Dementia Neurobiology Flashcards
In order to diagnose dementia you need?
6 months of memory decline or other cognitive abilities
And progressive character
What percent of dementia is Alzheimer’s?
50-60%
What are the changes in dementia?
Intra neuronal inclusion bodies, lewy and picks
Extra neuronal inclusion bodies e.g amyloid beta plaques/ tau
Atrophy brain region
Enlarged ventricles
Misfolding of protein in brain?
B amyloid
Abnormal accumulation that is due to?
Tau
Amyloid precursor protein to plaque generation?
If done by the beta secretase then gamma secretase which will give you AB peptide, forming a plaque
Paired helical filaments are made of?
Phosphorylated tau
Tau is normally important for?
Stabilising Microtubules
Braak and braak staging?
Transentorhinal 1 and 2
Limbic 3 and 4
Isocortical 5 and 6
Which neurons and where are they atrophied in AD?
Cholinergic neurons in nucleus basalis
Risk factors for Alzheimer’s?
Age Vascular risk factors Lack of exercise Low level of education Diet Family history Genetic
What is atypical presentation of AD?
Posterior cortical atrophy
Logopenic aphasia
Behavioural frontal AD
Lewy body dementia contains 2 types?
Dementia with a Lewy bodies
Parkinson’s disease dementia
How common is LBD?
2nd most common with 23% of people
Lewy bodies are found where?
Dopaminergic neurons of substantia nigra in about 90% of patients with PD
What are Lewy bodies made of?
Alpha synuclein
Where is alpha synuclein normally found?
In cytosolic and mitochondria, mostly in neuronal cells some glial
Why is alpha synuclein important?
Interaction with microtubule network
Involved in synaptic vesicle formation
Catecholamine metabolism in DA ergic neurons
Ca homeostasis
What is alpha synuclein encoded by?
SNCA gene in 3 splicing isoforms
What is the staging of PD alpha synuclein
- Autonomic and olfactory disturbances
- Sleep and motor disturbances
- Emotional and cognitive disturbances
CLINICAL PRESENTATION OF DLB?
Essential feature - dementia defined as progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational function or with usual daily activities.
• Disproportionate attentional, executive and visual processing deficits relative to memory and naming.
• Fluctuating cognition with pronounced variations in attention, alertness and arousal
• Recurrent visual hallucinations, typically well formed and detailed
• REM sleep behaviour disorder
• Spontaneous features of parkinsonisM
Frontotemporal lobar degeneration?
Classical syndromes:
Semantic dementia
Progressive non-affluent aphasia
Behavioural variant FTD
Motor disorders:
Parkinsonian syndromes
Motor neuron disease
What is the second most common neurodegenerative dementia after AD in people under 65?
FTLD
Pathologies in TFLD?
Atrophy of frontal and temporal lobes
Tau, TDP43 and FUS
Vascular dementia is not…?
Neurodegenerative dementia
What can vascular dementia be due to?
Ischaemia or haemorrhagic brain damage
Common mechanisms causing vascular dementia?
Single strategically placed infarcts
Multiple cortical infarcts
Subcortical small vessel disease
Huntington’s disease due to?
Autosomal dominant mutation in Huntington gene on chromosome 4, chroea, cognitive and behavioural symptoms
neuropsychiatric syndrome includes anxiety and depression, apathy, irritability, disinhibition, psychosis, compulsive behaviou
Cognitive impairment in HIV?
Rare with antiretroviral treatment 2%
A prion can?
Adopt 2 conformational states, one of which is self-perpetuating
Prions account for what percent of creutzfeldt Jakob disease?
85
Incidence of CJD?
1 per million
Prion disorder due to varian CHD is caused by?
Eating BSE or blood transfusion
People with prion disease, variant cjd show?
Pulvinar sign- hyperintensity of pulvinar nuclei
Painful paraesthesisas
Psychiatric prodrome
Recent licensing for dementia drug?
Aducanumab
