Neurodegenerative Diseases

Question 1

How is Huntington’s disease passed on?

Answer 1

Autosomal dominant inheritance

Question 2

List the Tx of Huntington’s disease

Answer 2

no cure so multidisciplinary care and management of disease Sx

Question 3

In the progression of Huntington’s disease, what is generally the first to decline?

Answer 3

Functional abilities (can begin in the prodromal stages and leads to the motor diagnosis)

Question 4

Which three signs and symptoms increase throughout the progression of Huntington’s disease?

Answer 4

motor impairment, cognitive impairment, chorea

Question 5

Where in the world is the prevalence of Huntington’s disease increasing?

Answer 5

Western populations

Question 6

What is the main pathological hallmark of Huntington’s disease?

Answer 6

degeneration and atrophy (size decrease) of the striatum (in the brain)

Question 7

Which pathway is dysfunctional in Huntington’s disease?

Answer 7

Major stress response pathway

Question 8

Which protein is ‘responsible’ for Huntington’s?

Answer 8

HTT

Question 9

Cell autonomous and non cell autonomous death occurs in which neurodegenerative disease?

Answer 9

Huntington’s disease

Question 10

Chorea is a symptom of Huntington’s disease and can be treated or managed with which drug?

Answer 10

Tetrabenazine

Question 11

Explain the 2 mechanisms of action for Tetrabenazine and which condition it is contraindicated in

Answer 11

1. Tetrabenazine binds to vesicles and prevents dopamine from entering them for release into the synapse
2. Tetrabenazine competitively blocks dopamine binding to its receptors and passing an electric signal

Contraindicated in Parkinson’s disease

Question 12

What is the experimental therapy being tested for HD?

Answer 12

prevent the translation of the HTT protein in the nucleus (changing the DNA)

Question 13

Which neurodegenerative disease can be inherited or sporadic and which is more common?

Answer 13

Parkinson’s - more likely to be sporadic

Question 14

Dopaminergic, non-dopaminergic drugs and deep brain simulation are treatments for which neurodegenerative disease?

Answer 14

Parkinsons disease

Question 15

Which symptoms become apparent first in Parkinson’s disease?

Answer 15

Non-motor symptoms (sleep behaviour, depression, fatigue)

Question 16

The diagnosis of Parkinson’s disease comes after the beginning of which type of symptoms?

Answer 16

Motor symptoms (tremor, rigidity, falls)

Question 17

Is Parkinson’s disease more prevalent in men or women?

Answer 17

men

Question 18

What are the pathological hallmarks of Parkinson’s disease?

Answer 18

loss of neurons in the substania nigra (SN) and widespread intracellular accumulation of alpha-synuclein

Question 19

Which feature is found in the limbic and neocortical regions as Parkinson’s progresses?

Answer 19

Lewy bodies

Question 20

What does the acronym TRAP stand for and which disease does it relate to?

Answer 20

Tremor at rest, rigidity of the limbs, Akinesia, Postural problems&raquo_space; Parkinson’s disease

Question 21

The loss of neurons in the SN leads to…

Answer 21

dopamine deficiency in the striatum

Question 22

What caused the increased actions of excitatory transmitters in Parkinson’s disease?

Answer 22

loss of inhibitory dopamine

Question 23

Dysfunction of the UPS and LAS systems is prevalent in which neurological condition?

Answer 23

Parkinson’s

Question 24

Which two drugs work outside the BBB on AADC which converts L-DOPA to dopamine?

Answer 24

Benserazide and Carbidopa

Question 25

Which endogenous molecule can be given as a drug to increase the production of dopamine in the brain?

Answer 25

L-DOPA (levodopa)

Question 26

List the MOA and target site of Pramipexole

Answer 26

MOA: dopamine agonist | Target site: D2 receptor

Question 27

List and briefly explain a non-pharmacological Tx for Parkinson's disease

Answer 27

Deep Brain Stimulation | - high frequency stimulation of brain targets can alter neuronal circuits back to a more physiological state

Question 28

In general terms, when is the onset of Alzheimers and what is the average survival?

Answer 28

Around 60yrs old and average survival is 8-10 years

Question 29

While there is no cure for Alzheimers disease, which 3 components can be implemented in a patients life?

Answer 29

multidisciplinary care, management of disease Sx and treatment for co-morbidities

Question 30

Gene mutations are thought to be linked to which neurological diseases?

Answer 30

Alzheimers and ALS

Question 31

List the 5 elements of the disease progression (in the order which they occur) for Alzheimers.

Answer 31

Amyloid-beta plaques, tau-mediated neuron injury and dysfunction, brain structural changes, memory impairment, functional deficits

Question 32

Which neurological disease is one of the leading causes of death in Australia?

Answer 32

Alzheimers disease

Question 33

Explain the pathological hallmarks of Alzheimers disease.

Answer 33

The accumulation of Amyloid-beta plaques and Tau neurofibrillary tangles. In some cases, you may also see alpha-synuclein and TDP-43 pathology There is cortical atrophy, medial temporal atrophy of the amygdala and hippocampus and loss of neuormelanin in the coeruleus

Question 34

What are the effects of Amyloid-beta?

Answer 34

APP is chopped by alpha or beta secretase that produces soluble fragments; simultaneous cutting leads to aggregates. This leads to cell autonomous and non-cell autonomous death

Question 35

What are the effects of Tau?

Answer 35

stabilises microtubules and their collapse leads to tau tangles which leads to cell autonomous and non-cell autonomous death

Question 36

Which Tx is used in Alzheimers which improves memory, attention, mood and behaviour?

Answer 36

Cholinesterase inhibitors which increase the concentration of ACh at the synapse

Question 37

What does ALS stand for?

Answer 37

Amyotrophic Lateral Sclerosis

Question 38

ALS is a type of which disease?

Answer 38

MND

Question 39

The degeneration of upper and lower motor neurons of the corticospinal tract os the pathological hallmark for which disease?

Answer 39

ALS

Question 40

ALS is a complex disease with multiple proposed pathogenic mechanisms. These mechanics are mostly linked to what and lead to what?

Answer 40

Gene mutations which lead to cell autonomous and non-cell autonomous

Question 41

Which two drugs are a proposed Tx for ALS?

Answer 41

Riluzole and Edaravone

Question 42

Describe the MOA of Riluzole? (3 points)

Answer 42

inhibition of glutamic acid release, inhibition of voltage gated sodium channels and blocking of excitatory amino acid transporters

Question 43

An experimental therapy states: Hyper metabolism in ALS is associated with....?

Answer 43

...greater functional decline and shorter survival

Question 44

Frontotemproal dementia can overlap with which neurodegenerative condition?

Answer 44

ALS