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Neurodegenerative diseases Flashcards

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1
Q

What are the major areas affected in AD?

A

Hippocampal and cortical neurons

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2
Q

Are neurodegenerative disorders genetic or environmental?

A

Both

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3
Q

What is the major pathological mechanism associated with neurodegenerative disorders?

A

Aggregation of misfolded proteins

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4
Q

What is the pathological basis for ALS?

A

Degeneration of cortical and spinal motor neurons

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5
Q

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

A

Loss of dopaminergic neurons in basal ganglia

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6
Q

How fast does death come with AD?

A

6-12

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7
Q

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

A

beta-amyloid plaques

Neurofibrillary tangles

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8
Q

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

A

alpha synuclein

Forms Parkinson Lewy bodies

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9
Q

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

A

Huntingtin protein (intranuclear)

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10
Q

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

A

Prion amyloid proteins

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11
Q

When in life do the neurodegenerative disorders usually present?

A

65+

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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
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13
Q

What are the ssx of Alzheimers?

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

What are the neurocognitive ssx of Alzheimer’s?

A

Depression

Psychotic symptoms

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15
Q

What is aphasia?

A

Difficulty remembering words

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16
Q

What is apraxia?

A

Inability to carry out motor activities

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17
Q

What is agnosia?

A

Inability to recognize object, people, etc

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18
Q

How do you diagnose AD?

A

Progressive cognitive impairment

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19
Q

What are the elements of the neurofibrillary tangles in AD?

A

Hyperphosphorylation of tau proteins

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20
Q

What are the elements of amyloid plaques in AD?

A

Insoluble amyloid B proteins

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21
Q

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

A

Deficiency in cortical ACh

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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

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23
Q

What are the ssx of mild AD?

A

Memory loss
Confusion
Impaired judgement
Decreased congition

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24
Q

What are the ssx of moderate AD? (4)

Study These Flashcards
A
  • Language impairment
  • Decreased comprehension
  • Disorientation
  • Sleep disorders
25
What are the ssx of severe AD? (4)
- Dependence - Delusions - Agitation - Incapacitation
26
What is the cholinergic hypothesis in AD?
Degeneration of ACh in subcortical cholinergic neurons
27
True or false: there is a strong correlation between the accumulation of beta-amyloid proteins and neuronal loss in AD
False --poor correlation
28
Why is it that pts with Down syndrome are predisposed to AD?
APP gene for beta-amyloid is located on chromosome 21. These pts get an extra copy of the chromosome
29
What is the role of APP? PSEN1-(2)?
APP = encodes amyloid beta precursor peptide PEN1/2 = Membrane proteins involved in cleaving APP
30
What is the role of epsilon3 allele of APOE?
Encodes apolipoprotein E, which enhances the breakdown and clearance of A-beta within and between cells
31
What is the Tau hypothesis?
Hyperphosphorylation of Tau causes microtubular instability, and subsequent collapse of the neuronal transport system. This leads to cell death
32
What is the function of Tau normally?
Provides support for microtubule structures
33
What are the histological characteristics of AD?
Plaques and tangles surrounded by halo of nerve endings, with microglia
34
What is the primary intervention for AD?
nonpharmacologic therapy
35
What are the two goals of pharmacological therapy with AD?
- Symptomatically treat cognitive difficulties | - Treat behavioral and psychiatric symptoms
36
What are the three current focuses of R&D toward AD?
Drugs targeting Beta amyloid, Tau, and ApoE
37
What is the role of AChE (BChE) inhibitors in AD?
Slow down the degradation of ACh
38
What is the effect of AChE inhibitors on Tau function?
Rebalance the overly phosphorylated Tau protein state back to normal
39
What is the effect of AChE inhibitors on APP?
Increase in soluble APP and decreased production of Abeta
40
What are the 5 AChE inhibitors used to treat AD?
Tacrine Donepezil Rivastigmine Galantamine
41
What is the MOA of tacrine?
AChE inhibitor
42
What is the MOA of Donepezil?
AChE inhibitor
43
What is the MOA of Rivastigmine? How is it administered?
AChE and BChE inhibitor Transdermally
44
What is the MOA of Galantamine?
AChE inhibitor
45
What are the side effects of the AChE inhibitors?
Diarrhea N/v Insomnia Weight loss
46
Why did Tacrine have such a low compliance rate?
Short half life meaning need for frequent dosing, which is hard for those with memory impairment
47
What is the half-life of Donepezil?
70-80 hours
48
What are the general side effects of cholinesterase inhibitors?
``` Salivation Lacrimation Urinary incontinence Diarrhea Intestinal cramps Emesis ```
49
What is the MOA of Memantine? Halflife?
Non-competitive antagonist of NMDA receptors 60-80 hour half life
50
How does Memantine provide neuroprotection?
Reducing intracellular Ca influx and glutamate induced excitotoxicity
51
Is estrogen effective in preventing or treating AD?
No
52
What is the role of vitamin E and AD?
Not valid, mixed results
53
What is the role of Ginkgo in AD?
Not valid, mixed results
54
What is the role of NSAIDs in AD treatment?
Decrease the inflammatory process of microglia, but not evidence for influencing existing A
55
What are the drugs used to treat the psychosis/agitated behavior associated with AD?
Atypical antipsychotics
56
What are the two SSRIs that are used to treat depression associated with AD?
Sertraline | Citalopram
57
Why should you avoid TCAs in AD?
Anticholinergic effect and the orthostatic hypotension
58
What is the mood stabilizers for AD pts?
Carbamazepine

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