6.5 Dementia Flashcards

1
Q

Define dementia

A
  • Collection of symptoms that are caused by disorders affecting the brain
  • Affects thinking, behaviour and everyday life
  • Interferes with normal social/working life
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2
Q

Is dementia a disease?

A

No. it is a group of diseases.

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3
Q

What are some causes of dementia?

A
  • Alzheimer’s
  • Vascular dementia
  • Dementia with lewy bodies
  • Parkinson’s Disease Dementia
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4
Q

What causes vascular dementia?

A

Damage to brain tissue caused by decreased blood flow (multiple emboli/diffuse small vessel disease)

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5
Q

Alzheimer’s is a neurodegenerative disease that causes loss of neurons, particularly in the…

A

Cortex

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6
Q

What is the role of amyloid precursor protein (APP)?

A
  • Neuron growth and repair
  • Used, broken down, and recycled
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7
Q

Which enzyes usually break down Amyloid Precursor proteins?

A

alpha and gamma secretase (secretion = soluble)

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8
Q

Which enzyme, when cleaving amyloid precursor protein, causes formation of amyloid beta?

A

Beta secretase

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9
Q

What plaques are formed when beta secretase cleaves amyloid precursor protein? What does this cause?

A
  • Beta amyloid plaques
  • Can interfere with neuron to neuron signalling, causing neurological deficits that lead to Alzheimer’s
  • Can also start up an immune response, causing immune response
  • Can also lead to amyloid angiopathy
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10
Q

How are neurofibrillary tangles thought to be formed? What are the consequences of this?

A
  • Beta amyloid buildup prompts phisphate deposition on tau within microtubules
  • Causes conformational shape change that leads to tau leaving microtubules and forming tangles
  • Disrupts microtubules, and can lead to apoptosis
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11
Q

What is the level of memory impairment between age-based memory impairment and dementia?

A

Mild cognitive impairment

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12
Q

How is dementia different from age based memory loss and mild cognitive impairment?

A

Extra symptoms include:
- Affecting daily life
- Difficulty in learning
- Difficult to complete familiar tasks
- Others are starting to notice changes in abilities

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13
Q

Is dementia more commonly caused by primary or secondary brain tumours?

A

Secondary (meaning metastases from other areas)

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14
Q

What kinds of trauma can cause dementia?

A
  • Haematoma (particularly subdural)
  • Post head injury (often years later)
  • Chronic traumatic encephalopathy (common in pro athletes)
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15
Q

What toxins/deficiencies can cause dementia?

A

Toxins: alcohol, heavy metals, carbon monoxide

Deficiencies: Thiamine, B12

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16
Q

What infections can cause dementia?

A
  • Syphilis
  • HIV
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17
Q

Dementia diagnostic criteria

A

New, significant decline in:
- Learning and memory
- Language
- Executive function
- Complex attention
- Social skills

Must affect everyday life. Cannot exclusively occur during delirium, and should not be better accounted for by another disorder.

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18
Q

What is a big difference in presenting symptoms of vascular dementia vs Alzheimer’s?

A
  • Alzheimer’s tends to involve memory loss
  • Vascular dementia more often affects speed of thinking and problem solving (and can occur in the setting of a stroke)
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19
Q

What is the cholinergic hypothesis of AD?

A

AD shows substantial deficit in:

  • Choline acetyltransferase (synthesis)
  • Reduce choline uptake/release
  • loss of cholinergic neurons from basal forebrain

We can treat dementia with cholinesterase inhibitors, but only symptomatically.

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20
Q

What factors influence our choice of diagnostic test in a patient with suspected Alzheimer’s?

A
  • Education
  • Culture
  • Suspected stage of disease
  • Logistical constraints
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21
Q

What diagnostic cognitive tests might we use in a patient with suspected Alzheimer’s?

A
  • MMSE (good initially, but cannot detect subtle changes)
  • Montreal cognitive assessment; MCS; (more detailed and more sensitive than MMSE)
  • Clock drawing test (good for testing executive function, which may be affected in frontotemporal dementia)
  • Alzheimer’s Disease Assessment Scale (ADAS): not commonly used due to length, but can be useful for detailed assessment
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22
Q

What medications might we give for dementia?

A
  • Cholinesterase inhibitor (prevents breakdown of ACh)
  • Memantine (NMDA receptor antagonist) {see if you can recall why…}
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23
Q

Why do we use memantine (an NMDA receptor antagonist) to treat dementia?

A
  • NMDA are ionotropic glutamate receptors
  • In dementia, glutamate can play a role in activating neuronal apoptosis, thus leading to neurodegeneration
  • By inhibiting receptors, we inhibit degeneration. Big win.
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24
Q

Side effects of memantine

A
  • Dizziness
  • Confusion
  • Drowziness
  • Insomnia
  • Agitation

Need to know underlying symptoms; otherwise, meds might literally make it worse.

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25
Side effects of Cholinesterase inhibitors
- Diarrhoea - Nausea/vomitingA - Loss of appetite - Sleep disturbance (More ACh overactivates Parasympathetic Nervous System, leading to hypermotility which causes GI side effects)
26
Is current pharmacological management of dementia considered very effective?
No :(
27
What is lecanemab? How might it be effective in treating dementia?
- Monoclonal antibody directed against beta amyloid plaques - Removes disruption of neuronal flow
28
What lifestyle factors can improve dementia prognosis?
- Cognitive exercise - Physical exercise - Healthy diet
29
What supports might a dementia patient and family need (not meds, and not lifestyle changes)
- Education and counselling - Social engagement - Removing hazards, putting cues up around house - Legal/financial planning - Advanced care directive - Palliation, at the end
30
Neurodegenerative diseases arise largely due to dysfunctions in 4 main proteins. What are these proteins?
- Amyloid - Tau - Synuclein - TDP43
31
Which cognitive functions decline most/least in old age?
Most: speed of processing, motor speed, visuo-spatial skills (Joe Biden) Least: reading, vocabulary, factual memory (Charlie Munger)
32
What are dementia and mild cognitive impairment also called in the guidelines?
Minor and major neurocognitive disorder
33
Memory changes can be seen __ to __ years before dementia onset
10 to 20 years !!! (Holy fuck)
34
Which are the first two regions of the brain to be affected by Alezheimer's?
- Entirohinal cortex - Then hippocampus
35
What are the early features of preclinical AD?
- Misplacing items - Forgetting recent events - Getting lost easily
36
As we progress from preclinical to mild/moderate AD, which areas of the brain become affected?
Disease process spreads to the cerebral cortex (particularly frontal, temporal, parietal lobes). Modest enlargement of ventricles.
37
What are some signs of mild AD?
- Memory loss - Confusion - Trouble with money - Poor judgement
38
What are some signs of moderate AD?
- Increased memory loss - Confusion - Problems recognising people - Difficulty with language - Wandering - Repetitive statements - Agitation (Starting to struggle more with activities of daily living)
39
What is "sundowning behaviour", and what might it look like?
- Alzheimer's symptoms get worse in evening/night - Could be agitation, disorientation, agitation etc. - ?Suprachiasmatic nucleus
40
What changes macroscopically from moderate to severe AD?
- XTREME brain shrinkage - Complete dependence
41
What are some symptoms of severe AD?
- Weight loss - Seizures - Increased sleep - Loss of bladder/bowel
42
In which cells of the CNS is amyloid precursor protein expressed?
- Neurons - Glial cells - Also other cells throughout the body
43
Amyloid oligomers vs plaques
Oligomers: smaller, soluble. Can impair synaptic function. Plaques: formed by aggregation of beta amyloid fibres. Cause neuroinflammation.
44
What are some negative affects of amyloid beta accumulation in the brain?
- Axonal damage - Synaptic damage - Exctitotoxicity - Mitochondrial dysfunction - Inflammation
45
What is the role of tau in neurons?
Stabilises microtubules and regulates axonal transport.
46
The location of which proteins better predicts cognitive decline in AD: tau or amyloid beta?
Tau. (Of course, it shows the way)
47
How to tauopathies spread through the brain
- A sick neuron "sneezes" tau into a healthy one with vesicles - Leads to formation of fibrillary tangles in previously healthy neuron
48
What kind of brain injury are boxers prone to?
Chronic traumatic encephalopathy
49
What proteins are seen more prominently in chronic traumatic encephalopathy? Where in the brain?
Frontal and temporal tau deposition (frontotemporal tauopathy)
50
Frontotemporal Dementia vs Alzheimer's symptoms
Frontotemporal is more behavioural (e.g. socially inappropriate behaviour), whereas Alzheimer's is more memory.
51
Is frontotemporal dementia an amyloidopathy?
No. It is a tauopathy.
52
Give three examples of synucleinopathies. In which layers of the brain are lewy bodies found in each example?
- Parkinson's (substantia nigra) - Dementia with Lewy Bodies (cortex) - Multiple system atrophy (brainstem, cerebellum, basal ganglia)
53
Greg is 64, and we have found Lewy Bodies in his brain. Does this mean he has a disease?
- No - Found in 10% of neurologically normal people over the age of 60
54
What components of mental status should be examined in a patient who may have dementia?
- Orientation - Memory - Language - Attention - Abstract thinking - Ability to use objects - Perceptual abilities
55
What conditions might we look for on neuroimaging of a patient with suspected dementia?
- Stroke - Tumour
56
What are some legal aspects of dementia care
- Advance care directives - Assessment of capacity - Drivers/gun license - Consent to treatment (can they consent?)
57
What happens to levels of tau/amyloid beta 42 in the CSF of patients with dementia?
- A beta 42 is decreased - Tau is increased
58
What diseases can be ruled out using a lumbar punctured in a dementia-like picture?
- Prion diseases - Infectious diseases (e.g. HIV, syphillis)
59
Give 3 examples of anticholinesterases
- Donepezil - Galantamine - Rivastigmine
60
What are some absolute/relative contraindications for anticholinesterases?
Absolute: - GI/ureteric blockage - Peptic ulcer Relative: - Parkinson's (tremor) - Bradyarrhytmia/heart block (para. slows heart) - Seizures
61
Is denepezil (or other anticholinesterases) close to 100% effective for patients with dementia?
- No - Only works and 26% of cases, and placebo works in 8%... - Important to communicate upfront; if it doesn't work, stop the meds.
62
After how many months should we review patients to see if cholinesterase inhibitors are effective?
- 6 months - Remember Shakib's grammar shirt, and the green column on the graph
63
Describe deprescription of dementia meds (and potential perils)
- If condition deteriorates, may deprescribe - But this may make things worse - It's not always the case that re-prescription fixes the problem
64
Which herbal medication is often taken throughout the community for AD? What are its effects thought to be?
- Gingko - Thought to have neuroprotective effect, and increased flexibility of RBCs - Antioxidant effect
65
What lifestyle factors can decrease dementia risk?
- Mediterranean diet - Fish oil - Exercise - Sleep - Mental challenges - Social interaction