Alzheimer disease (AD) Flashcards
True or false: Drugs may reduce AD symptoms for a time, but the disease is eventually fatal
True
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)
1) 5.7
2) 30s
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
1) Bc men are most likely die from cardiovascular disease prior to age of onset
2) Pneumonia
3) False; not completely understood
List 3 causes of early-onset AD
1) Amyloid precursor protein (APP)
2&3) Presenilin 1 and Presenilin 2: increase γ-secretase
What does the Amyloid cascade hypothesis say is the cause of AD?
Accumulation of Aβ peptides
What is responsible for ensuring that APP is broken down into nonpathologic fragments?
α-secretase
Late-onset AD:
1) What causes it?
2) Are there subtypes?
3) What accounts for much of the genetic risk in late-onset AD?
1) Apolipoprotein E (APOE) cholesterol transport genotype
2) Three major subtypes or alleles of APOE—*2, *3, and 4
3) APOE4 allele
List risks for vascular disease
Hypercholesterolemia, hypertension, atherosclerosis, coronary heart disease, smoking, elevated homocysteine, obesity, metabolic syndrome, diabetes
What is the tl;dr of the pathophys of AD?
Signature lesions: Amyloid plaques + Neurofibrillary tangles (NFTs)
Which Aβ peptide is prone to aggregation and plaque formation?
Aβ42
Neurofibrillary tangles (NFTs):
1) What is abnormal here?
2) What is its job?
1) Abnormal tau protein [phosphorylation]
2) Provide structural support to microtubules
What happens when tau filaments undergo abnormal phosphorylation [at a specific site]?
They cannot bind effectively to microtubules
Inflammatory mediators:
1) Aβ induces _________ activation and ___________ recruitment
2) What does this do?
1) microglia; astrocyte
2) Promote ongoing inflammation
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
List some things you should rule out regarding AD
1) Syphilis
2) B12 deficiency
3) Anemia
4) Infection
US Preventive Services Task Force concluded that there are _______________ data to recommend for or against cognitive screening for AD
insufficient
Alzheimer’s Association (AA) is currently promoting cognitive screening as part of the __________ Annual Wellness Visit
Medicare
List 2 diagnostic tools for AD
1) Mini-Mental State Examination (MMSE)
(a 30-point assessment tool for AD, very common)
2) Montreal Cognitive Assessment (MoCA)
True or false: Dementia has only one definition
False
How do the NINCDS-ADRDA + National Institute on Aging (NIA) and the Alzheimer’s Association (AA) criteria view AD?
AD as a spectrum beginning with a preclinical phase progressing to increasingly severe clinical stages of AD
List the stages of AD and their associated scores
1) Mild: MMSE 26-21
2) Moderate: MMSE 20-10
3) Severe: MMSE 9-0
1) What is recommended if a pt has dementia?
2) What labs do you need to get from them? Why?
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
Is APOE genotyping is clinically recommended? Explain
APOE genotyping is not clinically recommended at this time; unless the person developed dementia before age 60 years, genotyping is usually not indicated
Mild cognitive impairment (MCI): people diagnosed with MCI carry a ____% to ____% chance per year of progressing to an AD diagnosis
10-15%
True or false: There are lots of non-pharmacological interventions for AD
True
What info can help you decide between using Donepezil and Transdermal rivastigmine?
Donepezil = more effective
Transdermal rivastigmine = less prominent GI effects
True or false: There’s a great variation exists between clinicians, and duration of treatment ranges from months to years
True
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?
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
Cholinesterase inhibitors:
1) With these meds, what do you need to differentiate between?
2) Explain
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
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.
May not be; the progressive nature of AD is likely to become more noticeable over time
1) What type of drug is Memantine?
2) What is its MOA?
1) NMDA antagonist
2) Blocks glutamatergic neurotransmission by antagonizing NMDA receptors
[logic: blocking NMDA receptors can mitigate excitotoxic neurotoxicity]
Do you need to dose Memantine differently for renal impairment? Explain
Do you need to tell pts to take Donepezil at a certain time? Explain
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
1) What is the initial dose of Donepezil?
2) Do you need to dose Donepezil differently for anyone? Explain
1) 5mg Qday at night
2) No; no special population dosing.
Do you need to dose Rivastigmine differently for anyone? Explain
Renal impairment, hepatic impairment, or low body weight (<50kg/ <110lb)
Do you need to dose Galantamine differently for anyone? Explain
1) Moderate renal or hepatic impairment: max dose of 16mg
2) NOT RECOMMENDED in severe renal or hepatic impairment
Do you need to renally dose memantine? Explain
Severe renal impairment (creatinine clearance of 5-29 mL/min): 5mg BID (reg) or 14mg Qday (XR)
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?
a) Galantamine
b) Rivastigmine
2) D/c w/o taper if rash occurs; don’t rechallenge
What are cholinesterase inhibitors associated with?
1) Nausea/ vomiting, diarrhea, weight loss
2) Insomnia, abnormal/ vivid dreams, nightmares
What AD drug carries the risk of hallucinations?
Memantine (SE of NMDA antagonists in general)
List the 3 types of medical foods, the cost, and noteworthy contents of each
1) Axona (caprylidene)
-$125 / month
2) Souvenaid: B complex, choline, vitamin E
3) CerefolinNAC: L-methylfolate
-$215 / month
2) Can you Tx neuropsychiatric symptoms (psychotic, hyperactive, affective disorders, apathy) with SSRIs?
2) What about tricyclic antidepressants (TCAs)?
1) Yes SSRIs
2) NO Avoid due to anticholinergic side effects
What is the argument against antipsychotics for AD psychiatric Sx?
Chemical restraint
Patients should generally be monitored for adverse events within ____ to ____ weeks of initiation of AD therapy
2 to 4
What should you do if the patient significantly deteriorates in cognition or function?
Some clinicians recommend withdrawing drug therapy, while others wait until the patient has lost all cognitive and functional abilities
Nuedexta (controversial therapy; dextromethorphan and quinidine)
1) What is a side effect?
2) What does NPR have to say about this drug?
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.”
What does Prevegan contain?
1) Soy products: Estrogen like molecules
2) Apoaequorin: Calcium regulation
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?
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
1) What was the first new Alzheimer’s drug approved since 2003?
2) Is this an uncontroversial drug?
3) How much is it?
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
