Pathophysiology + Pharmacology of Dementia Flashcards
What are the different types of dementia?
Alzheimer’s
Lewy body dementia
Vascular dementia
Front temporal dementia
Parkinson’s/ Huntington’s
What are the type of dementia characterised?
Accumulation + aggregation of misfolded proteins
What is the protein for Alzheimer’s?
Tau
Amyloid-beta
What is the protein for Lewy body?
Alpha-syn
When can you officially diagnose dementia?
After death, when receive brain tissue
What is seen in the brain with Alzheimer’s disease?
Enlargement of lateral ventricle
Severe atrophy of medial temporal lobe
Enlargement of inferior horns of ventricle
Thinning of gyri + deepening of sulci
What is amyloid-beta?
Amyloid precursor protein
= forms extracellular plaque + accumulates around blood vessels
What is tau?
Stabilise microtubules
Phosphorylated under disease conditions
= destabilise microtubule network
What is neuritic plaques?
Core = amyloid-beta
Distended halo = tau
What does Lewy Body dementia manifest with?
Parkinson’s Disease
What does the brain look like with Lewy Body dementia?
Depigmentation of substantia nigra
What is vascular dementia?
Cognitive impairment in context of altered cerebral flow
eg. after a stroke
What is neuronal loss mirrored by?
Loss of brain weight
What are the mainstay of dementia therapeutics?
Acetylcholinesterase inhibitors
What does acetylcholinesterase inhibitors do?
Stop the breakdown of Ach
= stay for longer
What are examples of acetylcholinesterase inhibitors?
Donepezil
Rivastigmine
Galantamine
What is 1st line?
Donepezil
What is the risk of Donepezil?
Neuroleptic malignant syndrome
What is the risk of Rivastigmine?
Atrial fibrillation
Depression
Agression
What is the risk of Galantamine?
Not indicated for patients with hepatic or renal dysfunction
What are the drawbacks of AChEIs?
Not disease-modifying
ACh is not only the system effected
What is alternative to AChEIs?
Memantine
What is Memantine?
NDMA receptor antagonist
= inhibits excitotoxic glutamatergic signalling + reduce neurodegeneration
When is Memantine more effective?
When combined with AChEIs
What does Lecanemab do?
Targets amyloid-beta when it is just starting to stick together
