EXAM #3: NEURODEGENERATIVE DISORDERS Flashcards

1
Q

What are the main characteristics of Neurodegnerative Disorders?

A

1) Loss of neurons
2) Due to BOTH genetic and environmental factors
3) Pathology= aggregation of misfolded proteins

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2
Q

What specific region is associated with neuronal loss in AD?

A

Hippocampus

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3
Q

What specific region is associated with neuronal loss in PD?

A

Basal Ganglia

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4
Q

What specific region is associated with neuronal loss in ALS

A

Cortical and spinal motor neurons

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5
Q

What protein accumulates in AD?

A

1) Beta-amyloid plaques
2) Neurofibrillary tangles

(Intracellular)

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6
Q

What protein accumulates in PD?

A

Alpha-synuclein

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7
Q

What protein accumulates in Huntington’s Disease?

A

Huntington Protein

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8
Q

What protein accumulates in Prion Disease?

A

Extracellular prion amyloid plaques

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9
Q

Who first diagnosed Alzheimer’s Disease?

A

Alois Alzheimer

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10
Q

Who was the first patient diagnosed with AD?

A

Frau August Deter

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11
Q

What is the most prevalent form of gradually progressive dementia?

A

AD

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12
Q

What are the cognitive symptoms of AD?

A

1) Loss of short-term memory
2) Aphasia
3) Apraxia
4) Agnosia
5) Disorientation

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13
Q

What is apraxia?

A

Inability to carry out motor activity despite intact motor system

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14
Q

What is agnosia?

A

Inability to recognize objects, persons, sounds, shapes, or smells

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15
Q

What are the noncognitive symptoms of AD?

A

1) Depression

2) Psychotic symptoms

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16
Q

What typically causes death in AD?

A

Complications of immobility i.e. pneumonia or PE

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17
Q

What is the Cholinergic Hypothesis of AD?

A

Memory deficits are due to a degeneration of subcortical cholinergic neurons

18
Q

Describe the pathology of AD.

A

1) Amyloid Precursor Protein is cleaved to Beta-Amyloid
2) There is an imbalance between Beta-Amyloid production and clearance
3) Beta-Amyloid is toxic to neurons

19
Q

What is the connection between Beta-Amyloid, AD, and Down’s Syndrome?

A

APP gene (which is cleaved to Beta-Amyloid) is located on chromosome 21

20
Q

What genes are mutated in early onset AD?

A

1) APP

2) Presenilin 1 and 2

21
Q

What is the function of Presenilin?

A

Cleavage of APP

22
Q

What genetic variation is late onset AD associated with?

A

Epsiolon 4 allele of ApoE

23
Q

What is the role of ApoE in AD?

A

ApoE clears Beta-Amyloid

24
Q

What is the function of Episolon 4 ApoE in AD?

A

This form of ApoE does not clear Beta-Amyloid as well as other isoforms and increases the development of AD

25
Q

What is the Tau Hypothesis of AD?

A
  • Tau normally supports microtubules and the neuronal cytoskeleton
  • HYPERphosphorylation of Tau causes aggregates i.e. neurofibrillary tangles to form
26
Q

What are the outcomes of neuofibrillary tangles in AD?

A

1) Microtubular disintegration and instability
2) Collapse of neuronal transport
3) Altered NT release and synaptic function
4) Cell death

27
Q

What class of drug is the first line treatment for cognitive symptoms of AD?

A

Cholinesterase inhibitors

28
Q

What is the mechanism of action of the Cholinesterase Inhibitors?

A

Block AChE and Butyrylcholinesterase mediated breakdown of ACh to choline and acetate

29
Q

List the drugs that are used as Cholinesterase Inhibitors in the first line treatment of AD.

A

1) Tacrine
2) Donepezil
3) Rivastigmine
4) Galantamine

30
Q

Why is Tacrine no longer used today for the treatment of AD?`

A

Hepatotoxicity

Note that is also had a very short half-life and needed to be taken 4x per day*

31
Q

What is the mechanism of action of Donepezil?

A

AChE inhibition

32
Q

What is unique about Donepezil compared to the other AChEs used to treat AD?

A

Long half life (70 hrs) that allows for ONCE A DAY dosing

33
Q

Which of the first line agents for AD blocks BOTH AChE and Butyrylcholinesterase?

A

Rivastigmine

34
Q

How often does Rivastigmine need to be dosed?

A

Twice per day

35
Q

What AChE can be given as a transdermal patch? What are the clinical implcations?

A

Rivastigmine–less GI adverse effects

36
Q

What are the typical side effects of AChEs used to treated AD?

A

1) Nausea
2) Vomiting
3) Diarrhea

37
Q

What are the side effects of AChE overdose?

A

SLUDGE

  • Salivation
  • Lacrimation
  • Urination
  • Defecation
  • GI cramps
  • Emesis
38
Q

What is the MOA of Memantine?

A

Non-competitive NMDA antagonist

39
Q

What is the role of Memantine in AD?

A

Neuroprotection by reducing glutamate excitotoxicity

40
Q

What class of drugs are primarily used to treat the psychotic symptoms of AD?

A

Atypical antipsychotics

41
Q

What drugs should be used to treat depression in AD?

A

SSRIs

42
Q

What drugs should NOT be used to treat depression in AD?

A

TCAs–alpha-1 effects cause orthostatic hypotension (fall risk)