Alzheimer's Flashcards
is Alzheimer’s progressive or reversible
progressive and non reversible
onset of Alzheimer’s
insidious
what age is classified as early onset Alzheimer’s
<65
how may early onset Alzheimer’s presentation vary
may be atypical
are genetic factors or environemental factors more important in the development of early onset/Alzheimer’s
early onset, thinking genetic factors - maybe a mutation
population risk for AD is more due to multifactorial - genes, environement etc
look at ice Berg triangle
are females or males more likely to get Alzheimer’s
females
genetics of AD - which 3 mutations are associated
- multifactorial, but increased risk with 1st degree relative (25%)
- APP gene mutation - produces amyloid precuros protein, excess leads to formation of beta amyloid palques and tau tangles
- PSEN genes
- Inheriting Apoe4
do lifestyle factors have an influence on the development of Alzheimer’s
yes, smoking midlife obesity, diet high in sat fats are risk factors
also, diabetes, smoking in mid-life, hypertension are found to be the greatest modifiable risk factors for dementia.
cerebrovascular disease and Alzheimer’s
is a strong risk factor for vascular dementia, which often overlaps with Alzheimer’s
diabetes increases the risk of both
Down’s and Alzheimer’s
Down’s is assoicated with early onset Alzheimer’s
the presence of 3 copies of the APP gene on chromosome 21 accounts for this
which allele is a risk factor for Alzheimer’s
ApoE e4 allele
which 3 things point towards a familial cause o disease
early onset
atypical form
relatives affected
senile plaques
EC deposits of amyloid beta in grey matter
how does amyloid beta form
mutations in the amyloid precursor protein leads to formation of abnormal amyloid beta
what do senile plaques do
Senile plaques cause an inflammatory process through microglial activation, cytokine formation and activation of complement cascade. Inflammation leads to formation of neuritic plaques à cell death.
Leads to cortical atrophy.
what are neurofibrillary tangles made of
abnormal aggregates of tau protein
is the number of neurofibrillary tangles important in disease severity?
number of tangles roughly proportional to severity of disease and cognitive decline
what happens to cholinergic neurotransmission
the collection of neurons that produce ACh (called the nucleus basalis of Meynert) is affected early on in the disease process - decreased levels of cholingeric neurotransmission
what happens to glutamine transmission
there are changes to the NMDA receptors - results in overativation of glutamate - excito!!!
what are important points to elicit from history
- timeline of progression
- how ADL are affected eg financial affairs and medications
what are the 3 common presenting symptoms
loss of recent memory
difficulty with exectuve function
nominal dysphasia
what other features are common
- Disorientation (e.g. things getting lost at first – this could also be due to visuo-spatial dysfunction)
- Apathy
- Deficits in visuo-spatial function (e.g. impaired performance in clock-drawing) and driving become evident as the disease progresses
- Features such as prosopagnosia (not recognizing familiar faces) and auto prosopagnosia tend to develop later
do changes in personality occur?
later in disease, unlike in other dementias
physical examination
unremarkable in early stages.
In advanced disease patients may appear sloppily dressed, confused, apathetic, disorientated.
what is a good cognitive test to use initially
mini mental state examination
what tests would be done to rule out other causes on diagnosis
- FBC: to rule out anaemia
- Metabolic panel
- TSH – rule out hyper/hypothyroid associated dementia
- Serum vitamin B12
- CT – exclude SOL etc.
what is seen on an MRI
generalised atrophy, temporal and lateral parietal predominance
compensatory dilation of ventricles
what would examination of CSF show
increased tau level and decreased amyloid beta
what is the first step of management
to provide education, support and resources to patient and family
which risk factors must be addressed during management
vascular risk factors
pharmacological management
- Cholinesterase inhibitors (boost ACh):
- Donepezil, Rivastigmine, Galantamine
- Anti-glutaminergic treatment (NMDA blockers)
- Memantine
how do cholinesterase inhibitors work
Increase brain ACh levels by inhibiting breakdown by CNS acetylcholinesterase
what benefit will cholinesterase inhibitors provide
they will not affect the underlying disease process, but will imrpove function and help pt maintain independece
what other dementia forms are cholinesterase inhibtors used in
DLB, parkinson’s dementia
how does memantine work
it is an antagonist of the NMDA receptors - inhibits excessive glutamine activity
who would be prescribed memantine
- Moderate AD who are intolerant of/contraindication to cholinesterase inhibitors
- Add on drug to cholinesterase inhibitors for moderate/severe AD
- Monotherapy in severe AD
