Cognition and disorders - neurological disorders

Question 1

What happens in the early stage of Alzheimer’s? (2)

Answer 1

Early stage - memory and language problems e.g. forgetfulness, shrinking vocabulary, difficulties finding words (anomia)

Question 2

What happens in the middle stage of Alzheimer’s? (2)

Answer 2

Middle stage – speech difficulties (aphasia), effect on daily living (BADL), behavioural changes, etc

Question 3

What happens in the later stage of Alzheimer’s? (2)

Answer 3

Late stage – complete dependence on care, some entirely lose speech, apathy or exhaustion, etc

Question 4

Describe epidemiology of Alzheimer’s? (3)

Answer 4

Age is a primary risk factor – a challenge of an ageing population

More common in women (likely due to longer average life expectancy)

Becoming more common as a cause of death – ageing population but also improved diagnosis & characterisation

Question 5

Describe the pathology of epidemiology (2)

Answer 5

Amyloid plaques - extracellular accumulations of amyloid beta

Neurofibrillary tangles (intracellular accumulations of hyperphosphorylated tau) – possibly more predictive of decline

Cortical atrophy

Question 6

How do cells degenerate? (1)

Answer 6

Neurodegeneration may include cell death but also changes/loss of function without cell loss.

Question 7

What are the common mechanisms to neurological disorders? (4)

Answer 7

Metabolic stress (mitochondrial dysfunction, oxidative stress)

Elevated intracellular Ca2+ or excitotoxicity

Neuroinflammation

Protein misfolding or aggregation

Question 8

What are the causes of Alzheimer’s? (8)

Answer 8

Age and gender
Genetic factors
Infections
Head injuries
Cardiovascular disease
Lifestyle
Environmental factors
Others - obesity, diabetes etc

Question 9

What do current treatment for Alzheimer’s do? (3)

Answer 9

Can relieve and/or slow down progression of symptoms but 1) don’t work in everyone and 2) the disease still progresses (currently no cure).

Question 10

What are the current treatments against Alzheimer’s? (2)

Answer 10

NMDA receptor antagonist such as memantine (protect cells from excitotoxicity)
Acetylcholinesterase inhibitors such as donepezil (restore cholinergic deficit)

Question 11

How does NMDA receptor antagonist work? (2)

Answer 11

Inhibit activation of NMDA and suppress neurodegeneration

Question 12

How does acetylcholinesterase inhibitors work? (2)

Answer 12

Increase neurotransmitter levels and provide symptomatic relief

Question 13

What are movement of disorders? (3)

Answer 13

Diseases of the basal ganglia
Two broad categories – hypokinetic (e.g. Parkinson’s disease) and hyperkinetic (e.g. Huntington’s)

Question 14

What are the core symptoms of Parkinson’s disease? (4)

Answer 14

Tremor
Bradykinesia (slowed movement - hypokinesia)
Postural instability
Rigidity

Question 15

What are the other symptoms of Parkinson’s disease? (5)

Answer 15

Changes in cognition
Behaviour
Sleep
Gastrointestinal function, etc. Anosmia (change or loss of smell) can be one of the earliest symptoms!

Question 16

What does the basal ganglia do? (2)

Answer 16

Facilitation of desired movement (direct pathway)
Suppression of unwanted movement (indirect pathway).

Question 17

Why is dopamine a modulatory neurotransmitter? (2)

Answer 17

D1 receptors are excitatory, D2 receptors are inhibitory

Question 18

Pathology of Parkinson’s disease (2)

Answer 18

Loss of dopaminergic neurons in the substantia nigra pars compacta
Intracellular accumulations of the protein alpha-synuclein to form Lewy bodies

Question 19

Describe the mechanism of Parkinson’s disease in terms of the basal ganglia circuit (4)

Answer 19

Loss of dopaminergic neurons in the SNc

Reduced direct pathway:
- Less inhibition of the GPi = more inhibition of the thalamus = less movement

Increased indirect pathway:
- More inhibition of the GPe = less inhibition of the STN = more excitation of the GPi = more inhibition of the thalamus = less movement.

Question 20

Describe the epidemiology of Parkinson’s (3)

Answer 20

Age is a primary risk factor – a challenge of an ageing population

More common in men (unknown why)

Question 21

What are the causes of Parkinson’s disease? (1)

Answer 21

5-10% of cases linked to a clear genetic cause (mutation)

Question 22

What are the treatments available for Parkinson’s disease? (3)

Answer 22

Precursor L-DOPA, which can cross the blood brain barrier
Block peripheral DDC/AADC to reduce peripheral breakdown with carbidopa or benserazide

Question 23

Define seizures (3)

Answer 23

A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain

Question 24

What are the different types of seizures (3)

Answer 24

Focal onset
Generalise onset
Unknown onset

Question 25

What is tonic clonic? (2)

Answer 25

Tonic = loss of consciousness, muscles contract, likely fall to floor

Clonic = convulsions as muscle contracts and relaxes rapidly

Question 26

Describe epilepsy (2)

Answer 26

A disorder of the brain characterised by an enduring predisposition to generate epileptic seizures
The definition of epilepsy requires the occurrence of at least one epileptic seizure

Question 27

What is idiopathic epilepsy? (2)

Answer 27

No structural, metabolic, pathogenic, or immune cause

Question 28

Prevalence of idiopathic epilepsy (1)

Answer 28

Bimodal distribution: peaks in children and elderly.

Question 29

What occurs during a seizure? (2)

Answer 29

Generally involves imbalance of excitatory (E) and inhibitory (I) networks at the level of ion channels and/or synapses