AD bolded/ important content

Question 1

Late-onset AD:
1) What causes it?
2) What accounts for much of the genetic risk in late-onset AD?

Answer 1

1) Apolipoprotein E (APOE) cholesterol transport genotype
2) APOE*4 allele

Question 2

List the highlighted environmental factors for AD

Answer 2

1) Age
2) Low educational level
3) Risk factors for vascular disease

Question 3

What is the tl;dr of the pathophys of AD?

Answer 3

Signature lesions: Amyloid plaques + Neurofibrillary tangles (NFTs)

Question 4

Neurofibrillary tangles (NFTs):
1) What is the job of tau proteins?
2) What happens to them when abnormally phosphorylated?

Answer 4

1) Provide structural support to microtubules
2) Cannot bind effectively to microtubules, and the microtubules collapse

Question 5

Which Aβ peptide is prone to aggregation and plaque formation?

Answer 5

Aβ42

Question 6

Inflammatory mediators:
1) Aβ induces _________ activation and ___________ recruitment
2) What does this do?

Answer 6

1) microglia; astrocyte
2) Promote ongoing inflammation

Question 7

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 ___________

Answer 7

cholinergic; hippocampus and cortex

Question 8

The Cholinergic Hypothesis
What do presynaptic nicotinic receptors do?

Answer 8

Control the release of acetylcholine as well as other neurotransmitters important for memory and mood, including glutamate, serotonin, and norepinephrine

Question 9

Neurotransmitters in AD:
1) What are lost?
2) What activity is increased? What does it do?
3) What pathways do abnormalities appear in? Where?

Answer 9

1) Serotonergic neurons
2) Monoamine oxidase type B activity; dopamine metabolism
3) Glutamate pathways of the cortex and limbic structures

Question 10

True or false: A single common mechanism for producing AD does not exist.

Answer 10

True

Question 11

List 2 things you need to educate a newly Dxd pt abt

Answer 11

Legal decisions and QOL issues

Question 12

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

Answer 12

True

Question 13

(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)

Answer 13

1) Galantamine or rivastigmine
2) Donepezil and Transdermal rivastigmine
3) Add memantine

Question 14

Why are therapeutic benefits and prescribing habits so variable?

Answer 14

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]

Question 15

What objective data may I use to determine drug efficacy?

Answer 15

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

Question 16

What 2 things do Donepezil, Rivastigmine, and Galantamine have in common?

Answer 16

1) Cholinesterase inhibitors
2) Inhibit the action of ACTH

Question 17

Cholinesterase inhibitor benefit varies from ____ to ____ months

Answer 17

3 to 24 months

Question 18

Which one of the Cholinesterase inhibitors directly reversibly inhibits acetylcholinesterase?

Answer 18

Donepezil

Question 19

(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?

Answer 19

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

Question 20

List the other potentially effective treatments for AD

Answer 20

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)

Question 21

What does research say about estrogen and AD?

Answer 21

Most, but not all, retrospective epidemiologic studies show a lower incidence of AD in women who took estrogen replacement therapy after menopause

Question 22

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?

Answer 22

1) Cholinesterase inhibitors
2) GI bleeding
3) Cardiovascular outcomes (ie, MI and stroke)

Question 23

HMG-CoA reductase inhibitors (aka statins): What is a rare adverse event?

Answer 23

Cognitive impairment

Question 24

Can NSAIDs or statins help AD?

Answer 24

1) NSAIDs = old studies say yes, new studies say no
2) Statins = no (just cardiovasc. health)

Question 25

1) Should you recommend vitamin E to help treat AD? 2) Do B6 and B12 help treat AD?

Answer 25

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)

Question 26

Is there any evidence for the use of Gingko biloba or Omega 3 fatty acids for AD Tx?

Answer 26

No

Question 27

True or false: You need to avoid TCAs in AD

Answer 27

True

Question 28

In 2005, the FDA mandated the addition of a “black box warning” to all atypical antipsychotics. Why? **will be on exam**

Answer 28

Due to increased risk of mortality in older adults with dementia-related psychosis

Question 29

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**

Answer 29

atypical antipsychotic; FDA-approved

Question 29

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**

Answer 29

Was expanded in 2008 to include all typical antipsychotics as well

Question 30

List the controversial therapeutics for AD

Answer 30

1) Nuedexta 2) Prevagen 3) Aducanumab (Aduhelm) 4) Lecanemab (Leqembi)

Question 31

What is pseudobulbar effect?

Answer 31

Involuntary, sudden, uncontrollable, and frequent episodes of laughing and/or crying

Question 32

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?

Answer 32

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.

Question 33

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?

Answer 33

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

Question 34

Lecanemab (Leqembi): 1) What is it directed against? 2) What are 2 side effects? 3) What is the drawback?

Answer 34

1) Monoclonal antibody against **amyloid beta** 2) Brain edema and microhemorrhage 3) Expensive

Question 36

Is monotherapy or combination therapy preferred for memantine and a cholinesterase inhibitor?

Answer 36

Dual therapy is beneficial, start with monotherapy, then add memantine until neither are effective anymore