Dementia Flashcards
What is the definition of a neurodegenerative disease?
Systematic symmetrical neuronal death which follows a specific pattern of neuron loss over time and is often the result if the accumulation of abnormal proteins
Give an example of a neurodegenerative disease which is always genetic.
Huntington’s disease
Give an example of a neurodegenerative disease which is often genetic.
Cerebellar ataxia
frontotemporal dementia
Give an example of a neurodegenerative disease which is often sporadic.
Alzheimer’s disease
Parkinson’s disease
What normal changes in cognition can be expected with age?
Increase in forgetfulness
slowing of response times
changes in vision, hearing, sensory and motor function
Dementia affects consciousness level. T/F?
False
Dementia only affects memory. T/F?
False - it affects other cognitive abilities such as visuospatial function,
Give examples of reversible causes of cognitive impairment/dementia.
Hypothyroidism normal pressure hydrocephalus drugs - opiates, sedatives anticholinergics tumour neurosyphilis chronic subdural haematoma whipple's disease nutrition -vit B3 deficiency psychiatric disorders
What are the four main types of dementia?
Alzheimer’s
Lewy-body
vascular
frontotemporal
What are the risk factors for dementia?
Increasing age head injury female downs syndrome genetics - APP, APOE4, presenilin
What is the most common type of dementia?
Alzheimer’s
What is the survival of Alzheimers patients?
6-12 years
Formal diagnosis of Alzheimers can only be achieved at autopsy. t/f?
true
What abnormal proteins characterise Alzheimers?
Neurofibrillary tangles (tau protein) Beta amyloid plaques
There is cerebral atrophy of Alzheimers disease. T/F?
True
What are the symptoms of moderate Alzheimer’s disease?
Memory loss confusion problems recognising people language dificulties restlessness agitation wandering repeptitive statements
What are the symptoms of mild Alzheimer’s disease?
memory loss confusion trouble handling money poor judgement mood changes anxiety
In addition to cognitive symptoms,What are the symptoms of severe Alzheimer’s disease?
Seizures
weight loss
increased sleeping
loss of bladder and bowel control
How does death often occur in patients with Alzheimers?
Infection such as pneumonia
What are the symptoms of Lewy-body dementia?
Progressive cognitive decline
fluctuating consciousness
visual hallucinations
Parkinsonism
Which type of dementia results from accumulation of the same abnormal protein that is seen in Parkinson’s disease?
Lewy body dementia
What are the symptoms of Parkinson’s disease with dementia?
Bradykinesia rigidity tremor autonomic dysfunction cognitive impairment
What abnormal protein makes up Lewy bodies?
alpha synuclein
How can Lewy body dementia and Parkinson’s disease be differentiated pathologically?
by where in the brain the primary pathology exists - mainly cortex for LBD, and mainly substantial migrants for PD
What age of patients typically get frontotemporal dementias?
45-65 year olds
Define frontotemporal dementias
a heterogeneous group of dementias which can be sporadic or inherited
What symptoms are particularly associated with frontal lobe dysfunction in frontotemporal dementia?
Behavioural and personality changes
disinhibition
depression
agitation
In what type of frontotemporal dementia is there accumulation of abnormal tau protein?
Pick’s disease
In what type of dementia is there a characteristic stepwise progression in memory impairment and cognitive symptoms?
Vascular dementia
What genes are associated with Alzheimers disease?
APOE4
Presenilin 1 and 2
APP
Beta amyloid plaques develop within the neuron. T/F?
False - they develop in the extracellular space
Neurofibrillary tangles develop in the cytoplasm. T/F?
True
Describe the amyloid hypothesis.
The secondary structure of APP changes from an alpha helix to beta related sheet resulting in the formation of alpha beta peptide monomers and oligomers which cause plaque formation
this induces an inflammatory response which results in aggregation of tau proteins, forming tangles
the tangles and plaques together cause synaptic and neuronal loss
Which protein are neurofibrillary tangles composed of?
Tau
What is the physiological role of tau?
neurite growth
axonal transport
microtubule dynamics
What pathophysiological role does tau play when hyperphosphorylated in a proteinopathy?
causes formation of tangles
microtubule dysfunction
cell death
Other than Alzheimer’s give examples of tauopathies
pick disease
frontotemporal dementia
corticobasal degeneration
progressive supranuclear palsy
There is a switch from beta pleated sheets to alpha helixes in the misfoldign of alpha synuclein which causes formation of Lewy bodies. T/F?
False - the opposite is true, alpha helixes to beta pleated sheets
Give examples of neurodegenerative disease characterised by the accumulation of abnormal alpha-synuclein.
parkinson’s
Lewy body dementia
multiple system atrophy
neuroaxonal dystrophies
What are the two classes of cognitive enhances used in. the treatment of dementia?
Cholinesterase inhibitors
Partial glutamate antagonists
What severity of Alzheimer’s is memantine used to treat?
moderate to severe
Give examples of cholinesterase inhibitors used to treat dementia?
Donepezil
galantamine
rivastigmine
What severity of Alzheimer’s are cholinesterase. inhibitors used to treat?
mild to moderate
What is the normal action of cholinesterase?
Breakdown of ACh at the post-synaptic terminal
Cholinesterase inhibitors have a high efficacy against dementia. T/F?
False
What are the adverse effects of cholinesterase inhibitors?
Nausea, vomiting, diarrhoea, muscle cramps, dizziness, fatigue, anorexia, GI bleeding, cardiac events
Cholinesterase inhibitors are used in the treatment of frontotemporal and vascular dementia. T/F?
False
Cholinesterase inhibitors are used in the treatment of Lewy body dementia and Parkinson’s with dementia. T/F?
True
Antipsychotics can be prescribed in dementia with Lewy bodies. T/F?
False
Describe the normal functioning of glutamate and AMDA and NMDA receptors.
Glutamate acts on both NMDA and AMPA but initially NMDA channels are blocked by magnesium. During a weak electrical stimulation, EPSP is entirely mediated by AMPA receptors. If there is a stronger presynaptic action potential, AMPA receptors depolarise the membrane, expel the magnesium from the NMDA channel and allow NMDA to also respond to glutamate. this leads to insertion of more AMPA receptors
How does the action fo glutamate and AMPA/NMDA result in learning?
Long term potentiation
calcium activated kinases increase effectiveness of existing receptors and increase number of receptors
In Alzheimer’s there is glutamate loss in which areas of the brain?
Entorhinal cortex and hippocampus
What is the mechanism of action of memantine?
Blocks NMDA receptors to stop overactivity of the glutamatergic system
In what types of dementia does memantine have no significant effect?
mild dementia
vascular dementia
frontotemporal dementia
What are the side effects of memantine?
Dizziness Headache constipation somnolence hypertension
How can depression be managed in dementia?
SSRIs such as sertraline and citalopram
Describe the use of antipsychotics in dementia
atypical antipsychotics (risperidone, aripiprazole) can be used in severe agitation or aggression
these increase mortality and increase risk of cerebrovascular accident so should be used sparingly
not used to treat insomnia, wandering or abnormal vocalisation
if patient stable for three months on antipsychotics then cautiously withdraw
How can dementia be distinguished from learning disability?
In dementia there is a decline from a previously higher cognitive function
For a diagnosis, dementia must be impacting on day to day function otherwise it is classified as…?
Mild cognitive impairment
In what type of dementia are changes in personality most commonly present in early disease?
Frontotemporal dementias
What are the main psychiatric differentials for dementia?
delirium mild cognitive impairment amnesic syndrome chronic brain damage depression late onset schizophrenia learning disability malingering presentations dissociation
What are the possible intracranial causes of dementia?
Tumour
head injury
What are the possible infectious causes of dementia?
prion disease
neurosyphilis
His associated dementia
TB
What are the possible endocrine causes of dementia?
hypothyroidism
hyperparathyroidism
cushing’s
Addison’s
What are the possible metabolic causes of dementia?
uraemia hepatic encephalopathy hypoglycaemia hypo/hyperclacaemia hyper/hypomagnesiamia
What are the possible nutritional causes of dementia?
B12, folate, thiamine or niacin deficiency
What are the possible toxic causes of dementia?
lead
alcohol
What is involved in clinical assessment of dementia?
corroborative history general physical examination MSE standard bloods structured cognitive testing structural imaging
What blood tests are commonly used when investigating possible dementia?
FBC glucose U/Es LFTs TFTs bone profile urinalysis Vit B12 / folate erythrocyte sedimentation ate c reactive protein
Other than standard bloods, what further investigations may be used when investigating possible dementia?
HIV and syphillis serology CXR lumbar puncture ECG EEG CT/MRI
How many points is the mini mental state exam scored out of?
30
How many points is the addenbrooke’s assessment scored out of?
100
The Addenbrroke’s assessment is more thorough than the mini mental state exam. In particular, what aspects of cognition does the Addenbrooke’s test cover better than the mini mental state exam?
Executive function
The mini mental state exam is influenced by age, education and socio-economic status. T/F?
True
The mini mental state exam is used to diagnose dementia. T/F?
False - it is used as a screening tool
What factors comprise ‘cognitive function’?
attention memory executive function language calculation praxis visuospatial ability
How can attention be tested?
orientation in time and place digit span - forwards and backwards recite months of the year backwards serial 7s spell a word backwards stroop test
What is anterograde amnesia?
Loss of recent memories or memories occurring after onset of disease
What is retrograde amnesia?
Loss of past memories of memories occurring before onset of disease
Describe Ribot’s gradient of memory loss?
A pattern of memory loss where Patients lose more recent memory first then progressively lose past memories
What functions are encompassed by executive function?
goal setting and motivation judgement social behaviour personality abstract reasoning planning and organising problem solving
What is Agraphia?
inability to write
What is Alexia?
inability to read
Where in the. brain is calculation carried out?
Left angular guys of parietal lobe
What is acalculia?
inability to comprehend or write numbers properly
What is anarithmetria?
Difficulty with arithmetic
What is dyspraxia?
Inability to move a body part despite intact motor and sensory functioning
Dyspraxia can affect both conception and production of movements. t/f?
ture
What is meant by visuospatial ability?
Ability to process visual information and link this to spatial positioning of objects to their orientation in space
Which areas of the brain control visuospatial ability?
Visual cortex Parietal lobe (tells you where object is) temporal lobe (tells you what object is)
What problems can be caused by visuospatial deficits?
topographical disorientation difficulties with dressing misreading for objects visual neglect visual object agnosia prosopagnosia
What is prosopagnosia?
The inability to recognise familiar faces
Give examples of rarer types of dementia.
Corticobasal degeneration progressive supra nuclear palsy HIV infection Niemann Pick disease type C Cruetfeldt Jakob disease
Which enzymes normally break down APP in the brain?
alpha and gamma secretase
Which enzymes degrade APP in Alzheimer’s disease?
beta and gamma secretase
What is the term for when plaques build up around the blood vessel walls of the brain?
Cerebral amyloid angiopathy
Cerebral amyloid angiopathy increases the risk of haemorrhage. T/F?
True
What gene is associated with late-onset Alzheimers?
APOE-E4
What genes are associated with early onset Alzheimers?
PSEN-1
PSEN-2
Other than genetics, what factors can increase the risk fo developing alzheimers?
Smoking
midlife obesity
diet high in saturated fats
Why does Down syndrome result in an increased likelihood of early onset Alzheimers?
In Down syndrome there is an extra copy of chromosome 21. The gene which produces APP is located on this chromosome and so Down syndrome likely causes over expression of APP
In vascular dementia, executive functions are typically more prominently affected than memory. T/F?
True
How is vascular dementia treated?
Prevention of further cerebrovascular disease by optimal control of major risk factors - anti platelet therapy, anticoagulation, carotid angioplasty, stenting, risk factor modification
