Webinar: Younger Onset Dementia
Dementia Australia webinars are free videos where subject experts discuss topics relating to dementia for a general audience.
In this webinar, Professor Dennis Velakoulis explains the most common forms of dementia in younger people, including symptoms and progression. He also explores the common challenges faced with diagnosis and provides an overview of treatments and support.
You’ll learn about:
- younger onset dementia and what it is
- the differences observed with younger onset dementia
- common symptoms and challenges with diagnosis.
Transcript
[Beginning of recorded material]
[Title card: Dementia Australia]
[Title card: Young onset dementia]
Professor Velakoulis: Hi, I'm Dennis Velakoulis. I'm from Neuropsychiatry at The Royal Melbourne Hospital. I'm going to be talking about young onset dementia today, and this is part of a Dementia Australia expert webinar series. I am going to just start off with a brief discussion about what is dementia, what causes dementia, how it progresses, and then some more recent information about what might help from a treatment point of view.
Dementia is a condition which leads to ongoing changes to one or more areas of cognitive function. These areas include memory, attention, what's called visuospatial, or understanding where we are in space and our sense of direction, executive function, or our ability to know what to do, when to do it, when not to do it, and our ability to plan and organise things. And finally, language. There are multiple areas of cognitive function, and different types of dementias may affect any one of those areas at different times.
Many diseases cause young onset dementia. Alzheimer's disease is probably the commonest in the young onset dementia space, but frontotemporal dementia is probably the second commonest. And I understand there's been another talk on frontotemporal dementia by Professor Amy Brodtmann as well. Vascular and Lewy Body dementias are the third and fourth-commonest causes of dementia in younger people, and then there are a number of other conditions including genetic conditions like Huntington's disease, which cause dementia in young people under the age of 65. There are many other rare causes of dementia, many of them affecting a small number of people, but still having the same impact on patients' families that Alzheimer's disease or frontotemporal dementia will have.
So, this is just a brief overview of what causes dementia. It's not necessarily applicable to all types of dementia, but it's something that I've used to explain to people why dementia happens in brain cells. And our brain cells are like little factories. They're always making and breaking down substances called protein. So proteins are essential for brain cells and every other cell in our body to work, and that's how all of our cells work. They work through the use of proteins. Most dementias are caused by a build-up of abnormal proteins in the brain cell.
This is a cartoon of a brain cell. You can see the little orange squares. They're the amino acids, the little squares. All these little amino acids accumulate into proteins, which then go off and do their business in the cell, and then the cell breaks down the proteins and we start the cycle again. So it's a little factory that's making proteins. When something goes wrong, so for example, if the cell isn't able to break down the proteins anymore, then all those bigger squares start to accumulate and clump together in the brain cell. If there are too many of those little squares, they clump into what are called plaques, and those clumps then just take over the entire brain cell, and unfortunately, the brain cell dies. This is a very just a very general description of what happens in brain cells when there's a build-up of proteins.
So, why do proteins build up? Well, unfortunately, like any piece of machinery, our brain cells are subject to wear and tear. And that wear and tear can lead to abnormalities in this production of and breakdown of proteins, or genetic mutations can lead to a breakdown in this production and breakdown.
Different dementias have different proteins. In Alzheimer's disease, for example, it's amyloid that's the abnormal protein that builds up. In frontotemporal dementia, it's either a protein called tau or TDP-43. In Parkinson's disease and Lewy body dementia, it's a protein called synuclein. In Huntington's disease, it's a protein called Huntingtin. And in a very rare disorder called Creutzfeldt-Jakob disease, it's a protein called the prion protein. These proteins vary across the different types of dementia, so each dementia has its own protein. I might just add that vascular dementia is an exception to this protein rule. In vascular dementia, the abnormality that causes brain cells to die is blockage or bleeding in arteries of the brain.
Now, why do different types of dementia cause different types of problems? Alzheimer's disease, for example, begins with memory problems. Now, not all Alzheimer's disease begins with memory problems, but in general, it's the memory, the short-term memory, that's the first thing that's affected. Why is that? Well, it's because the amyloid, the abnormal protein, first starts to build up in areas that help or that are responsible for the memory, like the hippocampus, or the temporal lobes, or the parietal lobes of the brain. So, amyloid starts building up in those areas first in Alzheimer's disease, and leads to the early symptoms of memory problems. We don't really know why amyloid starts building up in those areas and not in other areas of the brain first.
In frontotemporal dementia, the abnormal proteins, the tau and the TDP, start building up in the frontal areas of the brain, so that leads to changes in personality, or behaviour, or psychiatric changes. Again, we really don't know why that happens – why do these proteins start building up in these parts of the brain first? We don't know. In Parkinson's disease, the synuclein begins to build up in a part of the brain called the brainstem or the back of the brain; but in Lewy body dementia, it often will start to build up in other areas of the brain like the hippocampus and lead to memory problems. Huntington's disease, the abnormal protein there starts to build up in movement areas of the brain and in the frontal lobes, which is why people will often develop movement problems first, and then behaviour and personality changes. So, different dementias have different proteins, and often, those proteins will often start to build up in different areas of the brain, and therefore, that's why different dementias will often begin with different types of symptoms early on.
Now, some conditions we know will occur together. So, Alzheimer's disease and Parkinson's disease will often occur together, as will Alzheimer's disease and vascular dementia. Frontotemporal dementia will sometimes occur together with a condition called motor neurone disease. And Parkinson's disease will, as I've already mentioned, often occur together with a condition called Lewy body dementia. People with Parkinson's disease may ultimately develop a dementia. Not all of them, but some, and that dementia is usually associated with what's called Lewy body dementia.
I'm often asked by people when we are talking about brain changes and different types of dementia, what do you mean when you talk about brain shrinkage on an MRI scan? In terms of making a diagnosis of any dementia, we will usually do our own tests, our questions, our memory tests, and then we'll go on and do MRI scans or PET scans. We do rely quite a lot on CAT scans and MRI scans as the first scans we do in people, and what we are looking for there is brain shrinkage, or what's called atrophy in the brain. So, because I'm often asked, I thought it's worthwhile just letting people know what we're actually referring to. Many people will often want to look at their brain scans and understand what it means.
So this is a brain scan, which is done in a certain slice if you like. This slice is, if you like, we are looking at the person who's standing right in front of us. Their eyes and their noses are somewhere a little bit ahead of this scan, but we're taking slices through from the front to the back, and we've stopped about halfway now. So, if we had another slice, if this was a few slices backwards, we might see the person's ears here, for example. This is the top of their head and this is the bottom. What we're seeing here is the grey and the white matter of the brain. This is the grey on the outside, this is the white matter on the inside. These are the normal fluid-filled areas of the brain called the ventricles. These are normal, these black areas.
What we're seeing here on the left is pretty much a normal brain with normal white and grey matter. This is the hippocampus in here on the left. The area that is not normal on this scan and where there is shrinkage is on the right-hand side of the brain, and it's this area here, this is the hippocampus, and you can see this is shrunken compared to the other side. You can see there's more fluid in this area compared to the other side, and you can also see that these areas here are much smaller and shrunken compared to the equivalent areas on the other side. When we're referring to brain shrinkage, these are the sort of changes that we are referring to.
This is another example, again, of a scan taken in the same way where you can see that, if we just go back to the other scan, you can see the fluid filled areas of the brain here, these are of normal size. In this area, they're much bigger because the brain is much more shrunken in a general sort of way, so we can see the hippocampus shrunken here, like the previous scan, like that; but you can see it's happening on both sides, and that these areas of the brain which is equivalent to this area, are much, much bigger. There are more fluid-filled areas than there should be. This brain scan shows what's called generalised atrophy or generalised shrinking across all areas of the brain.
The other question that will often arise when we see people with a diagnosis of vascular dementia, and we talk about mini strokes is, well, what are we actually talking about? What are we actually looking at on a scan? Most of us will be familiar with a stroke, which causes either weakness on one side of the body, or problems with your speech, or problems with your vision. There are, on occasion, strokes that don't affect the eye or the movement parts of the brain, but affect the white matter of the brain. And this is the part of the brain, the white matter in here, where all the wiring of the brain occurs, so the wiring of the brain connects different brain cells from one region to another. That's what the white matter is doing and what it's for.
When there are lots of these what are called “mini strokes”, if you like, these are strokes, or these are changes affecting the white matter of the brain, where there's not enough blood going to these parts of the brain because of blockage in the blood arteries, and it leads to very slow, and often, silent changes in the brain. So, we don't necessarily see paralysis or visual problems, what we see are very slow changes in cognition, and thinking, and memory. So, a typical story when we see a patient who has a brain scan looking like this is of personality changes, behaviour changes, maybe changes in judgement or insight, and also, some difficulties with memory. But it's usually a lot more the personality, behaviour changes that occur first, rather than the memory changes. This is a scan where there's been quite a lot of these mini strokes, if you like, so many in fact, that they've all, many of them have joined up and it looks like one large area of what's called ischemic change – ischemia means lack of blood supply to the brain.
So, a lot of what I've already spoken about refers to all types of dementia, not just people with younger onset dementia. Younger onset dementia makes up about 10% of all cases of dementia. The average age of onset, if we look at everyone who's under 65, the people we see here at The Royal Melbourne, is about 51 to 52. This is pretty typical for other clinical services that see people with young onset dementia. Now, that's an average age. So, because we're seeing people under 65, the maximum obviously is 65, but the minimum can be in some cases even teenagers who are very young can develop very, very rare types of dementias, often what are called metabolic dementias, which cause brain changes, particularly to white matter, for example.
What's important here is that the younger the onset of a dementia, the more likely it is that it's going to be diagnosed as a psychiatric condition. So, it's understandable that in those very, very rare cases where someone is in their 20s, and is developing a type of dementia, let's say a white matter type of dementia, that they will usually have problems with personality, behaviour, or psychiatric changes. When they see their local doctor or even a psychiatrist, people won't necessarily think of a dementia as the main reason for this presentation, it'll be depression, or anxiety, or in some cases, schizophrenia or bipolar disorder. That's understandable because 99% of young people who present who have those issues will have a psychiatric problem, not a dementia. We do know from the literature and evidence that the younger the dementia, the more likely people will present with a psychiatric condition, often, a psychosis, and be diagnosed with schizophrenia or bipolar disorder.
Because younger onset dementia is so rare and not something that most general practitioners are used to seeing, the diagnosis will be delayed. And it's not uncommon for us to hear from someone that it was hard to convince the doctor that anything was wrong. We were told that it was age, or stress, or maybe alcohol related. We've done some work in our own unit, and the people coming to see us had seen, when we did this study, an average of five specialists before actually being referred to a specialist service, and that the waiting time was around three or four years. This is consistent with what other people around the world have identified in different studies as well, that it takes three to four years for a diagnosis, which is, obviously, three to four years too long.
So why is younger onset dementia important to diagnose early? There is a significant impact – three or four years of behaviour, personality, psychiatric, and cognitive problems have a significant effect on patients, families, carers. It's not uncommon for us to see people whose work has broken down, marriages have broken down, relationships have broken down, because the diagnosis has been attributed to alcohol, or substance use, or depression, or midlife crisis. So, the earlier we can make the diagnosis, the earlier people understand what's going on, and it could well avert some of these significant impacts on families and carers.
There are genetic implications. For example, in certain cases of Alzheimer's disease or frontotemporal dementia, they can be genetic, and there can be up to a 50% risk for the children of people with Alzheimer's or frontotemporal dementia, in those cases which are genetic. And this is very similar to the condition I mentioned called Huntington's disease, where people who have Huntington's disease, their children, each of their children will have a 50% risk of inheriting the condition. So, the earlier one can make a diagnosis, the earlier that a genetic condition can be looked for, and then that can also then have implications for children. When I say children in the genetic context, referring to adult children, rather than children children, or adolescent children, because genetic testing will generally not be done in children or people under the age of 18 for a dementia, unless it's one of those very rare dementias for which there's a known treatment. So, if we are going to test the children of our patients, they need to be over the age of 18.
The diagnosis is important because there's a relative lack of social supports and services. And as soon as the diagnosis is made, we do have access to a lot more supports, particularly through the NDIS, which has been very useful for people in the last five or six years. Prior to the advent of the NDIS, it was really difficult for people to find appropriate supports and services. Younger onset dementia is also important because there is not as many research studies being done, and it's important that we try and understand the younger onset dementia perspective from a research perspective.
As I've mentioned, diagnosis is delayed, and it does take longer to diagnose younger onset dementia than in the older person. As I've mentioned, first symptoms are often interpreted as stress, midlife crisis, problems at work, depression, alcohol, or mental illness. We have done a study on the people we've seen over a period of time, so looking at different types of dementia, the delay to diagnosis, and what diagnosis people received. And it is important that even in an expert facility where we have access to all sorts of scans, and specialists, and tests, a fifth to a quarter of people may leave without a clear diagnosis. So that's not an uncommon point for us to reach with people where we say, "Look, something's going on. Unfortunately, we just don't know what it is. We can't give it a name at the moment." And that is clearly, can be frustrating to people, the patient themselves, the carers, the families.
We see lots of different types of dementias as I mentioned before. There are three or four common types, but in this study that we did, there were 29 different types of dementia. We also, in association with this study, looked at the time to diagnosis, and we've been seeing people with younger onset dementia for many years, and we did a study looking at our patients from the 2000, or actually the 1990s through the 2000s, and up to 2014, looking at how long it had taken to make a diagnosis in this group, and what we found was that on average, it was about 3.8 years. Though, in the period after we established a younger onset dementia service, which is around 2010 or '11, from that period on, the delay was much shorter, so it was 2.8 years. Now, it wasn't just because we established a service that the delay was reduced, but I think that certainly had an impact that people knew where to go, and we established a service that was available at a state-wide level. Getting the diagnosis may not be the most welcome of news, but at least it provides people with an understanding of what's happened. As this lady has said in this quote, "Getting the diagnosis is so important, and the doctors understand..." As mentioned, there can be an impact. The diagnosis has an impact on relationships, children. It has financial impacts and social impacts, which is why it's so important to diagnose early.
In terms of the diagnosis, there is often loss and grief associated with the diagnosis of younger onset dementia, but in some situations, it comes as a relief to know and to show that there is something going on, and now we can deal with it. We can get on and actually deal with what this is, because we know what it is now. And there's been a number of media articles and shows on the younger onset experience, and this was one of these that is on the slide here for Andy and his partner. The impact on carers is significant, and needs to be a significant focus when seeing people with younger onset dementia. And it is probably greater than the impact on those carers of people who are older when they're diagnosed. There's been very limited research on the impact of younger onset dementia on couples, and on the impact on couples.
Genetics, as I've mentioned earlier, there is a high proportion of younger onset dementia of genetic diagnosis in people with younger onset dementia. And this can have a very complex impact on people. Making a genetic diagnosis is something that has to be discussed with the person and their immediate family, because it has impact on the wider family. As I've often said to people, making a genetic diagnosis will have an impact, not just on yourself and your children, but may have an impact on siblings. It may have an impact on parents. That information is not always welcome though, and this is something that has to be considered when thinking about whether to have genetic testing, and then on who to tell. The knowledge, or the new knowledge that there's a genetic condition within a family needs to be thought about very carefully, because it's not always welcome news.
So, how does younger onset dementia progress? Well, we actually were very keen to understand this and provide an answer to our patients and their families, and there there's been some literature and medical research looking at this, but we decided we would do it in our own group, and look at what's happened to people with younger onset dementia that we had seen over a 20-year period. We looked at a research study of 500 people who'd been through our service, diagnosed with young or onset dementia, trying to understand what's happened to those people through a resource which is known as the National Death Index. So, we're actually able to identify when people passed away compared to when they were first diagnosed. What this showed us is most diagnoses of young onset dementia, the average duration of life from diagnosis was around 10 years. That was about the same for Alzheimer's disease, frontotemporal dementia, it’s a little bit less for people with vascular dementia, but by and large, the average was 10 years. Now, it's important to note this is an average. So what an average means is that there were some people whose illness lasted three or four years, other people whose illness lasted 15 to 20 years. People with Huntington's disease, on average, had a duration of life from diagnosis of about 20 years.
Now, this is one of the graphs that we've done which shows you what's happened to people. So, this is where we begin at time zero for a person or the diagnosis, and what we're seeing along the bottom here is how many years people live for, and you can see that for Alzheimer's disease, frontotemporal, and vascular dementia patients, which are these coloured lines here, the red, the orange, the blue, and the green, it's a similar pathway that the red line is where 50% of people have died, and you can see that that red line is at about the 10-year mark. But there are people whose diagnosis and duration of illness went for 20, 25 years, and then a proportion of people for whom it was less than 10 years.
Unfortunately, at the of the illness or when we diagnose people, we don't necessarily know where they're going to fall on this chart. We don't, unfortunately, have any blood tests that tells us how quick or how slow the dementia is going to progress in any one person. The best indicator is usually what's happened in that person, themselves, over time, and how rapid or slow it's been for them.
Community supports. I don't have to... I suppose I do have to, but I don't really have to mention the role that Dementia Australia play in providing supports to people across the nation. Huntington's Victoria and Huntington's associations in other states also provide similar support to people with Huntington's disease.
Now, what about treatments? We'll finish with this, just a brief discussion on treatments of Alzheimer's disease particularly, but also other dementias. Despite numerous Alzheimer's trials, we've yet to find a drug which helps to slow down or stop the progression. There have been some promising newer trials using antibodies against amyloid, and I actually prepared this talk, or updated this talk a couple of days ago, but just to show you how quickly things move, I woke up yesterday morning and found that the FDA in America has granted an accelerated approval for an Alzheimer's drug on June the 7th, 2021. This is a drug called Aducanumab, and hopefully, that similar approval will be provided here in Australia for this drug, which does work against amyloid, and for which there's some reasonable evidence that it can help slow things down in Alzheimer's disease.
We, at The Royal Melbourne and The Alfred Hospital with Professor Terry O'Brien, are looking at a frontotemporal dementia study. Frontotemporal dementia drug studies have been few and far between, unfortunately. We've now have a large grant to look at frontotemporal dementia using a drug called sodium selenate, which was discovered by some local scientists here in Melbourne. That study is now open and recruiting for frontotemporal dementia.
I might just mention there are what are called gene silencing trials in Huntington's disease. What this means is that in Huntington's disease, we know what the abnormal protein is, and there are drugs being used to track down this abnormal protein and get rid of it, and stop the protein itself accumulating. These drugs are part of a family called the gene silencing drug family, and there are potentially treatments on the horizon for that particular type of frontotemporal dementia that's associated with motor neurone disease. These just some of the people involved in our work at The Royal Melbourne Hospital in the Young Onset Dementia Service, our crack team. Maybe not the best choice of words, but they are a very, very good team, and involved in the diagnosis, and assessment, and treatment of people with younger onset dementia. That's my last slide. Thank you very much for listening.
[Title card: Together we can reshape the impact of dementia]
[Title card: Dementia Australia. 1800 100 500. Dementia.org.au]
[END of recorded material]
More for you
- Younger onset dementia: the facts
Younger onset dementia is any form of dementia diagnosed in people under the age of 65. Learn the facts for people living with younger onset dementia.
https://www.dementia.org.au/about-dementia/younger-onset-dementia/younger-onset-dementia-facts - Living With Younger Onset Dementia Program
A program for people recently diagnosed with younger onset dementia, including information, advice and support.
https://www.dementia.org.au/get-involved/events/living-younger-onset-dementia-program - National Disability Insurance Scheme (NDIS) support
If you’ve been diagnosed with dementia and you’re under 65, you may be eligible for Australian government support through the National Disability Insurance Scheme (NDIS).
https://www.dementia.org.au/get-support/national-disability-insurance-scheme-ndis-support
The National Dementia Helpline
Free and confidential, the National Dementia Helpline, 1800 100 500, provides expert information, advice and support, 24 hours a day, seven days a week, 365 days a year. No issue too big, no question too small.