Alzheimer's

Question 1

is Alzheimer’s progressive or reversible

Answer 1

progressive and non reversible

Question 2

onset of Alzheimer’s

Answer 2

insidious

Question 3

what age is classified as early onset Alzheimer’s

Answer 3

<65

Question 4

how may early onset Alzheimer’s presentation vary

Answer 4

may be atypical

Question 5

are genetic factors or environemental factors more important in the development of early onset/Alzheimer’s

Answer 5

early onset, thinking genetic factors - maybe a mutation

population risk for AD is more due to multifactorial - genes, environement etc

look at ice Berg triangle

Question 6

are females or males more likely to get Alzheimer’s

Answer 6

females

Question 7

genetics of AD - which 3 mutations are associated

Answer 7

• multifactorial, but increased risk with 1st degree relative (25%)
• APP gene mutation - produces amyloid precuros protein, excess leads to formation of beta amyloid palques and tau tangles
• PSEN genes
• Inheriting Apoe4

Question 8

do lifestyle factors have an influence on the development of Alzheimer’s

Answer 8

yes, smoking midlife obesity, diet high in sat fats are risk factors

also, diabetes, smoking in mid-life, hypertension are found to be the greatest modifiable risk factors for dementia.

Question 9

cerebrovascular disease and Alzheimer’s

Answer 9

is a strong risk factor for vascular dementia, which often overlaps with Alzheimer’s

diabetes increases the risk of both

Question 10

Down’s and Alzheimer’s

Answer 10

Down’s is assoicated with early onset Alzheimer’s

the presence of 3 copies of the APP gene on chromosome 21 accounts for this

Question 11

which allele is a risk factor for Alzheimer’s

Answer 11

ApoE e4 allele

Question 12

which 3 things point towards a familial cause o disease

Answer 12

early onset

atypical form

relatives affected

Question 13

senile plaques

Answer 13

EC deposits of amyloid beta in grey matter

Question 14

how does amyloid beta form

Answer 14

mutations in the amyloid precursor protein leads to formation of abnormal amyloid beta

Question 15

what do senile plaques do

Answer 15

Senile plaques cause an inflammatory process through microglial activation, cytokine formation and activation of complement cascade. Inflammation leads to formation of neuritic plaques à cell death.

Leads to cortical atrophy.

Question 16

what are neurofibrillary tangles made of

Answer 16

abnormal aggregates of tau protein

Question 17

is the number of neurofibrillary tangles important in disease severity?

Answer 17

number of tangles roughly proportional to severity of disease and cognitive decline

Question 18

what happens to cholinergic neurotransmission

Answer 18

the collection of neurons that produce ACh (called the nucleus basalis of Meynert) is affected early on in the disease process - decreased levels of cholingeric neurotransmission

Question 19

what happens to glutamine transmission

Answer 19

there are changes to the NMDA receptors - results in overativation of glutamate - excito!!!

Question 20

what are important points to elicit from history

Answer 20

• timeline of progression
• how ADL are affected eg financial affairs and medications

Question 21

what are the 3 common presenting symptoms

Answer 21

loss of recent memory

difficulty with exectuve function

nominal dysphasia

Question 22

what other features are common

Answer 22

• Disorientation (e.g. things getting lost at first – this could also be due to visuo-spatial dysfunction)
• Apathy
• Deficits in visuo-spatial function (e.g. impaired performance in clock-drawing) and driving become evident as the disease progresses
• Features such as prosopagnosia (not recognizing familiar faces) and auto prosopagnosia tend to develop later

Question 23

do changes in personality occur?

Answer 23

later in disease, unlike in other dementias

Question 24

physical examination

Answer 24

unremarkable in early stages.

In advanced disease patients may appear sloppily dressed, confused, apathetic, disorientated.

Question 25

what is a good cognitive test to use initially

Answer 25

mini mental state examination

Question 26

what tests would be done to rule out other causes on diagnosis

Answer 26

• FBC: to rule out anaemia
• Metabolic panel
• TSH – rule out hyper/hypothyroid associated dementia
• Serum vitamin B12
• CT – exclude SOL etc.

Question 27

what is seen on an MRI

Answer 27

generalised atrophy, temporal and lateral parietal predominance

compensatory dilation of ventricles

Question 28

what would examination of CSF show

Answer 28

increased tau level and decreased amyloid beta

Question 29

what is the first step of management

Answer 29

to provide education, support and resources to patient and family

Question 30

which risk factors must be addressed during management

Answer 30

vascular risk factors

Question 31

pharmacological management

Answer 31

• Cholinesterase inhibitors (boost ACh):
  
  • Donepezil, Rivastigmine, Galantamine
• Anti-glutaminergic treatment (NMDA blockers)
  
  • Memantine

Question 32

how do cholinesterase inhibitors work

Answer 32

Increase brain ACh levels by inhibiting breakdown by CNS acetylcholinesterase

Question 33

what benefit will cholinesterase inhibitors provide

Answer 33

they will not affect the underlying disease process, but will imrpove function and help pt maintain independece

Question 34

what other dementia forms are cholinesterase inhibtors used in

Answer 34

DLB, parkinson’s dementia

Question 35

how does memantine work

Answer 35

it is an antagonist of the NMDA receptors - inhibits excessive glutamine activity

Question 36

who would be prescribed memantine

Answer 36

• Moderate AD who are intolerant of/contraindication to cholinesterase inhibitors
• Add on drug to cholinesterase inhibitors for moderate/severe AD
• Monotherapy in severe AD