AD bolded/ important content Flashcards
Includes starred slides, bolded stuff, etc
Late-onset AD:
1) What causes it?
2) What accounts for much of the genetic risk in late-onset AD?
1) Apolipoprotein E (APOE) cholesterol transport genotype
2) APOE*4 allele
List the highlighted environmental factors for AD
1) Age
2) Low educational level
3) Risk factors for vascular disease
What is the tl;dr of the pathophys of AD?
Signature lesions: Amyloid plaques + Neurofibrillary tangles (NFTs)
Neurofibrillary tangles (NFTs):
1) What is the job of tau proteins?
2) What happens to them when abnormally phosphorylated?
1) Provide structural support to microtubules
2) Cannot bind effectively to microtubules, and the microtubules collapse
Which Aβ peptide is prone to aggregation and plaque formation?
Aβ42
Inflammatory mediators:
1) Aβ induces _________ activation and ___________ recruitment
2) What does this do?
1) microglia; astrocyte
2) Promote ongoing inflammation
The Cholinergic Hypothesis states: In the late stage of AD, the number of __________ neurons is reduced, and there is loss of nicotinic receptors in the ____________ and ___________
cholinergic; hippocampus and cortex
The Cholinergic Hypothesis
What do presynaptic nicotinic receptors do?
Control the release of acetylcholine as well as other neurotransmitters important for memory and mood, including glutamate, serotonin, and norepinephrine
Neurotransmitters in AD:
1) What are lost?
2) What activity is increased? What does it do?
3) What pathways do abnormalities appear in? Where?
1) Serotonergic neurons
2) Monoamine oxidase type B activity; dopamine metabolism
3) Glutamate pathways of the cortex and limbic structures
True or false: A single common mechanism for producing AD does not exist.
True
List 2 things you need to educate a newly Dxd pt abt
Legal decisions and QOL issues
True or false: current AD treatments have not been shown to prolong life, cure AD, or halt or reverse the pathophysiologic processes of the disorder
True
(not bolded but seems important):
1) How would you Tx mild-to-moderate AD? (MMSE 10-26)
2) What 2 medications can work for any severity of AD?
3) What should you do for moderate-to-severe AD? (MMSE 0-20)
1) Galantamine or rivastigmine
2) Donepezil and Transdermal rivastigmine
3) Add memantine
Why are therapeutic benefits and prescribing habits so variable?
1) Individuals given a diagnosis for AD often lack the hallmark pathologies (i.e., amyloid plaques and NFTs) on postmortem examination
2) Confounders [i.e. confounding variables]
What objective data may I use to determine drug efficacy?
1) An untreated person with AD has an average decline of two to four points in MMSE score per year
2) Successful treatment would reflect a decline of less than two points a year
What 2 things do Donepezil, Rivastigmine, and Galantamine have in common?
1) Cholinesterase inhibitors
2) Inhibit the action of ACTH
Cholinesterase inhibitor benefit varies from ____ to ____ months
3 to 24 months
Which one of the Cholinesterase inhibitors directly reversibly inhibits acetylcholinesterase?
Donepezil
(not bolded but seems important)
Memantine:
1) What dose do you start with?
2) What do you have to do with this med? Explain
3) Do you need to do anything different for extended release form?
4) What patients need to start at a double dose?
1) 5mg Qday
2) Titrate weekly with starting dose
3) Start at 7mg Qday instead
4) Those w. severe renal impairment (creatinine clearance of 5-29 mL/mi
List the other potentially effective treatments for AD
1) Estrogen
2) NSAIDs
3) HMG-CoA reductase inhibitors (aka statins)
4) Vitamin E
5) B6 & B12
6) Gingko biloba
7) Omega 3 fatty acids
8) Medical foods (3 types)
What does research say about estrogen and AD?
Most, but not all, retrospective epidemiologic studies show a lower incidence of AD in women who took estrogen replacement therapy after menopause
1) NSAIDs increase the risk of GI ulcers when taken with what?
2) NSAIDs have a black box warning for what?
3) What else do NSAIDs increase the risk of?
1) Cholinesterase inhibitors
2) GI bleeding
3) Cardiovascular outcomes (ie, MI and stroke)
HMG-CoA reductase inhibitors (aka statins): What is a rare adverse event?
Cognitive impairment
Can NSAIDs or statins help AD?
1) NSAIDs = old studies say yes, new studies say no
2) Statins = no (just cardiovasc. health)
1) Should you recommend vitamin E to help treat AD?
2) Do B6 and B12 help treat AD?
1) Maybe not; meta-analysis found that high-dose vitamin E increases mortality in supplemented subjects
2) Parkinson’s yes, AD no (reduces homocysteine levels)
Is there any evidence for the use of Gingko biloba or Omega 3 fatty acids for AD Tx?
No
True or false: You need to avoid TCAs in AD
True
In 2005, the FDA mandated the addition of a “black box warning” to all atypical antipsychotics. Why?
will be on exam
Due to increased risk of mortality in older adults with dementia-related psychosis
In 2011, the Office of Inspector General released its “Medicare Atypical Antipsychotic Drug Claims for Elderly Nursing Home Residents” report, which described that the majority (83%) of ___________________ drug claims were for residents without _____________ indications for use
will be on exam
atypical antipsychotic; FDA-approved
In 2005, the FDA mandated the addition of a “black box warning” to all atypical antipsychotics due to increased risk of mortality in older adults with dementia-related psychosis.
What happened regarding this warning in 2008?
will be on exam
Was expanded in 2008 to include all typical antipsychotics as well
List the controversial therapeutics for AD
1) Nuedexta
2) Prevagen
3) Aducanumab (Aduhelm)
4) Lecanemab (Leqembi)
What is pseudobulbar effect?
Involuntary, sudden, uncontrollable, and frequent episodes of laughing and/or crying
From 2013 and 2016, Avanir and its parent company Otsuka spent nearly $20 million in doctor kickbacks and benefits, including promotional speaking, consulting, travel, diners, and more, according to CNN.
This resulted in what?
The number of Nuedexta pills prescribed to nursing homes and long-term care facilities soared within this period of time, jumping nearly 400 percent in just four years.
Aducanumab (Aduhelm)
1) What is the MOA?
2) How is it administered?
3) List 2 important adverse effects
4) What are other adverse effects?
5) What monitoring is required?
1) Monoclonal antibody directed @ forms of amyloid beta
2) Infusions
3) Microhemorrhage and brain edema,
4) Anaphylactic rxns, injection site rxns, flu sx for 48-72 hrs after, etc
5) Via MRI
Lecanemab (Leqembi):
1) What is it directed against?
2) What are 2 side effects?
3) What is the drawback?
1) Monoclonal antibody against amyloid beta
2) Brain edema and microhemorrhage
3) Expensive
Is monotherapy or combination therapy preferred for memantine and a cholinesterase inhibitor?
Dual therapy is beneficial, start with monotherapy, then add memantine until neither are effective anymore
