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Flashcards in Neurodegenerative diseases Deck (58)
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1
Q

What are the major areas affected in AD?

A

Hippocampal and cortical neurons

2
Q

Are neurodegenerative disorders genetic or environmental?

A

Both

3
Q

What is the major pathological mechanism associated with neurodegenerative disorders?

A

Aggregation of misfolded proteins

4
Q

What is the pathological basis for ALS?

A

Degeneration of cortical and spinal motor neurons

5
Q

What is the pathological basis for Parkinson’s and Huntington’s disease?

A

Loss of dopaminergic neurons in basal ganglia

6
Q

How fast does death come with AD?

A

6-12

7
Q

What is the protein that accumulates in AD? How do these aggregate?

A

beta-amyloid plaques

Neurofibrillary tangles

8
Q

What is the protein that accumulates in PD? How do these aggregate?

A

alpha synuclein

Forms Parkinson Lewy bodies

9
Q

What is the protein that accumulates in Huntington’s disease? How do these aggregate?

A

Huntingtin protein (intranuclear)

10
Q

What is the protein that accumulates in creutzfeldt-jakob disease?

A

Prion amyloid proteins

11
Q

When in life do the neurodegenerative disorders usually present?

A

65+

12
Q

What is the gene that is implicated in early onset AD? Late?

A
Early = APP gene (gene for precursor amyloid protein), and PSEN1/2
Late = epsilon4 APOE allele
13
Q

What are the ssx of Alzheimers?

A
  1. Loss of short term memory
  2. Aphasia
  3. Agnosia
  4. Disorientation
14
Q

What are the neurocognitive ssx of Alzheimer’s?

A

Depression

Psychotic symptoms

15
Q

What is aphasia?

A

Difficulty remembering words

16
Q

What is apraxia?

A

Inability to carry out motor activities

17
Q

What is agnosia?

A

Inability to recognize object, people, etc

18
Q

How do you diagnose AD?

A

Progressive cognitive impairment

19
Q

What are the elements of the neurofibrillary tangles in AD?

A

Hyperphosphorylation of tau proteins

20
Q

What are the elements of amyloid plaques in AD?

A

Insoluble amyloid B proteins

21
Q

What is the neurotransmitter that is lacking in AD? Which area of the brain is involved?

A

Deficiency in cortical ACh

22
Q

What is the pre-AD state called? What are the symptoms of this? Does this always lead to AD?

A

Mild cognitive impairment

Cognitive impairment NOT reducing function

Does not guarantee AD

23
Q

What are the ssx of mild AD?

A

Memory loss
Confusion
Impaired judgement
Decreased congition

24
Q

What are the ssx of moderate AD? (4)

A
  • Language impairment
  • Decreased comprehension
  • Disorientation
  • Sleep disorders
25
Q

What are the ssx of severe AD? (4)

A
  • Dependence
  • Delusions
  • Agitation
  • Incapacitation
26
Q

What is the cholinergic hypothesis in AD?

A

Degeneration of ACh in subcortical cholinergic neurons

27
Q

True or false: there is a strong correlation between the accumulation of beta-amyloid proteins and neuronal loss in AD

A

False –poor correlation

28
Q

Why is it that pts with Down syndrome are predisposed to AD?

A

APP gene for beta-amyloid is located on chromosome 21. These pts get an extra copy of the chromosome

29
Q

What is the role of APP? PSEN1-(2)?

A

APP = encodes amyloid beta precursor peptide

PEN1/2 = Membrane proteins involved in cleaving APP

30
Q

What is the role of epsilon3 allele of APOE?

A

Encodes apolipoprotein E, which enhances the breakdown and clearance of A-beta within and between cells

31
Q

What is the Tau hypothesis?

A

Hyperphosphorylation of Tau causes microtubular instability, and subsequent collapse of the neuronal transport system. This leads to cell death

32
Q

What is the function of Tau normally?

A

Provides support for microtubule structures

33
Q

What are the histological characteristics of AD?

A

Plaques and tangles surrounded by halo of nerve endings, with microglia

34
Q

What is the primary intervention for AD?

A

nonpharmacologic therapy

35
Q

What are the two goals of pharmacological therapy with AD?

A
  • Symptomatically treat cognitive difficulties

- Treat behavioral and psychiatric symptoms

36
Q

What are the three current focuses of R&D toward AD?

A

Drugs targeting Beta amyloid, Tau, and ApoE

37
Q

What is the role of AChE (BChE) inhibitors in AD?

A

Slow down the degradation of ACh

38
Q

What is the effect of AChE inhibitors on Tau function?

A

Rebalance the overly phosphorylated Tau protein state back to normal

39
Q

What is the effect of AChE inhibitors on APP?

A

Increase in soluble APP and decreased production of Abeta

40
Q

What are the 5 AChE inhibitors used to treat AD?

A

Tacrine
Donepezil
Rivastigmine
Galantamine

41
Q

What is the MOA of tacrine?

A

AChE inhibitor

42
Q

What is the MOA of Donepezil?

A

AChE inhibitor

43
Q

What is the MOA of Rivastigmine? How is it administered?

A

AChE and BChE inhibitor

Transdermally

44
Q

What is the MOA of Galantamine?

A

AChE inhibitor

45
Q

What are the side effects of the AChE inhibitors?

A

Diarrhea
N/v
Insomnia
Weight loss

46
Q

Why did Tacrine have such a low compliance rate?

A

Short half life meaning need for frequent dosing, which is hard for those with memory impairment

47
Q

What is the half-life of Donepezil?

A

70-80 hours

48
Q

What are the general side effects of cholinesterase inhibitors?

A
Salivation
Lacrimation
Urinary incontinence
Diarrhea
Intestinal cramps
Emesis
49
Q

What is the MOA of Memantine? Halflife?

A

Non-competitive antagonist of NMDA receptors

60-80 hour half life

50
Q

How does Memantine provide neuroprotection?

A

Reducing intracellular Ca influx and glutamate induced excitotoxicity

51
Q

Is estrogen effective in preventing or treating AD?

A

No

52
Q

What is the role of vitamin E and AD?

A

Not valid, mixed results

53
Q

What is the role of Ginkgo in AD?

A

Not valid, mixed results

54
Q

What is the role of NSAIDs in AD treatment?

A

Decrease the inflammatory process of microglia, but not evidence for influencing existing A

55
Q

What are the drugs used to treat the psychosis/agitated behavior associated with AD?

A

Atypical antipsychotics

56
Q

What are the two SSRIs that are used to treat depression associated with AD?

A

Sertraline

Citalopram

57
Q

Why should you avoid TCAs in AD?

A

Anticholinergic effect and the orthostatic hypotension

58
Q

What is the mood stabilizers for AD pts?

A

Carbamazepine