Neurodegenerative disorders/Alzheimer

Question 1

what is the 1st sign of alzheimers?

Answer 1

Loss of short term memory

Question 2

what are the cognitive symptoms?

Answer 2

loss of short term memory, Aphasia, apraxia, agnosia, disorientation

Question 3

noncognitive symptoms

Answer 3

depression, psychotic symptoms. behavioral disturbances (aggregation, motor hyperactivity, repetitive manners). occurs later in later stages

Question 4

Whats the best tool to dx Alzheimers

Answer 4

clinical assessment

Question 5

what are the requirements to be dx of AZ?

Answer 5

presence of Dementia.

Cognitive impairment are BEYOND normal aging process (>65)

Question 6

what correlates with the severity of AD?

Answer 6

loss of ACh activity

Question 7

Early onset AD

Answer 7

cleavage defect on APP protein to form beta amyloid–>so improperly cleaved amyloid cant be properly cleared. Accumulation of beta amyloid–>imbalance between production and clearance of beta-amyloid

PSEN1 and PSEN2 mutatuion can cause overproduction of B-amyloid

Question 8

LATE onset of AD

Answer 8

APOE-e3 isoform–>accumulation of amyloid

Microtubule-associated protein Tau–>hyperphosphorylation of TAu–>neurofibrillary tangles

microtubular disintegration and instability–>collapse of neuronal transport system–>altered NT release and synaptic function–>Cell death

Question 9

what is the 1st line of therapy for symptomatic treatment of cognitive impairment

Answer 9

Cholinesterase inhibitor agents used to stop progression of disease and block AChE and BChE breakdown

Question 10

Donepezil

Answer 10

Cholinesterase inhibitor agent; used in all stages of AD
Primarily inhibit AChE
LONG1/2 life**daily dose (70-80 hrs)
-once you start taking donepezil, will need to continue it for the rest of your life

Question 11

which agent has transdermal patch that could be used? whats the benefit to that?

Answer 11

Cholinesterase inhibitor agent

Rivastigmine; improve GI effects

Question 12

Galantamine

Answer 12

Cholinesterase inhibitor agent

1/2 life: 2x day

Question 13

what are the major side effects for cholinesterase inhibitor

Answer 13

nausea, vomiting, diarrhea

Question 14

Memantine

Answer 14

Glutamate antagonist

non competitive antagonist that blocks NMDA glutamate receptor on postsynaptic side

1/2 life=60-80hrs
provides neuroprotection by reducing intracellular Ca influx and glutamate-induced excitotoxicity

Question 15

what is memantine commonly used in combo with? why?

Answer 15

cholinesterase inhibitors: help improve severe AD

Question 16

what is one tx needed to avoid for non-cognitive symptoms?

Answer 16

TCA!! it causes orthostatic hypotension–>NOT GOOD FOR ELDERLY

Question 17

what is used as antipsychotics for non-cognitive symptoms

Answer 17

Risperidone, olanzapine, quetiapine

Question 18

what’s used for depression?

Answer 18

Sertraline, citalopram, (fluoxetine, paroxetine)

Question 19

what makes neurofibrillary tangles

Answer 19

accumulation of tao proteins

Question 20

what are the functions of cholinesterase inhibitor

Answer 20

block AChE and/or BChE

reduce breakdown of ACh–>secondary effects:

• reduce phosphorylation of tau
• secretion of soluble APP returned towards normal
• reduce Beta amyloid production
• Glutamatergic NT returns towards normal

Question 21

which AChE inhibitor has longest half life

Answer 21

donezipil