Dementia Flashcards
Define dementia
Clinical syndrome characterised by a cluster of symptoms manifested by difficulties in memory, language, behavioural, psychological changes and impairments in daily living
What are the common symptoms of dementia?
Memory loss Confusion and disorientation Difficulty with language Changes in mood Social withdrawal Difficulty with day to day tasks
What are the main dementia screening methods?
MMSE - mini mental state exam
GPCOG - GP Assessment of Cognition
MoCA- montreal cognitive assessment
What are the features of the GPCOG?
- Out of 9
- Time orientation (ask date)
- Clock drawing (visuospatial functioning) where you ask them to draw the numbers on a clock and draw a specific time, point for each
- Information - can you tell me something that happened in the news recently
- Recall - give name and address at start of test and ask to repeat at end which totals up to 5 points
What are the scores significant of in GPCOG?
5-8 = mild impairment <4 = cognitive impairment
What are the risk factor of dementia?
Non modifiable: age, genetic pre-disposition, family history, down syndrome
modifiable: vascular risk factors, cognitive inactivity, environment (head injury), depression
What are the types of dementia and which are more common?
- Alzheimers is most common
- Vascular
- mixed
Dementia with Lewy bodies - Parkinson’s and frontotemporal
What is the pathophysiology Alzheimer’s?
- protein misfolding disease (plaque accumulation of protein in brain)
- beta-amyloid plaque deposits = senile plaques form EC
- Tau protein hyperphosphorylates = neurofibrillary tangles in cell bodies
Which genetic changes cause early-onset Alzheimer’s?
- Amyloid Precursor Protein - APP (related to downs syndrome as extra APP = extra synthesis) (chromosome 21)
- Presenilin 1 - PSEN1 (chromosome 14)
- PSEN2 (chromosome 1)
Which genetic changes causing Alzheimer’s are most common?
What do neurofibrillary tangles and senile plaques cause?
- neuritic dystrophy
- synaptic loss
- selective neuronal cell loss
= loss of cholinergic cells
What is the normal pathway of APPs?
- protein expressed in neurons/glial cells/endothelial SM and is involved in neuron growth and repair
- protein cleaved by secretase enzymes
- protein becomes soluble so can be recycled
What are the features of the secretase protein which cleaves amyloid?
PSEN1 and PSEN2 subunits
mutations in these cause Alzheimer’s, PSEN1 most common
What is the diseased pathway of APPs?
- protein is wrongly cleaved by beta and gamma secretases= non-soluble amyloid-beta peptides (most commonly of types 40 and 42)
- peptides aggregate forming senile plaques
What do senile plaques do?
- potentially get between neurons disrupting signalling so therefore impair memory
- start an immune response causing microglia activation
- amyloid angiopathy = haemorrhage risk increased as weakens walls
What is the normal function of the tau protein?
- neurons held together by cytoskeleton which ships nutrients/molecules along the cell
- Tau stabilises microtubules making up cytoskeleton by binding via kinases/phsophates
- encoded by MAPT
What can a mutation in MAPT cause?
MAPT encodes Tau
Mutation can cause fronto-temporal dementia
What is the diseases pathway of Tau?
- oxidative stress from amyloid plaques = dysregulation of kinase activity
- Forms neurofibrillary tangles
- Stop microtubules from signalling = apoptosis
What does kinase do to Tau?
Binds phosphate to tau protein causing it to become tangled (hyperphosphorylation) = neurofibrillary tangles
What genetic changes cause late onset Alzheimer’s?
- associated with Apolipoprotein E
- important in cholesterol metabolism
What are the isoforms of apolipoprotein E?
- ApoE4 poses greatest risk @ chromosome 19
- ApoE2 has protective role
What are the biomarkers of Alzheimer’s disease?
- high amyloid beta peptide levels even before onset of symptoms
in CSF: - decreased amyloid beta levels (as forms in plaques so would be less in CSF)
- increased total tau levels
What are the 2 cholinergic treatments for Alzheimers?
- acetylcholinesterase inhibitors
- NMDA receptor antagonists
What are some examples of acetylcholinesterase inhibitors?
- donepezil
- galantamine
- rivastigmine
