9.1.1 Dementia

Question 1

What is dementia?

Answer 1

Chronic, progressive syndrome insidious onset

Question 2

What are the cognitive symptoms of dementia?

Answer 2

Impaired:
- Memory (temporal)
- Orientation (temporal)
- Learning capacity (temporal)
- Judgement (frontal lobe)

Question 3

What are the non-cognitive symptoms?

Answer 3

Behavioural symptoms
Depression and anxiety
Psychotic features
Sleep symptoms

Question 4

What are some examples of behavioural symptoms of dementia?

Answer 4

Agitation
Aggression (frontal lobe)
Wandering
Sexual disinhibiton (frontal lobe)

Question 5

What are some examples of psychotic features?

Answer 5

Visual and auditory hallucinations
Persecutory delusions (false beliefs)

Question 6

What are some examples of sleep symptoms of parkinson’s?

Answer 6

Insomnia
Daytime drowsiness (decreased cortical activity)

Question 7

How is dementia diagnosed?

Answer 7

By exclusion
Look for features of progressive cognitive decline, impairment of daily living in a patient with normal concscious level

Exclude delirium

Question 8

What are some organic causes of cognitive decline?

Answer 8

• Hypothyroidism
• Hypercalcaemia
• B12 deficiency
• Normal pressure hydrocephalus:
  Abnormal gait
  Incontinence
  Confusion

Question 9

What are the different types of dementia?

Answer 9

Alzheimer’s disease
Vascular dementia
Lewy body dementia
Frontotemporal dementia
AIDS dementia complex

Question 10

What are the pathological features of Alzheimer’s disease?

Answer 10

Macroscopic
- Global cortical atrophy
- Sulcal widening
- Enlarged ventricles (mainly lateral and third affected)

Microscopic
- Plaques, made of amyloid beta
- Tangles, hyperphosphorylated tau

Question 11

What are the different types of Alhzeimer’s disease

Answer 11

Sporadic
- 90-95%,
- 1% of 60 year olds, 50% of 85 year olds

Familial
- 5-10%
- Early onset dementia
- PSEN 1/2 genes, mutation of gamma secretase

Trisomy 21
- Disease may present as early as 40

Question 12

How do plaques form?

Answer 12

Amyloid precursor protein normally repairs neurones following damage

APP is replaced periodically, it is chopped up by alpha and gamma secretase normally into soluble parts

If beta secretase gets involved, resulting parts of APP are no longer soluble

Insoluble peptides accumulate outside the cell forming beta amyloid plaques, fillnig space between neurones and reducing signal transmission

Question 13

What do plaques do within the brain?

Answer 13

Can induce inflammatory response killing neurones, accumulation around blood vessels and reduced signal transmission

Neurogenesis is limited in the CNS, neurones that die are unlikely to be replaced

Question 14

How do tangles form?

Answer 14

Tau proteins stabilise microtubules in neuronal cytoskeleton- within the cell

Beta amyloid plaques outside neurone cause hyperphosphorlyation of tau proteins

Shape change of tau proteins, no longer able to support cytoskelton

Tau proteins aggregate forming tangles intracellular accumulation

Neuron death

Question 15

Why is there doubt that plaques and tangles cause Alzheimer’s?

Answer 15

New drug, Aducanumab

Targets and removes amyloid plaques, evidence for its effective is minimal

Does not seem to make improvement in alzheimer’s symptoms

Question 16

What neurones are affected primarily in alzheimers?

Answer 16

Cholinergic
Noradrenergic
Serotonergic

Somatostatin expressing neurones

Question 17

How is mental state assessed in Alzheimer’s?

Answer 17

Mini-mental state exam

30 points, higher the better

21-26 mild
15-20 moderate
10-14 moderately severe
< 10 severe

Question 18

What happens in vascular dementia?

Answer 18

Cognitive impairment caused by cerebrovascular disease

(mutliple small strokes)

Question 19

What are the risk factors of vascular dementia?

Answer 19

Same as any other vascular disease:
- Previous stroke/MI
- Hypertension
- Hypercholesterolaemia
- Diabetes
- Smoking

Question 20

How does vascular dementia present?

Answer 20

Stepwise, may have focal neurological features

Question 21

What is the relation of lewy body dementia to parkinsons?

Answer 21

Essentially the same disease

If movement disorder is followed by dementia- Parkinsons

If dementia is followed by movement disorder- Lewy body dementia

Question 22

What is the pathophysiology of lewy body dementia?

Answer 22

Aggregation of alpha synuclein
-Forms spherical intracytoplasmic inclusions
-Forms deposits across the brain

Question 23

Where does alpha synuclein deposit across the brain?

Answer 23

Substantia nigra
Temporal lobe
Frontal lobe
Cingulate gyrus

Alpa synuclein can be labled used imaging

Question 24

How does Lewy body dementia present?

Answer 24

• Fluctuating cognition and alertness
• Vivid visual hallucinations- often small people and furry animals
• Depression
• REM sleep disorders, sleep walking/talking
• Parkinsonian features - may lead to falls

Question 25

Why do you not give antipsychotics in lewy body dementia?

Answer 25

Can cause neuroleptic malignant syndrome-psychiatric emergency

Treat with levodopa or symptom basde treatment

Question 26

What happens in neuroleptic malignant syndrome?

Answer 26

• Fever
• Encephalopathy (confusion)
• Vital signs instability, tachycardia, tachypnoea, fluctuating BP
• Elevated creatine phosphokinase
• Rigidity- due to dopamine antagonism

Question 27

What causes frontotemporal dementia?

Answer 27

Frontal and temporal lobe atrophy

Question 28

What are the symptoms of frontal lobe dysfunction?

Answer 28

Symptoms are related to frontal lobe dysfunction:
- Behavioural disinhibition
- Inappropriate social behaviour
- Loss of motivation without depression- caused by damage to anterior cingulate cortex
- Repetitive/ritualistic behaviours
- Non-fluent aphasia

Question 29

Why is AIDS dementia complex increasing?

Answer 29

Patients with HIV infection live longer due to modern treatment

Chance of developing AIDs associated dementia is increasing

Question 30

What is the pathophysiology of AIDs dementia complex?

Answer 30

HIV infected macrophages into the brain is thought to lead to indirect neurone damage

Question 31

How does AIDs dementia progress?

Answer 31

Insidious onset, rapid progression once established

Question 32

What are the clinical features of AIDs dementia?

Answer 32

Related to global damage, also some manifestations of cerebellar involvement :
- Cognitive impairment
- Psychomotor retardation (slow thoughts and movements- also in depression)
- Tremor
- Ataxia
- Dysarthria
- Incontinence

Question 33

How is AIDs dementia managed?

Answer 33

Using the bio-psycho-social model

Question 34

What is the biological management of AIDs dementia?

Answer 34

Acetylcholinesterase inhibitors:
- Donepezil
- Rivastigmine
- Galantamine

Mild effect for Alhzheimers too

NMDA antagonists
- Memantine

Useful for treating agitation

Question 35

Why are there few psychological treatments available for dementia?

Answer 35

Due to its progressive nature

Question 36

What is the social management of dementia?

Answer 36

• Explain diagnosis sensitively
• Talk about problems that will come and how to manage
• Give results of any special invesitgations
• Driving- difficult as patients want to maintain independence
• Finances, will and power of attorney
• Day care and respirate care- support and allow careres to rest
• Residential/ nursing home placement