Dementia and Alzheimer's

Question 1

decline in cognitive function

Answer 1

dementia

Question 2

multi-infarct dementia

Answer 2

• caused by a series of small strokes
• affects more men than women
• risk factors: DM, HTN, smoking

Question 3

dementia with lewy bodies

Answer 3

• buildup- of lewy bodies accumulated alpha-synuclein protein in the cytoplasm of neurons
• ares of the brain affected: memory/motor control
• symptoms similar to alzheimers but has some additional symot. like parkinsonian sympt
• common progressive dementia

Question 4

Frontotemporal dementia

Answer 4

• behavioral changes
• problems with language
• mutations in microtubule associated protein Tau and Progranulin
• highly genetically driven

Question 5

can dementia be reversed?

Answer 5

in some cases like those caused by infection, nutrition deficiency, brain tumors

Question 6

others suprisiing disorders linked to dementia

Answer 6

• HuNT’s
• HIV
• Prion disease

Question 7

Alzheimer’s disease location

Answer 7

temporo-parietal

Question 8

alzheimer’s dx.

macro

Answer 8

cerebral atrophy

Question 9

Alzheimer’s dx.

Micro

Answer 9

B-Amyloid plaques, neurofibillary tangles

Question 10

amyloid plaques are accumulations of the

Answer 10

AB peptide

Question 11

APP molecule

Answer 11

transmembrane protein–> cleavage of it gives B-amyloid

some cleavage results in protein that do not accumulate and not toxic

Question 12

PSEN2/PSEN1

Answer 12

involved in the formation of the gamma-secretease subunit

• high risk of developing
  early onset familial alzheimer’s

Question 13

APOE-4

Answer 13

major risk for late onset Ad

• weak familial involvement

Question 14

Protofibril

Answer 14

membrane disruptions- pore formation

Question 15

B-amyloid fibrils

Answer 15

gliosis and inflammations- free radical formation

Question 16

oligomer

Answer 16

synaptic dysfunction (LTP impairment)

Question 17

AD pathogenesis (4)

Answer 17

1. monomer
2. oligomer
3. protofibril
4. B-amyloid fibrils

Question 18

tx (managment of symptoms) for AD

Answer 18

1. cholinesterase inhibitor

2. NMDA receptor antagonists

Question 19

B secretase inhibitor

aim?

concern?

Answer 19

aim: inhibit BACE1 from cleaving APP and thus produce AB
concern: inhibiting BACE1 can cause other possible affects in the brain since it has extensive roles

Question 20

Verubecestat

Answer 20

bing to BACE1 with high affinity and inhibit

– patients got worsse

Question 21

gamma- secretase inhibitors

aim?

concern?

Answer 21

aim: inhibit gamma-secretase from cleaving APPBCTF and thus produce AB
- concern: can have SE to NOth that have a role in blood and GI tract

Question 22

Semagacestat

Answer 22

• inhibitor of gamma- secretase

- SE included skin cancer and infections; no improvement

Question 23

Tau- anti-aggregate agents

Answer 23

inhibit Tau aggregation

• no improvement

Question 24

Passive immunotherapy

solanezumab and aducanumab

Answer 24

• monoclonal antibody target to AB and aggregates

- failed

Question 25

is memory loss associated with brain therapy?

Answer 25

yassss - we see a widening of grooves and fissures of the cerebral cortex indicating loss of brain mass and severe brain atrophy

Question 26

reduced FDG signal indicated

Answer 26

hypometabolism in the affected brain region

Question 27

enhanced PiB signal indicated

Answer 27

elevated amyloid depostion

Question 28

CSF AB42

Answer 28

decreased in AD patients due to corticol amyloid deposition

Question 29

CSF total tau

Answer 29

elevated in AD patients due to corticol neuronal loss

Question 30

CSF phosphorylated TAY

Answer 30

elevated in AD patients due to cortical tangle formation