Dementia and Alzheimers

Question 1

What is dementia?

Answer 1

A progressive disease characterised by a decline in cognitive function

Question 2

What is alzheimer’s disease?

Answer 2

A type of dementia affecting mostly adults of advanced age.

Question 3

What are the four hypothesis of AD pathogenesis?

Answer 3

Cholinergic Hypothesis
Tau protein Hypothesis
Amyloid beta peptide Hypothesis
Inflammatory hypothesis

Question 4

What is the cholinergic hypothesis?

Answer 4

Suggests that a decrease in synaptic acetylcholinesterase causes AD. Forms the basis of most drug treatments for dementia.

Question 5

What is the tau protein hypothesis?

Answer 5

Suggests that hyperphosphorylation of tau proteins causes the production of paired helical filaments, which form neurofibrillary tangles which cause cell death.

Question 6

What is the amyloid beta peptide hypothesis?

Answer 6

Suggests that a buildup of amyloid beta peptides (increased production/decreased clearance) causes apoptosis by piercing the cell membrane.

Question 7

What is the inflammatory hypothesis?

Answer 7

Suggests that both tau hyperphosphorylation and amyloid beta peptide accumulation causes oxidative stress resulting in chronic inflammation that causes AD.

Question 8

What is vascular dementia?

Answer 8

Dementia caused by cerebrovascular disease or cerebral blood flow.

Question 9

What are the cholinesterase inhibitors?

Answer 9

Donzepeil, rivastigmine, galantamine

Question 10

Cholinesterase inhibitor MOA?

Answer 10

Inhibits the cholinesterase enzyme which increases the amount of acetylcholine at the synaptic cleft for cholinergic transmission.

Question 11

Cholinesterase inhibitor ADRs?

Answer 11

Nausea, vomiting, diarrhoea, bradycardia, sleep disturbance, hypotension, cholinergic symptoms

Question 12

What are the cholinergic symptoms?

Answer 12

Salivation
Lacrimation
Urination
Diarrhoea
GI upset
Emesis

Question 13

Cholinergic inhibitor place in therapy?

Answer 13

Evidence suggesting its benefit is limited although there is some evidence suggesting that it is effective for mild to moderate cases of dementia.

Question 14

NMDA antagonist moa?

Answer 14

Memantine is an antagonist at the NMDA receptor and down-regulates its activity. Over-stimulation has been attributed to excitotoxicity which can worsen dementia.

Question 15

NMDA antagonist place in therapy?

Answer 15

Not funded in NZ, therefore would only be considered in patients with advanced stage dementia or those who would benefit from AchEI treatment but are contraindicated. Benefits must outweigh risks.

Question 16

NMDA antagonsit ADRs?

Answer 16

CNS depression, respiratory depression

Question 17

What is the principle of vascular dementia treatment?

Answer 17

1. Secondary prevention of stroke

2. Treatment of dementia

Question 18

What therapies are involved in the secondary prevention of stroke?

Answer 18

1. Antihypertensives
2. Statins
3. Diabetes control
4. DAPT

Question 19

What is the principle of BPSD treatment in dementia?

Answer 19

1. Identify and rule out any precipitating factors
2. Non-pharmacological therapy
3. Pharmacological therapy

Question 20

What are the precipitating factors of BPSD?

Answer 20

Pain
Infection –> Delirium
Medication toxicity

Question 21

What are non-pharmacological therapies available for BPSD?

Answer 21

Aromatherapy
Exercise therapy
Light therapy (to stabilise circadian rhythm, prevent sundowning)
Music therapy

Question 22

What pharmacological therapies are available for BPSD?

Answer 22

Anti-dementia medications
Antidepressants
Atypical antipsychotics

Question 23

What monitoring is required for patients with dementia?

Answer 23

Monitoring of treatment for efficacy and side effects. If risks outweigh benefits then cease treatment.
Monitoring of cognitive function (mini-ACE, MoCA)
Monitoring of neuropsychiatric symptoms and any potential precipitating causes
Routine assessment by GP at 3 monthly intervals to assess current condition.

Question 24

What counselling is required for patients with dementia?

Answer 24

Refer caregivers and family to Dementia NZ website for family support. Patient may also benefit from exercise or social groups in early dementia.
Explain to family prognosis of disease and that it cannot be cured, and that medication may slow down progression (but this is not guaranteed), and will not stop it.
Suggest Advanced Care Directive/Enduring Power of Attorney to guide patient treatment in the case that their cognitive function declines considerably.

Question 25

What formulation considerations exist in dementia treatment?

Answer 25

Donezepil available in funded tablet which requires OD dosing. Rivastigmine also available in tablet form but unfunded and requires BD dosing. Rivastigmine also available as transdermal patch (matrix), but requires SA. Galantamine not available in NZ thus would not be considered unless all other options had been exhausted and there is clear benefit (that outweighs risks) for its use.