Cognitive impairment and confused states

Question 1

What is confusion?

Answer 1

• lack of clarity in thinking
• everyday issues can be challenging

Question 2

What is cognition?

Answer 2

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

Question 3

What is crystallised cognitive ability?

Answer 3

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

Question 4

What is ‘fluid’ cognitive ability?

Answer 4

• processing of new information to quickly solve problems

Question 5

In ageing does crystallised and fluid cognitive abilities decline equally?

Answer 5

• no
• fluid has a more dramatic decline

Question 6

What are some common conditions where a healthy individual may experience cognitive impairment?

Answer 6

• alcohol/drugs
• acute illness
• sleep deprivation
• extreme exercise

Question 7

What is delirium, often called acute confusional state?

Answer 7

• rapid acute onset
• causes serious impairments in mental abilities
• causes confused thinking and reduced awareness of the environment

Question 8

Are patients who experience delirium all old patients, or what is the other cause?

Answer 8

• can affect anyone
• usually caused by an acute illness
• always has a cause

Question 9

If a patient has delirium, will the impairment in mental thinking and confusion present before the cause or after?

Answer 9

• can be both
• patients may present with delirium and then the infection presents later

Question 10

What are some of the main presentations of delirium?

Answer 10

• impaired awareness, attention and concentration
• disorientated
• memory present, but lack of awareness
• hallucinations, especially visual
• delusions
• mood

Question 11

Can delirium be treated?

Answer 11

• yes
• treat the underlying cause, like the infection

Question 12

In patients with delirium, do they always experience a suppression of their normal cognitive state?

Answer 12

• no
• can be hyper, hypo or mixed

Question 13

Who is most at risk of experiencing delirium?

Answer 13

• older patients and young children
• patients with hospital stays
• polypharmacy patients
• multi-comorbidities
  ALL have increased risks of other disorder or increased infection risk

Question 14

If delirium and its underlying cause are not treated, will delirium just go away?

Answer 14

• no
• if left it can become worse
• increases risk of dementia

Question 15

What is potentially the most common cause of delirium?

Answer 15

• acute systemic infection
• infection that is in the blood and can spread throughout the body

Question 16

How can delirium be prevented?

Answer 16

• early diagnosis and treatment of underlying cause
• maximise healthy sleep patterns
• prevent dehydration and constipation
• ensure good nutrition

Question 17

How can a calm and quiet environment help treat delirium?

Answer 17

• patients have hallucinations and delusions
• so remove any stimulus making these worse

Question 18

Are medications commonly used to treat delirium?

Answer 18

• avoided at all costs
• generally last option for treatment

Question 19

What is dementia, which is latin for out of ones mind?

Answer 19

• umbrella term
• group of progressive, neurodegenerative brain disorders

Question 20

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

Answer 20

1 - progressive worsening of symptoms over time

Question 21

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

Answer 21

2 - impaired memory, thinking and behaviour and altered ADL

Question 22

Instead of using senile dementia, which is essentially an older patient living with dementia, what should we describe this as?

Answer 22

• late onset dementia
• or just dementia

Question 23

Instead of using demented, which is essentially someone living with dementia, what should we describe this as?

Answer 23

• living with dementia

Question 24

Instead of using dementia patient, which is essentially someone living with dementia, what should we describe this as?

Answer 24

• a person living with dementia

Question 25

Instead of using 'this person is dementing', which is essentially someone who may be developing dementia, what should we describe this as?

Answer 25

- person who may be developing dementia

Question 26

Instead of using 'presenile dementia', which is essentially a younger person who may be developing dementia, what should we describe this as?

Answer 26

- young onset of dementia

Question 27

Instead of using 'depressive pseudodementia', which is essentially someone who may be developing dementia associated with depression, what should we describe this as?

Answer 27

- cognitive due to depression

Question 28

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

Answer 28

2 - 1 in 100

Question 29

What is the prevalence of dementia in the 70-79 year olds? 1 - 1:10 2 - 1:25 3 - 1:100 4 - 1:500

Answer 29

2 - 1 in 25

Question 30

What is the prevalence of dementia in the >80 year olds? 1 - 1:6 2 - 1:25 3 - 1:100 4 - 1:500

Answer 30

1 - 1 in 6 people

Question 31

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

Answer 31

- 850,000 people - £34.7 billion per year

Question 32

CVD, cancer and stroke are leading causes of disability in the UK, but what is the main cause of disability in later life in the UK?

Answer 32

- dementia

Question 33

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

Answer 33

- rapid onset = delirium - gradual decline = dementia

Question 34

When we compare dementia and delirium, which can cause a change in alertness?

Answer 34

- delirium = alertness can increase or decrease - dementia = remains normal

Question 35

When we compare dementia and delirium, which has changes in attention?

Answer 35

- delirium = impaired attention - dementia = normally preserved

Question 36

When we compare dementia and delirium, which is more likely to have hallucinations?

Answer 36

- delirium = common - dementia = rare (except in Dementia with Lewy bodies)

Question 37

When we compare delirium and dementia, which has fluctuations in cognition and awareness?

Answer 37

- delirium = fluctuations during day - dementia = gradual change over time

Question 38

When we compare delirium and dementia, which has changes in mood?

Answer 38

- delirium = mood often fluctuates - dementia = mood may be low, doesn't usually fluctuate

Question 39

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

Answer 39

3 - alzheimers disease

Question 40

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

Answer 40

4 - vascular dementia - dementia caused by cerebrovascular disease

Question 41

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

Answer 41

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

Question 42

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

Answer 42

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

Question 43

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 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

Answer 43

1 - Parkinsons disease and dementia with lewy bodies

Question 44

Most dementias are causes 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

Answer 44

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

Question 45

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

Answer 45

1 - stabilisation of the internal microtubules - important for neurogenesis

Question 46

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

Answer 46

2 - regulation of vesicle trafficking at synapse and neurotransmitter release

Question 47

What are amyloids?

Answer 47

- involved in growth and repair following injury - BUT can become misfolded and not destroyed by proteases - aggregate together and accumulate in tissue

Question 48

Amyloids are proteins which have incorrectly folded and have not been degraded by proteases. How can this lead to dementia?

Answer 48

- collect on outside of neurons and interfere with signalling - can also collect in blood vessel walls causing damage

Question 49

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

Answer 49

1 - B-amyloid (extracellular) 2 - Tau protein (intracellular)

Question 50

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?

Answer 50

- B-amyloid = plaques - Tau protein = tangles

Question 51

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

Answer 51

2 - a-synuclein

Question 52

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

Answer 52

1 - Tau protein

Question 53

It can be really difficult to diagnose patients with dementia, but what is potentially the most effective method?

Answer 53

- good clinical history

Question 54

It can be really difficult to diagnose patients with dementia, but a good clinical history is really important and potentially the most effective method. What other methods can be useful?

Answer 54

- physical examination - blood tests - neuroimaging - cognitive testing - lumbar puncture (mainly in young)

Question 55

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

Answer 55

2 - young dementia onset

Question 56

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

Answer 56

4 - 4-20 years

Question 57

In patients with Alzheimers disease, there are 2 pathological mechanisms, one intracellular and one extracellular involving tau protein and amyloid. What is the intracellular pathology?

Answer 57

- Tau protein becomes abnormally phosphorylated - forms paired helixes - form neurofibrillary tangles causing neuronal cell death

Question 58

In patients with Alzheimers disease, there are 2 pathological mechanisms, one intracellular and one extracellular involving tau protein and amyloid, respectively. What is the extracellular pathology?

Answer 58

- B-amyloid plaques form around neurons and in blood vessels - inhibit neuronal function - damage blood vessels

Question 59

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

Answer 59

1 - cholinergic activity - nicotinic and muscarinic receptors - BOTH are linked with memory and learning, so if damaged this is affected

Question 60

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

Answer 60

- initially short- term memory - later impairs long-term memory

Question 61

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

Answer 61

- 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

Question 62

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

Answer 62

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

Question 63

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

Answer 63

2 - apolipoprotein 4 cholesterol carrier - supports lipid transport and injury repair in the brain - LARGEST KNOWN RISK FACTOR IN LATE ONSET DEMENTIA!!!!!

Question 64

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

Answer 64

- ratio between alpha and beta (we want more alpha) - GOOD = gamma and alpha - BAD = beta and gamma

Question 65

Vascular dementia shares common risk factors with atherosclerosis and thrombosis. What are the most common risk factors for this?

Answer 65

- age - vascular risk factors (hypertension, cholesterol) - inactivity

Question 66

Which 2 forms of dementia from the image can often co-exist due to the cross over of risk factors? 1 - alzheimers and parkinsons disease 2 - alzheimers and vascular dementia 3 - parkinsons disease and vascular dementia 4 - lewy body dementia and vascular dementia

Answer 66

2 - alzheimers and vascular dementia

Question 67

Patients can develop dementia following a common cause of cerebrovascular disease neuropatholgy. What is a cerebrovascular disease neuropatholgy?

Answer 67

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

Question 68

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

Answer 68

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

Question 69

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

Answer 69

3 - gait (walking) - increased risk of falls

Question 70

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

Answer 70

2 - a-synuclein misfolding - folded proteins aggregate forming Lewy bodies

Question 71

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 form in dementia with Lewy bodies and Parkinson’s disease dementia?

Answer 71

- dementia with Lewy bodies = cortical = cognitively impaired - parkinson’s disease dementia = subcortical = motor function

Question 72

In Dementia with Lewy bodies and Parkinson’s disease dementia the lewy bodies form in the cortical and subcortical structures, respectively. How do we know this is the case in each of these diseases?

Answer 72

- dementia with Lewy bodies = cortical, which is involved with cognitive thought - Parkinson’s disease dementia = subcortical, which is involved with movement, memory etc..

Question 73

Patients who have parkinsons who live with the disease for long periods are likely to develop what? 1 - stroke 2 - CVD 3 - dementia 4 - CKD

Answer 73

3 - dementia

Question 74

How can we distinguish between dementia with Lewy bodies and Parkinson’s disease dementia?

Answer 74

- dementia with Lewy bodies - begins with cognitive symptoms (cortical) - Parkinson’s disease dementia - begin with movement symptoms (subcortical)

Question 75

What clinical features do patients with dementia with Lewy bodies present with?

Answer 75

- motor features of Parkinsons disease - visual hallucinations - marked fluctuations in cognition and alertness - rapid eye movement sleep behaviour disorder

Question 76

Patients with dementia with Lewy bodies are highly sensitive to antipsychotic drugs, what does this mean?

Answer 76

- can have dangerous reactions - AVOID AT ALL COSTS

Question 77

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?

Answer 77

- 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

Question 78

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?

Answer 78

- 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)

Question 79

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?

Answer 79

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

Question 80

What is frontaltemporal dementia?

Answer 80

- least common dementia - group of conditions commonly cause young onset dementia - progressive atrophy of frontal and/or temporal lobes

Question 81

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

Answer 81

3 - typically people aged 50-60s - generally genetically causedYEAR

Question 82

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

Answer 82

- behavioural - personality, memory - language - speech

Question 83

Dementia has multiple brain process involvement that are disrupted. Although cognitive impairment is a central feature behavioural and psychological symptoms of dementia (BPSD) are also very important. What aspects of a patients behavioural and psyche are generally affected?

Answer 83

- perception - thought content - mood - behaviour

Question 84

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

Answer 84

1 - Alzheimers disease - mild to moderate onset - slows disease, but does not reverse

Question 85

Memantine is a drug that is used to treat mild to moderate Alzheimers 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

Answer 85

1 - NMDA antagonist, reducing glutamate binding

Question 86

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?

Answer 86

- 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

Question 87

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

Answer 87

4 - binds reversibly to acetylcholinesterase - inhibits the hydrolysis of ACh - increases ACh and cholinergic activity

Question 88

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

Answer 88

- 4.4. years - very little in specialist services

Question 89

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

Answer 89

- limited education - smoking - obesity/diabetes - depression - inactivity - social isolation - hearing loss