Dementia Flashcards
Define ‘dementia’
A syndrome that may be caused by a number of illnesses in which there is a progressive decline in multiple areas of function, including memory, reasoning, communication and ability to carry out daily activities
What are the non-modifiable risk factors for dementia?
Age, genetic predisposition, family history and Down’s syndrome
What are the modifiable risk factors for dementia?
High cholesterol, hypertension, diabetes, cognitive inactivity, head injury and depression
What are the main types of depression?
Parkinsons, vascular dementia, Alzheimers, dementia with Lewy bodies, frontal temporal dementia and mixed
What are the two components implicated in Alzheimer’s disease?
Neurofibrillary tangles (from hyperphosphorylated Tau protein) and amyloid plaques (B-amyloid peptide)
What are the consequences of neurofibrillary tangles?
These hyperphosphorylated Tau protein segments present in cell bodies and neuritis which causes synaptic loss and dystrophy which leads to significant loss of cholinergic cells
What is ‘early-onset’ Alzheimer’s disease?
When it occurs around 35 years of age
What genes are involved in the development of early-onset Alzheimer’s disease?
Amyloid precursor protein (APP) on chromosome 21, PSEN1 (chromosome 14) and PSEN2 (chromosome 1)
Which chromosome is APP on?
Chromosome 21
Why is there a greater risk of developing Alzheimer’s disease in those with Down Syndrome?
Down syndrome is a trisomy 21 condition, APP (conveys greater risk of early-onset AD) is present on chromosome 21, so there is a greater likelihood of it’s influence
Which chromosome is PSEN1 found on?
Chromosome 14
Which chromosome is PSEN2 found on
Chromosome 1
What is the function of PSEN1/2?
To cleave APP (amyloid precursor protein).
A subunit of gamma-secretase (aspartyl protease) for cleaving APP to Ab peptides
What type of mutation is present in APP/PSEN1/PSEN2 to give rise to early onset Alzheimers?
Missense mutation
Outline the pathogenesis of early-onset Alzheimers disease
Genetic mutation in APP/PSEN1/PSEN2 –> increased proteolysis of APP to Ab peptides or increased production of APP –> accumulation of A-beta peptides in interstitium –> deposition and aggregation to form plaques –> inflammatory response –> microglial activation and astryocytosis –> altered metabolism, damage, oxidative stress and altered kinase/phosphatase activity –> hyperphosphorylation of Tau –> tangles –>neuronal dysfunction and death in hippocampus and cerebral cortex
What is ‘late onset’ Alzheimer’s?
Occurs in those aged 60
What gene is associated with late-onset Alzheimers disease?
Apolipoprotein E on chromosome 19
By what two pathways may APP be cleaved?
Non-amyloidogenic: by alpha or gamma secretes
Amyloidogenic: by beta and gamma secretase to make amyloid peptides (Abeta)
How does the presence of ApoE4 affect a persons chance of developing Alzheimers?
ApoE4 increases risk for late-onset AD as it decreases the clearance of extracellular amyloidogenic Ab peptides which contribute to plaque formation
Which iso form of ApoE may be neuroprotective against late-onset Alzheimers disease?
ApoE2
How may Alzheimers disease be diagnosed from CSF?
Amyloid decreases in CSF and more hyperphosphorylated tau in the CSF
Explain how acetylcholinesterase inhibitors may be used in the treatment of Alzheimers disease
Increase cholinergic stimulation in the forebrain –> stimulates cortical and limbic structures
What type of drugs are donepezil, galantamine and rivastigmine?
Acetylcholinesterase inhibitors
What type of drug is memantine?
NMDA receptor antagonist
