NCD Alz Dz- 15D

Question 1

In Major NCD due to Alz Dz, what is unusual about diagnostic criteria?

Answer 1

-decrease in cognitive function in TWO domains (as opposed to 1 domain)

Question 2

Risk factors for Alz Disease

Answer 2

• age
• family history (increases risk for 2-3 fold)
• ApoE epsillon 4 allele
• female sex
• high homocysteine levels
• less education
• usual cardiovascular/cerebrovascular risks

Question 3

Protective factors for Alz Disease

Answer 3

• physical activity
• high n-3 fatty acids
• ApoE episilon 2 allele

Question 4

The average time to death from diagnosis in Alz Dz

Answer 4

-10 years

Question 5

Most common cause of death in Alz Dz

Answer 5

-aspiration pneumonia

Question 6

Features for severe Alz Dz

Answer 6

• Folstein < 10
• complete care and feeding needed
• apathy, lack of recognition, disconnection from environment

Question 7

Differences between senile plaques and neurofibrillary tangles

Answer 7

-senile plaques are extracellular; NFTs are intracellular
-senile plaques consist of AB42; NFT’s consist of tau and ubiquitin
-

Question 8

List the pathologic findings in Alz Dz

Answer 8

• senile plaques
• neurofibrillary tangles
• early neuronal loss in hippocampus
• cerebral amyloid angiopathy- amyloid-B arterial plaques

Question 9

The use of biomarkers is currently recommended for the diagnosis of Alz Dz. True or False

Answer 9

FALSE

Question 10

What are the 2 genetic types of early onset (before age 65y) Alz Dz?

Answer 10

• early onset familial AD (eFAD): AUTOSOMAL DOM (50%)

- non-familial: SPORATIC (50%)

Question 11

Describe the gene mutations that cause eFAD

Answer 11

• presenilin 1 (chromosome 14)-knife
• presenilin 2 (chromosome 1)-knife
• Amyloid precursor protein (chromosome 21)-mellon
• NORMAL/UNMUTATED forms of these genes are responsible for creating the soluble/functional amyloid AB-40 protein

Question 12

In eFAD, the genes produce products that results in production of:

Answer 12

• Amyloid AB-42 insoluble protein that kills cells leading to formation of senile plaques
• AB-42 causes extra influx of Ca++
• therefore when cells are killed the plaques that remain contain AB-42, glial cells, abnormal neuronal axons

Question 13

Describe the genetics that assigns RISK of developing Alz Dz

Answer 13

• Alleles of Apoprotein E (Apo E)
• ApoE2-is protective (2 t’s protective)
• ApoE3-is neutral
• ApoE4-increases risk (4 increases risk FOUR Alz Dz)

Question 14

What do Apolipoproteins (Apo proteins) do?

Answer 14

-remove excess cholesterol and Amyloid-Beta from the brain

Question 15

Describe the genetics of ApoE4

Answer 15

• 25% of population has at least 1 E4 allele present
• E4 allele is present in ~60% of pts with Alz Dz
• increases risk of Alz Dz by 2.5 times compared to general population

Question 16

Name the categories of cognitive enhancers used in the management of Alz Dz

Answer 16

• cholinesterase inhibitors
• NMDA-antagonists
• Ketone diet

Question 17

Four rules of thumb for prescribing cholinesterase inhibitors

Answer 17

• start treatment early
• continue treatment long term
• switch meds in class if med becomes ineffective or develops side effects
• prescribe with memantine

Question 18

Name the cholinesterase inhibitors FDA approved for management of Alz Dz

Answer 18

• Donepezil
• Galantamine
• Rivastigmine
• all approved for the treatment of mild-moderate Alz Dz

Question 19

Which of the cholinesterase inhibitors is approved for the management of severe Alz Disease

Answer 19

-Donepezil, Rivastigmine

Question 20

Which of the cholinesterase inhibitors is also approved for management of NCD due to Parkinson’s Dz

Answer 20

-Rivastigmine

Question 21

Which of the cholinesterase inhibitors IS NOT hepatically metabolized

Answer 21

-RIVASTIGMINE

Question 22

Hepatically metabolized cholinesterase inhibitors are metabolized by CYP450

Answer 22

-2D6, 3A4

Question 23

Which of the cholinesterase inhibitors should be avoided in severe renal and hepatic disease and or require dose adjustments

Answer 23

-GALANTAMINE

Question 24

What is memantine?

Answer 24

• NMDA antagonist

- treatment of moderate to severe Alz Dz

Question 25

What is Caprylidene?

Answer 25

• FDA approved
• nutritional management of Alz Dz
• increases ketones in brain as alternative source of energy for neurons
• no drug-drug interactions