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Part 3 – PM3B > (PM3B) Dementia & Alzheimer's > Flashcards

(PM3B) Dementia & Alzheimer's Flashcards

1
Q

What are the types of dementia?

A

(1) Alzheimer’s disease – 62%
(2) Mixed dementia – 10%
(3) Vascular dementia – 17%
(4) Rarer causes of dementia – 5%
(5) Dementia with Lewy bodies – 4%
(6) Frontotemporal dementia – 2%

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2
Q

What is dementia?

A

Chronic progressive mental disorder that adversely affects higher cortical functions

Including:

  • memory
  • thinking
  • orientation
  • comprehension
  • calculation
  • learning capacity
  • language
  • judgment
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3
Q

What is Alzheimer’s disease?

A

Most common form of dementia

Degenerative cerebral disease with characteristic neuropathological and neurochemical features

Onset and development is slowly but steadily over several years

Progressive deterioration in cognition, function and behaviour

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4
Q

What are the major categories of symptoms of Alzheimer’s disease?

A

(1) Cognitive
(2) Non-cognitive
(3) Disability

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5
Q

What are some cognitive symptoms of Alzheimer’s disease?

A

(1) Memory loss
(2) Disorientation/ confusion
(3) Poor concentration
(4) Failing intellect
(5) Language impairment

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6
Q

What are some non-cognitive symptoms of Alzheimer’s disease?

A

(1) Depression
(2) Anxiety
(3) Delusion
(4) Aggression
(5) Sleep disturbances
(6) Dis-inhibition – inability to suppress inappropriate behaviour

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7
Q

What are some disabling symptoms of Alzheimer’s disease?

A

(1) Difficulties with daily living
(2) Self-neglect
(3) Incontinence

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8
Q

What may the symptoms of Alzheimer’s disease be confused with?

A

(1) Diabetes
(2) Thyroid problems
(3) Vitamin deficiency
(4) Infection
(5) Anxiety
(6) Brain tumour
(7) Depression

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9
Q

With regard to dementia, what are plaques and tangles?

A

Alzheimer’s disease

1) Amyloid plaques (Aß
(2) Neurofibrillary tangles (Tau)

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10
Q

How does the brain tissue of a patient with Alzheimer’s disease compare to the brain tissue of a healthy patient?

A

(1) Enlargement of the ventricles – loss of tissue
(2) Hippocampus is degenerated
(3) Grooves of cerebral cortex are much more defined

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11
Q

What is the significance of the weight of an orange with regard to dementia?

A

Approximately the mass of the brain lost in a patient with dementia

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12
Q

What molecule composes amyloid plaques?

A

Aß – amyloid beta

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13
Q

What molecule composes neurofibrillary tangles?

A

Tau

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14
Q

What are the significant toxic peptides in dementia or Alzheimer’s disease?

A

(1) Tau

(2) Amyloid beta – Aß

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15
Q

How is Alzheimer’s disease diagnosed?

A

(1) Symptom + memory assessment

(2) MRI + PET scans for biomarkers

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16
Q

Why are memory tests used to diagnose Alzheimer’s disease?

A

Show problems in particular areas

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17
Q

Why are CT and MRI scans used to diagnose Alzheimer’s disease?

A

Can show brain shrinkage (atrophy)

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18
Q

What questionnaire is often used for diagnosis of Alzheimer’s disease?

A

Mini Mental State Exam (score /30)

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19
Q

What is the clock drawing test?

A

A test for Alzheimer’s disease diagnosis

Points are lost for incorrect drawing of a clock

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20
Q

Describe the common level of amyloid beta (Aß) levels in a patient first diagnosed with dementia.

A

Almost at its maximum

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21
Q

What is the purpose of using an MRI in dementia or Alzheimer’s disease diagnosis?

A

(1) Highlights atrophy in hippocampus
(2) Can detect pre-symptomatic changes
(3) Non-invasive
(4) Reproducible

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22
Q

What is the purpose of using an FDG scan in dementia or Alzheimer’s disease diagnosis?

A

(1) Highlights deficits in parietal lobe
(2) Links metabolic state to synaptic activity
(3) Useful in differentiating between types of dementia

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23
Q

What is the predominant risk factor for dementia?

A

(1) Age

24
Q

What are some of the risk factors for dementia?

A

(1) Age – >65yrs old
(2) History of stroke
(3) Head injury
(4) Vascular diseases
(5) Diabetes
(6) Smoking
(7) Drinking
(8) ApoE4 genotype
(9) ApoJ genotype
(10) TREM2 status

25
Q

What is dementia pugilistica?

A

Punch drunk

Head injuries in sport

Subsequent development of dementia

26
Q

What are some of the biomarkers that increase following a traumatic head injury?

A

(1) Hyperphosphorylated Tau

(2) Amyloid plaque deposition

27
Q

Name 3 early onset genes for Alzheimer’s disease.

A

(1) APP
(2) PSI
(3) PSII

28
Q

What is the amyloid cascade hypothesis?

A

(1) Amyloid beta accumulation
(2) Amyloid beta oligomerisation (clump) + deposition
(3) Inflammatory response – from glial cells?
(4) Synapse loss
(5) Oxidative stress
(6) Ca2+ overload
(7) Neuronal death

29
Q

What treatment strategies are available for dementia?

A

No disease modifying therapy exists

Management of symptoms

Focus on cholinergic + glutamatergic signalling

30
Q

What are the two major types of cholinergic receptor?

A

(1) Muscarinic – M1-M4

(2) Nicotinic – nAChR

31
Q

Which molecule breaks down acetylcholine in the synaptic cleft?

A

Acetylcholinesterase

32
Q

What are some acetylcholinesterase inhibitors?

A

(1) Donepezil
(2) Galantamine
(3) Rivastigmine

33
Q

What is the purpose of acetylcholinesterase inhibitors?

A

To limit the breakdown of neurotransmitter acetylcholine

34
Q

What are some of the effects of acetylcholinesterase inhibitors?

A

(1) Enhance cholinergic transmission - improve cognitive function
(2) Therapeutic effectiveness decreases with disease progression
(3) Does NOT affect disease progression
(4) Cognitive assessment repeated to assess benefit
(5) Poor response = discontinue treatment

35
Q

What are some key issues acetylcholinesterase inhibitors in the treatment of dementia?

A

(1) Do not affect disease progression
(2) Effect decreases as disease progresses
(3) Only a subset of patients respond well
(4) Side-effects at high dose

36
Q

What is anticholinergic burden (ACB)?

A

Score given to anticholinergic drugs (1-3)

1 = least severe

3 = most severe

37
Q

What is a drug with an ACB score of 1?

A

Warfarin

38
Q

What is a drug with an ACB score of 2?

A

Cyclobenzaprine

39
Q

What is a drug with an ACB score of 3?

A

Diphenhydramine

40
Q

What is glutamatergic transmission?

A

Neurotransmitter glutamate

41
Q

What are some of the receptors for glutamate?

A

(1) MGluR5
(2) NMDAR
(3) AMPAR
(4) KainateR

42
Q

What role does an astrocyte have in glutamatergic transmission?

A

Deals with excess glutamate

Recycles + repackages

(1) Takes in glutamate via GLT1
(2) Converts to glutamine
(3) Re-enters presynaptic membrane via GlnT

43
Q

Name an antagonist of NMDA receptors.

A

Memantine

44
Q

What are some of the potential effects of antagonism of NMDA receptors?

A

(1) Improves cognitive function

(2) Effects evident at late stages of disease

45
Q

What are some of the possible drug interactions of NMDA receptors antagonists?

A

(1) Antipsychotics
(2) Anticoagulants
(3) Analgesics
(4) Muscle relaxants

46
Q

What are the current NICE guidelines for management of mild-moderate Alzheimer’s disease?

A

(1) Donepezil
(2) Galantamine
(3) Rivastigmine

47
Q

What are the current NICE guidelines for the management of severe Alzheimer’s disease, or those who cannot take acetylcholinesterase inhibitors?

A

Memantine

48
Q

Is a combination of an acetylcholinesterase inhibitor and a glutamatergic inhibitor recommended for the treatment of Alzheimer’s disease?

A

Not currently

49
Q

What are some potential areas for future development of drugs to treat Alzheimer’s disease?

A

(1) Modulation of neurotransmission
(2) Amyloid-based therapies
(3) Tau-based therapies
(4) Oxidative stress reduction
(5) Mitochondrial-targeted therapies
(6) Modulation of calcium homeostasis
(7) Anti-inflammatory therapy

50
Q

What is aducanumab?

A

Monoclonal antibody

Anti-amyloid antibody

51
Q

What is the neuroAD system?

A

Neuronix

Combines transcranial stimulation + cognitive training

52
Q

What are behavioural and psychological symptoms of dementia?

A

Experienced by ~90% of patients

Potentially treatable

(1) Marked agitation
(2) Ideation
(3) Anxiety
(4) Hallucinations
(5) Misperceptions
(6) Aggressive behaviour
(7) Depression

53
Q

When are antipsychotics recommended for patients with dementia?

A

Mild-moderate non-cognitive symptoms should NOT be given antipsychotics

Patients with psychosis/ agitated behaviour

54
Q

When are sedatives recommended for patients with dementia?

A

For challenging behaviour

Violence/ aggression/ severe agitation

e.g. lorazepam/ haloperidol/ olanzapine

55
Q

When are antidepressants recommended for patients with dementia?

A

Emotional disorders

Dementia + major depressive disorder

AVOID TCA + MAOI due to anticholinergic properties

Part 3 – PM3B (32 decks)

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