15
Q
Huntington disease is associated with [protein] and specifically affects [locations]
A
Huntington disease is associated with mutant huntington protein and specifically affects caudate and putamen
* Intranuclear inclusions with polyglutaminated huntingtin due to CAG repeat expansion
16
Q
CJD is an issue of [proteins]
A
CJD is an issue of prions forming amyloid
17
Q
Diagnosis
A
Alzheimer disease: neurofibrillary tangles
* Hyperphosphorylated tau protein
18
Q
Diagnosis
A
Alzheimer disease: amyloid plaques
19
Q
Diagnosis
A
CJD: spongiform change
20
Q
Ach gets made in [nucleus]
A
Ach gets made in basal nucleus of meynert
21
Q
Dopamine is made in [nucleus]
A
Dopamine is made in ventral tegmentum (and the SNc)
22
Q
GABA is made in [nucleus]
A
GABA is made in nucleus accumbens
23
Q
NE is made in the [nucleus]
A
NE is made in the locus ceruleus
* In the pons
24
Q
Serotonin is made in [nucleus]
A
Serotonin is made in raphe nuclei
* In the medulla, pons
25
Anxiety is associated with an increase in [NTs] and decrease in [NTs]
Anxiety is associated with an increase in **NE** and decrease in **GABA, Serotonin**
26
Depression is associated with an increase in [NTs] and decrease in [NTs]
Depression is associated with an increase in **nothing** and decrease in **dopamine, NE, serotonin**
27
Schizophrenia is associated with [NT change]
Schizophrenia is associated with **increased dopamine**
28
Alzheimer disease is associated with [NT change]
Alzheimer disease is associated with **decreased Ach**
29
Huntington disease is associated with an increase in [NTs] and decrease in [NTs]
Huntington disease is associated with an increase in **dopamine** and decrease in **Ach, GABA**
30
Parkinson disease is associated with an increase in [NTs] and decrease in [NTs]
Parkinson disease is associated with an increase in **Ach** and decrease in **dopamine, serotonin**
31
Cognitive fluctuation is a feature of [neurodegenerative disease]
Cognitive fluctuation is a feature of **dementia with lewy bodies**
32
Visual hallucination is a feature of [neurodegenerative disease]
Visual hallucination is a feature of **dementia with lewy bodies**
33
REM sleep behavior disorder is associated with [neurodegenerative disease]
REM sleep behavior disorder is associated with **dementia with lewy bodies**
34
Alzheimer disease may be detectable on MRI by the presence of _
Alzheimer disease may be detectable on MRI by the presence of **hippocampal atrophy**
* Also see widened sulci, enlarged ventricles, and shrinkage of cortex
35
Frontotemporal dementia is associated with _ and _ (cell inclusions)
Frontotemporal dementia is associated with **Tau** and **TDP-43** (cell inclusions)
36
The pattern of atrophy in Alzheimer disease is _
The pattern of atrophy in Alzheimer disease is **diffuse and symmetric**;
* *Seen in frontal, temporal, parietal and usually spares the occipital*
37
Individuals with [chromosomal abnormality] are at an increased risk for Alzheimer
Individuals with **down syndrome** are at an increased risk for Alzheimer
* Due to **third copy of chromosome 21 --> APP gene**
* All patients with downs will eventually develop AD
38
What is APO-E and how is it related to Alzheimer?
APO-E is involved in **cholesterol transport to neurons & breakdown of beta-amyloid**
39
_ form of APO-E increases the risk of Alzheimer while _ form decreases risk
**E4** form of APO-E increases the risk of Alzheimer while **E2** form decreases risk
40
Alpha secretase/ alpha cleavage results in soluble, nontoxic protein whereas beta secretase/beta cleavage results in _
Alpha secretase/ alpha cleavage results in soluble, nontoxic protein whereas beta secretase/beta cleavage results in **insoluble protein --> A-beta deposits**
41
_ is a functional subdivision of the prefrontal cortex that is involved in moedulation of emotional behavior, decision making, and social recognition
**Orbitofrontal cortex** is a functional subdivision of the prefrontal cortex that is involved in moedulation of emotional behavior, decision making, and social recognition
42
Grossly, the brain would appear with _ in frontotemporal dementia
Grossly, the brain would appear with **asymmetric atrophy of frontal and temporal lobe** in frontotemporal dementia
* Note that it tends to be *asymmetric* (unlike Alzheimer)
* It tends to spare the parietal lobes
43
Frontotemporal dementia presents with [signs]
Frontotemporal dementia presents with **market personality change > memory loss**
* *Apathy, disinhibition, loss of insight and emotional control*
* *Global cognitive decline*
44
Frontotemporal dementia involves tau-positive spherical _ cytoplasmic neuronal inclusions called _
Frontotemporal dementia involves tau-positive spherical **intracytoplasmic** neuronal inclusions called **pick bodies**
45
Hereditary frontotemporal dementia (common) tends to be [inheritance]
Hereditary frontotemporal dementia (common) tends to be **autosomal dominant**
46
Three types of primary progressive aphasias include:
Three types of primary progressive aphasias include:
* **Agrammatic** Nonfluent, impaired repetition but preserved naming
* **Logopenic** Reduced fluency, impaired word retrieval (AD) and impaired repetition
* **Semantic** fluent speech and repetition but impaired word comprehension (naming)
47
Progressive supranuclear palsy is caused by _
Progressive supranuclear palsy is caused by **midbrain atrophy, "hummingbird sign"**
48
Huntington disease is an autosomal dominant trinucleotide repeat: _
Huntington disease is an autosomal dominant trinucleotide repeat: **CAG**
49
Huntington disease involves a repeat expansion in the [gene] on [chromosome]
Huntington disease involves a repeat expansion in the **HTT** on **chromosome 4**
* Variable penetrance depending on repeats
* Anticipation results from expansion of CAG
50
Huntington symptoms usually present around age _ and include _
Huntington symptoms usually present around age **20-50** and include **chorea, athetosis, aggression, depression, dementia**
51
In huntington disease we see atrophy of the _ structures with ex vacuo ventriculomegaly
In huntington disease we see atrophy of the **caudate and putamen** with ex vacuo ventriculomegaly
52
Neuronal cell death in huntington occurs via NMDA-R binding and _ excitotoxicity
Neuronal cell death in huntington occurs via NMDA-R binding and **glutamate excitotoxicity**
53
The clinical hallmark of ALS is _ motor neuron findings
The clinical hallmark of ALS is **mixed upper and lower motor neuron** findings
* *Muscles will undergo denervation atrophy*
54
Degeneration of lower motor neurons in ALS occurs in the _
Degeneration of lower motor neurons in ALS occurs in the **anterior horn cells**
55
Degeneration of upper motor neurons in ALS occurs in the _
Degeneration of upper motor neurons in ALS occurs in the **corticospinal tract**
56
_ are small eosinophilic intraneuronal inclusions in the remaining lower motor neurons of ALS patients
**Bunina bodies** are small eosinophilic intraneuronal inclusions in the remaining lower motor neurons of ALS patients
57
ALS can also affect _ , resulting in bulbar muscle dysfunction (dysphagia, dysarthria, difficulty chewing/breathing)
ALS can also affect **motor nuclei in brainstem** , resulting in bulbar muscle dysfunction (dysphagia, dysarthria, difficulty chewing/breathing)
58
ALS will spare the extraocular muscles and _
ALS will spare the extraocular muscles and **spincters (no incontence)**
59
Many sporadic and familial cases of ALS involve a mutation in [gene]
Many sporadic and familial cases of ALS involve a mutation in **SOD1**
60
Mutations in [gene] is linked to both ALS and FTD
Mutations in **C9ORF72** is linked to both ALS and FTD
61
The pyramidal system involves _ and _ tracts
The pyramidal system involves **corticospinal** and **corticobulbar** tracts
62
The extrapyramidal system involves (4 tracts):
The extrapyramidal system involves (4 tracts):
1. **Rubrospinal**
2. **Tectospinal**
3. **Reticulospinal**
4. **Vestibulospinal**
63
Name 5 parts of the basal ganglia:
Name 5 parts of the basal ganglia:
1. Caudate nucleus
2. Putamen
3. Globus pallidus
4. Substantia nigra
5. Subthalamic nucleus
64
ID the substantia nigra and the subthalamic nucleus
65
All input to the basal ganglia comes through the _
All input to the basal ganglia comes through the **striatum**
* *Recall that the striatum is caudate + putamen*
66
The [globus pallidus i or e] is the major output from the basal ganglia
The **globus pallidus internus** is the major output from the basal ganglia
67
The direct basal ganglia pathway _ movement
The direct basal ganglia pathway **facilitates/increases** movement
68
The indirect basal ganglia pathway _ movement
The *indirect* basal ganglia pathway **inhibits** movement
69
The GPi is involved in the (direct/ indirect) pathway
The GPi is involved in the **direct** pathway
70
The substantia nigra pars compacta uses _ to project to the striatum
The substantia nigra pars compacta uses **dopamine** to project to the striatum
71
The substantia nigra reticulata uses _ to project to the globus pallidus
The substantia nigra reticulata uses **GABA** to project to the globus pallidus
72
The subthalamic nucleus uses _ to project to the globus pallidus
The subthalamic nucleus uses **glutamate** to project to the globus pallidus
73
The motor symptoms of parkinson disease can be remembered with the mneumonic:
The motor symptoms of parkinson disease can be remembered with the mneumonic: **TRAP**
* **Tremor**
* **Rigidity**
* **Akinesia**
* **Postural instability**
74
Benign essential tremors are characterized by occuring with (rest/action)
Benign essential tremors are characterized by occuring with **action**
* Includes both postural and intention tremors
* Difficulty with eating, drinking, fine motor tasks
* Worse with emotional distress and relieved by alcohol
75
Treatment for benign essential tremor is _
Treatment for benign essential tremor is **beta-blockers (propranolol)**
76
Cerebellar tremors are coarse and are often worse during _
Cerebellar tremors are coarse and are often worse during **end of purposeful movement**
76
Parkinsonism-associated tremor is activated by (rest/action)
Parkinsonism-associated tremor is activated by **rest**
77
Differential for conditions that cause chorea:
Differential for conditions that cause chorea:
* **Huntington's**
* **Parkinson's meds**
* **Antipsychotics**
* **Post-strep infection (sydenham's chorea)**
* Lupus associated
* Chorea gravidarum
78
Antipsychotic drugs can cause a chorea movement called _
Antipsychotic drugs can cause a chorea movement called **tardive dyskinesia**
79
When extension of the wrists causes "flapping" motion we call it _
When extension of the wrists causes "flapping" motion we call it **asterixis**
* *Can be associated with Wilson disease*
80
Restlessness or intense urge to move is called _ ; can be seen as a side effect of Parkinson treatment
Restlessness or intense urge to move is called **akathisia**; can be seen as a side effect of Parkinson treatment
81
Slow, snake-like, writhing movements (especially in the fingers) is called _ and is a feature of _ disease
Slow, snake-like, writhing movements (especially in the fingers) is called **athetosis** and is a feature of **Huntington disease**
* *Suggests issue of basal ganglia*
82
_ are sudden, jerky, purposeless movements
**Chorea** are sudden, jerky, purposeless movements
* *Seen in Huntington*
83
Dystonia is _
Dystonia is **sustained, involuntary muscle contractions**
* Ex: writher's cramp, blepharospasm, torticollis
* Treat with botox
84
Sudden, wild flailing of one side of the body is called _
Sudden, wild flailing of one side of the body is called **hemiballismus**
* *Caused by contralateral subthalamic nucleus lesion (lacunar stroke)*
85
The goal of most parkinson drugs is to _
The goal of most parkinson drugs is to **increase or enhance dopamine signaling**
86
Levodopa works as [mechanism of action]
Levodopa works as a **precursor of dopamine synthesis**
* *It does cross the blood brain barrier, which is good because we need dopamine in CNS*
87
The issue with giving levodopa alone is that _ breaks it down in the periphery
The issue with giving levodopa alone is that **DDC (DOPA decarboxylase)** breaks it down in the periphery
* *Side effect is dopamine in periphery = vasoconstriction*
88
Carbidopa mechanism is _
Carbidopa mechanism is **blockage of peripheral DDC**
* *It does not cross the BBB so it cannot block central DDC which is a good thing --> we want conversion to dopamine in CNS*
89
_ is another drug which blocks peripheral degradation of levodopa by blocking COMT
**Entacapone** is another drug which blocks peripheral degradation of levodopa by blocking COMT
90
_ and _ are two dopamine agonists sometimes used to treat Parkinson disease
**Pramipexole** and **Ropinirole** are two dopamine agonists sometimes used to treat Parkinson disease
91
_ and _ are two drugs that can be used for Parkinson disease but also alternate treatments for restless leg syndrome
**Pramipexole** and **Ropinirole** are two drugs that can be used for Parkinson disease but also alternate treatments for restless leg syndrome
92
Toxicities of dopamine agonists like pramipexole and ropinirole:
Toxicities of dopamine agonists like pramipexole and ropinirole:
* **Inhibits prolactin secretion**
* **Sleep attacks**
* **OCD/ICD**
93
_ and _ are selective MAO-B inhibitors that slow the degradation of dopamine (and all other monoamine neurotransmitters)
**Selegiline** and **Rasagiline** are selective **MAO-B inhibitors** that slow the degradation of dopamine (and all other monoamine neurotransmitters)
* *They also increase the release of dopamine*
94
Selegiline and Rasagiline are _ type drugs
Selegiline and Rasagiline are **MAO-B inhibitors** and also increase release
95
An off-target toxicity of selegiline and rasagiline is _
An off-target toxicity of selegiline and rasagiline is **inhibition of MAO-A in the gut --> hypertensive crisis**
* This is rare because the drugs are selective for MAO-B
* However, tyramine containing foods can cause hypertensive crisis
96
Selegiline and rasagiline should not be combined with other [type drugs]
Selegiline and rasagiline should not be combined with other **serotonergic drugs**
* Can cause serotonin syndrome
97
All Parkinson drugs can have _ as a side effect due to enhanced signaling via the mesocortical and mesolimbic dopaminergic pathways
All Parkinson drugs can have **hallucinations** as a side effect due to enhanced signaling via the mesocortical and mesolimbic dopaminergic pathways
98
Amantadine can be used to treat Parkinson disease; it works by _
Amantadine can be used to treat Parkinson disease; it works by **increasing dopamine release** and **inhibiting reuptake**
99
Benztropine and trihexyphenidyl are two [category of drugs] that help Parkinson's patients by _
Benztropine and trihexyphenidyl are two **anti-cholinergics** that help Parkinson's patients by **rebalancing Ach & DA** in the basal ganglia
100
Benztropine and trihexyphenidyl act in the [location] and they only help to improve _ symptoms
Benztropine and trihexyphenidyl act in the **striatum** and they only help to improve **tremor and rigidity**
* Does not improve bradykinesia or gait instability
101
Benztropine and trihexyphenidyl have _ toxicities
Benztropine and trihexyphenidyl have **anti-parasympathetic** toxicities
102
"-Benazine" drugs are [drug type] that can be used for Huntington's
"-Benazine" drugs are **vMAT inhibitors** that can be used for Huntington's
* *They deplete the DA from vesicles*
* Ex: deutetrabenazine & tetrabenazine
103
_ , _ , and _ are three anti-psychotic drugs that treat Huntington's by antagonizing dopamine receptors
**Aripiprazole** , **Olanzapine** , and **Risperidone** are three anti-psychotic drugs that treat Huntington's by antagonizing dopamine receptors
104
_ , _ , and _ are three AchE inhibitors that improve Alzheimer disease by slowing the breakdown of Ach
**Donepezil** , **Galantamine** , and **Rivastigmine** are three AchE inhibitors that improve Alzheimer disease by slowing the breakdown of Ach
105
**Donepezil** , **Galantamine** , and **Rivastigmine** are AD drugs that have _ toxicities
**Donepezil** , **Galantamine** , and **Rivastigmine** are AD drugs that have **parasympathetic toxicities**
106
Abeta plaques in Alzheimer disease can affect the reuptake of _ , causing an increase in synaptic levels, spilling over into extrasynaptic receptors and causing excitotoxicity
Abeta plaques in Alzheimer disease can affect the reuptake of **glutamate** , causing an increase in synaptic levels, spilling over into extrasynaptic receptors and causing excitotoxicity
107
_ is an AD drug that inhibits NMDA receptors in the postsynaptic neuron to prevent glutamate excitotoxicity
**Memantine** is an AD drug that inhibits NMDA receptors in the postsynaptic neuron to prevent glutamate excitotoxicity
108
Lecanemab and Aducanumab are two AD drugs that work by _
Lecanemab and Aducanumab are two AD drugs that work by **clearing amyloid beta plaques**
* *However, they do not improve neurofibrillary tangles*
109
_ is an ALS drug that inhibits glutamate excitotoxicity and cell death
**Riluzole** is an ALS drug that inhibits glutamate excitotoxicity and cell death
110
Edaravone is an ALS drug with [MoA]
Edaravone is an ALS drug that **scavenges O2-radicals**
