Millions of people around the world live with a form of dementia, which severely affects both their own and their carers’ quality of life. The specific causes behind dementia remain unclear, but researchers are making steady progress in finding out more about its mechanisms. This instalment of In Conversation looks at some of the realities of dementia, and presents new directions in dementia research.
Dementia is a neurocognitive syndrome that refers to a collection of symptoms related to memory loss and the decline of cognitive function.
The most common form of dementia is Alzheimer’s disease, which affects millions of people worldwide. According to data from the Centers for Disease Control and Prevention (CDC), in the United States alone, in 2020, as many as
Research conducted by the Alzheimer’s Society in 2019 indicates that over 850,000 people were living with dementia in the United Kingdom that year, and globally, more than
There are some treatments that can help alleviate some dementia symptoms, but most forms of dementia are currently incurable, and researchers continue to investigate the mechanisms through which this syndrome develops with a view to developing better treatments and prevention strategies.
In our latest instalment of In Conversation, we spoke with Paula Field, who is a caregiver for her mother who lives with Alzheimer’s disease, and with Dr. Kamar Ameen-Ali, who is a lecturer in biomedical science at Teesside University in the United Kingdom, and who specializes in neurodegenerative diseases, including Alzheimer’s.
This article provides an edited and shortened record of this instalment of our podcast. We have added reference links to key research findings mentioned in it. Please listen to the podcast — below or on your preferred platform — for the full discussion.
Dr. Hilary Guite: Let’s start with an overview of dementia and its causes.
Dr. Kamar Ameen-Ali: I always think that it’s good when we are discussing dementia to start off with a definition of what we mean by it. Often you might hear people use it interchangeably with things like Alzheimer’s disease, but they’re very distinct things.
Dementia, we kind of describe it as an umbrella term. It describes a set of symptoms, it’s a clinical syndrome — those symptoms are often associated with memory impairment. But for a diagnosis of dementia, you also have to have an impairment in one or more other cognitive domains as well — this might be personality, it might be visual-spatial skills, for example.
And as I mentioned, dementia as a clinical syndrome is distinct from something like Alzheimer’s disease, which is a type of brain disease that leads to dementia.
Dr. Guite: Is dementia hereditary?
Dr. Ameen Ali: It depends on what brain disease we’re talking about. So if we’re going to talk about Alzheimer’s disease — which I think is a good idea, because it’s the most common brain disease that leads to dementia — there are some types of Alzheimer’s disease that are hereditary and some types that aren’t.
The most common type of Alzheimer’s disease is what we call sporadic Alzheimer’s disease, and that counts for 97% of Alzheimer’s disease cases. So 3% of cases of Alzheimer’s disease will have that known genetic origin, and this is caused by genetic mutations.
So only a small percentage of actual Alzheimer’s disease cases have got that genetic, known hereditary link.
Dr. Guite: Thank you. So Paula, you’ve been looking after your mother with dementia alongside working. Can you tell us what you first noticed?
Paula Field: Yes, I am. I think my sister and I first noticed that there were some issues with her memory after my father had died. I think that she had started to develop some form of dementia before that, but [our parents] sort of helped each other out. And I think [our father] helped her through a lot of those daily things.
After he died, I think it became much more obvious [that something was wrong], but, you know, at that stage, we weren’t sure whether [her symptoms were] sort of a grief thing. But it gradually progressed. And it probably took us about 6 months or so after he died to realize that, you know, we probably did need to take her to the doctor, and to find out what was happening.
Dr. Maria Cohut: Paula, how did this affect you and your sister financially and during day to day life?
Paula: Well, I think in the early days, you could have a conversation [with our mother]. [My sister and I] were both working full-time, we’d go visit weekends, so we were there really regularly. In terms of financial impact, at that stage, there wasn’t very much, we just carried on as usual. We didn’t have any [additional] carers or anybody at that stage, we used to just go in as often as we could.
Then, once it got to the point when we had to take her to the doctors for her first memory test, and once the results came back, that’s when we had to start thinking about [arranging] more care. And that’s resulted in my sister having to take a day off a week from her work and spend two afternoons a week with my mom.
She has been doing that for nearly 4 years now. And we have other carers going in about twice a day now want to make sure that she gets up, and give her some lunch and the other one in the evenings, to give her some dinner. They do that about 4 days a week, and we pick up the rest.
Dr. Guite: What sorts of scans and diagnostic process happens nowadays?
Dr. Ameen-Ali: There are different types of scans that can be done, [such as] PET scans and MRI scans.
In terms of how well they can contribute to the diagnosis of brain diseases? Questionable, I think, because if we’re looking for brain changes that are associated with Alzheimer’s disease, for example, the question is how well can we see that pathology in the brain in life. Something like Alzheimer’s disease can actually only be diagnosed post mortem, when we can confirm that those pathological changes in the brain are actually there.
But something like a PET scan or a CT or an MRI scan, they can see whether there is that general atrophy in the brain, and that is something that we would expect to see in something like Alzheimer’s disease, particularly atrophy around the hippocampus, which is the part of the brain that is responsible for different memory processes.
So to a certain degree, these brain scans can help with the diagnosis of a certain brain disease that is leading to dementia, but we have to remember that it can only ever be confirmed post mortem.
Dr. Guite: You mentioned there atrophy, what does that mean?
Dr. Ameen-Ali: Atrophy is basically where the brain tissue degrades. If you were to see a brain that had atrophy, you’d see essentially shrinkage of certain areas of the brain.
Dr. Guite: My understanding is that the new PET scans can look at how the brain metabolizes nutrients, like sugar, and that they can show whether or not there are are some some proteins that get misfolded. Can you just explain what those proteins are — amyloid and tau — and how important they are?
Dr. Ameen-Ali: Amyloid and tau are the kind of characteristic pathological features of Alzheimer’s disease. Amyloid is a protein that will aggregate and clump together in the brain and form plaques, and that’s what we see in Alzheimer’s disease.
These plaques then disrupt neuronal cell function, and then that leads to a lot of those cognitive issues that we talked about earlier.
There’s also tau, which is [another] protein in the brain. Again, it’s another characteristic pathological feature of Alzheimer’s disease. Normally, it’s a protein within axons of nerve cells, and it helps to form what we call microtubules that are responsible for transporting nutrients within the cells.
What we see in Alzheimer’s disease, is that it aggregates into these tangles, and it disrupts cell function in that way, and it affects how cells communicate with one another.
Dr. Guite: Paula, after that initial phase and the the memory loss, what else did you start to notice [in your mother]?
Paula: Well, we noticed that she became quite isolated. She didn’t leave the house, she did start to leave her peas on the cooker. And I think, you know, that was the point where we started to go, “Eek, this is getting quite serious.”
She still has some sort of instinctual habit, so she’ll still switch off the switches at the end of the day. That’s something that she’s done forever. But pretty much everything else…
She knows there’s a fridge in her house, and she knows that there should be something on the shelves, and she will put stuff in the fridge. It could be a packet of crisps or it could be a cup. She has this sort of visual memory of the fridge, she sort of knows what it’s for, but she doesn’t quite know how to use it.
But that’s about it. She doesn’t feed herself. If she won’t drink water, she certainly couldn’t take medicines. She does not wash [on her own]. If we ask her to wash her face or something, she’s quite canny, she’ll go in the bathroom, close the door, won’t let you in, and then come out again.
She still believes that she cooks her own dinner, she still believes that she can do all the things that she’s always done. I don’t think it’s denial, necessarily. I think she just [thinks that] it’s happened, therefore, she must have done it.
She has no idea who myself and my sister are — she recognizes us [as familiar faces], but she doesn’t know who we are. She has no knowledge of people going in every day to help her.
She’s not very active, she pretty much sits on her chair everyday with the TV on and looks into space.
Dr. Guite: Kam, can I come back to you from that devastating description of change in personality change in behavior, what’s actually happening in the brain? Because earlier you said [changes] started in the hippocampus, which is the area related to managing memories. But it sounds like more things are happening. What what would actually be happening as the dementia progresses?
Dr. Ameen-Ali: This is one of the complexities of these types of brain diseases that lead to dementia: First of all, how they can affect people very differently based upon the parts of the brain that are affected by the disease.
With something like Alzheimer’s disease, we we know that the pathology progresses into certain areas. And as the disease progresses, it starts to affect more areas of the brain, which is why you might initially see some memory problems.
But a lot of people might dismiss them as just getting older until then the disease progresses, and more and more cognitive domains start to be affected. So as the disease progresses to more of the cortical areas, you might see more issues around language around personality, and then visual-spatial issues that you might see later on as the disease progresses into those cortical areas.
Dr. Guite: Can we just look back to and understand why these things are happening? What are the risk factors related to chronic disease and exposures?
Dr. Ameen-Ali: If you remember, earlier on I mentioned sporadic Alzheimer’s disease — the Alzheimer’s disease that occurs in most cases. And it’s usually over the age of 65 that we would see that, so that when we’re talking about risk factors, they’re associated with that type of Alzheimer’s disease.
We have what we call non-modifiable risk factors. Those are those risk genes that I mentioned earlier on. Age and sex are also non-modifiable risk factors. Age is actually the biggest risk factor for something like Alzheimer’s disease.
But we also have these 12 modifiable risk factors. These are things that we do in our life that potentially we could change that can reduce our risk of dementia. And there are also, generally, things that we can do to promote good brain health, generally.
These modifiable risk factors include things like obesity, hypertension, diabetes, smoking, physical inactivity, loneliness… Brain injury is a big one as well.
Dr. Cohut: So some of the risk factors, but also the preventive interventions that get a lot of press are education and social activity. Presumably, the the longer you stay in education, and the more socially active and involved that you are the lower the risk of dementia. What about your mom, Paula? What was her experience of education and also social life?
Paula: Education minimal, if at all. You have to remember, she was born in the early ’30s. Her social social life was pretty good. [My parents] did have a group of friends when they were into their 50s–early 60s. They’d go on holidays together and and stuff like that. But that was quite sporadic.
And then they might see their friends every now and then. But predominantly, I would say they sort of stuck together. My dad was the social one, he had a much more active life.
Dr. Guite: How old was your mom when she left school?
Paula: Certainly no more than about 13. She wasn’t there very often. You’ve got to remember the [impact of the] war and evacuation and all that sort of stuff.
Dr. Guite: What is happening when we’ve got these elements of education, hearing impairment, social contact — how are they protecting against or reducing the incidence of dementia?
Dr. Ameen-Ali: These risk factors that we’ve talked about, we know that they’re associated with an increased risk of dementia. But what we’re trying to work out as scientists and as researchers is: What actually is the mechanism that is linking these risk factors with the kind of the disease that we see that then leads to dementia?
Because we can do studies where we can find out whether there is a significant correlation between these factors and dementia, but what exactly is causing something like brain injury to increase somebody’s risk significantly to then develop dementia?
The way that I like to imagine it is that our research into trying to understand these mechanisms is like the black box, that we’re trying to work out what’s happening inside that black box. So we’ve got these risk factors on one side, which is the input, and then the disease and the pathology, which is the output, but what is happening on the inside?
It’s almost like you’ve got risk factors and protective factors. And, you know, it’s all about that balance between minimizing your risk factors and maximizing the protective factors.
And it’s a game of probability, really, because there’s no guarantee that doing any of these things, you will get dementia. And there’s no guarantee that if you don’t do any of the things that you’ll be protected from it, but it’s all about managing risk, essentially.
Dr. Guite: I read that all of those 12 risk factors only account for 40% of dementia cases. So you’ve got the other 60%, which is in your black box. Can I come back to your black box now? Because we’ve got amyloid and tau, and we’ve got these risk factors, but what else is going on?
Dr. Ameen-Ali: Neuroinflammation is quite a significant area of research in terms of looking at a potential mechanism that would be driving brain diseases that lead to dementia.
Neuroinflammation is something that I’m interested in. There is a type of immune cell in the brain called microglia, and they’re involved in an inflammatory response in the brain.
A lot of the research that I’ve done is around brain injury. So I’ve looked at these cells, these microglial cells, and both the acute inflammatory response and also a chronic inflammatory response as a result of brain injury, and how that might be the mechanism that is increasing the risk of dementia after brain injury.
So it’s all about how the cells respond as part of a neuroinflammatory response in the brain. And how, over time, if there is a chronic response, because we know that neuroinflammatory responses are originally designed to be protective, but if it’s if the cells are activated long term, as in chronic activation, could they actually be causing damage? And could that be what is then leading to the development of the pathology that we see in something like Alzheimer’s?
Dr. Cohut: I was also thinking about some recent research that’s been looking at the gut-brain axis, so the link between the bacteria in our gut and what goes on in our brain. And there’s been some talk about the influence of gut bacteria on the brain in the context of dementia. So I’m wondering if that might have anything to do with neuroinflammation at any level?
Dr. Ameen-Ali: It’s possible, because when we’re talking about neuroinflammation, this could be systemic inflammation. It could be inflammation that’s happened at some point in a person’s life. It could be inflammation that has happened and then affected the brain.
So there is the possibility of inflammation that’s happened somewhere else in the blood, in the body that has then led to an inflammatory response in the brain. It doesn’t necessarily have to be from an injury that I look at in the brain, it can be systemic inflammation as well.
Dr. Guite: How are you feeling about the future for dementia and Alzheimer’s?
Paula: It’s a tricky one. I think, in our situation, if we’re to be brutally honest, it’s too late for any sort of treatment for my mom. For us, it’s just about keeping her safe, making sure she’s fed, making sure she drinks…
You know, my question is at what point do you think that people should approach their doctor for a diagnosis or a brain scan? Because, you know, in her case, we didn’t notice it, it was too late. I’m not saying they could have stopped it.
But at what point do you think that we need to get on top of this, and actually not wait until the diagnosis? Because once you’ve got a diagnosis, you know, there’s pretty little that you can do, and it’s sad, it’s a waiting game, and we don’t know what to expect. We had no warning, there was nothing that we could do about it in advance.
Dr. Ameen-Ali: I would say that [obtaining a] diagnosis as early as possible is the best thing to do, really. And that can be really challenging, because often, those early signs can be just dismissed as getting older or not really significant enough.
[However,] the earlier the diagnosis, the better, because [then] treatments will be the most effective. They can’t stop the disease, but they can have a much more significant impact on symptoms the earlier that they’re delivered.
I do think that going forward, we need to be able to diagnose much earlier, if we want to have effective treatments. And in terms of developing treatments, it’s unlikely that we’re going to have one single drug that is going to have a significant impact. Because there’s lots of these different potential disease mechanisms, it’s likely that we’re going to need different drugs that administered together, in parallel that will have any significant effect on disease progression.
Paula: Do you think that, potentially, we could get to a place where testing for or diagnosing dementia will be something like you’d have for breast cancer screening that becomes a routine part of your everyday medical self-care?
Dr. Ameen-Ali: I think so. I think if we have better cognitive tests that are more sensitive to certain types of memory decline, because different types of memory decline at different rates.
If we have sensitive tests, then we can certainly administer them at a certain age when your risk increases. And then hopefully that will start picking people up at an earlier rate when the disease is in its earliest stages. And that’s what I think will have a significant effect on on dementia in the future.
Source - Medical News Today
