Alzheimer's 2 (PB)

Question 1

pathological events that lead to AD

Answer 1

1. abnormal hydrolysis of APP - A beta40, 42 production
2. fibrillogenesis
3. aggregation - formation of neuritic plaques
4. neurofibrillary degenreation - neurofibrillary tangles
5. glutamate ecxess in synapses - excitatory
6. activation of microglia and presence of infammatory proteins
7. imbalance in ntracellular ion homeostasis - Ca, Cu, Fe, Zn
8. oxidative stress - free radicals toxicity
9. alternations of the mitochondrial membrane

Question 2

tests for diagnosis of AD

Answer 2

• med Hx and symptoms
• physical exam, neurologogical exam
• mental status evaluation, test memory/attnetion span
• problem solving, social, language skills
• genetic tests (blood test for APOE-E4 gene)
• imaging - CT, MRI, PET scans
• MRI preferred for early diagnosis, can use CT

Question 3

preventative care for AD

Answer 3

• healthy diet
• fatty cold-water fish (tuna, salmon) - lower risk of dementia
• antioxidants VIT A, E, C in dark fruit/veg may prevent damage from free radicals
• maintaining normal BP levels may reduce AD risk
• mentally/socailly active slow progression of AD
• exercise regularly

Question 4

evaluations for AD

Answer 4

1. mini-mental state exam
2. clinician’s interview-based impression of change-plus caregiver input (CIBIC-plus)
3. function activites questionnaire
4. physical self-maintenance scale and instrumental activities of daily living
5. neuropsychiatric intevtory-questionnaire

Question 5

goals of AD Tx

Answer 5

• slow progression of the disease
• manage behavioural problems, confusion and agitation
• change the home environment to be safe
• support family members and caregivers

Question 6

lifestyle changes for AD

Answer 6

• regular walk with caregiver/family to improve communication skills and reduce chance of wandering
• bright light therapy may reduce insomnia and wandering
• calming music may reduce wandering, restlessness, boost brain chemicals and improve behavior
• pets can help to improve behaviour
• relaxation training and exercises that need focused attention to help with social interaction and make it easier to do tasks
• ID bracelets, wallet catds, labels on clothes

Question 7

3 hypothesis for AD

Answer 7

1. cholinergic hypothesis
2. amyloid hypothesis
3. tau hypothesis

Question 8

changes in neurons in early AD

Answer 8

…… slide 17

Question 9

…….

Answer 9

……….

Question 10

examples of cholinesterase inhibitors

Answer 10

rivastigmine
galantamine
donepezil

Question 11

donepezil

Answer 11

AchE inhibitor
non-comeptitive
mild-moderate AD
peak concs after 3-4hrs
half life is 70hrs

Question 12

side effects of donepezil

Answer 12

diarrhoea
anorexia
N&V
muscle cramps
fatigue

Question 13

rivastigmine

Answer 13

AchE and BuChE enzyme inhibitor
non-competitive inhibition
mild/mod AD
peak concs after 1hr

Question 14

side effects with rivastigmine

Answer 14

N&V

diarrhoea

Question 15

galantamine

Answer 15

AchE enzyme inhibition
comeptiitve inhibition
mild/mod AD
peak concs after 1hr

Question 16

side effects wiht galantamine

Answer 16

N&V
anorexia
diarrhoes
weight loss

Question 17

dose of donepezil

Answer 17

initially 5mg OD

increased after 1 month to max 10mg

Question 18

forms of donepezil

Answer 18

tablets

orodispersible tablets

Question 19

dose of rivastigmine

Answer 19

1.5mg BD

inc in steps of 1.5mg BD every 2 weeks according to tolerance

max dose of 6mg BD

patch:
initially 4.6mg patch per day

inc to 9.5mg patch per day for at least 4 weeks

Question 20

forms of rivastigmine

Answer 20

capsules

oral solution

patches

Question 21

dose of galantamine

Answer 21

initially 4mg BD for 4 weeks

inc to 8mg BD for 4 weeks

maintenance 8-12mg BD

Question 22

forms of galantamine

Answer 22

tablets

oral solution

MR preparation

Question 23

glutamate and AD

Answer 23

………..

Question 24

………..

Answer 24

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Question 25

..............

Answer 25

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Question 26

.........

Answer 26

...........

Question 27

How does memantine work in AD?

Answer 27

................

Question 28

What type of drug is memantine and how does it work?

Answer 28

voltage dependent, moderate affinity, uncompetiitve NMDA receptor antagonist blocks the effects of elelvated tonic levels of glutamate that can lead to neuronal dysfunction

Question 29

When is memantine used?

Answer 29

patinets with moderate to severe AD

Question 30

dose of memantine

Answer 30

initially 5mg OD increased in steps of 5mg at weekly intervals to max of 20mg daily

Question 31

side effects fo memantine

Answer 31

``` dizziness headache constipation somnolence hypertension ```

Question 32

memantine caution

Answer 32

excreted by the kidney reduce dose in kidney disease

Question 33

main drugs used for AD Tx

Answer 33

``` antipsychotics antidepressants benzodiazepines hypnotics anxiolytics mood stabilisers ```

Question 34

1st line for mild/mod AD

Answer 34

cholinesterase inhibitors - rivastigmine - donepezil - galantamine titrate to max tolerated dose within therapeutic range

Question 35

2nd line if cholinesterase inhibitor intolerant/no benefits/failure

Answer 35

switch to another cholinesterase inhibitor - donepezil to rivastigmine to galantamine - rivastigmine to galatamine or donepezil - galantamine to rivastigamine ot donepezil

Question 36

What to do if 2nd line monotherapy/all cholinesterase inhibitors don't work?

Answer 36

add memantine or substitution to memantine in moderate AD

Question 37

What to do if 3rd line memantine alone/comb with ChEI doesn't work?

Answer 37

withdrawal of cholinesterase inhibitor and mmeantine therapy

Question 38

How often to monitor MMSE score?

Answer 38

every 6 months

Question 39

When id Tx continued according to MMSE score?

Answer 39

if score remains at or above 10/30

Question 40

interactions with AD drugs

Answer 40

inc risk fo arrhythmias with agents that reduce HR - beta blockers, digoxin, amiodarone antimuscarinics antagonise effects

Question 41

What to exclude before starting Tx for AD?

Answer 41

exclude reverrsible casues of cognitive impairment eg. hypothyroidism

Question 42

benefits of AchE inhibitors

Answer 42

only 10% improvement in short term memory, language, praxia abilities at best