Alzheimer's Disease Flashcards
What is dementia?
Progressive deterioration of memory and cognitive function.
What is reversible dementia?
Theoretically treatable underlying cause.
What is irreversible dementia?
Caused by incurable condition.
What are some causes of reversible dementia?
Brain tumors, vitamin B-12 deficiency.
What are some causes of irreversible dementia?
Alzheimer’s, strokes.
What is the most common type of dementia?
Alzheimer’s Disease.
What gross findings are found in Alzheimer patients?
Cortical atrophy.
What historical findings were thought to be only associated with Alzheimer’s Disease?
Amyloid Plaques and neurofibillary tangles
What are amyloid plaques?
Contains primarily aggregated (fibrillary) forms of beta amyloid.
What are neurofibillary tangles?
Contain primarily abnormal tau.
What is cortical atrophy?
Caused by cell death and loss of neurons.
What 3 genes are associated with early-onset Alzheimer’s disease?
APP, PSEN1, PSEN2.
What is now thought to be the major driver of Alzheimer’s disease?
Smaller soluble A(beta) oligomers. They can block neurotransmitters, may trigger inflammation, may be toxic to neurons.
How could soluble A(beta) oligomers cause Alzheimer’s disease?
They can block neurotransmitters, may trigger inflammation, may be toxic to neurons.
What are the two main drug groups used to treat Alzheimer’s disease?
Acetylcholinesterase Inhibitors and Glutamate receptor partial antagonist. Or both together.
What is the role of acetylcholine in Alzheimer’s?
Loss of acetylcholine cells results in some of the symptoms of AD.
What does Acetylcholinesterase do?
It breaks down Acetylcholine.
How do Acetylcholinesterase Inhibitors help those with AD?
It stops the breakdown of ACh by Acetylcholinesterase, allowing for more ACh to be available.
Do Acetylcholinesterase Inhibitors alter the course of the disease?
No, but they may slow cognitive decline.
What are the 3 Acetylcholinesterase Inhibitors?
Donepezil (Aricept), Rivastigmine (Exelon), and Galantamine (Razadyne).
How does Donepezil (Aricept) work? Are its effects reversible? When can it be used?
It is a reversible inhibitor of AChE. It can used for all stages of AD.
What are the pros of using Donepezil (Aricept)?
Long half-life, fewer GI side effects.
How does Rivastigmine (Exelon) work? Are its effects reversible? When can it be used?
Inhibition of AChE, slowly reversible “Psuedo irreversible”. It can be used for mild-moderate AD.
What are the pros of using Rivastigmine (Exelon)?
Patch available (all stages AD, mild-moderate PD).
What are the cons of using Rivastigmine (Exelon)?
More GI side effects than Donepezil (Aricept) (oral dosing).
How does Galantamine (Razadyne) work? Are its effects reversible? When can it be used?
Reversible ACHE inhibition. May also have actions at Nicotinic receptors.
What is the role of glutamate in creating the symptoms of Alzheimer’s disease? How do plaques play a role?
Glutaminergic excitotoxicity. Too much glutamate, or too much glutamate signaling can have toxic affects a neurons. Plaques may make neurons release too much glutamate.
How does Memantine (Namenda) work? When is it used?
It is a glutamate NMDA-type receptor non-competitive partial antagonist. It can be used in moderate to severe AD.
What is the one drug that is a Glutamate receptor partial antagonist?
Memantine (Namenda).
How does the NMDA channel normally work if excited?
Normal excitatory transmission: glutamate released.
When glutamate is absent, what block the NMDA receptor?
Mg ions.
When does the NMDA channel open?
NMDA (Ca) channel opens if: neuron is depolarized, glutamate is bound, and co-transmitter glycine is also bound.
What effects occur if you chronically block NMDA receptors?
It can interfere with memory formation and plasticity.
How does Memantine (Namenda) work, specifically, on NMDA channels?
With excitotoxicity, the channel is mainly open. Memantine basically only blocks the channel when it is open, that block is quickly reversible.
What is Ginko biloba? What effects did it have on AD patients?
Extract from ginko tree used as a supplement. There were no benefits for AD patients.
What is the goal of immunotherapy?
To get the body’s immune system to react to A(beta), thus preventing worsening of plaques, could lead to clearance of plaques and potentially reverse disease.
How could immunotherapy work?
Create anti Ab antibodies to get eaten by macrophages.
What are the two types of ways Immunotherapy can work for AD?
Actively (vaccination) and passively (supply antibodies).
Does the passive way of immunotherapy (supplying antibodies) work? What is the name?
No efficacy in AD trials. Solanezumab.
