Alzheimers Disease

Question 1

What is the obvious sign of AD?

Answer 1

reduced functional capacity along with mild cognitive impairment

Question 2

What is the specific genotype that causes a 2-10 fold risk of AD?

Answer 2

APOE4

Question 3

What are the 3 causes of AD?

Answer 3

1. beta-amyloid misfolding
2. Tau misfolding
3. low amount of cortical neurons due to misfolding

Question 4

What is the AD pathophysiology?

Answer 4

increase amount of Amyloid plaques due to misfolds

Question 5

What neurotransmitter is decreased in AD?

Answer 5

Ach

Question 6

What is the cholinergic hypothesis?

Answer 6

a deficiency of Ach is critical for the genesis of the AD symptoms

Question 7

What are the two therapeutic strategies in AD?

Answer 7

1. Acetycholinesterase Inhibitors
2. N-methyl-D-aspartate glutamate receptor antagonists

Question 8

How do acetylcholinesterase Inhibitors work?

Answer 8

prevent Ach from being broken down and increasing it in the synaptic cleft; therefore increasing its chances of binding the receptor

Question 9

What are the three Acetylcholinesterase Inhibitors?

Answer 9

1. Donzepil (Aricept)
2. Rivastigmine
3. Galantamine

Question 10

What are the main side effects of Acetylcholinesterase Inhibitors?

Answer 10

1. nausea
2. vomiting
3. diarrhea

Question 11

What is unique about Donzepil (Aricept)?

Answer 11

used to treat mild-severe AD

Question 12

What is unique about Rivastigmine?

Answer 12

utilizes esterases not CYP for metabolism

Question 13

What is unique about Galantamine?

Answer 13

• competitive inhibitor
• allosterically modulates nicotinic receptors which improves cholinergic neurotransmission

Question 14

How does Memantine (Namenda) work?

Answer 14

• NMDA-receptor antagonist; prevents CA and other ions; while also lowering the amount of glutamate lowering excitation

Question 15

What is unique about Memantine?

Answer 15

reduces the rate of clinical deterioration in moderate-severe AD
used as an adjunct therapy

Question 16

What is unique about Memantine/Donepezil (Namzaric)?

Answer 16

does a good job with cognitive symptoms, but not with Non-cognitive symptoms

Question 17

How do monoclonal antibodies work?

Answer 17

attach to protein and target it for removal

Question 18

What is unique about Lecanemab?

Answer 18

recognizes protofibrils and prevents amyloid-beta deposition (attacks before the plaque preventing it from growing into a serious plaque

Question 19

What is unique about Aducanumab?

Answer 19

targets and removes beta-amyloid that accumulate into plaques

Question 20

When are monoclonal antibodies used in treatment for alzheimers disease?

Answer 20

early symptoms

Question 21

What is Huntington’s Disease?

Answer 21

gradual onset of motor incoordination and cognitive decline

Question 22

How is Huntington’s Disease presented?

Answer 22

• corea (brief jerk like symptoms)
• personality changes

Question 23

What is the pathology of Huntington’s Disease?

Answer 23

expansion of CAG near the huntingtin protein

Question 24

What neurotransmissions are decreased in Huntington’s Disease?

Answer 24

• GABA
• Ach
  this leads to an imbalance with dopamine

Question 25

What are the treatment options for Huntington's Disease?

Answer 25

VMAT2 inhibitors; take up dopamine lowering the amount of dopamine fixing the imbalance

Question 26

What is unique about Tetrabenzine (Xenazine)

Answer 26

- reversible inhibitor (VMAT2) which will cause chorea

Question 27

What is unique about ALS?

Answer 27

- fast acting - affects the spinal cord and cortical neurons

Question 28

What neurotransmitter is important in ALS?

Answer 28

glutamate

Question 29

What is unique about Riluzole (Rilutek)?

Answer 29

only drug shown to have any effect on survival reduces glutamate-induced excitotoxicity - non-competitive block of NMDA receptor mediated responses