PBL 5: I'm Losing My Mind Flashcards
Define dementia
Progressive neurodegenerative disease, characterised by deterioration of intellect, behaviour and personality. It comes as a consequence of disease affecting the cerebral cortex and hippocampus
What is a cholinesterase inhibitor?
AChE inhibitors prevent the breakdown of AChE
What are physical signs and symptoms of dementia?
Tremor Balance problems Speech and swallowing difficulties Wandering Visual issue
What are behavioural and psychological S+S of dementia?
Agitation Short-term memory loss Depression Disorientation and confusion Agitation Aggression Sleep disturbances Mood swings Psychosis
Risk factors of dementia?
Age Genetics Downs syndrome High cholesterol Diabetes Environment (trauma) Depression
What classification of dementia is there?
Alzheimer's disease Vascular dementia Mixed AD and vascular Lewy body dementia Frontal-temporal/Pick's disease Immunologically mediated (HIV/AIDS)
What is the presentation of Alzheimer’s disease?
Pre-dementia -> early -> moderate -> late
What symptoms worsen in Alzheimer’s disease?
Memory deficits
Impaired judgement and thought collection
Mood changes
Unusual behaviour acts
What is Alzheimer’s characterised by?
Formation of senile neuritic plaques from aggregations of beta amyloid peptide
What else is presented in Alzheimer’s apart from senile neuritic plaques?
Neurofibrillary tangles which are deposits of hyperphosphorylated tau proteins
What happens to structurally in AD?
neuronal loss
cerebral atrophy
loss of cholinergic projections
What are Amyloid precursor protein?
Gene responsible for making transmembrane, which can be cleaved to make amyloid-beta peptides (39-43 AA) in length
What usually cleaves APP?
Alpha-secretase then gamma secretase
What happens in AD with APPs cleaving wise?
Cleaved by beta-secretase then gamma secretase
What happens to the APP pathway in AD producing?
Beta-amyloid peptides (usually 42AA long) which aggregate to form senile plaques
What is presence of beta-amyloid plaques due to
formation of oligomers from peptides
What is a characteristic of oligomers which causes what?
Toxic leading to neuronal cell death as they are failed to be cleared away
What is the function of microglia?
recognise misfolded proteins which triggers inflammatory response
What do cytokines do?
Cause oxidative stress which alters activity of kinase and phosphorylation
What happens after activity of kinase and phosphorylation is altered?
Phosphorylation of tau proteins
What do tau proteins do?
Stabilise microtubules in brain
THEY ARE NOT USUALLY PHOSPHORYLATED
What does phosphorylation of tau do?
Regulate its ability to bind to and stabilise the microtubules
What happens when tau becomes hyperphosphorylated?
Detaches from microtubules
What do hyperphosphorylated tau proteins form?
neurofibrillary tangles in cell bodies
What do neurofibrillary tangles do?
Impair axonal transport processes -> neuronal death + synapse loss
What are the subunits of gamma secretase?
PSEN 1
PSEN 2
What is related to early onset AD?
APP mutations
PSEN 1/2 (mainly 1)
Where is PSEN 1 coded for?1
chromosome 44
Where is PSEN 2 coded for?
chromosome 1
Where do APOE4 mutations occur?
chromosome 19
Which gene has relations to late onset AD?
APOE4
What is APOE4 responsible for?
Clearance of beta-amyloid peptides
Where is APP coded for?
Chromosome 21
What is the Ach pathway?
Cholinergic forebrain pathways degenerate in AD so inhibit the breakdown of Ach by Ach inhibitors to increase Ach levels
How to diagnose AD?
History + clinical presentation
MRI, PET or CT scans to image cerebral cortex
What CSF biomarkers in AD?
Tau protein levels raised
Beta amyloid levels reduced
What blood tests results may occur in dementia?
B12 deficiency
hypothyroidism
What brain imaging can occur in dementia?
Compare hippocampal/ temporal loss in AD compared to frontal-temporal loss in other forms
What brain regions are affected in AD?
Hippocampus in temporal lobe
What are two processes of cellular plasticity linked with learning and memory?
Long term potentiation and long term depression
What transmission are LTP and LTD?
glutamatergic transmission
What do LTP do?
LTP strengthen synapses based on recent activity
What do beta-amyloid plaques do to LDP?
increases LDP
reduces LTP
What drugs are given for cholinergic pathway?
Donepezil
Rivastigmine
Galantamine
What management of AD can be used?
Beta amyloid vaccine
ACh inhibitor
Anti-glutamatergic agents
Why give anti-glutamatergic agents?
AD is associated with slow form of excitotoxicity involving glutamate
What is excitotoxicity caused by in AD?
Influx of Ca2+ causing oxidative stress
What is a NMDA receptor antagonist?
Memantine
What are non-pharmalogical treatments of AD?
Cognitive stimulation therapy
Music therapy
Counselling
Reminiscent therapy
