Alzheimers

Question 1

Define dementia

Answer 1

1. multiple cognitive deficits - memory dysfunction and +1 additional cog defect
2. cognitive disturbances - impairment of occupational/ social functioning

must represent a DECLINE from a previous level of functioning

Question 2

top 2 causes of dementia

Answer 2

1. alzheimers

2. vascular(mostly stroke)

Question 3

alzheimers early onset and late onset are caused by?

Answer 3

early = familial 
late = sporadic

Question 4

life expectancy of alzheimers from diagnosis?

Answer 4

5-8 years (disease starts 10Y before diagnosis)

Question 5

decribe the 2 main causes of neuropathy in alzheimers

Answer 5

1. extracellular amyloid plaques- aggregates of amyloid. TOXIC - causes neurodegeneration
2. Interneuronal neurofibrillary tangles- inside neurone, bundles of filament in cytoplasm - hyperphosphorylated tau proteins (excitotixicity from AB causes altered phosphatase activity)

Question 6

Describe the progression of brain atrophy in alzheimers

Answer 6

early AD - degen of hippocampus (forgetful, maths, repeat themselves)
mild AD - atrophy cerebral cortex (forget tasks, cant think, emotional outbursts)
advanced AD - increased death of nn cells (agitation, wondering, inability to recognise faces)

Question 7

Which NTs areinvolved in alzheimers

Answer 7

Ach, NA, 5HT

Question 8

How do donepezil, rivastigmine, galantamine work?

Answer 8

acetylcholinesterase inhibitors, may slow decline of mild AD

Question 9

Why do nerve cells die in alzheimers?

Answer 9

loss of intracellular Ca homeostasis:
amyloid precursoe
oxidative stress
neurotoxic insult
to much glutamate activation
apoptosis

Question 10

Name the 2 genetic categories in alzheimers

Answer 10

familial - to much AB produced (dominant)

sporadic - AB not cleared fast enough (non dom)

Question 11

name 3 biochemical and 5 ‘other’ factors that can lead to neuropathy and therefor alzheimers

Answer 11

nn GF, inflammation, free radicals

stress, age, gender, head size, education

Question 12

describe how the metabolism of APP can lead to alzheimers

Answer 12

APP metabolised by
a- secretase and y- secretase = non amyloidogenic GOOD
b- secretase and y- secretase = amyloidogenic BAD forms AB

Question 13

why do we have APP?

Answer 13

regulates proteases, involved in cell adhesion, protects against neurotoxic insult, regulates intracellular CA, regulates cytokine release - PROTECTIVE

Question 14

how is AB plaques neurotoxic

Answer 14

disrupts Ca homeostasis
promotes inflammation
toxic
makes neurones vulnerable to excitotoxicity

Question 15

What is the most toxic type of AB and what do they do?

Answer 15

ADDL 12 mer - impair long term potentiation (strengthening of synapse)

Question 16

List 4 mechanisms of drug approaches for alzheimers

Answer 16

increased blood flow VASODIL
enhanced glutamate
cholinesterase inhibs
muscarinic agonist

Question 17

What other mechanisms can we use to halt the alzheimers disease process?

Answer 17

AB aggreg inhibs
anti inflammatory drugs (AB cause inflammation)
tau kinase inhibitors