Case 4

Question 1

What is Alzheimer’s?

Answer 1

50-80% of dementia cases
Gradual onset

Question 2

What are symptoms of Alzheimer’s?

Answer 2

Memory loss
Language deficits
Rapid forgetting
Impaired visuospatial skills
Normal gait and neuro exam early on

Question 3

What is the pathology of Alzheimer’s?

Answer 3

Generalised atrophy
Beta amyloid plaques
Neurofibrillary tangles

Question 4

What is vascular dementia?

Answer 4

20-30% of dementia cases
Abrupt, stepwise progression

Question 5

What are symptoms of vascular dementia?

Answer 5

Focal neurological signs
Signs of vascular disease

Question 6

What is the pathology of vascular dementia?

Answer 6

Strokes
Lacunar infarcts
White matter lesions
Vulnerable to cerebrovascular events

Question 7

What is Lewy body dementia?

Answer 7

10-25% of cases
Protein aggregates in nerve cells
Insidious, progressive onset (symptoms not obvious at first)

Question 8

What are symptoms of Lewy body dementia?

Answer 8

Hallucinations
Fluctuating awareness

Question 9

What is the pathology of Lewy body dementia?

Answer 9

Generalised atrophy
Lewy bodies in cortex and midbrain

Question 10

What is frontotemporal dementia?

Answer 10

10-15% of cases
Frontal lobe (behaviour and speech) or temporal lobe (language and knowledge) affected
Insidious onset, rapid progression

Question 11

What are symptoms of frontotemporal dementia?

Answer 11

Disinhibition
Behavioural changes

Question 12

What is the pathology of frontotemporal dementia?

Answer 12

Frontal and temporal atrophy
Pick cells and pick bodies in cortex

Question 13

How are amyloid plaques formed?

Answer 13

Amyloid precursor protein normally cleaved by alpha-secretase
In plaque formation, cleaved by beta- and gamma-secretase
Results in excessive amyloid beta peptides
AB peptides form oligomers and fibrils with beta-pleated sheet structures
Fibrils deposit in insoluble plaques outside neurones

Question 14

How are neurofibrillary tangles formed?

Answer 14

Tau is a protein involved in microtubule formation
Microtubules are involved in neurone shape, development, transport inside cells, and communication between neurones
When Tau is hyperphosphorylated –> oligomers form
Oligomers aggregate into NFTs inside neurones
NFTs disrupt microtubule formation

Question 15

Where are neurofibrillary tangles deposited?

Answer 15

Hippocampus
Medial temporal lobe
Frontal cortices
Lateral parietotemporal region

Question 16

How can AB oligomers lead to NFT formation?

Answer 16

Microglial cells promote inflammation to clear amyloid plaques
Inflammation triggers Tau hyperphosphorylation

Question 17

How does neuronal death lead to acetylcholine deficiency in Alzheimer’s?

Answer 17

Loss of neurones in nucleus of basalis of Meynert
These neurones are rich in acetylcholine
They supply the amygdala, hippocampus and neocortex
Neuronal death results in acetylcholine deficit in these regions
Acetylcholine involved in memory

Question 18

What causes serotonin deficiency in Alzheimer’s?

Answer 18

Neuronal death in median raphe of brainstem

Question 19

What causes noradrenaline deficiency in Alzheimer’s?

Answer 19

Neuronal death in locus coeruleus (small nucleus in brainstem)

Question 20

What is cerebro-cortical atrophy?

Answer 20

Loss of neurones and synapses
Decrease in amount of brain tissue and brain size

Question 21

What parts of the limbic system are affected in Alzheimer’s?

Answer 21

Cingulate gyrus
Hippocampus
Anterior thalamus

Question 22

What is the cingulate gyrus involved in?

Answer 22

Orientation –> memory of time and place

Question 23

What is the hippocampus involved in?

Answer 23

Short term memory

Question 24

What is the anterior thalamus involved in?

Answer 24

Attention –> ability to focus on tasks