CNS degenerative disorders Lecture #2 Flashcards
What does Huntington’s disease affect?
-The GABA pathway (it wipes it out)
What are the clinical manifestations of Huntington’s disease?
-Early onset (around 30-40 yrs)
Huntington’s disease is associated with abnormal moves, what are they?
- Chorea forms (sudden/jerky movements)
- Facial grimacing/oral facial movements
What drives the abnormal movements in Huntington’s disease?
-You have too much Dopamine
If you get the huntington’s gene will you get huntington’s?
-Yes it is a genetic disorder
What is the progressive intellectual dysfunction associated with huntingtons disease?
- Decreased judgement
- Withdrawl from others
- Depression
- Schizophrenia
- Become compulsive
What is the incidence of huntingtons disease?
-.01%
What is the duration of diagnosis till death?
-5-10 yrs
What are the features of the pathophysiology of huntingtons disease?
- To much dopamine and cholinergic activity in the striatum
- To little GABA projections
- Lose cell bodies
The lateral ventricles in brain of a person with huntington’s disease are enlarged, why is this the case?
-Because the loss of caudate neurons
What is the cause of huntington’s disease?
-A gene known as huntington gene (deals with NMDA and AMPA receptors)
What happens if you activate NMDA receptors?
-Ionotropic Ca2+ release (causing problems with GABA if too much Ca2+)
How do you diagnose of huntingtons disease?
-Genetic screening for diagnosis
What is the pharmacological treatment for Huntington’s disease?
- DA antagonists (antipsychotics) (D2 antagonists)
- Dopamine agonists for bradykinesia/rigidity
- DA depletion (reserpine) for choreiform movement
- SSRIs for depression
- Antipsychotics for hallucination/delusions
What is haloperidol?
-D2 antagonist
What is Olanzepine?
-atypical anti-psychotic
What can haloperidol lead to?
-Parkinsonism because of the lack of Dopamine
What is the most common degenerative brain disease?
-Alzheimer’s disease (3-4 million)
What is the life expectancy for a person diagnosed with alzheimer’s disease?
-5-20 yrs
What are the three categories of Alzheimer’s disease?
- Early
- Moderate
- Late
How is early memory loss characterized?
-Short term memory
What do you see in early alzheimer’s disease?
- Short term memory loss
- annoying
- Don’t like change
What do you see in moderate alzheimer’s disease?
- Decreased function
- Stop working
- Stop remembering the important things
What do you see in late alzheimer’s disease?
- Decreased motor
- No judgement
- Immobile
- Stop eating
What is the epidemiology of alzheimer’s disease?
- Old age
- Family history
- Inflammatory disease
What are three places in the brain the you can see alzheimer’s disease?
- Hippocampus (memory)
- Cortex (function)
- Nucleus basalis
What neurons are severely damaged in alzheimers?
-The neurons from the nucleus basalis to the hippocampus (causes a deficiency in cholinergic activity)
What histologies are associated with alzheimers?
- Senile plaques
- Neurofibrillary tangles
What do senile plaques have in them?
-Beta amyloid (is abnormal form of amyloid and becomes sticky)
What protein is associated with the neurofibrillary tangles?
-Tau protein (microtubule protein)
What is the precursor protein for beta amyloid?
-APP
What happens to cholinergic activity when you have senile plaques?
-It decreases acetyl choline and muscarinic receptors
What types of drugs do you use for alzheimers?
-Acetylcholinesterase inhibitors
What type of genes do you see in alzheimers patients?
- Apolipoproteins that turn into the APP that turn into the Beta amyloid
- Chromosome #21
When there is a protein aggregate in the brain what is usually associated with it?
-Inflammation
What cholinesterase inhibitor drugs are used for the treatment of Alzheimers?
- Donepezil (Aricept)
- Galantamine
- Rivastigmine
What is the only way you can have a definitive diagnosis of Alzheimers disease?
-Post mortem look at the brain
What are the functional consequences of alzheimers?
- Diminish capacity of the brain so you’re not able to do multiple tasks concurrently
- Protein aggregates that cause inflammation
What are antipsychotics used for alzheimers?
- Olanzapine
- Quetiapine
- Risperidone
- Ziprasidone
