Clinical dementia Flashcards
what is the prevalence of dementia and what is the hypothesis for this?
Individual risk of dementia is decreasing
UK: over age of 65+ 7%
850,000 people have dementia in the UK and can increase to over million by 2025
worldwide: 50 million
2 main hypotheses for this:
-an element of dementia is vascular disease in brain both on its own or in combination with other disease like Alzheimer’s disease (there’s a much wider uptake of vascular risk modifications than before i.e., lots of people in treatment for blood pressure, high cholesterol, diabetes, smoking-predisposeto dementia) therefore there’s lots of vascular prevention which could be a reason why fewer people are developing dementia
-if you are well educated, the brain is skilled in resilience. So, there could be same amount of pathology or vascular pathology in brain but it’s not going to present symptoms as your brain is better wired. It may present if you live long enough but somehow you can defer it
define dementia
Dementia is a syndrome of progressive decline in cognitive function and social function (Impairment in ability to perform activities in daily living)
If you have cognitive impairment without impairment in activates of daily living its known as mild cognitive impairment MCI
It’s expected to travel from being healthy to unhealthy cognitive function then to dementia
There is an idea that MCI is sort of pre-dementia which determines risk of progressing into dementia over time. (It doesn’t necessarily mean they’ll get dementia it’s just a risk state). Therefore, can be a stable
what are some causes of dementia?
The term dementia implies that this progressive decline in social and cognitive function is due to a brain disease.
The commonest brain diseases that cause dementia is Alzheimer’s disease, other common diseases that give this is Parkinson’s disease, dementia with Lewy bodies, pure vascular dementia, mixed dementia.
It turns out majority of old people have mixed pathologies in brain not just one process. That just because patient is presenting clinical symptoms of Alzheimer’s diseases there is still mixed pathology in brain. The older you get the ore likely to have mixed pathology in brain.
Sometimes conditions such as depression and delirium can mimic features of dementia however its revisable and treatable so it is important to note which cognitive impairment conditions can be reversed. Organic states such as vitamin B12 deficiency, hyperthyroidism, alcohol related brain injury. Can do the same thing and are also treatable
What determines whether you are likely to develop dementia later on in life, what study was used to support this view?
Data from 2 American population studies looking at older people 80years + and following them up and assessing them clinically until they died and observed their brains after they died. This is the final assessment before they died, they were labelled as either with dementia, mild cognitive impairment, or they were cognitively normal. The vast majority of those who were cognitively healthy, still had pathology in their brain but was still cognitively normal.
So, it’s important to note that the older you get the more likely to have pathology in the brain but not necessarily have dementia as those cognitively healthy elderly people have biological markers of neuropathology (vascular disease) in their brain but didn’t have dementia.
The results with great difference were when looking at combined neuropathology within each category not when you have one pathology. Therefore, to have dementia later in life, you most likely need to have several pathologies present as having just AD, or VD isn’t enough as you still may be cognitively normal with just that one disease
How is dementia diagnosed?
-Observe the patient
-A collateral history includes patients physical and mental health, their social circumstances, and functional capabilities.
-cognitive tests
-Performing appropriate investigations to rule out any other condition mentioned several slides up and rule in to tell you what they have
-You can’t make accurate diagnosis just by asking patient, it’s important to ask close ones too, this is important as were poor witnesses to our cognitive function. (forgetfullness, disorinetation, personality chnages and functional level) Majority of people complaining about memory disturbance don’t have one hence why it’s best to ask family too. And its when we stop noticing the normal failing of our memory, that’s when it is most likely to be dementia. You won’t realise if you don’t know how to do something you used to do as they don’t have that memory as they have memory deficits.
-educational history - insight into cognitive function
-psychiatric history
-adlcohol and drug history
-vascular risk factors
Taking family history is very important but there one exception to that which is behaviour in frontotemporal dementia is quite genetic dementia which is super important to take family history.
Educational history gives you insight into cognitive function
-To rule out things like B12 deficiency or hyperthyroidism you might do a blood test.
-To rule out brain tumour you’d do a brain scan, or you might or might not need to do any of the other things listed here.
-DAT scan looks at dopamine transport, used in diagnosis of PD.
-CSF examination (Lumbar puncture)
-EEG
-cranial PET scans
What is the method used to test cognitive decline in those patients that may be presenting with symptoms of dementia?
IQ (informant questionnaire for cognitive disorders in the elderly). Is a 16-point questionnaire.
-ask 16 questions and for each question you give a score between (much improved)1-5(much worse) based on what the informant says. Then add it up and divide by 16 to get an average score.
Any score higher than 3.44 significantly predicts that person has dementia by an 80% chance
What are the different mental functions exmained in a cognitive examination
mental functions divided into:
-alertness
-attention and concentration
-STM and LTM
-language
If it sounds as if their cognitive function is declining, they will want to perform a cognitive examination.
-qualitative (trying to test different domains of cog function and see what the pattern is- problem with memory and language or speech and executive function)- use that pattern to determine subtype
-quantitively (assigning a score and there are cut offs to see how likely someone has dementia) cut offs are just a guide not an absolute
What are the 2 cognitive screening tools used?
MMSE
MoCA
what are some of the challenges of diagnosing dementia?
To know how well their cognitive and social function has declined, you would need to know how they were prior. Like a score of 24 out of 30 on the MoCA or MMSE, how do you know if that’s not normal for them.
So might need to make assumptions via reading or knowledge ability
it can be challenging to comapre levels to the nomral levels and comparison of this
sometimes taking history from other family member/family history cannot be provided
what brain imaging can be used in dementia?
-brain imaging help to rule out other conditions and the level of impairment in affected brain regions.
-CT is used in older patients- shows clear clinical features
-MRI - shows vascular pathology- to see vascular disease and any changes.
-MRI/CT scan on Alzheimer’s. (on right is healthy brain, on left is Alzheimer’s), there’s atrophy, hippocampi is also atrophy, and has vascular damage which are little dots changes.
Alzheimers disease - as a cause of dementia
what are the 2 pathologies - for AD
-tauopathy and amyloidopathy
(amyloid precursor protien is abnormally brokecn down by beta-secretase and gamma-secretases, that lead to formation of amyloid beta proteins which are more prone to aggregation then others. these then can form tiny clusters known as oligemers - you can alos have tau oligemers.are more soluble and toxic compared to the larger fibrillar aggregates that form plaques)-accumulatesand impairs cell fucntion affectingdifferent regions of the brain.
-Presents with abnormal tau and beta amyloid plaques. APP (amyloid precursor protein) is cleaved by various enzymes and they’re likely to form amyloids- these can clump together as extracellular deposits forming amyloid plaques.
Amyloid is deposited in brain 10-20 years before people develop clinical features of AD.
The issue is whether by the time people go see doctors, if the amyloid is causing symptoms, the evidence is that amyloid arises very early before they present with symptoms. So, although there’s presentation of amyloid it’s not sufficient to cause AD. So significant minority of cognitively healthy people over 70, who have amyloid in their brain but do not have dementia. Amyloid is a risk factor for development of AD but not necessarily a biomarker.
early recognition and early treatment is needed.
What are PIB scans
-a type of PET scan
-We can know visualise amyloid in the brain in vivo (In living patients), developed amyloid ligand that is a compound that can bind to amyloid, fix it to a radio nucleotide tracer. Then show which parts of brain take up amyloid ligand. Usually in parietal lobes that are targeted in amyloid deposition.
what drug is used to target the amyloid beta?
lucanumab same fucntion as aducanumab but actually slowed congnitive decline.
We can get amyloid out of brain with therapeutic drugs. Aducanumab, is a monoclonal antibody that binds to amyloid beta and pulls it out of the brain. The problem is that this treatment to remove amyloid from the brain, all clinical trials so far have failed in terms of clinical features of AD. They do not stop or slow down progression of AD.
Lecanemab is a medicine given to slow the progression of mild Alzheimer’s disease (AD). This medicine reduces clumps of proteins called amyloid-beta proteins that play a key role in AD.
(van Dyck et al., 2022)
slowed the rate of cognitive decline by 27% in an 18-month study
what are some other therapeutic approaches in AD?
Davunetide-NAP microtubule stabiliser in AD
-Ant-tau therapeutics
-Anti-diabetic drugs
-Anti-inflammatory drugs
-Targetting unfolded protein responses
-Stem cells
Tau is another problem that is abnormal and that it may go wrong after amyloid in temporal sequency. Anti-inflammatory drugs (still conducting research on it). Targeting unfolded protein response (maybe the brain cells stop knowing how to handle protein and so if by unblocking that you can clear this abnormal protein-still yet to show results). And lastly, replacing damaged cells, neurorestorative technology, (still yet to see meaningful trials (J.Savingy et al, 2016)
