9.1.1 Dementia Flashcards
What is dementia?
Chronic, progressive syndrome insidious onset
What are the cognitive symptoms of dementia?
Impaired:
- Memory (temporal)
- Orientation (temporal)
- Learning capacity (temporal)
- Judgement (frontal lobe)
What are the non-cognitive symptoms?
Behavioural symptoms
Depression and anxiety
Psychotic features
Sleep symptoms
What are some examples of behavioural symptoms of dementia?
Agitation
Aggression (frontal lobe)
Wandering
Sexual disinhibiton (frontal lobe)
What are some examples of psychotic features?
Visual and auditory hallucinations
Persecutory delusions (false beliefs)
What are some examples of sleep symptoms of parkinson’s?
Insomnia
Daytime drowsiness (decreased cortical activity)
How is dementia diagnosed?
By exclusion
Look for features of progressive cognitive decline, impairment of daily living in a patient with normal concscious level
Exclude delirium
What are some organic causes of cognitive decline?
- Hypothyroidism
- Hypercalcaemia
- B12 deficiency
- Normal pressure hydrocephalus:
Abnormal gait
Incontinence
Confusion
What are the different types of dementia?
Alzheimer’s disease
Vascular dementia
Lewy body dementia
Frontotemporal dementia
AIDS dementia complex
What are the pathological features of Alzheimer’s disease?
Macroscopic
- Global cortical atrophy
- Sulcal widening
- Enlarged ventricles (mainly lateral and third affected)
Microscopic
- Plaques, made of amyloid beta
- Tangles, hyperphosphorylated tau
What are the different types of Alhzeimer’s disease
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
How do plaques form?
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
What do plaques do within the brain?
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
How do tangles form?
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
Why is there doubt that plaques and tangles cause Alzheimer’s?
New drug, Aducanumab
Targets and removes amyloid plaques, evidence for its effective is minimal
Does not seem to make improvement in alzheimer’s symptoms
What neurones are affected primarily in alzheimers?
Cholinergic
Noradrenergic
Serotonergic
Somatostatin expressing neurones
How is mental state assessed in Alzheimer’s?
Mini-mental state exam
30 points, higher the better
21-26 mild
15-20 moderate
10-14 moderately severe
< 10 severe
What happens in vascular dementia?
Cognitive impairment caused by cerebrovascular disease
(mutliple small strokes)
What are the risk factors of vascular dementia?
Same as any other vascular disease:
- Previous stroke/MI
- Hypertension
- Hypercholesterolaemia
- Diabetes
- Smoking
How does vascular dementia present?
Stepwise, may have focal neurological features
What is the relation of lewy body dementia to parkinsons?
Essentially the same disease
If movement disorder is followed by dementia- Parkinsons
If dementia is followed by movement disorder- Lewy body dementia
What is the pathophysiology of lewy body dementia?
Aggregation of alpha synuclein
-Forms spherical intracytoplasmic inclusions
-Forms deposits across the brain
Where does alpha synuclein deposit across the brain?
Substantia nigra
Temporal lobe
Frontal lobe
Cingulate gyrus
Alpa synuclein can be labled used imaging
How does Lewy body dementia present?
- 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
