Week 4 P&I Flashcards
1
Q
What is cognition?
A
the process of thinking, knowing, understanding and making sense of the world around you
2
Q
What 4 categories can attention be classified into?
A
Arousal, sustained attention, divided attention, selective attention
3
Q
What are the 6 specific tests for attention?
A
Orientation in time and place, digit span, reciting months of the year, serial 7s, spell WORLD backwards, the STROOP test
4
Q
What is the STROOP test?
A
Lots of multicoloured words on the page and the patient has to tell you what colour the word is rather than just reading the word
5
Q
What is anterograde memory loss?
A
Memory loss for newly gained information (information gained after an injury occurs is forgotten)
6
Q
What is retrograde memory loss?
A
Memory loss of old information (information from before the injury is lost)
7
Q
What is Ribot’s gradient?
A
More recent material is forgotten first and then eventually they forget older information
8
Q
What area of the brain is involved in short-term (working) memory?
A
The frontal lobe
9
Q
What areas (3) of the brain is involved in implicit memory (a type of long term)
A
Basal ganglia, cerebellum, cortex
10
Q
Where are episodic memory stores found?
A
medial temporal lobe
11
Q
Where are semantic memory stores found?
A
anterior temporal lobe
12
Q
What is dyspraxia?
A
Inability to move a body part despite having intact motor and sensory function.
13
Q
What are 6 visuospatial deficits?
A
Topographical disorientation, difficulties with dressing, mis-reaching for objects, visual neglect, visual object agnosia, prosopagnosia
14
Q
What is topographical disorientation?
A
Problems finding their way around
15
Q
What is dressing apraxia?
A
When someone has difficulties with dressing. This is not a problem with praxis its an issue with visuospatial
16
Q
What areas of the brain cause visuospatial deficits?
A
Parietal and temporal lobe
17
Q
What is visual neglect?
A
patient could only eat half of their plate or dress half of their body
18
Q
What is prosopagnosia?
A
Patients cant recognise familiar faces but might be able to recognise their voice
19
Q
What is the ACE?
A
A 100 point test that is more sensitive than a MMSE and can pick up patients with mild impairment
20
Q
What are the 2 cut off scores of the ACE?
A
88 and 82
21
Q
What is a MMSE?
A
Mini-mental state examination gives a score out of 30. It is more reliable between different raters and you can expect similar scores from different doctors carrying it out.
22
Q
What is the MMSE more heavily weighted towards?
A
memory and attention and is not very good for executive function
23
Q
What are some hallmark feature of delirium?
A
Impaired consciousness, fluctuation, acute onset, visual hallucinations, affect changes.
24
Q
What are the two possible subtypes of delirium?
A
hyperactive (can be violent) and hypoactive (sleepy and could be misdiagnosed as depression)
25
How can delirium be managed non-pharmacologically? (4)
- Noise control and lighting
- reality orientation
- Limit variation in staff
- avoid ward transfers
26
what are the options for pharmacological management of delirium?
Antipsychotics, benzodiazepines, specific treatment of underlying cause, melatonin, trazodone
27
Why is melatonin used in the treatment of delirium?
Melatonin levels are abnormal in delirium and dementia and supplementing it can help get a more normal sleep cycle
28
What are 2 examples of antipsychotics used in the treatment of someone who is actively hallucinating because of delirium?
Haloperidol, risperidone
29
What are the 2 classes of drugs used to treat dementia?
Cholinesterase inhibitors and partial glutamate antagonist
30
What do cholinesterase inhibitors do?
Block cholinesterase which breaks down Ach
31
What limits the efficacy of cholinesterase inhibitors?
Their toxicity
32
What are potential side effects of donepezil (cholinesterase inhibitor)?
Nausea and vomiting, diarrhoea, muscle cramps, dizziness, fatigue and anorexia
33
When is donepezil contraindicated?
In patients who have already had some kind of GI disease and is not usually given to patients who smoke
34
What types of dementia is donepezil used in?
| cholinesterase inhibitor
- Alzheimer's mixed with vascular dementia
| - PDD (NOT DLB)
35
What is rivastigmine licenced for?
DLB
36
What is glutamate?
An amino acid that is also the major excitatory transmitter
37
What are two receptors important in learning?
AMPA and NMDA
38
What are AMPA and NMDA permeable to?
Ions (Sodium and potassium) but AMPA is not permeable to calcium, only NMDA is.
39
What is excessive activation of the AMPA receptor called?
Excitotoxicity
40
What is the AMPA receptor mostly involved in?
Most Fast-synaptic transmission
41
What is the ion channel of the NMDA receptor blocked by?
Magnesium
42
What does memantine do?
Reduces the action potential of the NMDA receptor which prevents the hyperexcitation of it.
43
How is glutamate involved in AD?
Reduced glutamate clearance in AD brains so chronic overactivity could play a part in the pathological process
44
How does an NMDA receptor antagonist improve memory?
Restores homeostasis in the glutamatergic system - too little activation is bad but too much is even worse
45
What are potential side effects of memantine?
Dizziness, headache, constipation, somnolence and hypertension
46
What causes behavioural problems in dementia?
An interaction between an increasingly confused and vulnerable person and their environment and the reactions of carers.
47
What is melatonin licenced for?
Short term treatment of insomnia in people over 55 (when endogenous melatonin may be reduced)
48
Why are SSRIs used in dementia?
Useful for depression and apathy that can develop. sertraline and citalopram are associated with a reduction in agitation.
49
When do clinicians begin to consider prescribing memantine?
MMSE score below 20
50
What antipsychotics can be used in behavioural and psychological symptoms of dementia (BPSD)
atypicals like Risperidone and aripiprazole
51
When do clinicians move from donepezil to rivastigmine?
If there is side effects with donepezil or it doesn't work, tend to move onto a rivastigmine patch
52
When should antipsychotics be used (in dementia)?
Severe agitation that is a risk to themselves or others, psychosis
53
when should antipsychotics NOT be used (in dementia)?
insomnia, wandering, abnormal vocalisations
54
What drugs are most effective in the treatment of dementia?
Drugs that target the Acetylcholine system
55
What happens when there is neurodegeneration in the basal ganglia?
Movement disorder e.g. Parkinson's, Huntington's
56
What happens when there is neurodegeneration in the cerebellum and spinal cord?
Ataxia
57
What happens when there is neurodegeneration in the cortex?
Alzheimer's, FTD
58
When does increased forgetfulness start?
Age 50
59
What changes occur due to brain ageing?
Slowing of response times, physical changes (vision, hearing, sensory/motor impairment)
60
What are the potential differential diagnoses for dementia like behaviour?
```
A - Alzheimer's
V - Vascular disease
D - Drugs, Depression, Delirium
E - Ethanol
M - Metabolic
E - Endocrine
N - Neurologic
T - Tumour, Toxin, Trauma
I - Infection
A- Autoimmune
```
61
What are some reversible causes of dementia? (5)
Hypothyroidism, Drugs, Tumours, neurosyphilis, chronic subdural haematoma
62
How can a patient be described as potentially having Alzheimer's?
Significant decline in cognition that interferes with independence in everyday activities
63
What is the onset of AD like?
Insidious - family members can have varying opinions on when it started
64
What are the initial and most prominent deficits in a patient with suspected AD?
- Amnestic (episodic memory alteration)
| - Non-amnestic - progressive aphasia, visuospatial deficit, executive dysfunction
65
What can vary between patients with AD?`
- Age of onset
- Disease progression
- Disease duration
- Symptoms at onset
66
What does the brain look like in AD?
- A marked reduction in weight and you can see atrophy.
- The ratio of the weight of the forebrain to the hind brain is different in Alzheimer's
- Ventriculomegaly
- Sulcal spaces are enlarged as the Gyri have shrunk
67
What protein is involved in neurofibrillary tangles?
Tau protein (an abnormal version)
68
What is involved in the formation of neurytic plaques?
B-amyloid
69
What symptoms can be seen in mild AD? (7)
memory loss, confusion, trouble handling money, poor judgment, mood changes, and anxiety.
70
What symptoms can be seen in moderate AD? (7)
Increased memory loss and confusion, problems recognizing people, difficulty with language and thoughts, restlessness, agitation, wandering, and repetitive statements.
71
What happens in severe AD?
- Severe cortical atrophy.
- Pathology throughout the neocortex.
- Patients are completely dependent requiring nursing home care.
- Weight loss, seizures, increased sleeping, loss of bladder and bowel control.
- Death usually occurs from pneumonia
72
What are the risk factors for (Alzheimer's?) dementia?
- Increasing age
- Genetics
- Downs syndrome
- Female sex (2/3 of those with dementia are female)
- Head injury
73
What is the progression of vascular dementia like?
Stepwise - patient functions at a set level for a period of time and then this level drops of and they remain here for a period of time.
These are said to be in line with ischemic insults to the brain (more infarcts)
74
What is one of the earliest histological signs of ischaemic insult?
Shrunken, red eosinophilic neurons.
| These are usually bigger and more basophilic
75
What are signs of dementia with Lewy bodies?
- Progressive cognitive decline
- fluctuating consciousness
- Visual hallucinations
- Parkinsonism
76
What can be seen in the brainstem in DLB?
Pallor of brainstem pigmented nuclei
77
What signs/ symptoms can be seen in a patient with Parkinson's disease with dementia?
- Bradykinesia, rigidity, tremor
- Autonomic dysfunction
- Cognitive impairment
78
What protein causes Lewy body disorders?
A-synuclein
79
What forms the tertiary structure of a protein?
Interactions between side chains of various amino acids - in particular disulphide bonds formed between cysteine groups
80
What is protein conformation determined by?
Its primary structure
81
What is an important determinant of final conformation?
Hydrophobicity - you want hydrophobic parts on the inside and the hydrophilic parts are on the outside
82
Why is there an increased tendency for proteins to aggregate?
They don't have the molecular space to fold (although they clearly do)
83
What is a molecular chaperone?
Any protein that interacts with, stabilises or helps another protein to acquire its functionally active conformation, without being present in its final structure
84
What are 5 proteome-maintenance functions?
- de novo folding
- refolding
- oligomeric assembly
- protein trafficking
- proteolytic degradation
85
What is the first thing that happens to a newly synthesised glycoprotein?
It is immediately glycosylated
86
What happens to a newly synthesised glycoprotein after is it glycosylated?
A group of enzymes (glucosidases I & II) cleave off these sugar molecules which provides a binding site for the chaperones
87
What happens after the chaperones have helped with protein folding?
Glucosidase II cleaves off the sugar group and this removes the chaperones too
88
What happens if the protein is correctly folded?
It will be allowed to leave the ER and do its job
89
What enzyme is responsible for deciding if proteins are correctly folded?
Glucosyltransferase
90
How does glucosyltransferase check that proteins are folded correctly?
by checking if there are hydrophobic residues on the outside of the protein.
91
What happens if glucosyltransferase detects hydrophobic residues on the outside of a protein?
it goes back to the start of the folding process
92
How are proteins that need to be degraded sent to the proteasome?
They get a ubiquitin tag
93
What are the 5 steps in a protein being tagged and degraded?
1. Polyubiquitination
2. polyUb-protein recognised by CAP
3. polyUb removed; protein unfolded
4. protein threaded through proteasome
5. proteolysis
94
How many ubiquitin molecules must be attached to a lysine residue?
at least 4
95
What is a Proteinopathy?
accumulation of misfolded proteins resulting in aggregates, thereby gaining toxic activity or losing the normal function
96
What is the common characteristic of all amyloidoses?
The collection of plaques of insoluble protein in the extracellular tissue which cannot be broken down by enzymes.
97
What are amyloid plaques made up of?
Long filaments (fibrils) that are formed from densely packed B-sheets of identical proteins
98
What is APP?
A transmembrane protein that has unknown function and is found in all neurons.
99
What happens to APP once it is out of the transmembrane?
It is cleaved to form lots of different proteins with different functions
100
Where is APP cleaved in the non-amyloidogenic state?
The extracellular domain just above the transmembrane domain
101
What cleaves APP in the non-amyloidogenic state?
alpha-secretases
102
What happens with cleaving of APP in the amyloidogenic state?
cleaves again just above the transmembrane domain this time by beta-secretases but is also cleaved within the transmembrane domain by gamma-secretases releasing a small part of the protein – amyloid beta peptide.
103
What is the normal function of the tau protein?
as a bridge between the microtubules in axons, ensuring they run straight and parallel to each other
104
Where is tau expressed?
Throughout the CNS
105
Where is tau predominantly found?
Neuronal axons
106
What happens if tau is phosphorylated?
it dissociates from microtubules meaning it destabilises it which means they can lengthen or shorten etc.
107
What negatively regulates the binding of tau to microtubules?
Phosphorylation
108
What happens if tau is hyper phosphorylated?
prevents tubulin binding and thereby results in the destabilization of microtubules. The hyperphosphorylation also leads to the tangles --> cell death
109
What is the secondary structure of tau usually?
alpha helix but in abnormal cases it changes to beta sheets
110
What are tauopathies characterised by?
Abnormal hyperphosphorylation of tau
111
Where is alpha synuclein abundantly expressed?
The human brain - enriched at presynaptic terminals
112
What does alpha synuclein do at presynaptic terminals?
binds lipids and regulates the release of synaptic vesicles
113
What are alpha-synucleinopathies?
neurodegenerative diseases characterised by the abnormal accumulation of a-synuclein insoluble aggregates in neuronal or glial cells
114
What are transmissible spongiform encephalopathies (TSEs)?
A family of rare, progressive & fatal neurodegenerative disorders
115
What happens in transmissible spongiform encephalopathies (TSEs)?
loss of motor coordination and behavioural changes
116
How can people get transmissible spongiform encephalopathies (TSEs)?
inherited, sporadic, acquired
117
What does spongiform refer to in transmissible spongiform encephalopathies (TSEs)?
What the brain looks like
118
What is the causative agent of transmissible spongiform encephalopathies (TSEs) believed to be?
Prions
119
What are prions?
abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins called prion proteins
120
Where are prion proteins most abundantly found?
In the brain
121
What does the abnormal folding of the prion proteins lead to?
brain damage and the characteristic signs and symptoms of the disease
122
What is the normal prion protein?
PrPc
123
What is the infectious prion protein?
PrPsc
124
What does the infectious prion protein go on to form?
prion rods which form plaques leading to neuron disease
125
What characteristic of infectious prion proteins makes them so infectious?
They can self-aggregate and propagate
