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Welcome to the Oxford University podcast series. Today, we're going to be talking about cognitive impairment or dementia.

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This is brought to you by Daniel Maun and Charlotte Harmon.

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We're both advanced trainees or registrars and in psychiatry in the Oxford Dictionary and also affiliated with Oxford University.

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So, as I said, we are going to talk about cognitive impairment and well, this is a very big topic.

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And I think it could be quite well difficult to to begin to speak about because there are so many different facets of it.

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So, Charlotte, maybe you can begin by saying, well, maybe just introducing the subject by telling us how important it is.

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We live in an ageing population, and this means that there's a significant proportion of the population over the age of 65.

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So this group forms a significant part of the caseload in primary care.

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And two thirds of patients in general hospitals are over 65 because cognitive impairment is common in this age group,

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whatever speciality medical students end up working and they need to be familiar with the core elements of it.

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Yes, I mean, it's often sometimes talked about in the news as it is with the ageing population.

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And I think with the increasing demands on society are often discussed in the media.

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I think it is a very relevant topic to any animatic, really,

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anybody engaging with any form of health care to be aware of cognitive impairment with its ramifications so.

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Well, what's the timescale for chronic cognitive impairment?

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Because we're talking about an ageing population. Is it is it something which just sort of suddenly happens when you reach a certain

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age or how does it present wants to look like it develops over a number of months.

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So that's in contrast to delirium, which develops over a few days.

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And for a diagnosis of dementia, the symptoms need to have been present for at least six months.

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And so you mentioned symptoms there. What are the symptoms? The symptoms include multiple cognitive deficits.

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So it's not just about memory, it's about an impairment on many cognitive functions.

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Classically, we think about the four A's. So amnesia, aphasia apraxia and agnosia.

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Can you just tell us what each one of those things I know amnesia is, you know, reduced memory or impaired memory.

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Amnesia is about short term memory. Aphasia relates to language difficulties.

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Apraxia is difficulty sequencing actions and agnosia.

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It's a difficulty with recognising objects. God knows you might be a bit like Dr. Sacks novel, The Man who mistook his wife for a hat.

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Yes, that's right. Or to give a more simple example, it might be if you give somebody a key to hold and ask them what it is,

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they wouldn't be able to say, feel it and to know that it was a key. Right.

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Thank you. In addition to those cognitive deficits for a diagnosis of dementia, people also have to have functional impairments.

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And what do you mean by functional and what does that look like? That means a difficulty doing the day to day activities.

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So getting dressed, cooking food, remembering appointments, reading, writing, maybe difficulties with conversation as a practical day to day stuff.

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Right. And we talk about the fact this is a chronic condition.

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Could could there be an acute presentation in dementia?

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The symptoms of dementia can be exacerbated by acute illness, and people with dementia are more vulnerable to getting delirium.

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But the key is in the history. So unlike delirium, people with dementia would have had the symptoms for many months before the acute illness started.

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The new symptoms wouldn't be precipitated by the illness. Right?

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I understand. So there are many different types of dementia out there and many of us a common know the common ones, for instance, Alzheimer's disease.

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But maybe you could just maybe just outline the main different types of dementia for us.

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There are four main types that we're going to talk about today. So Alzheimer's disease, you're right, is the most common is important to think about.

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There's also vascular dementia, Lewy body dementia and frontotemporal dementia.

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Okay, so should we start with Alzheimer's? Yes. And and and talk about that.

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So how how is it by far the most common and and what how does that present?

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Well, what's the cause of it? It is the most common the most prominent feature is short term memory impairments.

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So that's amnesia. As the condition develops, there might be a loss of long term memory as well as other cognitive symptoms.

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Such as aphasia and they Braccio, the key to remember is that Alzheimer's isn't just about memory impairment,

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but about a broader cognitive impairment.

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So patients might have problems with language, with perception, attention, constructional abilities, orientation and problem solving.

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They might also have a range of non cognitive symptoms. So this includes mood and personality changes, things like apathy.

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They might also get delusions, hallucinations and sleep disturbance.

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You've got quite a range of symptoms there, actually. That's right.

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That might fit with the fact that it's what sort of globalised sort of later stages it becomes a sort of globalised cerebral disease.

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Is that right? That's correct. It's also associated with a range of neuropsychiatric and comorbidities, I suppose.

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So depression is very common and dementia, it's seen in 25 to 30 percent of people.

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Anxiety is seen in up 30 percent. And people get apathy and psychotic symptoms, as I mentioned before.

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Right. And just to go back, we're talking about cognitive impairment.

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I guess maybe some people aren't familiar with the term cognition or cognitive.

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How would you describe that?

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But mean it's sort of as I understand it, is sort of something to do with the sort of the higher functioning of the brain.

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If you've got a good way of understanding that, I suppose I've talked about the deficits that you can get.

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And if you think about the reverse of that, then that's what cognition is,

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cognition of the higher functions of the brain relating to language, to memory.

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Orientation, all those types of things, how do you diagnose Alzheimer's disease?

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Classically, a definite diagnosis can only be made at autopsy and at autopsy in the brain,

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it's the amyloid plaques and neurofibrillary tangles which are made of tau protein and those are visible throughout the whole cortex.

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But obviously, you can't wait for autopsy to make a diagnosis.

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And so there are various clinical criteria which help clinicians to make a diagnosis during somebody's life.

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It can be diagnosed clinically. Based on certain criteria, so where there's dementia and clinical assessments, where the symptoms are progressive,

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where more than two areas of cognition are affected and where the symptoms start between the ages of 40 or 90.

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And in addition to this, there needs to be functional impairments and no other explanation for the changes.

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Right. And so what I'm understanding here is that a definite diagnosis can only be made at autopsy,

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but there are very likely diagnosis made on clinical grounds,

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looking at what the patient is able to do and what they're unable to do in making it sort of a general diagnosis, but not a definite one.

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So with every family neuroimaging tests and these scans that we can do to help make us more sure about what's going on,

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there are a neuroimaging is a key part of an assessment of somebody with dementia on CT scans or MRI scans.

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You can see generalised atrophy, which is common, and Alzheimer's. And also specifically you get hippocampal atrophy.

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So that can be seen on imaging. There are also new amyloid imaging techniques which actually allow you to visualise the amyloid plaques in the brain.

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So it's similar to the sorts of pathological tests you'd be able to do at autopsy, and that actually might help make an accurate diagnosis.

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Wow, that's interesting. Imaging techniques, which can actually identify the specific pathology of the Alzheimer's.

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That's right. That's interesting to see what causes Alzheimer's disease.

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And we've talked a bit about amyloid plaques and neurofibrillary tangles. Are they there are there other sort of more specific genetic causes?

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There are in a very small number of people who get early onset Alzheimer's disease.

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Genetic factors are clearly causal and there seems to be an autosomal dominant pattern of inheritance.

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There are three genes that have been inherited in this way.

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So the gene for amyloid precursor protein on chromosome 21, then present in one on chromosome 14 and present linta on chromosome one.

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But I will stress that it's really a very small percentage of people with

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Alzheimer's who actually have this autosomal dominant pattern of disease right.

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In late onset Alzheimer's disease, which affects the majority of people,

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the upper E4 gene increases the risk of getting Alzheimer's disease so it doesn't determine who gets it,

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but it just increases the risk and lowers the age at onset.

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But overall, age is the most predictive factor for who gets Alzheimer's disease or other things that are relevant are people

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with vascular capabilities have an increased risk and people who get depression are also at increased risk.

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So those are the things to look out for. The other side of the coin, a higher educational level protects against Alzheimer's disease.

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And the theory is that if you've got a greater cognitive reserve,

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then you can tolerate the cognitive deficits and find alternative coping strategies for a longer period.

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That's a really helpful overview, actually, of the different causes.

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So there are actually a number of different causes, not a number of different genetic causes, actually.

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Yeah, but the specific genetic causal mechanisms in early Alzheimer's disease are quite

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different to the the risk factors of some genetic contribution in later onset.

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That's right. Yeah. What about vascular dementia then. That's another very common dementia.

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How well does that is that quite different presentation to Alzheimer's?

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There's a lot of overlap with all the different presentations of dementia, but there are certain features that make it different.

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And it's important to look out for to make a diagnosis of vascular dementia.

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A patient needs to have cerebrovascular disease, which is either evidence clinically or on neuroimaging.

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And in addition to this, they need to have cognitive and functional impairments.

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And there needs to be a clear relationship between the cerebrovascular disease and the cognitive and functional impairments.

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So an example of this would be if somebody has a stroke and then develops cognitive and functional changes,

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and that's likely to be a vascular dementia. Classically, because you can get vascular changes, which happen quite suddenly,

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patients present it with a stepwise deterioration, so they'll go along at a certain level,

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there'll be a sudden change in either cognition or behaviour, and things will carry on at that level before another sudden change.

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Is there a sense in which you can you can see the degree of the impairment,

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the cognitive impairment by looking at the degree of cerebrovascular disease? Generally speaking?

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Generally speaking, if you've got more cerebrovascular disease, you're likely to have more cognitive impairments.

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And specifically looking at the specific neurological deficit, which you wouldn't expect an answer, as I understand it, mostly.

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But in in vascular dementia, you might expect some specific new neuro neurological deficit,

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for instance, maybe an expressive dysphasia or some things.

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So you can have difficulty with actually naming quite specific things, looking at the specific language deficit.

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Yes. And that would be represented on the imaging as well. Yes, that's interesting.

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Okay, so we're looking at much more stepwise change and very much related to cerebrovascular damage on the scans.

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That's helpful. So what about the the characteristic features of Lewy body dementia?

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What was what was particular here in this condition? Lewy body dementia is characterised by a fluctuating cognition.

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People get quite a lot of rapid change in that cognition.

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They get visual hallucinations and they get Parkinsonism. They might also have a REM sleep disorder and they have severe neuroleptic sensitivity.

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And although they do get the memory loss, the a. a. great memory loss might not be as prominent as in other types of dementia.

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So and what you mean by anterograde memory loss is the laying down of new memories, right?

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Yes, OK. And just so so we're aware of this quarter, that triad of symptoms is quite particular to live body, isn't it?

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The fluctuating cognition.

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Sometimes they can be okay and sometimes they're really quite well impaired by their cognitive difficulties and the visual hallucinations.

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And the Parkinsonism has quite a distinctive trilaterally. Yes.

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And I think you can see that this is quite a good differential diagnosis for delirium, because, again,

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you've got the fluctuating cognition and the visual hallucinations, which are common in delirium.

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And the key to a diagnosis here is really thinking about the history. How long has this been going on for or is it an acute change?

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So it's called Lewy body dementia. What are Lewy bodies?

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Well, their inclusion inclusions, which are found within neurones,

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so neuronal inclusions and they're composed of abnormally fusspot related proteins called in and others nuclear and Lewy body dementia.

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These Lewy body are found throughout the brain and many structures, including the Paralympic and neocortical structures.

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And so because they're found throughout the brain,

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you can actually do your imaging to help with the diagnosis and you get changes on spectrum PET scans,

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which are quite characteristic of Lewy body dementia. But we're moving on.

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We do have a number of stories to do, much to cover in this podcast of frontotemporal dementia, differ again in frontotemporal dementia.

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There's a very early decline in interpersonal skills and a change in behaviour.

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Characteristically, people get disinhibition, hyper morality.

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So that might put a lot of things in their mouths. They might be inflexible and have poor personal hygiene.

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And patients frequently show a very early loss of insight and a difficulty with expressing emotions.

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Speech might change, so they might commonly have echolalia or perseveration where they repeat the same sentence repeatedly and

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they can have physical signs such as primitive reflexes or incontinence as frontotemporal dementia as well,

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at least in the early stages, or predominates as a personality change or perhaps a behaviour change to somebody who has

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been behaving maybe normally for them as quite a dramatic change in the way they are.

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Is it sudden or is it sort of a gradual thing? It's gradual again.

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But I think it can be difficult to to know what's going on.

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If somebody is having a very gradual personality change,

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it might be that it's not recognised immediately or people think somebody is just behaving strangely.

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And it's only when things have got a little bit worse that it's easier to to piece it all together and to work out what's going on.

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Often in frontotemporal dementia, people develop the symptoms in their mid to late 50s.

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So it happens a little bit earlier than other types of dementia, and that can make it more difficult to diagnose it first.

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Thank you. Are there any other causes of dementia that you think we should we should mention here?

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Well, there are quite a lot of other causes of dementia,

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but I just mentioned some of the reversible causes because it's important to think about those.

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So V12 deficiency, hypothyroidism and normal pressure hydrocephalus are all things that if you detect,

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you might be able to treat and to reverse the dementia symptoms.

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The classic symptoms of normal pressure, hydrocephalus, gait apraxia, cognitive impairment and incontinence,

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and some people develop this can actually have surgery which can stop symptoms getting worse and actually improve people's presentation.

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Right. And so there are some reversible causes. But what about some of the rare causes of dementia?

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Well, these are things like prion disease, Huntington's disease and multiple sclerosis.

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So those are rare. But you do come across them and it's important to think about them as part of the differential diagnosis.

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OK, thank I'm doing all right. I'm studying diseases along the lines of CJD.

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That's right. Yes. So there are some inherited forms of prion disease, but it can also be acquired and it can just occur sporadically.

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OK, so let's move on from defining the different types of dementia to the principles of assessment.

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If we have a patient who we are suspecting of dementia.

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What are the what are the steps of the assessment we should go through?

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If dementia suspected, then patients should be referred to a memory clinic.

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At a memory clinic, they'd have a history and a careful history is really important and needs to include the kind of natural history,

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they'd also have investigations to identify any potentially treatable causes of cognitive impairment.

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These are things like depression, delirium, vitamin deficiencies, stroke and tumours.

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The investigations would include blood tests for full blood counts,

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ESR using his liver function tests, thyroid function, V12, folate, glucose and cholesterol.

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So we're looking to identify the causes of dementia and also to think about potentially modifiable risk factors.

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Neuroimaging is important. So you need either a CT or an MRI scan to include some to exclude some of the other causes.

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And a thorough cognitive assessment is really essential. This needs to assess all the key cognitive domains and at a minimum,

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it would include something like an embassy or a Mocca, followed by a clocks and an HPLC.

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The clock starts about 2:00 or 3:00,

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be able to HPLC is a hopkins' verbal learning test that you have to learn a list of 12 words and you repeat those.

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You do that three times. So it's quite a difficult test and can be quite good at trying to distinguish some of

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the different types of dementia and whether or not somebody actually has a dementia. OK, what options are available for management?

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Because often we see dementia as something which is quite difficult to treat and we can quite easily lose hope.

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This may maybe what members of the general public and have this perception that

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there's not much to do but what what is clinicians will be able to achieve,

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even people with dementia? The management of dementia really depends on the stage of dementia.

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So very much needs to be tailored towards the individual at present.

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There's no cure for Alzheimer's disease and other dementias.

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And the focus of care is to reduce the symptoms and to enable patients to live healthy, fulfilling lives for as long as they can.

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There is medication available to delay the progression of the cognitive difficulties and cholinesterase inhibitors are useful for mild to moderate

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to moderate Alzheimer's dementia and Lewy body dementia and the glutamate antagonist Memantine is useful for moderate to severe dementia.

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As well as medication, psychosocial support is important, as important.

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So patients need to be advised on cognitive strategies,

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given assistance with financial planning and providing help with practical assistance if that's needed.

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There are two charities, Aid, UK and age concern and I hope can be very useful in helping advise patients about these things.

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And it's also important to remember carers support for carers is essential and they should

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have their own assessment and they should be given information about carers support groups.

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So I see if you use the management sort of structure, bio, psycho,

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social and biological elements mentioned Condoleezza Rice and hipsterism because there's been a lot of talk about Rice AstraZeneca

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in the media recently about the cost benefit analysis and all that actually efficacious enough because they're quite expensive,

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a new, reasonably new expensive medications. And you say that they they just they just delay the progression of the condition, is that right?

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That's right. Although I might correct you on that, because some of the drugs have been taken off patent recently.

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So they're actually becoming really very cheap. Although given the number of people with dementia, if you look at a population level,

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then obviously they can be quite expensive, but they do just delay the progression of the condition.

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How do you know when to stop treating them? Is there a window or something like that?

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This is, in a sense, the million dollar question. So for some people, they will get an improvement in their symptoms when they take them.

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Other people, they don't get an improvement, but things don't get worse.

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So it seems to stabilise the condition. And in some people, they might get a little bit worse.

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But this will be a less severe decline than if they weren't on medication.

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There are times when he would stop medication, for example, if somebody is having side effects from the tablets or if their cognitive function has

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dropped a lot and really they seem to be getting very little benefit at all from them.

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But usually we need to continue the tablets but review them regularly to make sure that that's appropriate.

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And although it might delay progression that could actually make quite a significant clinical difference to somebody, for example,

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it might mean that they can stay in their own home and function relatively independently rather than needing extra care or institutional care.

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So that has a benefit for the patients. But there's also population benefits to that if we're delaying the risk of institutionalisation.

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Right. And that's really helpful to get out because it's quite a difficult cut off in a ways

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to push a bit because the other pharmacological management as well that people have.

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Well, I wouldn't be undecided about, shall we say,

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which is the use of psychotic medication in people with behaviourally disturbed presentations of dementia.

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And there are people who are very against the use of maybe some sedative antipsychotic medication.

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What are the pros and cons of that are in people with advanced dementia and people with advanced dementia?

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Behavioural disturbance can be very difficult to manage. It can make patients vulnerable.

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It can make them very aggressive. So they're a danger to other people.

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And in those situations, although you can use expert nursing care and other non pharmacological management strategies, sometimes that doesn't work.

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And sometimes you do need to think about using medication to calm people down.

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Antipsychotic medication has been used as a sedative medication and that can be helpful for people.

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However, there's a lot of evidence now that using antipsychotic medication and people with dementia

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is actually not all that helpful as a long term behavioural strategy and more importantly,

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that it leads to increased cardiovascular disease and increases mortality.

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So, in fact, it can be very dangerous for people. Now, before clinicians start antipsychotic medication,

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they should really be a very careful discussion with patients and their relatives about whether or not this is appropriate and if it is used,

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it should be used at the lowest possible doses for a short time.

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So a couple of weeks and then stopped is not something that we should use now as part of long term care.

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Thank you. That's very helpful.

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So, I mean, thinking about dementia as an advancing condition and the the increasing difficulty we have in managing these sorts of patients,

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what are the risks that are associated with managing people with dementia?

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There are many risks to consider,

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although whether they're relevant will depend on the stage of dementia and on the individual patient things to consider self neglect,

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disinhibition and aggressive behaviour. For some people, wondering might be a problem.

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So people leaving the house at night and putting them in vulnerable situations and driving

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needs to be considered because that can be a risk for the patient and for other road users.

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You should also think about risk from carers, and although this is very rare, it does happen and it's important to keep it in mind.

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So carer abuse and financial abuse are things to look out for and the rare occasions that it happens.

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Thank you, Charlotte. Well, we've come to the end of our podcast today,

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we've gone through a brief overview of the presentation of different while the main different

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types of dementia and some of the causes and the principles of assessment and management.

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So thank you for that. I'm very aware that we've only covered the basic information about dementia.

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So what resources would you recommend for further information? For those interested?

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For a more detailed discussion, I'd recommend the shorter Oxford textbook of psychiatry or the Oxford textbook of old age psychiatry,

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which has got a lot of detailed information in it,

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might also be helpful for listeners to look at the latest nice guidelines on use of medication and

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to look at the British Association of Psychopharmacology guidelines on anti dementia medication.

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Finally, health talks online has got some very good interviews, particularly with carers.

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And I think understanding the carers perspective gives a good insight into how medical professionals might best help patients.

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So I'd also recommend that health talks online sites as well.

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Thank you. That sounds like a good list of resources for those interested. Thank you again, Charlotte, and thank you listeners for tuning in,

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listening to another episode of the Oxford University podcast series in psychiatry, please to listen to another goodbye.