Lecture 6 - Clinical Neuropsychology

Question 1

What is clinical neuropsychology?

Answer 1

Psychologists specializing in diagnosis and management of cognitive disorders.

Question 2

Neuropsychologists specialised in cognitive impairment, as opposed to just damage or disorders of the brain. Only when there is cognitive impairment do neuropsychologists come in.

Answer 2

True.

Question 3

Do neuropsychologists work in rehabilitation?

Answer 3

Yes.

Question 4

What are some examples of neurological disorders that cause cognitive impairment?

Answer 4

Dementia, stroke, epilepsy.

Question 5

Neuropsychology is especially important for disorders that are normally only diagnosable due to characteristic cognitive impairment.

This is called the clinical syndrome.

What is one example of this?

Answer 5

Alzheimer’s disease.

This disease is only definitively diagnosable postmortum.

The clinical syndrome is how it is diagnosed when individuals are still alive.

Question 6

What is a clinical syndrome?

Answer 6

The cognitive impairment that occurs due neuropathology or trauma.

Question 7

What do neuropsychologists do?

Answer 7

They normally reverse engineer what disorder someone has based on their clinical syndrome (cognitive impairments).

This guides diagnosis, prognosis, and treatment or management.

Question 8

What is demetia?

Answer 8

A condition where individual begins to forget recent past events. Older memories often remain in tact.

Question 9

What’s the difference between demetia and Alzheimer’s disease?

Answer 9

Dementia is a clinical syndrome. It is a presenting set of symptoms.
Alzheimer’s disease refers to the underlying process that brings out the clinical syndrome.

Dementia caused by Alzheimer’s disease is called Alzheimer dementia.

Question 10

Can dementia be diagnosed on a scan?

Answer 10

No. It is the experience of the pt that diagnoses this clinical syndrome.

Question 11

What are the differences between signs and symptoms?

Answer 11

Signs are observations by the clinician, such as pt finds it difficult to retrieve the word they are looking for.

Symptoms are experiences of the pt, such as having difficulty falling asleep or an inability to remember recent events.

Question 12

What is dementia?

Answer 12

The progressive impairment to cognitive functions, such as memory and language, that leads to difficulty engaging in or performing activities of daily living (ADL).

Question 13

What is one of the key characteristics of Alzheimer’s disease?

Answer 13

It is progresses. It always gets worse.

Question 14

What is the clinical syndrome evolution of Alzheimer’s dementia?

Answer 14

Individual is asymptomatic. There may be brain abnormalities, but it has not affected cognition ye.

Mild cognitive impairement. Individual is still able to engage in activities of daily living, such as remembering to pay the bills, or being able to plan a holiday, however, they are noticing some changes to their cognitive function, such forgetting things easily.

Diagnosable dementia. Individual is experiencing a clinical syndrome that is characterised by significant cognitive impairment, such as not recognising people they previously knew, and it is negatively impacting their activities of daily living.

Question 15

What is the second leading cause of death in Australia?

Answer 15

Dementia.

Question 16

Is dementia more prevalent in females?

Answer 16

Yes.

Question 17

Who first reported on Alzheimer’s disease?

Answer 17

Alois Alzheimer in early 1900s.

Pt at asylum named Auguste, 51 years old, presented with aphasia, memory loss, and auditory hallucinations.

Examined brain post mortem and found amyloid plaques and tau tangles.

Question 18

How are tau tangles and amyloid plaques the same and different?

Answer 18

They are both abnormally folded proteins.

Tau tangles are located within the cell.

Amyloid plaques are located outside the cell.

Question 19

Is dementia always caused by abnormally folded proteins?

Answer 19

Yes, according to lecturer.

Question 20

Why will individuals with down syndrome most likely develop Alzheimer’s disease?

Answer 20

Amyloid precursor (APP) protein gene is on chromosome 21. Amyloid is produced by the cleavage of APP. Those with down syndrome have three copies of chromosome 21. They therefore have 1/3 more amyloid than others, which increases the risk of amyloid misfolding and causing the build of beta amyloid plaques.

Question 21

Would you expect to see higher or lower levels of amyloid in the CSF in those with Alzheimer’s dementia?

Answer 21

Lower.

This is because the amyloid has aggregated into plaques within the brain and has not been cleared out of the brain.

Question 22

Why are beta-amyloid plaquest thought to cause disruption in the brain?

Answer 22

Amylo
They are thought to impair synaptic function, leading to cognitive impairment, such as memory loss.

Question 23

Describe how amyloid plaques are formed.

Answer 23

Amyloid precursor protein (APP) is cleaved at an abnormal site leading to the production of a peptide chain called beta amyloid outside the cell. Beta-amyloid peptides aggregate and form beta-amyloid plaques.

Question 24

What are some ways that amyloid palques can examined or abnormalities found, pre-post mortem biopsy?

Answer 24

Measuring levels of beta-amyloid in the CSF.

Using PET to look at amount of amyloid in the brain.

Question 25

What CSF characteristics are considered to be suggestive of Alzheimer’s disease?

Answer 25

Higher levels of tau.

Lower levels of beta-amyloid.

Question 26

What is tau and what are its known roles in Alzheimer’s disease?

Answer 26

Tau protein is a microtubule-associated protein in neurons. It helps stabilise microtubules, which are required for axon structure as well as the movement of molecules down the length of an axon.

In Alzheimer’s disease tau proteins become overly phosphoryalated and break away from the microbtules. They aggregate in neurofibrillary tangles within the neuron. The detachment of tau from the microtunes causes the microtubules to unwind and disintegrate, eventually leading to the death of the neuron. This causes the brian to atrophy.

Question 27

What is thought be responsible for the atrophy seen in those with Alzheimer’s disease?

Answer 27

The over-phosphorylation of tau proteins that leads to the disintegration of microtubules in neurons in the brain.

Question 28

Can tau aggregates also be imaged?

Answer 28

Yes, using PET.

Question 29

What is the amyloid cascade hypothesis of of Alzheimer’s disease?

Answer 29

Misfolding of amyloid comes first and then by some unknown process leads to the overphosphorylation of tau and the formation of tau aggregates (neurofibrillary tangles).

Hotly debated.

Question 30

What do most for Alzheimers treatments aim to do?

What is their efficacy, and what does this suggest about the disease?

Answer 30

They aim to remove beta-amyloid plaques from the brain.

They are not very effective and treating the symptoms or progression of alezheimer’s disease, suggesting that there is something else driving the disease.

Question 31

Where does pathology start to form in Alzheimer’s disease?

Answer 31

Medial temporal lobe.

Question 32

What structures are found in the medial temporal lobe?

Answer 32

The hippocampus and parahippocampal structures (structures surrounding the hippocampus), such as the amygdala.

These structures are essential for memory formation and retrieval and therefore the clinical syndrome of Alzheimer’s (dementia) is quite understandable.

Question 33

What is the progression of beta-amyloid plaques as Alzheimer’s progresses?

Answer 33

Start in neo-cortex, such as frontal lobes, and gradually moves inward toward the medial temporal lobe structures.

Question 34

What is the progression of hyper-phosphorylated tau?

Answer 34

Starts in the medial-temporal structures and progresses outward toward the cortex.

Question 35

Does amount of tau present in the brain (using Braak tau staging) correlate with degree of cognitive impairment in those with Alzheimer’s disease?

Answer 35

Yes.

The more tau present, the more severe the cognitive impairment experienced, the more impairment to cognitive function, the more advanced their dementia.

Question 36

Does amount of beta-amyloid plaques present in the brain correlate with degree of cognitive impairment?

Answer 36

No.

Question 37

How does knowing the progression of hyper-phosorylated tau inform diagnosis and stage of Alzheimer’s disease by neuropsychologists?

Answer 37

Observing client signs and symptoms of cognitive impairment can inform clinician of what stage of Alzheimer’s disease an individual is in.

For example, if individual is only have some trouble with memory formation and recall then it could be that the tau has not yet progressed throughout the rest of brain and is just wihtin the medial temporal lobe structures.

Question 38

What is the march of tau pathology in Alzheimer’s disease?

Answer 38

1. Starts in mesial temporal lobes.
2. Progresses to lateral temporal lobes.
3. Progresses to parietal lobe.
4. Moves into frontal lobes.

Question 38

What area of the brain is often not affected by tau neurofibrillary tangles until quite late in the progression of the diease?

Answer 38

The frontal lobes.

This means that clients will likely maintain cognitive function associated with this area till quite late into their disease.

Question 39

What is the significance if HM to understanding Alzheimer’s disease?

Answer 39

HM had both hippocampi removed, due to severe seizures that originated in these areas.

Severe anterograde amnesia was one of the outcomes of this surgery.

Question 40

What happens if mesiotemporal structures, such as the hippocampus, are removed or damaged?

Answer 40

You get anterograde amnesia. You are not able to make new memories, but you can recall old memories (that occurred prior to the removal or damage).

Question 41

What cognitive functions are relatively preserved in Alzheimer’s?

Answer 41

Those involving the frontal lobes, such as executive functions.

Question 42

What symptoms are seen when there are tau tangles in:

Medial temporal lobes

Lateral temporal lobes

Parietal lobes

Frontal lobes

Answer 42

Memory - e.g. episodic memory

Language - e.g. word retireval

Visuospatial difficulties - constructional praxis

Executive functions.

Question 43

What is a clinical prodome for AD demetia?

Answer 43

Amnesic MCI.

Question 44

For amnesia that is caused by bilateral medial temporal lobe impairment, what is this termed?

Answer 44

Encoding profile.

The lack of memory is not due to inability to recall, but an inability to encode.

Question 45

Where does tau pathology start to form initially in Alzheimer’s disease?

Answer 45

Between the entorhinal and perirhinal cortices.

Question 46

What is arbitrary associative learning?

Answer 46

Where we join together pieces of information that we do not have a prior association with, e.g crush/dark, as opposed to baby/cries, which would be a semantic association.

Question 47

What is hippocampal gating and what role does the perirhinal cortex play in this phenomenon?

Answer 47

When we already have an association between things, such as baby/cry, if we are asked to remember these words then we do not need to activate the hippocampus to encode this association, as it is already there. If the hippocampus was engaged to make the association between two things everytime we came across them then this would be very inefficient.
The perirhinal cortex is the point at which the brain checks whether it already has an association or if the hippocampus needs to be activated in order to make a new arbitrary association.

Question 48

What is an early indication that someone has tau pathology in their perirhinal cortices?

Answer 48

They cannot remember arbitrary associations, but they can remember somantic associations.

Question 49

What is one of the tests that detect impaired associative learning?

Answer 49

CANTAB Paired Associate Learning (PAL).

This involves being shown a random shape in one area of a screen, then being asked where that shape was shown.

Question 50

What is the Rey Auditory Verbal Learning Test used for?

Answer 50

To test for associative learning deficitis.

People are required to remember a list of arbitrary words.

Those with Alzheimer’s cannot remember them, even after multiple repeats, and when they are presented with cues.

Those with frontal lobe damage that cannot recall the words will perform better if they are given a cue, as they have made an association, but just struggle with spontaneous recall.

Question 51

Those with AD often have difficulty with language retrieval. What is one way to measure someone’s language retrieval abilities?

Answer 51

The SydBat Language test.

Individuals are shown images of objects or scenes and ask what it is they are seeing.

Normal number of correct responses is about 26/30.

Those with AD where tau pathology has progressed to the lateral temporal lobe will have difficulty finding the correct word and may often retreat to using a supra-ordinate word, or word from a class above the actual objects, such as animal instead of dog. Or building instead of the pyraminds.

Question 52

One symptom that those with AD can experience is getting lost when doing a familiar task, such as going to the local shops.

Where has tau pathology progressed to or passed?

Answer 52

The parietal lobe.

Question 53

When tau pathology progresses into the parietal lobe, what are some of the symptoms observed, and how can this be measured clinically?

Answer 53

People begin to get visuospatial impairments, such as being unable to navigate through space or copy complex images.

One way to measure this is through the Rey Complex Figure Test, where individuals are presented with a complex figure to copy. THose with AD find it difficult to accurately copy the image.

Question 54

What cognitive functions tend to be preserved in AD and why is this?

Answer 54

Cognitive functions, such as emotional regulation and response inhibition.

This is because the frontal lobes are the last to experience tau pathology and it only happens late into the disease.