T1 L15: Dementia - Neurobiology and clinical aspects Flashcards
What is the prevalence of different types of dementias?
50-60% Alzheimer's disease 15% Vascular dementia 10-15% Lewy body dementias 1-2% Frontotemporal lobar degeneration Mixed cases alcohol related (ARBI)
What are the presenting symptoms of dementia?
Forgetfulness Difficulty learning new things Giving up hobbies and interests Getting muddled in new situations Difficulty finding words Difficulty handling bills Social withdrawal Personality change Circadian rhythm disturbance Weight loss Poorly controlled medical conditions
What are some Microscopic changes in the brain due to dementia?
- Intraneuronal inclusion bodies (Lewy bodies)
- Extra neuronal changes (Amyloid-beta plaques)
What are some macroscopic changes in the brain due to dementia?
- Region specific atrophy
- Generalised brain atrophy
- Enlarged ventricles
Which structure is one of the first to shrink with Alzheimer’s?
The hippocampus
Which proteins create the neuropathological mechanism of dementia?
Beta-amyloid, Tau, TDP43, FUS, alpha-synuclein, and prion protein
What is the pathophysiology behind Alzheimer’s disease?
Beta-amyloid and Phosphorylated Tau cause cell loss, plaques, and tangles that impact neurotransmitters and result in cognitive deficits
What are the 2 types of products from the amyloid precursor protein and what is their clinical significance?
Alpha-secretase and beta-secretase create alpha and beta amyloids.
Only the beta-amyloids go on to from amyloid plaques
What is the Tau pathology behind Alzheimer’s disease?
The formation of it is normal but during phosphorylation, Tau will detach from the microtubules. Hyperphosphorylation of Tau will therefore cause accumulation of Tau-P that destabilises microtubules
What is Braak staging used for?
To classify the degree of pathology in Parkinson’s disease and Alzheimer’s disease
What is the nucleus Basalis?
A somewhat diffuse collection of large cholinergic neurons in the basal forebrain
What are some risk factors for Alzheimer’s?
Age, Vascular risk factors, lack of exercise, low level of education, diet, family history, genetics
What is familial Alzheimer’s disease?
Mutation in 3 genes that causes Alzheimer’s disease
What are some atypical presentations of Alzheimer’s disease?
Posterior cortical atrophy (PCA), Logopenic aphasia, behavioural (frontal) Alzheimer’s disease
What are some typical presentations of Alzheimer’s disease?
Impaired episodic memory Visuospatial dysfunction Word-finding difficulties Visual perceptual/spatial difficulties Apraxia Difficulties in arrhythmic Difficulties reading/spelling Apathy Behavioural problems
What are alpha-synucleinopathies?
Lewy bodies
What is Lewy body dementia?
Dementia and Parkinson’s disease together
Where are Lewy bodies found in patients?
Found in dopaminergic neurons of the substantia nigra
What is the gene behind familial Parkinson’s disease?
alpha-synuclein gene
Where is alpha-synuclein found?
Localised in the cytosol of mitochondria
What are some clinical features of Lewy body dementia?
- Progressive cognitive decline like in ordinary dementia
- Disproportionate attentional, executive, and visual processing deficits related to memory and naming
- REM sleep behaviour disorder
- Spontaneous features of Parkinsonism
- Recurrent visual hallucinations, typically well formed and detailed
What are some clinical presentations of Frontotemporal Lobar Degeneration (FTLD)?
Classical syndromes:
Behavioural variant
Progressive non-fluent aphasia
Sematic dementia
Motor disorders:
Parkinsonian syndromes
Motor neurones disease
These are all diseases affecting the frontal temporal lobe
What are the 3 main pathological proteins behind Frontotemporal Lobar Degeneration (LTLD)?
Tau, TDP43, and FUS
What is the Fazekes scale?
Used to quantify the amount of white matter T2 hyperintense lesions usually attributed to chronic small vessel ischaemia
It can be used to measure vascular dementia progression
What is Vascular dementia?
It’s not a neurodegenerative dementia. It’s caused by vascular pathologies that interact with neurodegenerative changes
It can be caused as a result of ischaemic or haemorrhagic brain damage
What are the 3 most common mechanisms behind vascular dementia?
- Single, strategically placed infarcts
- Multiple cortical infarcts
- Subcortical small-vessel disease
What causes Huntington’s disease?
It’s an autosomal dominant mutations in the Huntingtin gene on chromosome 4
What are some early symptoms of Huntington’s disease?
Chorea Anxiety Depression Apathy Irritability Disinhibition Psychosis Compulsive behaviour
What are the 2 types of prion?
Sporadic creutzfeldt-jakob disease that develops within the body
And variant creutzfeldt-jakob disease that is ingested
When is the peak age of onset for sporadic CJD?
55-75 years
What is the pathology behind CJ disease?
The transformation of the normal cellular prion protein PrP into an abnormal, structurally changed, disease-causing form
How is CJ disease diagnosed?
History Examination Blood screen cognitive screen neurological examination neuroimaging fluid biomarkers
What is the treatment for creutzfeldt-jakob disease?
There is no cure.
Only some symptoms can be treated Eg. psychiatric drugs
What are some ways of preventing dementia?
Minimise diabetes, treat hypertension, prevent head injury, stop smoking, reduce air pollution, reduce midlife obesity - to reduce neuropathological damage
Exercise, reduce occurrence of depression, avoid excessive alcohol, treat hearing impairments, maintain social contact, and attain high level of education - to maintain and increase the cognitive reserve
