Module 3 lecture notes

Question 1

What are the two strategies used to treat Alzheimer’s Disease?

Answer 1

Pharmacological

Behavioral

Question 2

What is considered more important?

Answer 2

behavioral treatment

Question 3

1970-1980: Suspected that Alzheimer’s was a disease of a specific neurotransmitter was ACh. What were the two findings that support that?

Answer 3

Those that died early that died of another cause (Cancer, heart attack) they found a massive fall off of neurons that create Acetylcholine. They were lost disproportionally.

In normal healthy individuals, if you block ACh production, it results in memory impairment. No improvement with repetition which showed an inability to transfer from working memory to long term memory.

Question 4

What is precursor loading?

Answer 4

loading Alzheimer’s patients with choline (precursor to ACh) and hoped that it would accelerate production of the ACh receptors that were left. Statistically significant improvement, but lacks any clinical significance (no real world benefit.)

Question 5

How does the brain produce ACh?

Answer 5

Neurotransmitter made from choline and acetyl coenzyme A. Choline acetyltransferase combines the two by taking an acetate ion from acetyl coenzyme A and creating acetylcholine, then the coenzyme A detaches.

Question 6

Rather than focusing on getting the brain to produce more ACh, they worked on the other end….

Answer 6

by getting the brain to use the ACh it was using for a longer period of time.

Question 7

what turns off ACh?

Answer 7

an enzyme called acetylcholine esterase. Become Choline and acetate neuron. Turns off ACh. Developed a molecule that blocks ACh. Acetylcholine esterase inhibitors (AChEI).

Question 8

What is the name of the first drug that is available that is an Acetylcholine esterase inhibitor?

Answer 8

tacrine/Cognex (person who implemented it did not follow protocols.) Liver toxicity killed two patients, so it was abandoned. It is not prescribed anymore.

Question 9

What is the most commonly used drug for Alzheimer’s right now?

Answer 9

donepizil/Aricept (one a day tablet, easy to remember)

Question 10

True or false. Aricept produces positive changes in patients.

Answer 10

False. It doesn’t improve memory, but slows down the course of the disease by approximately six months, so patients have longer quality of life. can cause GI side effects at first.

Question 11

What is rivastigmine/Exelon?

Answer 11

developed in 2000, in patch form. Effective for an extended period of time. Slightly different side effects.

Question 12

What is galantamine/Razadyne?

Answer 12

delays decline by six months. introduced in 2001.

Question 13

N-methyl D-aspartate inhibitors (NMDA) is used on what neurons?

Answer 13

glutamate neurons (most common excitatory transmitter) 
by reducing glutamate activity, it increases the life of the neurons that are there. The inhibitors block the neurons from firing, and keeps things getting worse, but doesn't improve their condition.

Question 14

What is memantine/Namenda?

Answer 14

approved in 2004 and is an NMDA inhibitor commonly used with AChEI’s.

Question 15

What pill combines the effects of both classes of drugs that prolong quality of life?

Answer 15

Namzeric (generic), which contains both types (donepizil and memantine) in a single pill, created in 2015.

Question 16

What are the two classes of medication used to slow the decline of Alzheimer’s disease?

Answer 16

AChEI’s and NMDA inhibitors.

Question 17

What book covers topics that patients and families need to know about Alzheimer’s disease?

Answer 17

the 36 hour day (Johns Hopkins) 8th edition

Question 18

What is the most important issue for families of patient’s with Alzheimer’s?

Answer 18

caregiver strain (seen physically as illness, fatigue, or exhaustion) (as emotional: frustration, burden, anger which can come out at the patient, guilt, depression, hopelessness)

Question 19

What can reduce caregiver strain?

Answer 19

spreading the burden out over multiple people and provide the primary caregiver breaks.

Question 20

What things need to be considered with the patient and their family when counseling them on what to expect with Alzheimer’s disease?

Answer 20

1. education
2. caregiver strain
3. simplification of the patient’s environment, reduce the patient’s cognitive load (if they are confused by a multitude of outfits, the caregiver can reduce the choice of outfits to three. This simplified the environment and helped her maintain her autonomy.)
4. safety: environment (turn off gas stove, unplug microwave, etc.) and ID bracelet w GPS tracker (they can get lost and wander) alarms at home w web cam, intercom system (NOT BABY MONITOR) or audio monitors.
5. reduce anxiousness and distress (find trigger, neutralize or redirect the patient)
6. Medical issues (take them to appts, health issues, dentist, pharmacy, monitor health status; fever, physical pain)
7. Financial/legal issues: explore general durable power of attorney (Protect from scams, control over finance, ex: 300$ limit. larger required co-signature.)
8. Long Term Care Options: assisted living, nursing facilities (well ahead of time, get on waiting list.) County Council on Aging (Senior services) Meals on Wheels (because they need to physically lay eyes on the person)

Question 21

What are the causal factors of Alzheimer’s disease?

Answer 21

1. mutation on Chromosome 1, 14, & 21.
   a. PSEN 2 is on CH 1 (presenilin)
   b. PSEN 1 is on CH 14. both are autosomal (not on a sex CH) dominant (only need one) genetic defects (mutation)
2. Chromosome 21: causes overproduction of APP, and produce too much beta amyloid.
   3.

Question 22

What is APP?

Answer 22

amyloid precursor protein

Question 23

What is the normal and abnormal cut off of amino acids in beta amyloid.

Answer 23

40 is normal and is washed out of the brain by CSF while you sleep. 42 builds up (sticky) and forms amyloid plaques.

Question 24

PSEN 2 and PSEN 1 are autosomal dominant genetic defects. What does this mean?

Answer 24

Autosomal (not on a sex chromosome) indicates it isn’t a sex-linked trait.
Dominant means you only need one allele of the mutated gene for it to create the disease, but it does mean that you cannot be a carrier, you either have it or dont.

Question 25

PSEN 2 and 1, as well as the APP defective gene on Chromosome 21 cause which type of Alzheimer’s?

Answer 25

early onset. rare. 5% of cases. Familial Alzheimer’s disease. 30-40 onset, and is rapidly progressing.

Question 26

For late onset Alzheimer’s, what is the most important risk factor?

Answer 26

advancing age

Question 27

Explain the sex risk factor in late onset Alzheimer’s disease.

Answer 27

sex refers to the biological chromosomes that produce male and female (1 of 5 factors that determine sex.)

Being female (sex) increases the risk of Alzheimer’s disease.

Question 28

What does gender involve?

Answer 28

sex, psychological variables, cultural variables, and is much more complex. not dichotomized like sex.

Question 29

True or False. After controlling for longevity, females still experience a higher incidence of Alzheimer’s disease.

Answer 29

True.

Question 30

Chromosome `19 involves which gene that increases your risk of Alzheimer’s?

Answer 30

apolipoprotein E (ApoE)
3 alleles APoE 2, 3, and 4
3 is normal, 2 has reduced risk but greater risk of other diseases, and 4 increases risk by 2.8x (heterozygous)for one allele, 8 times for both (homozygous).

Question 31

Explain the connection between Down syndrome and Alzheimer’s.

Answer 31

Individuals born with Trisomy 21 are born with increased production of APP. They almost always develop Alzheimer’s disease (40-50).

Question 32

What increases your risk of Alzheimer’s Disease?

Answer 32

Cerebral Vascular Disease (maybe due to inflammation)
Coronary Artery Disease/Hypertension
History of Traumatic Brain Injury (unconscious)
(Repeated traumatic brain injury produces CTE, not AD.)
Obesity
Sedentary lifestyle

Question 33

What protective factors reduce your risk of AD?

Answer 33

cardiovascular exercise (not improving oxygenation)
a. hormones are released by skeletal muscles and encourage growth of synapses in the brain.
higher levels of education
cognitive activity
increased social activity
estrogen (though lifelong use is not encouraged)
non-steroidal anti-inflammatory drugs (NSAIDS)

Question 34

What is the second most common cause of dementia (though disputed.)

Answer 34

Vascular dementia

Question 35

What two qualities does VD require?

Answer 35

1. dementia
   2neuroradiological evidence consistent with the type of dementia suspected (CAT scans) must correlate with function that has been affected by the disease.

Question 36

Stroke typically refers to…

Answer 36

a blockage or tearing open of a large blood vessel in the brain. (ie in cerebral arteries or major branches)

Question 37

ischemic stroke

Answer 37

occurs when a vessel supplying blood to the brain is blocked.

Question 38

hemorrhagic stroke

Answer 38

due to rupture of a blood vessel inside of the brain

Question 39

Vascular dementia is a disease in the….

Answer 39

microscopic lesions in small vessels of the brain. Their accumulation creates the disease.

Question 40

75% of people aged 70 and older have CVD at death, but…

Answer 40

most of those people don’t have dementia.

Question 41

pure VD only occurs in…

Answer 41

4% of patients with dementia.

Question 42

40% of Alzheimer’s disease also have….

Answer 42

VD.