4 types of dimentia and cause
Alzheimer’s disease -Amyloid plaques and NF tangles
Vascular Dementia - Disease/damage to blood vessels of brain
dementia with lewy bodies - lewy bodies intracellular
fronroremporal demntia – Atrophy in frontal and temporal lobes and Accumulation Tau, TDP-43 and FUS
6 non-cognative symptoms
- Depression
- Delusion
- Anxiety
- Aggression
- Sleep disturbances
- Disinhibition
6 cognative symptoms
- Memory loss
- Failing intellect
- Poor concentration
- Language impairment
- Disorientation/confusion
6 differntial diagnosis
- Vitamin deficiency (B)
- Thyroid problems
- Delirium
- Infection
- Anxiety
- Brain Tumour
- Depression
- Diabetes
3 pathology of brain
- extreme shrinkage of cerebral cortex
- extreme shrinkage of hippocampus
- severely enlarged ventricles
2 hallmarks
- amyloid plaques
- neurofibrillary tangles
6 risk factors
- age over 65
- head injury
- diabetes
- smoking
- drinking
- education
- vascular disease
- history of stroke
3 key genes of alzheimers
APP, PSEN1,PSEN2
how app mutation casues
cleave by beta secretase and gamma secretase creating a A beta this forms amyloid plaques
6, amyloaid cascade hypothesis
- increased Ab production and decreased Ab degradation
- increased Ab accumulation
- amyloid b oligomerisation and deposition
- inflammatory response (glial cells)
- synapse loss
- oxidative stress
- ca2+ overload and neuronal death
3 drug types to target APP processing and what they target
- B secretase- BACE-1 inhibitor
- gamma secretase - gamma secretase modulators and inhibitors
- A-secretase - a secretase activation
3 current pharmacological signalling
- cholinergic signalling
- glutamatergic signalling
- anti-amyloid monoclonal antibody
4 points of cholinergic hypothesis and how to treat
- ACh important excitatatory neurotransmitter
- Important for learning and memory
- Loss of cholinergic neurons and signalling in AD
- Cholinergic hypothesis of AD
- Therapy: boost ACh signalling
3 Acetylcholinesterase Inhibitors
- Donepezil (tablet, orodispersible, solution)
- Galantamine (tablet, MR-capsule, solution)
- Rivastigmine (capsule, solution, TD patch)
galantamine how work
- Improve cognitive function by increasing cholinergic signalling
- Not disease-modifying
- Only a subset of patients respond
Rivastigmine side effects and MOA
- Effect reduces as neuronal damage increases
- High doses have side effects e.g., nausea, vomiting, diarrhoea
glutamergic hypothesis and how treat
- Glu important excitatory neurotransmitter
- Important for learning & memory, cognition, and synaptic plasticity
- In AD, excess glut and excitotoxicity and neuronal loss
- Therapy: Reduce Glutamatergic signalling
NMDAR antagonist how work and example
- Memantine
- Non-competitive antagonist at NMDA receptors.
- Improves cognitive functions
3 drugs for mild Alzheimer’s disease and moderate Alzheimer’s disease
- Donepezil
- Galantamine
- Rivastigmine
1 drug moderate for Alzheimer’s disease for people who cannot take AChE inhibitors, severe Alzheimer’s disease, In combination with AChEi*
memantine
4 meds for Behavioural and Psychological Symptoms of Dementia - BPSD
- Hallucinations
- Misperceptions
- Aggressive behaviour
- Depression
example of sedative and when to use
For challenging behaviour: violence, aggression, severe agitation: i.m. Lorazepam, Haloperidol or Olanzapine
antidepressants to avoid and when use
- Antidepressants
- People with dementia who also have major depressive disorder can be offered antidepressant medication
- Avoid certain TCA and MAOI as they have anticholinergic properties
aducanumab MOA
- a monoclonal antibody that removes amyloid plaques.
- A key issue is whether the amyloid clearance protects patients from cognitive and functional decline
