Alzheimers Flashcards
amyloid plaques are ___ and consist of ______
extracellular, AB peptide (amloid beta)
neurofibrillary tangles are ____ and consist of _____
intracellular, hyperphosphorylated tau
a feature of neurons with tangles and close to amyloid plaques is destruction of ______
synapses
snapse loss results in reduced what
neurotransmitters - esp. acetylcholine, dopamine, serotonin, NE
APP gene is located on
chromomosome 21
things leading to early onset AD
mutations in APP
mutations in PSENs
things leading to 4th decade of life AD
Down syndrome
normal cleavage of AB from APP is by
alpha secretase
abnomal cleavage of AB from APP is by
beta and gamma secretase
which amyloid beta form can form more amloid fibrils
AB42 > AB40
mutations in APP lead to more
cleavage by beta and gamma so more AB42
mutations in PSEN1 or PSEN2 do what
alter the gamma secretase cleavage, more AB42
AB aggregation promotes what
tau hyperphosphorylation
tau hyperphosphorylation leads to what
neurofibrillary tangles, cytoskeletal abnormalities, disruption axonal trafficking
AB aggregation triggers ____ activation
microglia
immune cell
activated microglia do what
release inflammatory cytokines that cause neuroinflammation
PGs, ILs, TNF-a
release reactive nitrogen and oxygen species that cause oxidative stress
activated microglia cause what
neuroinflammation
oxidative stress
ApoE 2 vs ApoE4
2 - increased risk AD
4 - decreased risk AD
cholinesterase inhibitors
donepezil
rivastigmine
galantamin
donepezil MOA
specific reversible inhibitor AcE
rivastigmine MOA
inhiitor AcE and butyrlcholinesterase
galantamine MOA
selective reversible inhibitor AcE and enhances action of acetylcholine on nicotinic receptors
anti-glutamtergic drug
memantine
memantine MOA
NMDA antagonism that blocks glutamatergic neurotransmission via a noncompetitive mechanism,
REDUCES EXCITOTOXICITY
what is florbetapir
radiolabeled agent that binds b - amyloid and is visualized by PET scanning
dementia with Lewey bodies
cognitive decline and Parkinsons sx
VISUAL HALLUCINATIONS
cortical lewey bodies
frontotemporal dementia
Picks Disease
disinhibited behavior
tau accumulations (Picks bodies)
drug classes with anticholinergic burden
skeletal muscle relaxants
tricyclic antidepressants
antihistamines / emetics
bladder antispasmodics
change in MMSE score of what in 1 year is bad
3-4 points
scales used to assess cognitive function
MMSE, MoCA
first line therapy dementia
cholinesterase inhibitors
donepezil
rivastigmine
galantamine
when to use NMDA receptor antagonists?
moderate to severe dementia
which drug should you not take with memantine
carbonic anhydrase inhibitors
dementia MABs IV
aducanumab
lecanemab
aducanemab and lecanemab require what
brain MRI, ARIA
presence of amyloid beta pathology prior to initaition
what nonpharm intervention is more efficacious than antipsychotics for agitation
outside activities
agitation intervention
take outside
distraction techniques
antipsychotics for psychosis
risperidone and quetiapine
box warning antipsychotics
death or stroke increased in dementia
antipsychotics are not useful for what
repetitive behaviors or yelling
antidepressants used dementia
SSRIs, avoid paroxetine