What is the pharmacological management options for alzhimers dementia ?
- 1st line = donepezil (used 1st), rivastigmine or galantamine (cholinesterase inhibitors) - licensed for mild to moderate alzhimers
- 2nd line = Memantine (AChE inhibitors are not tolerated or are contra-indicated, can also be used in conjunction with cholinesterase inhibitors) - licensed for moderate to severe alzhimers
What are the general behavioural and psychological symptoms which can be experienced in dementia ? (BPSD)
- Hallucinations - note for exam purposes that hallucinations esp visual may be trying to suggest DLB
What is the mechanism of action of cholinesterase inhibitors and how do they help in alzhimers and DLB and dementia in parkinosons?
block the action of acetylcholinesterase, an enzyme that removes acetylcholine from the synapse ==> increasing the levels and action of ACh
They slow cognitive decline, treat BPSD
Recall that ACh neurones degenerate in alzhimers dementia as it progresses hence this slows down progression
What are the side effects of cholinesterase inhibitors ?
•GI (nausea and diarrhoea most common), headache, muscle cramps, bradycardias, worsen COPD/asthma
What are the contraindications to use of cholinesterase inhibitors and what should be checked prior to putting someone on one ?
- Check pulse before prescribing/ before dose increase
- Contraindicated in people with active peptic ulcer or severe asthma/COPD
What is the pharmacological management of DLB and dementia in parkinsons (DPD)?
- Cholinesterase inhibtor - rivastigmine is the only recommended one
- Has the same function and effect as in alzhimers disease
What is treatment of vascular dementia ?
Modifying vascular risk factors and stroke prevention (so essentially stroke prevention treatment covered in other lectures)
There is no fancy drugs tho like in alzhimers or DLB and DPD
What is the treatment of frontotemporal dementia ?
What is the mechanism of action of mametine and what are its potential side effects ?
It works by blocking NMDA-type glutamate receptors. Glutamate is the main excitatory neurotransmitter in the brain and it is thought that neurons are damaged by glutamate over-activation in Alzheimers as well as in many other neurodegenerative disorders. It is normally well tolerated even by frail patients.
It works by Slowing cognitive decline, may treat BPSD
Well-tolerated- may cause hypertension (check BP before starting), sedation, dizziness, headache, constipation
What are the potential CT/MRI and SPECT findings in alzhimers dementia ?
CT/MRI - may be normal in the early stages, in the later stages may show medial temporal lobe atrophy and temporoparietal atrophy
SPECT scan shows decreased uptake in the posterior cingulate gyrus, parietal and medial temporal lobes
What are the characteristic CT/MRI and SPECT findings suggestive of vascular dementia ?
- CT/MRI shows moderate-severe small vessel disease or multiple lacunar infarcts
- SPECT scan shows - patchy reduction in tracer uptake throughout the brain
What are the characteristic CT/MRI and SPECT findings suggestive of frontotemporal lobe dementia?
- CT/MRI shows frontotemporal atrophy
- SPECT scan shows reduction in uptake in the frontotemporal lobes
What is the characteristic appearance on SPECT scan of DLB ?
Reduction in uptake in occipital lobe
What scan will be positive in both DLB and DPD (also parkinsons for that matter but talking about dementia here)
DAT scan will be positive
This looks at the level of dopamine receptor cells in the brain. In parkinsons disease the dopamine cells degenerate causing problems with movement e.g. walking & dexterity
Essentially a diagnostic test for parkinsons which is positive in these 2 dementias as parkinsons is present (DPD is actually not a dementia but parkinsons which has got dementia)
How do you differentiate between DLB and DPD (dementia in parkinsons) as the clinical presenting features when first seeing someone will be pretty much the same ?
- In DLB the signs of parkinsonism can only be present for <1yr before the signs of dementia
- In DPD the signs of parkinsonism need to have been present for > 1yr before the signs of dementia occur otherwise it is DLB
How common is DPD ?
80% of people with parkinsons will develop dementia within 15-20yrs from diagnosis
What are the characteristic pathological features indicative of alzhimers dementia ?
Widening of sulci and narrowing of gyri due to frontal, temporal and parietal lobe atrophy, can see compensatory dilatation of the lateral ventricles
Note that the occipital lobe spared, brainstem and cerebellum normal
2 main hallmarks:
- Beta-Amyloid = insoluble AB agg extracellular, encoded for by APP gene
- Neurofibrillary Tangles = insoluble agg of hyper-phos tau protein inside neuron
There is also extensive neuronal loss resulting in loss of ACh neurotransmitter mainly
What is the first area in the brain to be affected by the pathological processes of alzhimers disease?
The nucleus basalis of Meynert in the basal forebrain
The nucleus basalis is the main source of acetylcholine for the cortex.
What scoring system can be used to quickly and easily help differentiate between vascular dementia and alzhimers ?
Hachinski Ischaemic Score.
A score of 4 or less for Alzheimers and 7 or more for vascular dementia has a sensitivity of 89% and specificity of 89%