Dementia Flashcards
How many dementia cases are Alzheimer’s?
60%
Where does Alzheimer’s and other dementias rank globally for causes of death?
Roughly third across the tables
What can cause reversible cognitive decline?
Thyroid disorder - having low folate/ Low B12
Is neurodegeneration reversible?
No - and it could be vascular related
What test is used to diagnosis Alzheimer’s?
MOCA test = Montreal Cognitive Assessment
Describe the MOCA test
- 5 random words
- 3 images
- easy question (name as many words beginning with the letter F in one minute)
- recall test a bit later on
marked for each section and answers collated
What is the issue with dementias having similar clinical presentation
easy to get a differential diagnosis - getting the wrong treatment for the wrong diagnosis
what do neurodegenerative dementias share?
basic processes
How do neurodegen dementias differ?
Pathologically different and different areas are affected
what is the typical aetiology of neurodegen dementias?
protein aggregates - misfolded/ deposition
Of what percentage of all Alzheimer’s cases are from young people?
31
When was Alzheimer’s First described?
1906 - rare disorder of a young onset, when previously seen in elderly
What did Tomlinson describe in 1960s?
Senile dementia - subgroup later to be called Alzheimer’s - progressive cog decline, psychiatric features, post-mortem confirmed
How many questions are there within the Hachinski Ischaemia Score?
12
What does Hachinski Score do?
differentiate between different dementias
- scoring 4 - primary dementia
- scoring 4-7 - indeterminate
- scoring 7+ - vascular dementia
used to detect vascular dementia
what are the 8 questions within Hachinski Score that score one point each?
- nocturnal confusion
- stepwise deterioration
- emotional incontinence
- depression
- history of hypertension
- atherosclerosis
- somatic complaints
- change in personality
what are somatic complaints?
the fixation on a physical problem eg SoB, pain
What 4 questions score 2 points each on the HIS diagnostic quiz?
- fluctuating score
- focal neuro symptoms
- history of strokes
- focal neuro signs
what are the three things within the cholinergic hypothesis?
- reduced choline acetyltransferase
- altered pattern of acetylcholinesterase
- loss of cholinergic neurones in basal forebrain
What is the implication of reduced choline acetyltransferase?
within cholinergic hypothesis
this enzyme then produces less ACh, therefore it has a smaller ability to dilate blood vessels, it can also slow heart rate - will not be able to as fast with a smaller conc
what is the implication of altered pattern of acetylcholinesterase?
within the cholinergic hypothesis
this enzyme hydrolyses ACh - will do this function at wrong time/ insufficiently
what are the implications of loss of cholinergic neurones in the basal forebrain?
Neurones here are responsible for learning, memory and attention
- less efficient
Name 2 ACh inhib that is used within cholinergic monotherapy?
- Donepezil known as the brand name of Aricept
- Galanthamine known as Reminyl and Nivalin
Name a cholinergic monotherapy that is an ACh inhib and BCH inhib
Rivastigmine known as Excelon
what is BCHe?
inhibitor that blocks neuromuscular agents
what is the side effects of cholinergic monotherapy
turn on all the taps
Describe the neuropathy of Alzheimer’s Disease
- alpha beta deposits - aggregation of protein, which is the amyloid precursor protein
- neurofibrillary tangles
what is the size of AB aggregation protein?
40-42 amino acids
what compound can all imaging of AB?
Pittsburgh compound B
how does alpha beta mediated therapy work?
mediated by microglia - breaks plaques into single strips
what is the name of the drug that acts as a alpha -beta mediated therapy
aducanumab - reduces plaques
what are the tau levels within Alzheimer’s?
high
what are the alpha beta levels within Alzheimer’s?
low
how does tau detach from a microtubule?
kinase mediated phosphorylation
after phosphorylation and tau detaches from microtubule what happens?
aggregation is promoted
what does PET scans for within the diagnosis of AD?
screens for tau - due to the neuroanatomical variability
what has a distinct uptake that causes tau pathology within AD?
18F- AV1451
what can be shown within CSF tests?
AB1-42, T- tau, P tau181
what are the advantages of using CSF?
has distinct markers, earlier diagnosis than blood work
what does blood work show within AD diagnosis?
p-tau217
what are the advantages of blood work within AD diagnosis?
easier to retrieve, less uncomfortable
why is PTau 181 so useful from CSF?
it is a neuronal fibrillary tangle protein, which is specific to AD - shows cognitive decline
what is the amyloid hypothesis?
the alpha beta related toxicity causing synaptic dysfunction
what is the amyloid hypothesis?
the alpha beta related toxicity causing synaptic dysfunction
what does aducanumab B11B037 do?
it is a human monoclonal antibody which selects aB- aggregates
how long does it take for aB aggregates to accumulate to reach the level of mild AD?
about 20 years
what was the name of the aducamunab drug study?
Sevigny, 2016
what was the Sevigny, 2016 study?
a randomised multicentre double blinded study with follow ups - using aducanumab to select aB
what were the documented side effects of using aducanumab as drug to select aB plaques?
headaches, UTI, respiratory infections
what was the AD study assessing CSF biomarkers?
Neimantsverdriet, 2017
how does the 2017 study describe a lumbar puncture
more tolerable than expected, low complication rate, high diagnostic yield
more direct to neuropathy, cheaper than a PET scan
what diagnostic test can be used to assess protein levels within the blood?
SIMOA
what is SIMOA?
ultra-sensitive immunoassay that detects proteins at very low levels
what protein can SIMOA detect?
ptau181 - specific to AD
what is a hallmark of AD?
the accumulation of amyloid beta plaques in the brain
what is the main Amyloid beta protein?
AB1-42
what is elevated homocysteine associated to?
AD and strokes
what are hallmarks of B12 deficiencies which can cause reversible cognitive decline?
elevated homocysteine and elevated methylmalonic acid
what can the elevated homocysteine and low B12 do to the brain?
silent brain injury through oxidative stress, ca2+ influx, apoptosis
what can interfere with vit B12 release from food sources
proton pump inhibitors eg lansoprazole
H2 receptor blocking agent (histamines)
what can prolonged B12 deficiency lead to in elderly?
can lead to irreversible cognitive impairment if it continues to deteriorate
how common is vascular dementia?
the second most common dementia after AD
what is vascular dementia?
decreased blood flow to the brain tissue - can be a partial block that can become completely blocked by a blood clot
what is the difference between a stroke and vascular dementia?
vascular dementia is a narrowing which decreases blood flow to the brain but a stroke is a complete block that occurs suddenly
what is MoCA scored to?
0-30
what is a normal MOCA score?
26/30
what score would indicate mild cognitive impairment within a MOCA test?
on average about 22
what is the average score on a MOCA test in AD patients?
16.2/30
why is MOCA used more than MMSE test?
it is more sensitive
can identify cognitive impairments within patients with Parkinson’s
what is MMSE?
mini mental state examination
what is MMSE scored to?
0-30
what is a normal score in MMSE?
24 or higher out of 30
in MMSE would scores would suggest mild cog impairment?
18-23
In MMSE what score would indicate severe cognitive impairment?
0-17
what does MMSE test?
orientation, attention, memory, language, visual spatial skills
in AD what would a MRI show?
diffuse atrophy within temporal and frontal lobes
what is the role of tau in normal functioning brains?
stabilises internal microtubules
what do neurofibrillary tangles contain?
tau
how does taus function change?
chemical alterations by phosphorylation causing tau to detach from microtubule and they can not bind back
what occurs when the chemicals are changed within tau?
it can cause disorganisation, smaller fragments of tau circulates among neurones and this interferes with cellular function
what has research suggested tau spreads and migrates within the brain?
by oligomer seeds that travel across the synapse and when not bound to microtubule it causes aggregation
in AD, in both older and early onset where is 18f-AV1451 have high uptake?
grey matter in comparison to white matter
what compromises of grey matter?
neuronal cell bodies, dendrites, unmyelinated axons, glial cells, synapses, capillaries
what makes up white matter?
myelinated axons - gives it the colour
in AD, what forms paired helical conformations?
18F-AV1451 with tau
as well as in AD, what is 18F-AV1451 also seen in?
corticobasal degeneration (CSB) and progressive supranuclear palsy - atypical parkinsons
what are are the 2 main pathological features of AD?
beta -amyloid plaques between neurones and neurofibrillary tangles containing tau between neurones that impact neuronal communication
what part of the brain does Alzheimer’s originate from?
hippocampus and entorhinal cortex - hence memories are impacted
what are the RF for AD?
age, family history, head injuries, CVD conditions
what is RT-QuIC?
real time quaking induced assay
what is the function of RT-QuIC?
in vitro amplification of abnormal prion protein (PrPSc) - quantifies prion seeding activity, only requires minute amounts
what sample is best to use in RT-QuIC?
CSF - less other things in it
what is Creutzfold-Jakob disease?
incurable neurodegenerative disease characterised progressive spongiform changes and the accumulation of abnormal prion protein in CNS
what are the causes of CJD?
85% are sporadic, the remaining are genetic or infectious linked
why is RT-QuIC better than sonification?
easier method and more consistent
