Dementias Flashcards

1
Q

What is confusion?

A
  • lack of clarity in thinking

- everyday issues can be challenging

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2
Q

What is cognition?

A
  • the mental process involved in making sense of and learning about the world around us
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3
Q

What is crystallised cognitive ability?

A
  • cumulative skills and memories from cognitive processing that occurred in the past
  • tests of general knowledge, vocabulary, reading comprehension, maths, science
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4
Q

What is ‘fluid’ cognitive ability?

A
  • processing of new information to quickly solve problems
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5
Q

In ageing does crystallised and fluid cognitive abilities decline equally?

A
  • no
  • fluid declines
  • crystallised typically remains

- fluid has a more dramatic decline

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6
Q

Which of the following are common conditions where a healthy individual may experience cognitive impairment?

1 - alcohol/drugs
2 - acute illness
3 - sleep deprivation
4 - extreme exercise
5 - all of the above

A

5 - all of the above

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7
Q

What is dementia (which is an umbrella term) latin for out of ones mind?

1 - generalised decline in intellect
2 - generalised decline in memory and personality
3 - unaltered consciousness
4 - functional impairments
5 - all of the above

A

5 - all of the above

  • it is commonly described as a syndrome rather that a diagnosis in itself

- group of progressive, neurodegenerative brain disorders

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8
Q

When we talk about dementia, what is one of the key attributes for it to be called dementia, regarding the symptoms?

1 - progressive worsening of symptoms over time
2 - rapid onset of symptoms
3 - rapid onset and then slow progression
4 - slow progression with intermittent rapid deterioration of symptoms

A

1 - progressive worsening of symptoms over time

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9
Q

What are some of the common signs of dementia?

1 - muscle pain, stiffness, impaired memory, thinking and behaviour
2 - impaired memory, thinking and behaviour and altered ADL
3 - insomnia, hyper-mania and and altered ADL
4 - depression, elation and impaired memory and thinking

ADL = activities of daily living

A

2 - impaired memory, thinking and behaviour and altered ADL

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10
Q

Do patients with dementia typically have insight into their condition?

A
  • no
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11
Q

What is the prevalence of dementia worldwide?

1 - 400,000
2 - 4 million
3 - 45 million
4 - 500 million

A

3 - 45 million

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12
Q

Are men or women more likely to get dementia?

A
  • men
  • 4 x more likely
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13
Q

What is the prevalence of dementia in the 65-69 year olds?

1 - 1:10
2 - 1:100
3 - 1:1000
4 - 1:10,000

A

2 - 1 in 100

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14
Q

What is the prevalence of dementia in the 70-79 year olds?

1 - 1:10
2 - 1:25
3 - 1:100
4 - 1:500

A

2 - 1 in 25

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15
Q

What is the prevalence of dementia in the >80 year olds?

1 - 1:6
2 - 1:25
3 - 1:100
4 - 1:500

A

1 - 1 in 6 people

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16
Q

How many people in the Uk are living with dementia, and what is the estimated cost of this per year?

A
  • 850,000 people

- £34.7 billion per year

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17
Q

What is the primary reason the incidence of dementia is increasing?

1 - poor health care
2 - waiting too long for treatments
3 - polypharmacy
4 - ageing population

A

4 - ageing population

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18
Q

Which of the following is the leading cause of disability in later life in the UK?

1 - CVD
2 - dementia
3 - cancer
4 - stroke are leading

A

2 - dementia

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19
Q

Diagnosing a patient with dementia is made more difficult by depression pseudodementia. Which of the following are typical characteristics?

1 - depressed mood preceding memory issues
2 - memory tests improve with increased arousal
3 - psychomotor retardation
3 - impaired intellect and concentration
4 - unwilling to cooperate with consultations
5 - all of the above

A

5 - all of the above

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20
Q

When we are looking to diagnose dementia, we come up with a list of differentials. Which of the following is NOT commonly a differential?

1 - psychosis
2 - depression
3 - delirium
4 - migraines

A

4 - migraines

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21
Q

When we compare dementia and delirium, which has rapid onset and which has a gradual development over time?

A
  • rapid onset = delirium

- gradual decline = dementia

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22
Q

Dementia is an umbrella term covering a number of neurodegenerative brain conditions. Which is the most common?

1 - Parkinsons disease
2 - Lewy body dementia
3 - Alzheimers disease
4 - Vascular dementia

A

3 - alzheimers disease

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23
Q

Dementia is an umbrella term covering a number of neurodegenerative brain conditions. The most common is Alzheimers, what is the second most common cause?

1 - Parkinsons disease
2 - Lewy body dementia
3 - Frontal-Temporal dementia
4 - Vascular dementia

A

4 - vascular dementia

  • closely followed by Lewy body dementia

- dementia caused by cerebrovascular disease

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24
Q

What is alpha synuclein?

1 - protein found inside neurons, maintains microtubule structure
2 - protein aggregates that form extracellular plaques in the brain
3 - protein in brain involved in synaptic trafficking and neurotransmitter release
4 - protein found outside neurons, maintains pre-synapse

A

3 - protein in brain involved in synaptic trafficking and neurotransmitter release

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25
Q

How can a-synuclein, a normal protein in the brain that is involved in synaptic vesicles trafficking and regulation of neurotransmitter release cause lewy bodies?

1 - clump together forming plaques that build up around synapses causing neuronal cell death
2 - mis-folded form of a-synuclein aggregate around synapse causing neuronal cell death
3 - excessive levels inhibit neurotransmitter release despite action potential
4 - binds to vesicles and inhibits vesicle binding to pre-synapse membrane

A

2 - mis-folded form of a-synuclein aggregate around synapse causing neuronal cell death

  • the aggregates of misfolded protein are called Lewy bodies
  • lewy bodies can cause neurons to die
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26
Q

There are 2 types of dementia (that we need to know about) that are associated with lewy bodies (misfolded a-synuclien), what are these?

1 - Parkinsons disease dementia and dementia with lewy bodies
2 - Lewy body dementia and Alzheimers disease
3 - Alzheimers disease and Parkinsons disease
4 - Vascular dementia and Lewy body dementia

A

1 - Parkinsons disease dementia and dementia with lewy bodies

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27
Q

Most dementias are caused by a misfolding of different proteins. What are the 3 main proteins we need to be aware of?

1 - Tau protein, a-synuclein, B-Amyloid
2 - SMN-1 protein, a-synuclein, B-Amyloid
3 - Tau protein, a-synuclein, SMN-1 protein
4 - Tau protein, SMN-1 protein, B-Amyloid

A

1 - Tau protein, a-synuclein, B-Amyloid

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28
Q

Tau protein is a protein located in the brain. What is one of the key roles of Tau protein?

1 - stabilisation of the internal microtubules
2 - regulation of vesicle trafficking at synapse and neurotransmitter release
3 - regulate neurotransmitter trafficking to and from nucleus
4 - ensure vesicles bind with pre-synaptic membrane

A

1 - stabilisation of the internal microtubules

  • essentially hold together the microtubules

- important for neurogenesis

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29
Q

Organise the following, which explain the pathology of Tau proteins?

1 - phosphorylation of Taus clump together
2 - kinase adds phosphate to Tau proteins
3 - Beta amyloid plaques signal neuron
4 - kinase is activated
5 - microtubules become less stable and neuronal signalling is impaired

A

2 - Beta amyloid plaques signal neuron
4 - kinase is activated
2 - kinase adds phosphate to Tau proteins
4 - microtubules become less stable and neuronal signalling is impaired
1 - phosphorylation of Taus clump together

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30
Q

What is amyloid precursor protein?

1 - protein located within neuronal cell bodies
2 - protein receptor located on neuronal cell bodies
3 - protein located across neuronal membranes (half inside and half outside)
4 - protein located in dendrites

A

3 - protein located across neuronal membranes (half inside and half outside)

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31
Q

Amyloid precursor protein is protein located across neuronal membranes (half inside and half outside). What is the function of this protein?

1 - aids growth of neurons
2 - repairs neurons
3 - synapse plasticity
4 - all of the above

A

4 - all of the above

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32
Q

Once amyloids precursor proteins (APP) have been used they are broken down by enzymes alpha and gamma secretase, become soluble and disappear. However, if beta and gamma secretase break down APP, this can cause what problems?

1 - parts of APP broken down are not soluble called amyloid Beta
2 - amyloid Beta is adhesive and stick to neurons
3 - amyloid Beta clump with other amyloid B monomers
4 - form amyloid beta plaques and impair neuronal communication
5 - all of the above

A

5 - all of the above

33
Q

Misfolded proteins are common in dementia. Which 2 of the following proteins are commonly reported in Alzheimers disease?

1 - a-synuclein
2 - Beta amyloid
3 - Tau protein
4 - SMN-1

A

2 - Beta amyloid
- extracellular effect
- PLAQUES

3 - Tau protein
- intracellular effect
- TANGLES

2 - Tau protein (intracellular)

34
Q

When examining the post mortem brain tissue in Alzheimers disease, which of the following occur when compared with controls?

1 - brain atrophy
2 - increased ventricle size
3 - cell loss and dendrite shrinkage
4 - reduced astrocyte proliferation
5 - increased gliosis (fibrous proliferation of glial cells)
6 - gyrus get narrower and sulci get wider
7 - all of the above

A

6 - all of the above

35
Q

In Alzheimers, which 2 parts of the brain generally remain unaffected?

1 - cerebellum
2 - temporal lobe
3 - frontal lobe
4 - parietal lobe

A

1 - cerebellum
4 - parietal lobe

36
Q

Cholinergic receptors on the post synapse are receptors able to to bind with acetylcholine released by the pre-synaptic of the preganglionic neuron. Are these predominantly located in the sympathetic or parasympathetic nervous system?

A
  • parasympathetic nervous system
  • few exceptions
37
Q

In Alzheimers, are cholinergic or adrenergic neurons affected more?

A
  • cholinergic
  • this is the basis for acetylcholinesterase inhibitors comes from
38
Q

in patients with Alzheimers disease, there are 2 pathological mechanisms, one intracellular and one extracellular involving tau protein and amyloid. There is also a markedly reduced activity in which receptors in the cerebral cortex?

1 - cholinergic receptors
2 - adrenergic receptors
3 - receptor tyrosine kinase receptors
4 - ligand gates channels

A

1 - cholinergic activity

  • nicotinic and muscarinic receptors
  • BOTH are linked with memory and learning, so if damaged this is affected
39
Q

It can be really difficult to diagnose patients with dementia. Which of the following are important in helping reach a diagnosis?

1 - detailed history taking
2 - physical examination
3 - cognitive testing
4 - laboratory investigations
5 - imaging (CT or MRI)
6 - all of the above

A

6 - all of the above

40
Q

It can be really difficult to diagnose patients with dementia, but a good clinical history is really important and potentially the most effective method. Although lumbar puncture is not commonly used, it can be useful in which group of patients?

1 - older patients with late dementia onset
2 - young dementia onset
3 - patients who have had dementia for a long time

A

2 - young dementia onset

41
Q

Alzheimers is the most common dementia. From the time of diagnosis, what is the general survival rate?

1 - 1-4 years
2 - 2-8 years
3 - 4-14 years
4 - 4-20 years

A

4 - 4-20 years

42
Q

In Alzheimers, amnesia is commonly reported. Does this affect short and long term memories equally?

A
  • initially short- term memory

- later impairs long-term memory

43
Q

In Alzheimers, amnesia is one of the most dominant clinical feature. What other clinical features do patients present with?

A
  • disorientation
  • loss of motor skills (apraxia)
  • disturbances in recognition of objects and faces (agnosia)
  • disturbances of speech (dysphasia)
  • difficulty in performing complex tasks
  • planning, organization, sequencing, abstraction
  • behavioural and psychological disturbances
44
Q

The genetics that can contribute to Alzheimers disease are complicated, but can be divided into young and late onset. Which 2 genes from the list below are commonly found to be mutated in young onset of dementia?

1 - amyloid precursor protein (APP)
2 - apolipoprotein 4 cholesterol carrier
3 - presenilin 1 and 2 (PSEN-1 and 2) (enzymes involved in amyloid formation)
4 - a synuclein

A

1 - amyloid precursor protein (APP)

3 - presenilin 1 and 2 (PSEN-1 and 2) (enzymes involved in amyloid formation)

45
Q

The genetics that can contribute to Alzheimers disease are complicated, but can be divided into young and late onset. What are the genes that are mutated involved in late onset?

1 - amyloid precursor protein (APP)
2 - apolipoprotein 4 cholesterol carrier
3 - presenilin 1 and 2 (PSEN-1 and 2) (enzymes involved in amyloid formation)
4 - a synuclein

A

2 - apolipoprotein 4 cholesterol carrier

  • supports lipid transport and injury repair in the brain
  • LARGEST KNOWN RISK FACTOR IN LATE ONSET DEMENTIA!!!!!
46
Q

Misfolded proteins are common in dementia. Which protein is commonly reported in frontal-temporal dementia?

1 - Tau protein
2 - a-synuclein
3 - B-Amyloid
4 - SMN-1 protein

A

1 - Tau protein

47
Q

Misfolded proteins are common in dementia. Which protein is commonly reported in Parkinsons disease dementia and Lewy bodies dementia?

1 - Tau protein
2 - a-synuclein
3 - B-Amyloid
4 - SMN-1 protein

A

2 - a-synuclein

48
Q

When doing a lumbar puncture, what are we looking for in the amyloid protein?

A
  • ratio between alpha and beta (we want more alpha)
  • GOOD = gamma and alpha
  • BAD = beta and gamma
49
Q

Vascular dementia shares common risk factors with atherosclerosis and thrombosis. Which of the following are common risk factors for this?

1 - age
2 - vascular risk factors (hypertension, cholesterol)
3 - inactivity/obesity
4 - all of the above

A

4 - all of the above

  • essentially anything that can cause cerebrovascular pathology
50
Q

When trying to diagnose
Alzheimers, it can be really difficult to distinguish from which other dementia without imaging?

1 - parkinsons disease
2 - vascular dementia
3 - parkinsons dementia
4 - lewy body dementia

A

2 - vascular dementia

51
Q

Which of the following have been identified using neuroimaging in patients with vascular dementia?

1 - white matter ischaemic lesions
2 - small brains
3 - increased ventricle sizes
4 - changes in blood flow
5 - bilateral pathology
6 - all of the above

A

6 - all of the above

- 15-30% of patients develop dementia 3 months following stroke

52
Q

The symptoms of vascular dementia are variable due to the range of underlying vascular pathology (stroke). But there is a classical stepwise progression. What does this mean?

1 - slow progression from onset
2 - rapid decline following vascular pathology but then improved symotins
3 - abrupt decline associated with an infarct (small stroke)
4 - slow progression, followed by a rapid decline

A

3 - abrupt decline associated with an infarct (small stroke)

53
Q

The symptoms of vascular dementia are variable due to the range of underlying vascular pathology. Patients are at increased risk of injury due to a slowing of what?

1 - heart rate
2 - working
3 - gait
4 - muscle contraction

A

3 - gait (walking)

  • essentially more likely to fall

- increased risk of falls

54
Q

What age does vascular dementia typically present?

1 - 30-40 y/o
2 - 40-50 y/o
3 - 60-70 y/o
4 - >75 y/o

A

3 - 60-70 y/o

  • generally late 60s
55
Q

What is the life expectancy of patients diagnosed with vascular dementia?

1 - 3-5 years
2 - 5-10 years
3 - 10-20 years
4 - >30 years

A

1 - 3-5 years

  • depression and apathy are common
56
Q

What are dementia with Lewy bodies and Parkinson’s disease dementia both linked with?

1 - Tau protein
2 - a-synuclein misfolding
3 - B-Amyloid
4 - SMN-1 protein

A

2 - a-synuclein misfolding

- folded proteins aggregate forming Lewy bodies

57
Q

Dementia with Lewy bodies and Parkinson’s disease dementia are both linked with abnormal folding of a-synuclein, which then aggregate and forms Lewy bodies. Where in the brain do these lewy bodies generally begin forming?

1 - motor cortex
2 - basal ganglia
3 - thalamus
4 - occipital lobe

A

2 - basal ganglia

  • can also then move to the cortex, which then affects cognition
58
Q

Which of the following are clinical features that patients with with Lewy body dementia present with?

1 - cognitive ability fluctuates
2 - some sparing of memory
3 - Parkinsonism
4 - visual hallucinations
5 - falls
6 - depression
7 - all of the above

A

7 - all of the above

59
Q

What is the life expectancy of a patient with Lewy body dementia?

1 - 4-10 years
2 - 5-15 years
3 - 10-20 years
4 - >20 years

A

1 - 4-10 years

60
Q

Patients with dementia with Lewy bodies are highly sensitive to which group of drugs?

1 - ACE inhibitors
2 - antipsychotics
3 - benzodiazepines
4 - glucocorticoids

A

2 - antipsychotics

  • can be hypersensitive to these medications

- AVOID AT ALL COSTS

61
Q

When we investigate patients with dementia with Lewy bodies, it is very difficult to be able to determine where the build up of lewy bodies (aggregates of a-synuclein misfolded proteins) is in the brain and therefore make a diagnosis until post mortem. What else can be used to help diagnose?

A
  • MRI/CT scans = may show atrophy or be normal
  • Single-photon emission computed tomography may be able to identify where the lewy bodies are or the atrophy of the involved receptors are
62
Q

Single-photon emission computed tomography (SPECT) imaging using a ligand for dopamine transporter proteins can be used to detect atrophy of dopamine receptors. This can help identify if a patients symptoms are due to dementia with lewy bodies (cortical) or parkinsons dementia disease (sub-cortical), due to where is affected in the brain. In the image below, which is Alzheimers?

A
  • 1
  • can see atrophy in hippocampus
  • large dark spaces in cortical area and ventricles
  • uptake of ligand in caudate putamen (involved in motor control, cognition, and emotion)
63
Q

Single-photon emission computed tomography (SPECT) imaging using a ligand for dopamine transporter proteins can be used to detect atrophy of dopamine receptors. This can help identify if a patients symptoms are due to dementia with lewy bodies (cortical) or parkinsons dementia disease (sub-cortical), due to where is affected in the brain. In the image below, which is dementia with Lewy bodies?

A
  • 2
  • some atrophy of cortical area
  • no significant hippocampus atrophy
  • poor uptake by the caudate putamen (motor control, cognition, and emotion)
64
Q

What is frontaltemporal dementia?

A
  • least common dementia
  • group of conditions commonly cause young onset dementia
  • progressive atrophy of frontal and/or temporal lobes
65
Q

Which patients are at risk of frontaltemporal dementia?

1 - 20-30 year olds
2 - 40-60 year olds
3 - adults aged 50-60 years old
4 - adults >75 years old

A

3 - typically people aged 50-60s

- generally genetically causedYEAR

66
Q

In frontaltemporal dementia there are 2 main symptoms that patients present with, what are they?

1 - mania
2 - personality changes
3 - memory loss
4 - depression

A

2 - personality changes
3 - memory loss

- language - speech

67
Q

Cholinesterase inhibitors essentially stop the breakdown of ACh in the synaptic clefts, and therefore maintain higher levels of ACh. This is especially relevant in disorders where there are low levels of ACh. Which form of dementia is this commonly used to treat and does this reveres the disease?

1 - Alzheimers disease
2 - Parkinsons disease
3 - Vascular dementia
4 - Lewy bodies dementia

A

1 - Alzheimers disease

  • mild to moderate onset
  • slows disease, but does not reverse
68
Q

Cholinesterase inhibitors essentially ensure more acetylcholine is present to bind on post synapse of neurons, and can be affective for up to 1 year in moderately severe Alzheimers. However, if they are ineffective how long should a patient try them before stopping?

1 - 3 months
2 - 6 months
3 - 1 year
4 - 2 years

A

2 - 6 months

69
Q

What is the name of the core Acetylcholinesterase inhibitor that we need to be aware of?

1 - Donepezil
2 - Memantine
3 - Levodopa
4 - Rasagiline

A

1 - Donepezil

70
Q

Donepezil is a core drug that is used to treat Alzheimers only, but not other dementias. What is the mechanism of action of this drug?

1 - increases vesicles containing ACh to be released into pre synaptic cleft
2 - ACh receptor agonist
3 - inhibitor of cholinesterase and degrades acetylcholinesterase
4 - binds reversibly to acetylcholinesterase

A

4 - binds reversibly to acetylcholinesterase

  • inhibits the hydrolysis of ACh
  • increases ACh and cholinergic activity
71
Q

Memantine is a drug that is used to treat mild to moderate Alzheimers disease, and is the 2nd line drug for this disease. What is its mechanism of action?

1 - NMDA antagonist, reducing glutamate binding
2 - NMDA agonist, increasing glutamate binding
3 - inhibitor of cholinesterase and degrades acetylcholinesterase
4 - binds reversibly to acetylcholinesterase

A

1 - NMDA antagonist, reducing glutamate binding

72
Q

Glutamate is the most abundant excitatory neurotransmitter released by nerve cells in your brain. Why would an NMDA antagonist, such as Memantine be good for treating Alzheimers disease?

1 - increases ACh levels
2 - inhibits glutamate binding, allowing more serotonin to bind
3 - reduces glutamate binding, reducing Ca2+ influx

A

3 - reduces glutamate binding, reducing Ca2+ influx

  • excessive Ca2+ leads to toxicity and neuronal cell death
73
Q

Young onset dementia is defined as those <65 years old. How long does it generally take to diagnose these patients?

A
  • 4.4. years

- very little in specialist services

74
Q

There is evidence that we can actually prevent dementia. Around 30% are described as modifiable risk factors, which are what?

A
  • limited education
  • smoking
  • obesity/diabetes
  • depression
  • inactivity
  • social isolation
  • hearing loss
75
Q

B-amyloid (extracellular) and Tau protein (intracellular) can become misfolded, and has been linked with dementia. One of these can build up and cause plaques, and one can causes tangles, which is which?

A
  • B-amyloid = plaques

- Tau protein = tangles

76
Q

Memantine is a drug that is used to treat mild to moderate Alzheimers disease, acting as a NMDA antagonist, reducing glutamate binding. Why is this important in Alzheimers?

A
  • glutamate continues to be released, even in neuronal cell death in Alzheimers
  • excess levels of glutamate results in over-excitation of nerve cells
  • over-excitation leads to excitotoxicity and cell death
77
Q

Which 2 drug classes can be used in dementia, but wherever possible should be avoided?

1 - antipsychotics
2 - benzodiazepines
3 - antiepileptics
4 - antidepressants

A

1 - antipsychotics
- ONLY used in severely distressed patients as can increase mortality

2 - benzodiazepines

78
Q

Depression is common in patients with dementia. Should the standard approach to treat depression be any different in dementia patients?

A
  • no
79
Q

What tool can be used to diagnose dementia? (not test, diagnose)

1 - CURB score
2 - Montreal Cognitive Assessment (MOCA)
3 - Mini-Mental State
Examination (MMSE)
4 - DiADem Tool

A

4 - DiADem Tool

  • Diagnosing Advanced Dementia Mandate