21 - Dementia Flashcards
Dementia
Term used to describe a syndrome in which there is progressive decline in multiple areas of function
Features of dementia
Decline in communication skills
Inability to carry out every day tasks
Decline in memory and reasoning
Behavioural and psychological symptoms of dementia
Agitation Aggression Psychosis Depression Sleep disturbance
Types of Dementia
Azheimers Mixed Lewy body dementia Vascular dementia Parkinson's Frontal temporal
Risk Factors for Dementia
Non modifiable - Family history, genetic predisposition, Age, Downs syndrome
Modifiable - Vascular disease RF, Cognitive inactivity, Head injury, depression
Pathophysiology of AD
Extracellularly deposits of B amyloid peptide in senile plaques
Neurofibrillary tangles in cell bodies and neurites
Neuronal cell loss
Loss of cholinergic cells
Genes associated with early onset alzheimer’s disease
APP - ch 21
Presenilin 1 - ch 14
Presenilin 2 - ch 1
Where is APP expressed
Neurones
glial cells
Endothelial and smooth muscle cells
What diseases do mutations in APP produce
Cerebral Amyloid Angiopathy (CAA)
Alzheimers
Which APP mutation decreases AB production and is protective of AD?
A673T
Which secretase enzymes cleave APP to produce the non amyloidogenic pathway
A secretase
Y secretase
Which secretase enzymes cleave APP to produce the amyloidogenic pathway
B secretase
Y secretase
What does PSEN1 code for
Presenilin 1
Subunit of Y secretase responsible fro AB generation
MOst common cause of early onset alzheimers
PSEN1
Genes associated with late onset AD
Apolipoprotein E - ch 19
ApoE2
Rare and protective isoform of APOE
ApoE3
AD risk
APoE4
Greatest AD risk
Decreases clearance of extracellular AB
What are neurofibrillary tangles composed of
Hyperphosphorylated Tau
Normal function of Tau
Stabilise the microtubules
MAPT
Encodes Tau
Mutations not linked to AD - can cause frontaltemporal dementia
What occurs to the cholinergic pathways in AD
Cholinergic forebrain pathways innervating cortical and limbic structures degenerate in AD
Basal forebrain Cholinergic System
Nucleus Basalis of Meynert
Horizontal and vertical diagonal bands of Broca
Medial Septal Nucleus
Treatment for AD
Anticholinesterase inhibitors
NMDA receptor antagonist
Symptomatic - Antidepressents, antipsychotics, mood stabilisers
Anticholinesterase examples
Rivastigmine
Donzepezil
Galantamine
NMDA receptor antagonist example
Memantine
Why does memantine work
AD may be linked to increased excitation
