Instant Genius - How new research is combatting Alzheimer’s disease

Episode Date: May 18, 2025

One in three people born today will develop dementia of some form in their lifetimes. Of these, around 60 per cent will suffer from Alzheimer’s disease, the most common form of dementia. Currently, there is no cure for this debilitating condition but by raising awareness we can help to reduce its impact until the many researchers working around the world develop more effective treatments. In this episode, which coincides with this year’s Dementia Action Week, we speak to Dr Richard Oakley, Head of Research at the Alzheimer’s Society. He tells us what happens in the brain as Alzheimer’s disease develops, points out some early warning signs to look out for and talks us through some of the latest breakthroughs that may one day help us beat dementia once and for all. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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now. Book on Hilton.com or the Hilton app and save up to 20% to get the stay you expected. When you want savings, not surprises. It matters where you stay. Hilton, for this day. This podcast is sponsored by name, audio and focal. Streaming has made music more accessible than ever, but true listening is about more than ease. It's about quality. British audio experts name Audio, alongside French acoustic specialist focal, combine handcrafted tradition with cutting-edge innovation and high-end materials, delivering digital precision with analogue warmth. So you can experience exceptional sound at home. Music just as the artist intended. Visit name audio.com to learn more. Hello and welcome to Instant Genius, a bite-size masterclass in podcast form. Every Monday and Friday,

you'll hear world-leading scientists and experts talking about the most fascinating ideas in science, and technology today. I'm Jason Goodyear, commissioning editor at BBC Science Focus. One in three people born today will develop dementia of some form in their lifetimes. Of these, around 60% will suffer from Alzheimer's disease, the most common form of dementia. Currently, there's no cure for this debilitating condition, but by raising awareness, we can help to reduce its impact until the many researchers working around the world develop more effective treatments.

In this episode, which coincides with this year's Dementia Action Week, we speak to Dr Richard Oakley, head of research at the Alzheimer's Society. He tells us what happens in the brain as Alzheimer's disease develops, points out some early warning signs to look for, and talks us through some of the latest breakthroughs that may one day help us beat dementia once and for all. So welcome to the podcast. Thanks very much for joining us. Thank you so much. Great to be here.

So today we're talking about Alzheimer's. disease. So let's get some sort of housekeeping out of the way first then. What exactly is Alzheimer's disease and how does it differ from dementia? Because the two are often confused. Yeah, absolutely. I think very often they use interchangeably and they are very different things. So dementia is an umbrella term for a whole bunch of different diseases of the brain. And it's kind of a collection of symptoms that we know, things like memory problems and challenges with speech that we'll come to talk about. And Alzheimer's disease is the biggest cause of dementia.

So about 60% of dementias are caused by Alzheimer's disease. So that's why they're used interchangeably often because they are, it is the biggest cause. But you also have things like Louis Body dementia, your frontal temporal dementia, Parkinson's dementia, vascular, you have many other forms. But Alzheimer's disease is the biggest cause of what we call dementia. So the comparisons to cancer are often used. Cancer is the umbrella term, but people don't. have cancer, they have breast cancer or leukemia or brain cancer. It's exactly the same

with dementia. You say dementia, but you should be able to say actually which disease is causing their dementia. Is it Alzheimer's disease? Is it a living body, is your frontal temporal dementia? So Alzheimer's is a disorder of the brain. So let's have a look. What's going on in the brain of somebody that has Alzheimer's? Yeah, I mean, one of the things you have to start with, I mean, the brain is the most complicated organ, one of the most complicated structures we know existing. So the only truth is we don't know exactly how a healthy brain works. So everything has to be taken here with, this is our best guess in some instances. But what we know does happen in an Alzheimer's disease, and then there's a few things we know do happen, is that over time we all have many processes

going on that involve many different components. And a number of these are different proteins that have different functions in a healthy brain. And what happens in Alzheimer's disease is a cup of of these proteins, start collecting, aggregated together, clumping together in your brain. And they do it in different places. Some of them do it inside the cells. Some of them do it outside the cells. But what it leads to, it's a kind of a toxic environment. And what that leads to is the death of your brain cells. And as your brain cells slowly die over the time, of course, that impairs the function of the brain. And that's why speech and language, orientation, memory, really gets affected over time. And it's just the accumulation of these proteins, which we all have.

And we all produce. But when we're younger, we clear them away more efficiently. And as we get older, as things happen, their environment and changes happen, the clearance of those proteins slows down often, and that's when they accumulate, cause the challenges which lead to the symptoms of dementia. So let's have a look at some of these symptoms then. You touched on them there. You know, what are they? How does it manifest? Yeah, and one of the things I want to point out, which I always find really interesting, is it actually takes a long time for the symptoms to manifest, so we believe these proteins, one of them called amyloids, starts building up actually 20 years before the onset of symptoms.

So we actually have this huge window where actually people's brains are managing to really mitigate the damage being done by the buildup of these proteins, one of them being amyloid, within the first one, another one being tau. And like I say, these are proteins in our body

that we need for different processes, but they do start accumulating and start causing damage. And it's in that 20-year window, your brain mitigates the damage. We call brains having elasticity, if they're able to kind of navigate around the kind of highways, if you imagine these highways are being broken

and they find them a back route to be road to get around the damage and you can still perform those functions. And over that 20 years, the damage becomes too great and unfortunately people's brains aren't able to mitigate. And one of the most common symptoms with Alzheimer's disease is memory problems. And that's due to the parts of the brain to get affected. And it can affect people in different ways.

And I think one of the things we say at Alzheimer's society when we speak to people living with dementia and people have cared for people. If you know one person living with Alzheimer's disease or dementia, you know one person. Everyone's different. Everyone interacts differently. Everyone has different support mechanisms. Everyone's brain has different kind of like say elasticity and abilities to affect it. But definitely one of the most common things is memory problems.

Certainly short-term memory is often one of the first things to go where people can still remember things for a long time ago. But one of the first things is they can't remember. a conversation you had that morning. And that is definitely one of the most common. You do get other things that can happen. And again, sometimes it's in different forms of dementia about Alzheimer's disease. Can have issues with language and communication, particularly towards the end.

And it's normally a five to seven year period after people's kind of symptoms really kick in that you have to live with this disease. Because it is a terminal brain disease. No one has ever really survived Alzheimer's disease in the real sense of the word. There are different causes that cause some of the symptoms of the disease. dementia that aren't Alzheimer's disease, like sometimes get misdiagnosed, and we've had able to do things like that. But in terms of Alzheimer's disease, it's a terminal brain disease. No one's ever survived for that. And towards the end, you normally lose your communication abilities. People can have issues with orientation and visual perceptions as well. Certainly like looking

on the ground, seeing a black space can be seen as a whole and something you don't want to fall in, difficulty navigating stairs is another one. And I think one of the ones that is most challenging and again is reasonably common, although not everyone experiences it, is changes in moods and emotions, you have sleep disturbances, getting aggression, and that's often because people are confused and scared because they don't recognise the person around them or they're not able to do tasks they're able to do anymore and they get agitated. And so the changes in the mood and emotions is definitely a reasonably common one and certainly one of the ones that's more difficult to manage. So you mentioned there that this sort of 20 year progression. So are there any kind of early

warning signs, you know, some sort of alarm signals. Yeah, I mean, there are, I think, again, it does vary from person to person. And certainly one of the things that I think is not appreciated enough is actually one of the best things is just a loved one, a care of, friends, them noticing differences, because everyone will experience dementia differently at different rates, like I say, different speeds as it progresses and in different ways, depending on exactly how their brain has been affected. So actually, it's really important for loved ones and friends and family. If you notice changes, someone struggling with their memory, someone getting more confused, more often,

asking the same thing repeatedly. I think that's actually one of the best indicators we have because often you don't have a baseline. You don't know what someone's like. Some people aren't very good at directions and regularly go out and get lost all the time. That's got nothing to do with dementia. That's just because they're not very good

at navigating their way around the world while someone else may never have got lost and when they do that happen. So it's really subtle changes in behaviours and differences that you start noticing. And again, it's a gradual process. One of the things that during the journey of someone developing dementia and how do you know it is dementia rather than just as we all age,

sometimes we do get more forgetful. We do forget where our keys are and things like there is a certain element of that. That is natural aging. Alzheimer's season dementia is not natural aging. And the difference is we may all forget our keys or may say, oh, where are we going again tomorrow? But if someone says, where are we going again tomorrow and you've had that conversation with them seven times in the last couple of hours,

that is dementia, that is the brain disease, Alzheimer's disease that is causing that. It's not, hey, like at the end of a long day, or where are we going to what we do. So I think it's the loved ones noticing those subtle changes, those forgetful moments, but occurring way more often than you would expect to happen. And people removing themselves in conversations when they used to be really social, again, not once at the end of a long day, but over a period a couple months you realize they're not engaging in conversations, they're not reaching for those social moments, things like that. So it is really difficult to say exactly what it is,

but it is changes to that person that someone close to them would notice that we would always highlight something that you should go get checked out. So you mentioned it at the start that it accounts for 60% of dementias. So sort of in the wider population, how common is it? Well, we say so people born today, one in three will develop dementia of some form. and there's about a million people today living with dementia. And so it is a highly prevalent disease is increasing. We know that by 2040 there we'll be 1.4 million people in the UK

and globally the numbers going up as well. And a huge part of that is due to the fact that we have an ageing population. And as you get an ageing population, that is one of the biggest risk factors. And I know that's something again we'll discuss later on. So it is a big problem. And I think one of the things with dementia that not uniquely, but certainly is one of the of the big factors it's not just a person with dementia. It is, of course, what happens is the family have to take on a lot of the caring responsibilities. We know we don't have the social

care system. There is no cure Alzheimer's disease right now. All we can do is mitigate the side effects for a limited period of time. And so the pressures on the loved ones, the family members, the friends to take on the caring responsibilities is also great. So it's not just a person that has Alzheimer's disease. It is also, of course, the carers that you have to consider as well. This is really, we always say, one the biggest, if not the biggest healthcare challenge facing the planet, because there aren't many conditions that are this prevalent, terminal brain diseases, where we just cannot treat them at all. And then Alzheimer's disease, dementia is certainly one of them.

You mentioned their age as being sort of one of the primary risk factors. What other risk factors are there? Yeah, there's a number. And actually, there's been a really fantastic piece of work done called the Lancet report into dementia and what that does is it kind of scans all the literature that commonly exists and it really looks at what are the causes and how can we go about mitigating some of those and again always have to remember it is different for different people but old age is definitely the biggest risk factor as we age we that we do have changes in our brains we do accumulate damage over time from

environmental genetic other factors and like i say that we all have these proteins we all create them, we clear them from our brains. And as we get older, those slow accumulations, and it's not making the difference. There is a genetic component as well. I would say it is much smaller than other conditions such as cancer. Typically speaking, it's not a genetic condition. I think the general accept it's about between 1, 3, 4% genetically driven. There are some subtypes of dementias that are more genetically driven than others. And early onset, Alzheimer's disease often has genetic components. That's kind of 60 and younger.

There's a more genetic component to those instances, but on the whole, it's not hugely driven by hereditary genetics. You do have other long-term conditions, things like diabetes, poor vascular health. We know what's good for your heart, it's good for your head. So we do know that some of these other conditions you can have are definitely risk factors. And actually, you don't often get pure outside of the disease.

You often have what we call comorbidities. other conditions that come along such as diabetes, you could have had a stroke and other things like that. There are called lifestyle factors. Like I've mentioned, what's good for your heart, it's good for your head, smoking, exercise, alcohol, those messages that I'm sure we're all familiar with. And we probably know do reduce their risk of cancer. They reduce her risk of cardiovascular seeds. We probably don't know, actually, they reduce your risk of dementia as well. But that that's absolutely true. There's some other things that are kind of more at risk. And the Lancet report pulls out things like education and staying socially active. These are things that we can do. And again,

we think this leans into this kind of social or your brain's plasticity. How able is your brain to cope with the damage that we know is caused by your Alzheimer's disease, by the buildup of these toxic proteins. And so definitely staying socially active, speaking languages, having higher education. These things generally tend to lead to a brain that's better able to mitigate some of these things. So not having them put you more at risk. So there are a number of things. There are other things that I looked at that some people think are also really clear risk factors and others aren't quite so sure on the evidence. But again, this is an active area of research, things like your environment and pollution, things like hearing loss. Again, is it the hearing loss? Is it the fact that you remove yourself

on social situations? There's good schools of thought and think both. I'm not sure we have a definitive answer. What world does pollution have? Again, is it causative or correlative? It's very difficult to know, does the pollution cause it, or is there some other factor that implies it that there's the two are linked? We're not sure, but definitely there's a lot of active research. But I think there are some things we can't control, like aging and genetics, but there are definitely things like lifestyle, exercise, diet, alcohol, because I'm just smoking, that we absolutely can control ourselves. No one goes to Hank's for his spreadsheets. They go for a darn good pizza.

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I mean, can that help? Yeah, it's a really great question. And I think one of the things where we're slightly more confident is staying social. So we definitely know that people that still have to think on their feet, have those social conversations, respond to questions, think about different things. That really helps keep your brain active. And again, we regularly use the kind of comparison to a muscle. if you don't use a muscle, it will not get picket, it will not get stronger, it will weaken.

And that's exactly the same with the brain. So absolutely staying social, learning languages. And exactly as you say, keeping your brain active by doing puzzles and other such things as doing musical instruments, they absolutely cannot harm. And they will keep you active. How much they make a difference for an individual is really difficult to say and when do you need to do it is really difficult. But I certainly think staying as active as you can, using, your brain to take on new challenges, learn new things. That's absolutely something that we'd encourage

people to do. So let's have a look at diagnosis then. So say somebody listening, oh, this sounds familiar to me or to one of my loved ones. You know, what's the next step then? Yeah, really great question. And actually, at the outside society, getting an early neck of diagnosis is currently our number one priority because getting that diagnosis unlocks everything. you know what you're facing, you understand your prognosis, you can get access to the care and support you need and hopefully treatments in the future, which again I know we'll touch on. So the first step is if you notice yourself or more often your loved one notices, those changes, those repeated questions, those changes in the behaviour that you've noticed every period of time.

The first step is definitely to go to your GP and have a conversation. At the OutSom Society, we have a symptom checklist that you can download from our website that kind of helps you identify the questions that you should ask your GP to help navigate that conversation because GPs have to know about a whole range of different things. It's very difficult for them to follow up on every single thing. And so this memory checklist kind of helps people go through that conversation with their GPs. And the GP will carry out an initial assessment that are checking with you. Again, it's often really difficult in one meeting to make any kind of assessment because really what dementia is it's a continual decline.

And so if you don't know what someone was like before, it's very difficult to know if they're on that decline. So it may take second meeting sometimes or see someone and see if you can see a difference. But often the caregivers, like saying, the loved ones, that if they are able to come with that individual, they are actually really helpful to saying actually a year ago, they cook Sunday roast every single Sunday and now they haven't been able to do that anymore. And so that that can be really helpful. And once your GP has been able to make that assessment, what they do is they then refer you to kind of more specialists to, undertake further testing, and that's normally at a memory clinic. And what they will then do is

kind of a cognitive assessment. And then there's a number of different ones, but essentially it's a written sheet of a number of different questions that kind of test things like your executive function, that's your kind of problem solving skills and your ability to copy images and diagrams. It's testing a whole range of brain functions that we know begin to suffer. And that's the most common test that people do, don't just get an initial idea. someone could have developed Alzheimer's disease. And then, like I say, really what they would do is that probably if you have someone has dementia rather than what is causing their dementia. And then you'd get referred to them for other tests, whether that be a lumber puncture.

So someone taking a little bit of liquid from your spinal column to have a look at whether these proteins that I mentioned are building up in the brain, they get circulated around your central nervous system and they can take out some of that and look for those proteins. Because if you have proteins in your spinal column, then chances are you can, you're, you going to have them building up in your brain, or they can do what's called a PETCT, essentially a brain scan, looking for those proteins building up in the brain and actually looking for the loss of brain volume. Because one of the things that happens over time is your new one start dying with these proteins. You can actually see the brain volume starts shrinking.

At the end of Alzheimer's disease, it's often by about the weight of an orange, it's how much brain volume you actually lose. And so they can look for things like that, but only actually some of the stats on diagnosis are the things that I find most shocking actually that, Only two-thirds of people in the UK can even get a diagnosis of dementia. And it's much less that get actually told what disease is causing their dementia. So a third of people don't even get a diagnosis. And that's the government's common target, actually, that only two-thirds of people get a diagnosis.

And less than 2% of people get that type of further, more accurate diagnosis that tells them what disease is causing their dementia. And of course, if you compare that to a name like cancer, that has a less than 30-day target for a diagnosis, and they're just over 60 day target for treatment. And then compare that to a third of people never knowing and two thirds of people finding out they have dementia, but with no time frame.

It can take five, six years to get that diagnosis. In fact, on average, it takes around two years. So the situation with diagnosis is challenging. And without that, you cannot get access to the care, the support that you need as someone who has Alzheimer's disease or your caring needs for the respite care. And you certainly can't get access to things like the symptomatic treatments, like to nepezeal,

that we have available now that do make a difference and keep people at home and independent for longer or for these new disease-modifying treatments that are coming down the track, which people we have to access, we hope, soon. Yeah, so say, unfortunately, somebody has received a diagnosis. What kind of, as you said earlier, there's no definitive cure. So what sort of managing strategies or drug therapies do we currently use? Yeah, I mean, so the first thing that happens is you can develop what we call a care plan. which is actually in nice guidance that everyone should have that.

And that really means that you have a good conversation with your loved ones, your families, with your GPs, about what you want to happen over time and how you want to manage your disease as it progresses. Because as I say, everyone is different and everyone wants different things, and everyone progresses at different speeds. So some of the really important milestones you can do is power of attorney. We know this is a terminal brain disease. It impairs your cognitive function.

And eventually at some point, won't be able to make decisions for yourself. And it's very then difficult if you haven't given power of attorney to a loved one. How do you do that when you're now cognitively impaired? And it just makes making any decisions very difficult later on. So if you can get that agreed early when you are able to make that decision independently, then that just helps everything along later on. You can choose about the type of care home you want, maybe even help pick your care home. You can get access to activities, dementia cafes, which are just kind of social environment, you can go to where you can find your local part where you can go there.

You can have a coffee, your care, a get a bit of respite, and you can meet other people. And again, you can only do that if you know you have dementia and you have a diagnosis. And the Alzheimer's Society, we have a helpline that you can call. We have dementia advisors who will come around your house and help you navigate how to get things like money off your cancer tax and other things like that and get your access to respite care potentially, although we know the social care system does not provide the support we'd like it to currently. You can't even ask and you can't even find it if you don't have that diagnosis.

And as I mentioned, there are some symptomatic treatments you can have. One of the most common commonly being a Denepazil. And what these symptomatic treatments do is they mitigate for the damage. They don't stop the damage or the accumulation of the proteins. They don't reverse it. But what they do do is they mitigate for the damage being called. And they essentially give a bit of a boost to your brain. And as I mentioned before, if you think of those high rays that are being discharged,

and your brain's having to find those B roads to go around that, what these symptomatic treatments do is they really help you speed along those B roads a bit more so that you can carry on functioning at a better level for longer. But eventually when those B roads break down as well, you're not able to form those activities. So there is actually a huge amount that you can do. And of course, the other thing we didn't talk about, if you do say active, if you do live a healthy lifestyle, these things can all help slow down your progression by making sure you

can mitigate the damage being done to your brain as well. So there are lots of things you can do, but we don't yet have a cure. And in the UK, we don't have access to treatments that slowed down progression. Okay, so let's have a look into the future then. Sort of what kind of promising new treatments are potentially in the pipeline? Yeah, and I think this is an area where I'm really excited about. I'm a basic researcher by background. And so I really love this area. And I will say up front, I'm a natural born optimist. I also believe that research is the best. Research will beat any disease. It's given enough time, effort and money to tackle. I think we have a lot of evidence to show that, whether that's the smallpox vaccine, whether it's the advances we've made in things

like HIV, which while we can't cure, we have been able to make a chronic condition, so that you can live very well with if you get access to the right treatments and the right time. And I believe research will beat dementia. Of that, I'm really confident. And I truly believe that there's no reason to think we won't be able to do that. Part of the reason is lack of investment and lack of attention to dementia, which is why I'm so delighted and thankful for your invitation today to talk about Alzheimer's disease and try and get it on people's radars, but also to say that we are at an absolute turning point. Based actually on Alzheimer's Society research, which I'm very happy to say from the 1980s, we now have two treatments that have been approved by the MHRA, and this is

an independent body of experts. And what their decision essentially means is, are these drugs safe and effective? And the conclusion that independent panel have reached, which is similar to the FDA in America, we're hearing just about now, actually, about Europe and in Japan it's already been approved. These two treatments are safe and they are effective.

And what these treatments do, one called Lacanamab, one called Denanamab, what these treatments do is they remove one of these proteins that I mentioned to you from your brain. So this amyloid protein that builds up in your brain that creates this kind of toxic environment that kills your brain cells, those kind of highways that your brain uses to communicate with your body, it removes very effectively and very quickly these proteins from your brain. And what there seems to do and what the data showed, what M Shire agrees it does do,

is it slows down the progression of disease by, on average, four to six months. And again, there's some people that respond less well, some people who respond more well, and we're trying to learn what that is. But these are the first ever, ever treatments that show we can slow down progression of Alzheimer's disease, not just mask the symptoms. And I think that is one of the biggest breakthroughs that there has ever been in this research, probably the biggest breakthrough, because I think what it shows everyone is five years ago there was a debate.

Could research be Alzheimer's disease? Can we treat it? Can we truly cure it? And while these treatments are not cures, they are far from perfect, they are moderately effective, they have side effects that need to be carefully managed. I think what they do show is that absolutely we can treat Alzheimer's disease. And this is only the first step in a very long journey, but I really think this is a pivotal moment where we know with more effort, more research, more money into research, research will

beat Alzheimer's disease, will beat dementia. And these treatments are the first thing that really show conclusively that that can happen. So, you know, are there a lot of trials going on at the moment? Yeah, absolutely. And I think this is one of the areas where you can see the research has been done over recent years is really feeding into it. So there's come the 164 trials assessing 127 drugs across the globe in Alzheimer's disease. And that is a really exciting period because there's only when the research taken from the lab is translated into these trials that you can really see the patient benefit. And even if you just go back 10 years, you're talking tens of trials globally. Well, actually, now we're into the hundreds of trials going. And then we still have a long

way to go. Again, if you're looking in cancer, you've got 12.5,000 trials globally. While in Alzheimer's disease, we're talking 164. But again, the progress we've made from 10 years to today shows that we really are one of those moments. And every condition, every disease has this, there was a time there was only tens of cancer trials and people weren't surviving cancer to the degree they are now. Now we do have that groundswell

where enough research has been done, enough trials have been conducted globally, that actually we are beginning to see that. And I think actually this year, we're having a number of phase three, that's the last stage trials. We've got seven of those finishing this year in outside of disease.

And every single one of those where they're positive and negative are moving this a little bit closer to that day when we know that Alzheimer's disease can become what we hope will be a chronic condition similar to something like HIV, which you can live with, live with well and you die with, but you do not die from. And I think this is one of the hopes we have. And just one other thing to add, it is not only the trials and the research. One of the other things in treatment, it's actually in diagnosis as well. So one of the things in Alzheimer'sitis funded recently is a blood test where at the moment, as I mentioned before, you need to have a memory test, you need to have a brain scan or a lumbar puncture.

They are invasive, they're expensive, a simple blood test that costs pounds rather than hundreds of thousands of pounds potentially. And it's obviously already used in healthcare systems such as the NHS. If these blood tests could help diagnose Alzheimer's or even help diagnose who should go on for a lumbar puncture or brain scanner who doesn't need to, because if we can't find the proteins in the blood, then we hope we won't be able to find them. in the scans, that could already help make the diagnosis quicker. So if you combine the innovations in diagnosis with these blood tests and the innovations coming down with these first DMTs, it's really the combination of we believe in our generation will have early in acrodiagnosis, access to treatments to slow down progression. And it's those two coming together at the same

time that really gives us the kind of hope and optimism to say that this is really a pivotal moment and a really exciting time to be involved in dementia research. Thank you for listening to this episode of Instant Genius, brought to you from the team behind BBC Science Focus. That was Dr Richard Oakley. If you liked what you just heard, then please do consider subscribing to Instant Genius on your preferred podcast platform. If you'd like to see our guests and presenters in person, then please also check out our YouTube channel at Science Focus. The current issue of BBC Science Focus magazine is out now. Pick up a copy wherever you buy your favourite magazines or download us on your app store of choice.

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