Dementia

Question 1

Describe the pathophysiology of Alzheimer’s disease (AD)?

Answer 1

Neurodegenerative proteinopathy (amyloid)
Disruption of cholinergic pathways in the brain + synaptic loss
- extracellular amyloid plaques
- intracellular neurofibrillary tangles

Question 2

In which genetic condition is early onset AD inevitable?

Answer 2

Down’s syndrome

Question 3

Which gene may be implicated in AD?

Answer 3

ApoE gene

Question 4

Which investigations can be done for suspected AD and what will they show?

Answer 4

MRI: atrophy of temporal/parietal lobes
SPECT: temporoparietal reduced metabolism
CSF: reduced amyloid:tau ratio

Question 5

Which treatments are available for AD and how do they work?

Answer 5

Acetylcholine boosting treatment:

• cholinesterase inhibitors
• NMDA receptor blockers

Question 6

Give two examples of cholinesterase inhibitors?

Answer 6

Rivastigmine

Galantamine

Question 7

Give an example of a NMDA receptor blocker?

Answer 7

Memantine

Question 8

What is another name for fronto-temporal dementia?

Answer 8

Pick’s disease

Question 9

What are the histopathological findings in fronto-temporal dementia?

Answer 9

Tau proteins

Pick bodies

Question 10

Which other neurodegenerative condition is linked with fronto-temporal dementia and what is the causative gene?

Answer 10

MND

C9orf72

Question 11

What are the clinical features of fronto-temporal dementia?

Answer 11

Disinhibition
Apathy (loss of interest)
Lack of empathy
Stereotyped or compulsive behaviours
Hyperorality (putting things in mouth)
Changes in food preferences 
Early loss of insight

Question 12

What would be seen on MRI in fronto-temporal dementia?

Answer 12

Frontotemporal atrophy

Question 13

What would be seen in the CSF of someone with fronto-temporal dementia?

Answer 13

Increased Tau

Normal amyloid

Question 14

Which drugs can be helpful for the behavioural features of fronto-temporal dementia?

Answer 14

Trazadone (antidepressant)

Antipsychotics

Question 15

What is the genetic mutation in Huntington’s disease and what does it cause?

Answer 15

Expansion of CAG trinucleotide repeat on huntingtin gene

–> produces neurodegenerative protein (hungingtin)

Question 16

What are the clinical features of Huntington’s disease?

Answer 16

Early onset dementia (30-50)
Changes in mood/personality
Chorea
Psychosis

Question 17

What is the pattern of inheritance in Huntington’s disease?

Answer 17

Autosomal dominant

Question 18

What would be seen on MRI in Huntington’s?

Answer 18

Loss of caudate heads

Question 19

What are the core criteria for vascular dementia?

Answer 19

1. Presence of cerebrovascular disease

2. Clear relationship between onset of dementia and CVD

Question 20

How do symptoms classically present and progress in vascular dementia?

Answer 20

Sudden onset

Stepwise progression

Question 21

How is vascular dementia managed?

Answer 21

Modify vascular risk factors

+/- cholinesterase inhibitor

Question 22

What is the causative protein in Lewy body dementia?

Answer 22

alpha-synuclein

Question 23

Which pathways are disrupted in Lewy body dementia?

Answer 23

Cholinergic + dopaminergic

Question 24

What are the 3 core criteria for Lewy body dementia?

Answer 24

1. Fluctuating cognition
2. Recurrent visual hallucinations
3. Extrapyramidal features (parkinsonism)

Question 25

What are the treatment options for Lewy body dementia?

Answer 25

Small dose levodopa | Trial cholinesterase inhibitor

Question 26

Who would you refer a patient to if they are over 65 with gradual onset dementia symptoms and no additional neurology?

Answer 26

Old age psychiatry

Question 27

What would warrant a referral to neurology for a patient with dementia symptoms?

Answer 27

- age < 65 - unusual features including speed of onset - additional neurology

Question 28

What are the different components of assessment in a memory clinic?

Answer 28

- history from patient - collateral history from relative - Addenbrook's Cognitive Assessment - MRI (patterns of atrophy)/ SPECT - dementia screen bloods - neuropsychology - possibly CSF

Question 29

What are the dementia screen bloods?

Answer 29

``` B12 TFTs syphilis HIV calcium etc +/- genetic test ```

Question 30

Which screening tests does NICE recommend for dementia?

Answer 30

MMSE - if suspected cognitive assessment | Addenbrookes - improves on initial cognitive assessment

Question 31

How is the MMSE score interpreted?

Answer 31

``` >27/30 = no cognitive impairment <24/30 = supports dementia ```

Question 32

What are the components of the Addenbrookes?

Answer 32

``` Orientation and attention Memory Fluency Language Visuospatial functioning ```

Question 33

How are the Addenbrookes scores interpreted?

Answer 33

>88/100 = likely no cognitive impairment | < 82/100 = supports dementia