Neurodegenerative Diseases

Question 1

What does healthy aging of the brain look like?

Answer 1

Over the course of healthy aging, neurons atrophy and die. Consequently, the ventricles and sulci expand.

Question 2

What does the term ‘atrophy’ mean?

Answer 2

Decrease in size or wasting away of a body part or tissue.

Question 3

What does the term ‘neurodegeneration’ refer to?

Answer 3

Neurodegeneration refers to a (normal) decline in the structure and function of brain cells.

Question 4

How are neurodegenerative disease characterised?

Answer 4

Neurodegenerative diseases are characterised by gradual and progressive loss of neural tissue in respect to a disease.

Question 5

Compare the nature of neurodegenerative diseases with tumours and strokes.

Answer 5

Tumours and neurodegenerative diseases = progressive decline.
Strokes = sudden difficulties and gradual improvement afterwards.

Question 6

What is dementia?

Answer 6

Dementia is a debilitating syndrome characterized by a loss of cognitive functions that interferes significantly with work or social activities.

Question 7

What causes dementia?

Answer 7

Dementia is caused by changes in the brain that result from disease or trauma (most commonly associated with Alzheimer’s Disease but there are other causes).
Although a person can become demented after an acute neurological incident, dementias are typically progressive and eventually lead to death.
Risk of dementia increases with age.

Question 8

How is dementia screened for?

Answer 8

Screening for dementia is often done using the Mini-Mental State Examination (MMSE).

Question 9

Does the Mini-Mental State Examination diagnose dementia? Why is it useful?

Answer 9

No, it’s not particularly accurate but if you score poorly enough that you possibly could have dementia then further tests would be done.
It’s very quick to administer and it’s usually relatively obvious if someone has dementia as they appear confused.

Question 10

What are the three types of neurodegenerative diseases?

Answer 10

1. Cortical Degenerative Diseases
2. Subcortical Degenerative Diseases
3. Mixed Degenerative Diseases

Question 11

Name two Cortical Degenerative Diseases.

Answer 11

1. Alzheimer’s Disease

2. Pick’s Disease

Question 12

Name two Subcortical Degenerative Diseases. Which one typically has earlier onset?

Answer 12

1. Huntington’s Disease
2. Parkinson’s Disease

Typically Huntington’s Disease has earlier onset, however, you can have ‘early-onset Parkinson’s Disease’.

Question 13

What’s the cause of Alzheimer’s Disease?

Answer 13

Primarily genetic mutation (but the exact cause is still unknown).

Question 14

Is Alzheimer’s Disease thought to be hereditary?

Answer 14

No, it’s 95% not hereditary.

Question 15

Explain the pathology of Alzheimer’s Disease.

Answer 15

Diffuse damage especially to cortical cells (including hippocampal cells).
There are Neurofibrillary Tangles which are abnormalities within neurons, and Senile Plaques which extracellular protein deposits.

Question 16

What are the symptoms of Alzheimer’s Disease?

Answer 16

Decline in memory and other aspects of cognitive function.

Question 17

Does having Dementia mean that you have Alzheimer’s Disease?

Answer 17

No. AD accounts for more than half of all dementia but you can have dementia associated with another disease process.

Question 18

Watching interviews with Alzheimer’s Disease patients and their families, what stood out?

Answer 18

The discrepancy in the opinions of the patient vs. the family members; the family members were very worried and distraught, the patient didn’t seem to be aware of their own decline; contrast to other diseases where the patient is very aware and tend to get depressed.

Question 19

Are neurofibrillary tangles and senile plaques only found in Alzheimer’s Disease patients?

Answer 19

No. Neurofibrillary tangles and senile plaques both occur with healthy aging; however, they are much more abundant in patients with Alzheimer’s disease and their prevalence positively correlates with dementia.

Question 20

How do Neurofibrillary Tangles and Senile Plaques affect neurons?

Answer 20

Neurofibrillary tangles and senile plaques disrupt the normal function of neurons, reducing neural communication (synapses) and causing cell death.

Question 21

Where are neurofibrillary tangles predominantly found in patients with Alzheimer’s Disease? Where are they not usually found?

Answer 21

Commonly found in medial temporal lobes (relates to memory), inferior parietal, and frontal cells (could link to the being not overly aware of their decline). Not found in primary motor or sensory areas.

Question 22

Which lobe of the brain is least affected by the pathology associated with Alzheimer’s Disease?

Answer 22

The occipital lobe is relatively unaffected.

Question 23

Describe a post-mortem brain from an Alzheimer’s Disease patient.

Answer 23

The pathology associated with Alzheimer’s disease leads to cerebral atrophy mostly involving the frontal, parietal, and temporal cortex (including the hippocampus). Posterior cortex is relatively unaffected.
Cortical atrophy leads to narrowed gyri, and thus widened sulci.
Also, characteristic ventricular dilation resulting from loss of brain tissue.

Question 24

How might the hippocampi appear in a patient with Alzheimer’s Disease?

Answer 24

AD patients have shrunken hippocampi relative to neurologically-healthy age-matched controls, which results in dilated temporal horns.

Question 25

Which method of brain imaging is being used for early diagnosis of Alzheimer’s Disease and why?

Answer 25

Since the pathology associated with Alzheimer’s disease (AD) greatly decreases brain metabolism, PET is being used to assist with early diagnosis of AD.

Question 26

What is the link between curry and Alzheimer’s Disease?

Answer 26

Curcumin is an orange-yellow component of turmeric, a spice often found in curry powder.
Curcumin has the potential to treat a wide variety of inflammatory diseases.

Question 27

How does Pick’s Disease appear outwardly different to Alzheimer’s Disease?

Answer 27

Pick’s Disease presents similarly to AD but less heavy on the memory and more heavy on the socially inappropriate behaviour.

Question 28

What’s the cause of Pick’s Disease? Is it thought to be hereditary?

Answer 28

Primarily genetic mutation, however 90% not hereditary.

Question 29

What is the pathology of Pick’s Disease?

Answer 29

Pale swollen neurons and Pick’s bodies in the cytoplasm of neurons in the cortex. This causes cerebral atrophy that typically involves mainly the frontal and temporal lobes (parietal and occipital cortex is relatively spared). Interrupts normal cell function and causes cell atrophy.

Question 30

What is the cause of Huntington’s Disease?

Answer 30

It’s hereditary.

Question 31

What’s the prognosis for someone with Huntington’s Disease?

Answer 31

HD often presents between the ages of 30 and 45; slow decline for about 10 to 15 years until death. HD typically leads to dementia.

Question 32

What is the pathology of Huntington’s Disease?

Answer 32

Huntington’s disease destroys neurons in the caudate and putamen.
The loss of cells causes the head of the caudate to shrink and the anterior horns of the lateral ventricles to dilate.

Question 33

What are the symptoms of Huntington’s Disease? And what does it lead to?

Answer 33

Presence of chorea (i.e., choreiform movements; jerky, rapid movements), and a decline in cognitive functioning (executive function and memory).
HD typically leads to dementia and death.

Question 34

Is Huntington’s Disease considered hyper- or hypo-kinetic?

Answer 34

Considered a hyperkinetic disease, contrast this to Parkinson’s disease which is hypokinetic.

Question 35

What is the cause of Parkinson’s Disease?

Answer 35

Unknown (idiopathic = arising from an unknown cause).

It’s not thought to be hereditary.

Question 36

What is the pathology of Parkinson’s Disease?

Answer 36

Dopaminergic cells in the substantia nigra die which leads to a dopamine deficit.
Part of the substantia nigra which deteriorates, in particular the part which extends to the striatum.

Question 37

What are the symptoms of Parkinson’s Disease?

Answer 37

Tremor that is most obvious at rest (tends to go away when the patient is moving).
Rigidity: resistance to passive movement of a limb (if moving their arm it feels as if they are resisting you even when they’re not).
Akinesia: poverty of movement (moving less).
Bradykinesia: slowness of movement.
Posture, gait, and balance problems.

Question 38

If a patient has Parkinson’s Disease is it expected that they will have dementia?

Answer 38

Only ~30% of PD patients have dementia, but ~75% of PD patients who survive for more than 10 years develop dementia. Your risk of dementia does increase with age but more so if your suffer from Parkinson’s Disease.

Question 39

What treatment helps patients with Parkinson’s Disease?

Answer 39

PD kills dopaminergic neurons in the substantia nigra, which leads to a dopamine deficit that can be treated with drugs such as the dopamine precursor L-dopa (DA agonist). Can’t just give dopamine - it doesn’t cross the blood-brain barrier.

Question 40

The striatum (caudate and putamen) and substantia nigra are part of what?

Answer 40

The basal ganglia.

Question 41

Aside from L-dopa, what are two other treatments for Parkinson’s Disease?

Answer 41

1. Under-activity in dopamine pathways results in over-activity in cholinergic pathways.
   Drug therapy to inhibit cholinergic receptors (acetylcholine antagonist).
2. Deep brain stimulation or thalamotomy (lesion part of thalamus)/pallidotomy (lesion part of the globus pallidus) - some patients opt for this if they have extreme tremors. They can freeze the tissue first and see if the patient can still move to make sure they will lesion the correct part, the patient must be awake for this.

Question 42

Do drug treatments always work for Parkinson’s Disease patients?

Answer 42

Unfortunately these drug treatments do not work for all patients. Many say it takes a while to start working, then they have a honeymoon period where they can move around and do things but then they say it wears off.
Some even experience freezing - can’t move at all when the drug wears off.

Question 43

Why does damaging the substantia nigra affect the functions of the caudate and globus pallidus?

Answer 43

The substantia nigra has a close anatomical and functional association with the caudate, putamen, and globus pallidus.

Question 44

Parkinson’s Disease relates to degeneration of the substantia nigra which effects functions of the caudate nucleus and globus pallidus. How might the caudate nucleus and globus pallidus relate to symptoms of PD?

Answer 44

Caudate Nucleus - tend to lend more to poverty of movement.

Globus Pallidus - tends to lend more to tremor.

Question 45

In general what does the basal ganglia do? What does this mean for Parkinson’s Disease?

Answer 45

The basal ganglia circuitry process motor signals that flow from frontal cortex in order to enable accurate execution of voluntary movements. So damage to this circuitry effects volitional movement more than reflexive movements.
In Parkinson’s disease, the degeneration of dopaminergic neurons in the substantia nigra triggers a cascade of functional changes that affect the entire basal ganglia network.

Question 46

What is a possible side effect of medication for Parkinson’s Disease?

Answer 46

Medication can cause dyskinesia = abnormal movements, particularly of the head and neck.

Question 47

What does oculomotor behaviour suggest about Parkinson’s disease?

Answer 47

Consideration of oculomotor behaviour in patients with PD suggests relatively intact reflexive eye movements but impaired voluntary control.

Question 48

In the example of a study of oculomotor control in patients with Parkinson’s Disease, what was the task and what were the results?

Answer 48

The task was an anti-saccade task.
Patients with Parkinson’s disease exhibit difficulty suppressing reflexive eye movements toward stimuli appearing in the periphery. Suggests difficulty with top-down control of eye movements.
It tends to be bilateral impairment unlike what is seen due to a stroke.
It’s likely that the projections from the Frontal Eye Field to Substantia Nigra are what is involved here.

Question 49

There’s also evidence that Parkinson’s Disease patients show control deficits during attention tasks. Describe a task used to assess this.

Answer 49

Flanker task. From the participant’s perspective the task is as follows: coloured squares appear on a screen, press left if it’s red and right if it’s green. But we’re really interested in the distractor and how it affects performance.
To measure the impact of distractor; whether the distractor is compatible or incompatible with the stimulus; this allows measurement of how much it slowed people down….
Compatibility Effect = Incompatible RTs‐ Compatible RTs
Compatibility effect provides a measure of distraction.

Question 50

You already know what the Flanker Task is, but what is the Flanker Task with a variable distractor-target delay.

Answer 50

This involves Stimulus Onset Asynchrony (SOA). This refers to the interval between the onset of two stimuli. So there’s some variation between when the distractor appears vs. the central target.
A short interval measures the initial distraction, and a long interval produces a measure of distractor inhibition.

Question 51

What do we see in patients with Parkinson’s Disease during the Flanker Task with a variable distractor-target delay?

Answer 51

In young healthy participants when you get to the longer intervals you start to see a negative compatibility effect, but patients with PD are still in the positives. They exhibit difficult ignoring stimuli that appear in the periphery during focused attention. This difficulty appears to reflect reduced inhibitory control.

Question 52

Describe the Negative Priming Task.

Answer 52

Fixate on the centre of the screen, a word appears in the centre, but there are distractor words above and below the target word. The participants must respond by indicating whether the central word is a word or a pseudoword. The first display is the primer and the following display is the probe. Key manipulation: On some trials, the distractors in the Prime Display matched the target in the Probe Display.

Question 53

What does the Negative Priming Task measure?

Answer 53

This allows indirect measurement of distractor processing (i.e., how does the identity of the distractor influence the response to the next target). Slowing typically occurs when the previous distractor matches the target.

Question 54

How did patients with Parkinson’s Disease compare to controls in the Negative Priming Task?

Answer 54

PD patients tend to show less negative priming than healthy controls, which indicates that PD patients inhibit distractors less than healthy controls.
In fact, in this study, healthy controls showed significant negative priming of 13 ms (as expected), whereas PD patients exhibited significant positive priming of 18 ms. Indicates that they did not inhibit the word previously, so it actually sped them up.
This suggests an inhibitory deficit in the PD patients, similar to the flanker task.

Question 55

What are some key differences between Huntingtons and Parkinsons?

Answer 55

• Huntingtons is hereditary, Parkinsons is thought not to be
• Both relate to the basal ganglia, but HD relates to cell death in the caudate and putamen, PD is where dopaminergic cells die in the substantia nigra
• Huntington’s (30 - 45 years) typically has an earlier onset than Parkinson’s
• Huntington’s usually leads to dementia, whereas only 30% of Parkinson’s patients have dementia (although risk increases more with age with PD)
• Huntington’s is hyperkinetic whereas Parkinson’s is hypokinetic
• Huntington’s has more emphasis on cognitive issues, like executive functioning and memory along with the choreiform movements; Parkinson’s symptoms are mainly motoric (although we did look at some cognitive deficits in class - motor and attention inhibitory control)

Question 56

With a decrease in dopaminergic neurons, what increases, and why is this important?

Answer 56

Under-activity in dopamine pathways results in over-activity in cholinergic pathways. Cholinergic pathways link to muscle contractions (increased muscle tone, rigidity, tremor).

Question 57

How do the substantia nigra and striatum relate to movement?

Answer 57

Basal ganglia participate in important feedback loops in which they project back to the cerebral cortex via the thalamus.

Question 58

Comparing HD and PD, who is more aware of their illness?

Answer 58

Parkinson’s Disease patients tend to be aware of their limitations and suffer from depression.

Question 59

If a Parkinson’s Disease patient and a stroke patient both struggle with anti-saccade tasks, what difference might set them apart?

Answer 59

So both patients might struggle with the top-down control on reflexive eye movements, but damage in bilateral for PD patients so they should struggle equally whether the stimulus is on the left or right. A stroke patient should show deficits contralesionally but not ipsilesionally.

Question 60

What three tasks illustrated inhibitory deficits in Parkinson’s Disease patients?

Answer 60

Motor control –> Anti-saccade task

Attention control –> Flanker task and negative priming task