Alzheimer disease (AD)

Question 1

True or false: Drugs may reduce AD symptoms for a time, but the disease is eventually fatal

Answer 1

True

Question 2

1) AD is most common cause of dementia (60-70%); _____ million adults in US have AD.
2) ≥ 65 years age of onset (≈96% of all cases); early onset may occur in people in their ________’s (≈4% of all cases)

Answer 2

1) 5.7
2) 30s

Question 3

1) AD affects women more than men, but that might be why?
2) The most common cause of death in people with AD is what?
3) True or false: the etiology is mostly known

Answer 3

1) Bc men are most likely die from cardiovascular disease prior to age of onset
2) Pneumonia
3) False; not completely understood

Question 4

List 3 causes of early-onset AD

Answer 4

1) Amyloid precursor protein (APP)
2&3) Presenilin 1 and Presenilin 2: increase γ-secretase

Question 5

What does the Amyloid cascade hypothesis say is the cause of AD?

Answer 5

Accumulation of Aβ peptides

Question 6

What is responsible for ensuring that APP is broken down into nonpathologic fragments?

Answer 6

α-secretase

Question 7

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

Answer 7

1) Apolipoprotein E (APOE) cholesterol transport genotype
2) Three major subtypes or alleles of APOE—*2, *3, and 4
3) APOE4 allele

Question 8

List risks for vascular disease

Answer 8

Hypercholesterolemia, hypertension, atherosclerosis, coronary heart disease, smoking, elevated homocysteine, obesity, metabolic syndrome, diabetes

Question 9

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

Answer 9

Signature lesions: Amyloid plaques + Neurofibrillary tangles (NFTs)

Question 10

Which Aβ peptide is prone to aggregation and plaque formation?

Answer 10

Aβ42

Question 11

Neurofibrillary tangles (NFTs):
1) What is abnormal here?
2) What is its job?

Answer 11

1) Abnormal tau protein [phosphorylation]
2) Provide structural support to microtubules

Question 12

What happens when tau filaments undergo abnormal phosphorylation [at a specific site]?

Answer 12

They cannot bind effectively to microtubules

Question 13

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

Answer 13

1) microglia; astrocyte
2) Promote ongoing inflammation

Question 14

The Cholinergic Hypothesis
What do presynaptic nicotinic receptors do?

Answer 14

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

Question 15

List some things you should rule out regarding AD

Answer 15

1) Syphilis
2) B12 deficiency
3) Anemia
4) Infection

Question 16

US Preventive Services Task Force concluded that there are _______________ data to recommend for or against cognitive screening for AD

Answer 16

insufficient

Question 17

Alzheimer’s Association (AA) is currently promoting cognitive screening as part of the __________ Annual Wellness Visit

Answer 17

Medicare

Question 18

List 2 diagnostic tools for AD

Answer 18

1) Mini-Mental State Examination (MMSE)
(a 30-point assessment tool for AD, very common)
2) Montreal Cognitive Assessment (MoCA)

Question 19

True or false: Dementia has only one definition

Answer 19

False

Question 20

How do the NINCDS-ADRDA + National Institute on Aging (NIA) and the Alzheimer’s Association (AA) criteria view AD?

Answer 20

AD as a spectrum beginning with a preclinical phase progressing to increasingly severe clinical stages of AD

Question 21

List the stages of AD and their associated scores

Answer 21

1) Mild: MMSE 26-21
2) Moderate: MMSE 20-10
3) Severe: MMSE 9-0

Question 22

1) What is recommended if a pt has dementia?
2) What labs do you need to get from them? Why?

Answer 22

1) CT or MRI
2) Blood cell counts, serum electrolytes, liver function tests, a test of thyroid function, and a vitamin B12 level; to rule out other causes of cognitive decline

Question 23

Is APOE genotyping is clinically recommended? Explain

Answer 23

APOE genotyping is not clinically recommended at this time; unless the person developed dementia before age 60 years, genotyping is usually not indicated

Question 24

Mild cognitive impairment (MCI): people diagnosed with MCI carry a ____% to ____% chance per year of progressing to an AD diagnosis

Answer 24

10-15%

Question 25

True or false: There are lots of non-pharmacological interventions for AD

Answer 25

True

Question 26

What info can help you decide between using Donepezil and Transdermal rivastigmine?

Answer 26

Donepezil = more effective Transdermal rivastigmine = less prominent GI effects

Question 27

True or false: There's a great variation exists between clinicians, and duration of treatment ranges from months to years

Answer 27

True

Question 28

Cholinesterase inhibitors: 1) What is recommended to have a washout period with these meds? 2) When is an overnight switch acceptable? 3) Do these meds need to be tapered when stopping?

Answer 28

1) When switching from one cholinesterase inhibitor to another 2) For patients that initially fail to respond to therapy, overnight switch is acceptable 3) Yes; stopping medication without a taper may result in acute cognitive decline

Question 29

Cholinesterase inhibitors: 1) With these meds, what do you need to differentiate between? 2) Explain

Answer 29

1) Acute cognitive decline vs. cholinergic toxicity 2) Cholinergic toxicity: salivation, tearing and sweating, bronchoconstriction, tightness in the chest, wheezing, bradycardia, vomiting,  increased gastrointestinal motility, abdominal tightness, diarrhea, and cramp

Question 30

If a pt begins to lose the benefit they were getting from their Cholinesterase inhibitor, is this an appropriate reason to switch to a different one? Explain your answer.

Answer 30

May not be; the progressive nature of AD is likely to become more noticeable over time

Question 31

1) What type of drug is Memantine? 2) What is its MOA?

Answer 31

1) NMDA antagonist 2) Blocks glutamatergic neurotransmission by antagonizing NMDA receptors [logic: blocking NMDA receptors can mitigate excitotoxic neurotoxicity]

Question 32

Do you need to dose Memantine differently for renal impairment? Explain

Question 33

Do you need to tell pts to take Donepezil at a certain time? Explain

Answer 33

Because nightly dosing can be associated with vivid dreaming or nightmares, we typically **start with morning dosing** to avoid sleep disturbances and then switch to nightly dosing if daytime nausea occurs

Question 34

1) What is the initial dose of Donepezil? 2) Do you need to dose Donepezil differently for anyone? Explain

Answer 34

1) 5mg Qday at night 2) No; no special population dosing.

Question 35

Do you need to dose Rivastigmine differently for anyone? Explain

Answer 35

Renal impairment, hepatic impairment, or low body weight (<50kg/ <110lb)

Question 36

Do you need to dose Galantamine differently for anyone? Explain

Answer 36

1) Moderate renal or hepatic impairment: max dose of 16mg 2) NOT RECOMMENDED in severe renal or hepatic impairment

Question 37

Do you need to renally dose memantine? Explain

Answer 37

Severe renal impairment (creatinine clearance of 5-29 mL/min): 5mg BID (reg) or 14mg Qday (XR)

Question 38

1) Which AD drug: a) Needs to be taken with food and is associated with SJS? b) Is associated with allergic dermatitis? 2) What do both of these drugs have in common?

Answer 38

a) Galantamine b) Rivastigmine 2) D/c w/o taper if rash occurs; don't rechallenge

Question 39

What are cholinesterase inhibitors associated with?

Answer 39

1) Nausea/ vomiting, diarrhea, weight loss 2) Insomnia, abnormal/ vivid dreams, nightmares

Question 40

What AD drug carries the risk of hallucinations?

Answer 40

Memantine (SE of NMDA antagonists in general)

Question 41

List the 3 types of medical foods, the cost, and noteworthy contents of each

Answer 41

1) Axona (caprylidene) -$125 / month 2) Souvenaid: B complex, choline, vitamin E 3) CerefolinNAC: L-methylfolate -$215 / month

Question 42

2) Can you Tx neuropsychiatric symptoms (psychotic, hyperactive, affective disorders, apathy) with SSRIs? 2) What about tricyclic antidepressants (TCAs)?

Answer 42

1) Yes SSRIs 2) NO Avoid due to anticholinergic side effects

Question 43

What is the argument against antipsychotics for AD psychiatric Sx?

Answer 43

Chemical restraint

Question 44

Patients should generally be monitored for adverse events within ____ to ____ weeks of initiation of AD therapy

Answer 44

2 to 4

Question 45

What should you do if the patient significantly deteriorates in cognition or function?

Answer 45

Some clinicians recommend withdrawing drug therapy, while others wait until the patient has lost all cognitive and functional abilities

Question 46

**Nuedexta** (controversial therapy; dextromethorphan and quinidine) 1) What is a side effect? 2) What does NPR have to say about this drug?

Answer 46

1) Pseudobulbar affect (PBA) 2) “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. 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 47

What does Prevegan contain?

Answer 47

1) Soy products: Estrogen like molecules 2) Apoaequorin: Calcium regulation

Question 48

Aducanumab (Aduhelm): 1) When do you need to do an MRI to monitor? 2) Are there any contraindications or interactions? 3) When should you consider this med?

Answer 48

1) Before first dose (within one year), and prior to infusion #7 and #12 2) No contraindications (aside from contraindications to MRIs) or drug-to-drug interactions 3) Consider with early stages of diagnosis

Question 49

1) What was the first new Alzheimer's drug approved since 2003? 2) Is this an uncontroversial drug? 3) How much is it?

Answer 49

1) First new Alzheimer's drug approved since 2003 2) FDA advisory panel had recommended against allowing the drug on the market before the FDA approved it; Alzheimer's Association is a strong supporter of the drug 3) $56,000 / year