PBL - Dementia Flashcards

1
Q

Delirium is diagnosed by what criteria?

A
Acute onset
Fluctuating consciousness levels
Is secondary to an underlying medical problem
Disordered thinking
Visual/tactile hallucinations 
Illusions
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2
Q

What are the most common causes of delirium?

A
Infection of the bladder, chest or brain
Fever
Medication side effect
Dehydration
Liver or kidney problem 
Cessation of drug or alcohol use
Epilepsy
Terminal illness
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3
Q

What are the signs and symptoms of delirium?

A
Reduced awareness of surroundings 
- inability to concentrate on one topic 
- being concerned with one idea and avoiding conversation or questions 
Cognitive impairment 
- reduced memory 
- poor understanding of speech, difficulty speaking
Changes in behaviour 
- hallucinations
- sleep disturbances 
- being agitated, irritable or restless
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4
Q

Describe the main differences between dementia and delirium.

A

Attention span
- people with delirium can’t focus on anything
Onset
- delirium is rapid onset, within a few hours or days, while dementia is a slowly progressing disease
Fluctuation in symptoms
- delirium symptoms fluctuate, coming and going throughout the day, while in dementia thinking skill and memory remain fairly constant

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5
Q

What is the differentia diagnosis for delirium?

A
A - Alzheimer's 
V - vascular disease
D - drugs, depression, delirium
E - ethanol
M - metabolic
E - endocrine
N - neurological (other primary degenerations)
T - tumour, toxins, trauma
I - infection
A - autoimmune
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6
Q

What are the four main types of dementia?

A

Alzheimer’s
Vascular
Lewy body
Fronto-temporal

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7
Q

What are the risk factors for Alzheimer’s disease?

A

Genetics
- a mutation in the APP gene found on chromosome 21
- a mutation in the gene for apoplipoprotein E4 on chromosome 19
Down’s syndrome
- 50% extra APP production due to the 3rd chromosome 21

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8
Q

What are the clinical features of Alzheimer’s?

A
Failing memory
Cognition decline 
- language
- writing
- reading 
- calculation 
- attention and problem solving 
Psychiatric - personality and mood changes 
Neurological - primitive reflexes, postural abnormalities 
Mute, bed ridden, death
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9
Q

What are the main pathologies seen in Alzheimer’s?

A

Neuritic plaque

Neurofibrillary tangles

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10
Q

Describe neuritic plaques.

A

A complex extracellular lesion
Aggregates of filaments with a central core of beta-amyloid protein
Found in the hippocampus and parietal lobes

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11
Q

Describe neurofibrilliary tangles

A

An intracellular lesion
Paired helical strands of protein close to the nuclei of affected neurons - derived from micro tubule-associated protein tau
- in a hyperphosphorylated state
Mainly affects the temporal and parietal lobes

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12
Q

Where are signs of Alzheimer’s first seen in the brain?

A

Entorhinal cortex, and then the hippocampus

  • atrophy with associated neuron loss
  • atrophy most evident in the temporal gyri
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13
Q

Describe what symptoms are seen in mild Alzheimer’s?

A
Memory loss
Confusion
Trouble handling money
Poor judgment 
Mood changes
Anxiety
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14
Q

Describe the symptoms seen in moderate Alzheimer’s.

A
Increased memory loss and confusion 
Problems recognising people 
Difficulty with languages and thoughts 
Restlessness
Agitation
Wandering
Repetitive statements
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15
Q

Describe the symptoms of severe Alzheimer’s.

A
Severe cortical atrophy 
Completely dependent on the care of others 
Weight loss
Seizures 
Increases sleeping 
Loss of bladder and bowl disease
Death
- usually from pneumonia
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16
Q

How is Alzheimer’ diagnosed?

A

A typical case history with progressive dementia and negative findings in routine tests
CT scans show non-specific cerebral atrophy with enlarged ventricles

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17
Q

What are the risk factors of vascular dementia?

A

Hypertension

Atherosclerosis

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18
Q

What is small and large vessel disease?

A

Small - subcortical
- ministries slowly block off the areas of the brain
Large - cortical multi-infarcts
- brain lesions may affect specific cognitive functions
- multiple infarcts are caused by an accumulations of bilateral multi focal ischaemic events
- dementia progresses in a step wise fashion

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19
Q

How is vascular dementia diagnosed?

A

History base
Presence of multiple-infarcts on CT and MRI scanning
- also look for presence of beta-amyloid plaques and neurofibrillary tangles
- just because the patient has had a stroke, it doesn’t mean that is the cause of dementia

20
Q

What are the signs and symptoms of dementia with Lewy bodies?

A
Progressive cognitive decline 
Fluctuating consciousness 
Visual hallucinations 
Parkinsonism 
- no resting tremor, no response to L-DOPA treatment
21
Q

What are the pathological findings of dementia with Lewy bodies?

A

Similar to Alzheimer’s and Parkinson’s disease
Cortical Lewy bodies form form, often instead of tangles
- present in basal ganglia
- little pink balls
Plaques and tangles can be present as well
Cholinergic deficit

22
Q

Describe the aetiology of frontotemporal dementia.

A

Sporadic and inherited
Affects a younger group of patients (aged 45-65 typically)
Frontal lobe dysfunction
- behavioural and personality changes, disinhibition, depression and agitation are common
Cognitive and memory impairment

23
Q

Describe the pathology of frontotemporal dementia.

A

Tau accumulations causes plaques called Pick’s bodies
- these contain tau and argyrophilic bodies
Significant fronto-temporal atrophy can be seen

24
Q

How is frontotemporal dementia diagnosed?

A

Functional MRI scans show the frontotemporal lobes of the brain to be less active than other areas .

25
Q

What are the possible treatments for dementia?

A

Acetylcholinesterase inhibitors
Memantine hydrochloride
Antipsychotics
Antidepressants

26
Q

Describe the mechanism of acetylcholinesterase inhibitors (e.g. Rivastigmine and Donepezil)

A

It prevents the breakdown of ACh that crosses the synapses, allowing more action potentials to be passed between neurons #.
Doesn’t treat, merely manages the effect

27
Q

What are acetylcholinesterase inhibitors used to treat?

A

Alzheimer’s disease
Dementia with Lewy bodies
Parkinson’s dementia

28
Q

What are the side-effects of acetylcholinesterase inhibitors?

A

Nausea, vomiting, diarrhoea, muscle cramps, dizziness, fatigue, anorexian cardiac adverse events and peptic ulcers/GI bleeding

29
Q

Describe the mechanism of action of Memantine hydrochloride.

A

Uncompetitive NMDA receptor agonists (NMDA being a major glutamate receptor)
- Alzheimers causes increased gutamate in the brain
- increased levels of glutamate counters the voltage-dependent block of the receptor by magnesium ions
- constant calcium influx
- neuron degeneration
Memantine blocks these channels more effectively than the magnesium ions to allow normal action of glutamate

30
Q

What are the risks of using antipsychotics to treat someone with dementia?

A

CV problems
Drowsiness
Dementia with Lewy bodies
- causes rigidity, immobility and inability to communicate

31
Q

What cleaves amyloid protein?

A

Alpha/bet/gamma - secretase

32
Q

Mutations in what gene is the cause of familial AD?

A

Presenilins 1 or 2

33
Q

How do plaques form in dementia?

A

Mutation in gamm-secretase causes abnormal cleaving of the amyloid precursor protein. Sticky, hydrophobic beta-amyloid plaques form and aggregate together.

34
Q

What is apoplipo-protein?

A

A lipoprotein produced by astrocytes, thought to be involved in lipid metbaolism.
Normal function promotes breakdown of A-beta

35
Q

What happens in an apolipo-protein mutations?

A

E4 mutation = 20x higher risk of Alzheimers

Inhibits breakdown of amyloid-beta, and this aggregates more easily

36
Q

What are the four main mutations that can cause Alzheimer’s?

A

Beta-APP mutations
ApoE4 polymorphisms
Presenilin 1 mutations
Preenilin 2 mutations

37
Q

What causes neurofibrilliary tangles?

A

Hyper-phosphorylation of tau protein
Causes soluble tau aggreagtes
Causes tau deposition
- more common in fronto-temporal dementias

38
Q

How can people maintain cognitive function during aging?

A

Higher levels of physical activity
Mental activity
Social interaction
Cognitive training intervention

39
Q

What is the organic pathology of vascular dementia?

A

Mainly atherosclerotic blood vessels, emboli or other vascular problems.
Can see some cerebral atrophy, beta-amyloid plaques and neurofibrillary tangles, because they are normal in ageing

40
Q

What are Lewy bodies made from?

A

Alpha synuclin

41
Q

Define a molecular chaperone.

A

Any protein that interacts with, stabilises or helps another protein to acquire its functionally active formation, without being a part of its final structure

42
Q

What is the name of the enzyme which determines whether a protein has been misfolded or not?

A

Glucosyltransferase

43
Q

Briefly describe a proteasome

A

A hollow cylindrical structure that consists of

  • a cap
  • alpha subunits (non-enzymatic)
  • beta subunits (proteolytic activity)
44
Q

Describe the formation of Lewy bodies?

A

Misfoldin into beta-pleated sheet structure of alpha-synuclein that further aggregate into high-order insoluble structures (fibrils)

45
Q

What is the affected protein in prion disease?

A

PrPc - becomes PrPsc