Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PMCOL 412 > Dementia II > Flashcards

Dementia II Flashcards

1
Q

AD definition

A

the prevalent cause of dementia in the elderly. It is a progressive neurodegenerative disorder characterized by gradual loss of memory followed by deterioration of higher cognitive functions

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

AD afflicts about _% in population over 65 yrs of age. It’s prevalence ____ every 5 yrs thereafter

A

5%, doubles

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

Etiologically only ___% AD are due to genetic abnormality and ___% sporadic

A

<10% AD are genetic and >90% sporadic

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

Gene defects (3) in AD

A

Beta-amyloid precursor protein gene; presenilin 1 gene ; presenilin 2 gene

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

Beta-amyloid precursor protein gene–chr #, age of onset, % of AD and implication

A

chr: 21
age of onset: 45-65 yrs
1% of all AD
causative

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

Presenilin 1 gene-chr #, age of onset, % of AD and implication

A

chr: 14
age of onset: 30-60 yrs
5-7% of all AD
causative

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

Presenilin 2 gene-chr #, age of onset, and implication

A

chr: 1
age of onset: 45-65 yrs
causative

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

Risk factors for AD

A

APOE4 allele, age, female gender, high mid-life cholesterol, head injury and stress

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

Average course of AD is __ years. Memory impairment is present ____

A

10 yrs; present at earliest stage of the the disease

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

Symptoms of AD

A

Access to distant memory is gradually lost.
Other losses include language, motor skills, orientation and judgment
Some patients show psychotic symptoms.

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

Late Stage AD

A

At late stages patients are often mute, incontinent and die of intercurrent illnesses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

AD diagnosis based on

A 
lacks a validated test or biological marker
Diagnosis is based on
- clinical histories
- physical examination
- neuropsychological tests
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

According to NINCDS-ADRDA criteria determine is AD is

A

Possible, Probable, Definite

likelihood that it is AD–confirmed with brain biopsy

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

DSM-IV-TR/NINCDS-ADRDA criteria divided AD into:

A

Preclinical, Prodromal, AD

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

Dementia markers in CSF used for diagnosis

A

Decrease A-beta, increased Tau and increased phospharylated Tau

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

Pet ligands used in AD diagnosis

A

11C-PIB, 18F-Florbetaben or 18F-AV-45 - A-beta deposition

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

AD is characterized neuropathologically by the presence of

A
  • Intracellular neurofibrillary tangles
  • Extracellular neuritic plaques
  • Loss of neurons and synaptic density
  • Cerebrovascular amyloid deposits
  • brain atrophy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

True/False: AD features can exist in healthy brains

A

TRUE

Features associated with AD are also observed in normal aged human brains but to a much lesser extent

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

NEUROFIBRILLARY TANGLES–what are they

A

NFTs are constitute paired helical and single straight filaments - made of phosphorylated tau protein - a microtubule associated protein

Tangle density correlates with dementia severity

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

NEUROFIBRILLARY TANGLES–where

A

Neurofibrillary tangles are present in cortex, amygdala, hippocampus and subcortical nuclei

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

Tau–types

A

six different isoforms

derived from a single gene which encodes proteins containing 352-441 a.a (different slicing –> different isoforms)

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

Tau’s role normally

A

Under normal conditions tau stabilizes microtubules by reversible phosphorylation and dephosphorylation mediated via protein kinases and phosphatases, respectively

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

Is tau phosphorylation bad?

A

Phosphorylated tau if not dephosphorylated
straight filaments –> PHF (paired helical filament)-Tau –> dysfunction
of neurons –> death of neurons

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

Tau pathologies

A

Apart from phosphorylation, cleavage of tau protein can also lead to neurodegeneration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Mutant tau transgenic mice leads to

A

tangles, loss of neurons and behavioral deficits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Tau may play a role in ____ of AD pathology

A

SPREADING

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Neuritic plaques–defintion

A

Spherical, multicellular lesions containing A-beta peptides surrounded by dystrophic neurites, activated microglia and reactive astrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Neuritic plaques life

A

Extracellular A-beta peptides deposited as diffuse plaques –> primitive plaques –> senile plaques –> burned out plaques

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Diffuse plaques –unaffected areas

A

thalamus, striatum, cerebellum (unaffected areas)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Neuritic plaques–affected areas

A

cortex, hippocampus, subcortical nuclei – affected areas

31
Q

T/F: Plaque density correlates to dementia severity

A

FALSE
Plaque density usually does not correlate
with dementia severity

32
Q

A-beta peptide makes up

A

The principal component of all plaques is a 39-43 a.a. A-beta peptide - generated from Amyloid Precursor Protein (APP)

33
Q

A-beta accumulation timeline

A

Intracellular A-beta accumulation precedes neurofibrillary tangles and extracellular A-beta deposition

34
Q

APP is processed by 2 pathways

A

amyloidogenic pathway and non-amyloidogenic pathway

35
Q

amyloidogenic pathway

A

amyloidogenic pathway mediated by beta- and gamma-secretases lead to the formation of A-beta peptides

36
Q

non-amyloidogenic pathway

A

mediated by alpha-secretase

Does not form A-beta peptides (cleaved APP so A-beta protein is not intact)

37
Q

A-beta peptide contributions to AD pathology

A

i) APP/PS mutations lead to AD pathology by increasing Aβ production
ii) intracellular A-beta accumulation precedes other lesions
iii) A-beta peptides are toxic to neurons
iv) APP transgenic mice recapitulate some features of AD

38
Q

Familial vs. Sporadic AD

A

Familial AD cases are caused by increased production of A-beta peptide, whereas sporadic AD cases are caused by decreased clearance of A-beta

39
Q

AD neuronal loss occurred in

A

Neurons and synapses are lost in selected brain regions: cortex, hippocampus, amygdala and certain subcortical nuclei

40
Q

Subcortical neurons affected in AD brains:

A
  • Forebrain cholinergic neurons (30-95%)
  • Noradrenergic neurons of locus ceruleus - (40-80%)
  • Serotonin neurons of dorsal raphe - (0-39%)
  • Glutamatergic neurons - (severe loss)
41
Q

T/F: Loss of synaptic density correlates with dementia severity

A

True

42
Q

Loss of basal forebrain cholinergic neurons leads to…

A

decrease of acetylcholine levels in the hippocampus and cortex – which correlate with dementia severity

43
Q

Neuronal cell loss

A

Cause of cell loss is not known

44
Q

AD pathologies in familial cases

A

at least for familial cases, is caused by amyloid cascade hypothesis i.e., increased production and/or lack of clearance can lead to AD pathology by enhancing A-beta levels –> neuronal death –> decreased levels of NTs –> cognitive deficits

45
Q

amyloid cascade

A

Enhancing A-beta levels

Through oxidation, excitability, A-beta aggregation, inflammation, Tau hyperphosphorylation

46
Q

T/F: AD drugs only provide symptomatic relief for AD patients

A

TRUE
At present there is no cure for AD
Available treatment provides symptomatic relief for a fraction of AD patients

47
Q

Main FDA approved drugs for AD

A

i) AchE inhibitors

ii) Memantine (NMDAR antagonist)

48
Q

AchE inhibitors for AD

A

ex. tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl)
increase acetylcholine level by blocking cholinesterase (AChE)

49
Q

memantine for AD

A

NMDAR antag

neuroprotection and enhancement of learning and memory – can be used with AChE blockers

50
Q

Other AD treatments under investigation

A
  • neurorestorative factors - neurotrophins, nutraceuticals, estrogens etc.
  • anti-inflammatory drugs - indomethacin
  • antioxidants, free-radical scavengers - vitamin E, selegiline, red wine etc.
  • inhibitors of A-beta production - blockers of beta- or gamma-secretases
  • vaccination using A-beta-related peptide
51
Q

VaD is caused by

A

caused by reduce or blockage of blood supply to the different parts of the brain, thus depriving them of oxygen and nutrients

52
Q

VaD prevalence ____ with age

A

increases

53
Q

Risk factors for VaD

A

Age, hypertension, history of strokes, diabetes, smoking, APOE4 genotype

54
Q

Etiology of VaD

A

most cases are sporadic,
whereas <1% are believed to be heritable:
- CADASIL: caused by mutations in NOTCH3 gene
- FCAA: caused by mutations in the APP, CST3 (Cystatin 3) and ITM2B (Integral
membrane protein 2) genes

55
Q

T/F: VaD often co-exists with other types of dementia

A

TRUE, includes AD, LBD

56
Q

VaD clinical presentation varies with…

A

location of infarcts.
Executive dysfunction rather than memory loss is
prominent

57
Q

VaD diagnosis based upon

A

family history, physical examinations,

cognitive tests and neuroimaging

58
Q

Pathology of VaD

A
  • Large vessel injury – multiple or single cortical/subcortical infarcts
  • Small vessel injury – multiple subcortical and white matter lacunae/lesions
59
Q

VaD treatment

A
  • Stroke prevention - aspirin or warfarin
  • Increasing acetylcholine levels - donepezil,
    rivastigmine and galantamine
  • Neuroprotection - memantine, statins,
    nimodipine, antioxidants
60
Q

FTLD definition

A

a cluster of disorders characterized by the atrophy of the frontal and anterior temporal lobes.

61
Q

FTLD’s 2 subtypes

A

a) behavioral and personality changes: includes i) fronto-temporal dementia and ii) Pick’s disease
b) language or communication changes: includes i) primary progressive aphasia and ii) semantic dementia

62
Q

FTLD is characterized by

A

apathy, loss of emotional control, loss of ability to recognize words/objects, language dysfunction and cognitive decline

63
Q

FTLD diagnosis includes

A

physical exam,
neuropsychological tests, family
history and neuroimaging using MRI
and CT to evaluate brain atrophy

64
Q

The majority of FTLD is caused by mutations of…

A

Tau and PGRN (progranulin) genes.

Others include CHMP2B (charged multivesicular body protein 2B), VCP (valosin containing protein) and c9orf72

65
Q

Neuropathology of FTLD

A

the disease is characterized by atrophy of frontal and

temporal lobes, neuronal loss, gliosis, inclusions of proteins such as tau or TAR-DNA binding protein-43 (TDP-43)

66
Q

Tau in FTLD

A

FTLD-Tau: hyperphosphorylated tau is deposited as paired helical and single straight filaments in neurons and glia

67
Q

TDP in FTLD

A

FTLD-TDP: ubiquitin-conjugated, hyperphosphorylated TDP-43 (a nuclear protein) is deposited in nucleus, cytoplasm and neuritis of the neurons

68
Q

Tretaments of FTLD

A

Not promising
Drugs used:
- peroxetine (SSRI) to reduce behavioral symptoms
- selegeline (MAOB inhibitor) to decrease agitation, aggressiveness and improve executive function

anticholinergic, NMDAR inhib do not work here

69
Q

Neurorestorative fators in AD

A

AD treatment includes neurotrophins, nutraceuticals, estrogens etc.
Goal: protect, rescue cell bodies

70
Q

anti-inflammatory drugs in AD

A

ex. indomethacin

work by interfering with microglial response

71
Q

antioxidants, free-radical scavengers in AD

A

ex. vitamin E, selegiline, red wine etc.

goal: protecting neurons against toxicity

72
Q

Inhibitors of A-beta production in AD

A

ex. blockers of beta- or gamma-secretase

inhibit A-beta production

73
Q

Vaccination using A-beta related peptide

A

Inject A-beta or anti-a-beta antibody

helps in animals, hasn’t worked in humans thus far

PMCOL 412 (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions