Alzheimers Disease

Question 1

AD is essentially what?

Remember ventricular enlargment, that’s a hint for one of them…

Answer 1

Neurodegeneration in of cholinergic neurons in the basal forebrain and hippocampus.

Question 2

2 histological signs of AD

Answer 2

Neurofibrillary tangles

Amyloid plaques

Question 3

2 signs of PD

Answer 3

Loss of pigmentetion in the SN

Lewy bodies.

Question 4

What makes acetylcholine from Acetyl CoA?

Answer 4

choline acetyletransferase

Question 5

What occurs with the anticholinergic TACRINE in addition to cholinergic effects?

Answer 5

hepatotoxicity.

Question 6

In addition to cholinergic effects (and hepatotoxicity if you’re tacrine) what is there that isn’t just the opposite of atropine effects?

Answer 6

nausea

vivid dreams

Question 7

What’s the point of cholinergic treatment for AD?

Answer 7

Reduce the FORMATION and TOXICITY of AB plaques.

Question 8

What is the biggest whore in AD cholinergic treatment?

Answer 8

Also inhibits BChE and isn’t selective for the CNS.

Question 9

4 cholinesterase inhibitors used in AD.

AD suffer was rescued by some galant person after falling into a river trying to save his pet thumb tac. Now he’s done a puzzle. Good for him.

Answer 9

Tacrine
Donepezil
Rivastigmine
Galantamine

Question 10

4 cholinesterase inhibitors used in AD.

Answer 10

Tacrine
Donepezil
Rivastigmine
Galantamine

Question 11

Which 2 anticholinesterases are CNS selective?

Which also has an eye for the BChE?
People who do puzzles are far to sensible for such promiscuous behaviour.

Answer 11

Donepezil

Rivastigmine

Question 12

Which 2 anticholinesterases are CNS selective?

Answer 12

Donepezil

Rivastigmine

Question 13

Do anticholinesterases have hepatic metabolism?

Answer 13

YES.

Question 14

What’s that extra galant effort that galantamine puts in?

Answer 14

It’s also a nAChR agonist.

Question 15

What is memantine?

Answer 15

It’s an NDMA competitive antagonist.

Question 16

What’s the point of inhibiting NMDA receptors?

Answer 16

Inhibiting exitotoxicity, which is mediated by glutamine. Same as in the antidepressants lecture.

Question 17

Excitotocity - what are the only two things you have to remember about that?

Answer 17

oxidative stress and apoptosis.

Question 18

What is key to the pathogenesis of AD?

What’s the other one?

Answer 18

Altered processing of amyloid precursor protein (APP)

Abnormal Tau phosphorylation.

Question 19

In the pathogenesis of AD, what’s the protein that whose phosphorylation gets fuck up?

Answer 19

Tau. No one’s sure why but the plaques don’t help.

Question 20

Which AchRs are downregulated in AD - muscarinic or nicotinic?

Answer 20

NICOTINIC.

mAChR density isn’t affected.

Question 21

If you hear any even slightly quack sounding therapies there’s no evidence for them.

Answer 21

Non-drug treatments are limited to pretty much counselling.

Question 22

Anticholinesterase therapy is kinda defeatist. BRIEFLY describe the treatment protocols.

Answer 22

Everything’s equally as effective. If something’s not working, try something else.