Potential Break Through in Dementia Treatment

This BBC podcast is supported by ads outside the UK. You get unlimited articles and videos, hundreds of ad-free podcasts and the BBC News Channel streaming live 24-7. From less than a dollar a week for your first year... Read, watch and listen to trusted, independent journalism and storytelling. It all starts with a subscription to BBC.com. Find out more at bbc.com slash unlimited. BBC Sounds. Music, radio, podcasts. Hello there and welcome to the Inside Health podcast. I'm James Gallagher.

This week I'm going to try on some robotic trousers. Yes, we're going full Wallace and Gromit to see if technology can keep us living independently into old age. We'll also be finding out why gonorrhea is becoming super gonorrhea. What makes it so good at resisting antibiotics? And is the sexually transmitted infection about to become untreatable? But first...

Do we already have a vaccine that can help prevent dementia? Because there are hints the answer is yes. Multiple studies now are suggesting the shingles vaccine can reduce cases or at least delay the onset of the disease. So we're going to look at the evidence today, see how the vaccine might be working in the brain, and figure out whether we should be excited about it. So to start, let's chat with Pascal Geldsutzer, who's Assistant Professor at Stanford School of Medicine and...

is at the cutting edge of this field. Pascal, thank you for coming on. And can we start by talking through how a vaccine rollout in Wales gave us these tantalising clues about dementia? Yeah, absolutely. It's a fascinating opportunity that was presented to us by this vaccine rollout in Wales and the NHS more generally. So usually we have the problem that when we want to get at the effect of vaccines on health outcomes...

that those who go get vaccinated are quite different to those who don't. They have got different health behaviors, different diets, physical activity levels, health motivations, etc. So what we really want, ideally, is a randomized clinical trial to really be able to say that a vaccine or a new medicine causes certain health outcomes.

the way in which the vaccine the shingles vaccine was rolled out in wales and the uk more generally is that they said that if you had your 80th birthday just prior to the start date of the program which happened to be September 1st 2013 you were ineligible and you remained ineligible for life well if you had it just after you were eligible and so we've got this beautiful situation where we have people who are born just a few days earlier or a few days later

And we know there must be really good comparison groups because that's pretty much random as well, right? So basically, the way the vaccine was rolled out, it created a randomized controlled trial. Yeah, exactly, exactly. And that's what makes this study so unique and why we're so excited about the findings, because they really are much more likely to reflect cause and effect rather than just a correlation.

And you did find that the people that got the vaccine seemed to have lower levels of dementia. Yes. We're estimating one in five new dementia diagnoses averted over seven years. That is massive. though let's not underplay that if you're talking about removing one in five cases of dementia or at least delaying them that is way more effective than some of the new drugs that we've been talking about recently

Yes, absolutely. And what is most exciting about this is that this is an intervention that is readily available. It's one off. It's not like we have to get people to adhere to some complex lifestyle intervention program for decades. It's safe and it's got additional benefits, right? Shingles prevention is not a bad thing to have as well. So to us, it could be a real game changer, both for population health and dementia research.

Do we have any idea what might be going on inside the brain in order to reduce the risk of dementia? I think broadly speaking, you can think about two mechanisms. One of them is... a chickenpox virus specific mechanism so we know that after you contract chickenpox in childhood the virus remains in your nervous system hibernates in your nervous system for life and is in this constant interplay with the immune

system causes some inflammatory process in the nervous system. And we know inflammation is a bad thing for many chronic diseases, including dementia. So that's certainly one very plausible pathway by which the vaccine. could act by reducing these reactivations of the virus. The other mechanism could be a broader immune system activation in older age where your immune system strength declines and it gives it sort of a boost to the immune system that is...

of benefit to dementia disease development. And we should say that your study isn't just like this one outlier. There have been other pieces of research that are all pointing in the same direction. Absolutely. But what's really exciting for us as a research group is that we have been able to use these quasi-randomization situations in other data sets, in other countries, Australia, New Zealand.

for example, where we just keep seeing the same strong protective signal. How radical an idea is it that a vaccine… that we take for something that nobody would necessarily have connected to dementia normally, seems to be having this effect. It used to be a very niche idea in the dementia field, but... There's increasing frustration with sort of the mainstay hypothesis of dementia and Alzheimer's disease and increasing openness.

to other hypotheses, a virus especially that preferentially targets the nervous system having a role in dementia disease development. also increasing evidence that vaccines have broader effects on the immune system beyond the specific antibody response that they have been designed to elicit. All of this comes now together where the dementia research community really

thinks this is maybe less of a crazy idea and actually quite plausible for at least a subset of dementia cases or a contributing factor. Exciting times. Absolutely. Well, Pascal, how certain are you or how certain can the science be today? Can we say that the shingles vaccine definitely reduces your risk of getting dementia?

I mean, in science, we can never say with 100% certainty that this is definitely the case. As a next step, what we think we need to conclusively prove that the Schengels vaccine... does have protective effects for dementia, for cognition, is a true randomized clinical trial. And that's what I'm currently focusing all my efforts on, is trying to raise the funds from philanthropy.

private foundations to get such a project off the ground. It takes a long time between somebody having a vaccine and then having a diagnosis of dementia. Are we going to be arguing about this for a decade or more? We don't think we would need a trial that runs for decades. I think a trial that runs for four to five years could already provide a very compelling answer to this question. So if we entered a world where...

We thought vaccines could prevent Alzheimer's disease, but we know that Alzheimer's disease starts... Much earlier than we think it does. There's probably a decade or more of that disease going on before we get any symptoms of it. And we're not giving these vaccines until, what, 65 on the NHS? Should we be giving the shingles vaccine?

to much younger people. It's entirely possible that the ideal strategy might be to start giving this vaccine in middle age, maybe 40s, 50s. Those are open questions for further research in the future. Pascal, I don't know how old you are, but are you going to go get an early shingle shot? I already did. I already did. You got to talk. You got to walk the walk if you're going to talk the talk. Thank you so much for chatting. All right. Thank you so much for having me.

Well, that's the evidence the shingles vaccine could be preventing dementia. But there's other things going on here.

What's really interesting is our understanding of the role viruses are playing in dementia. So I got friend of the programme and director of the Centre for Discovery Brain Sciences at the University of Edinburgh, Professor Tara Spires-Jones, to give us a... history lesson. This data started to really emerge in the early 1990s when scientists started finding that if you looked at the brains of people who died with dementia, specifically Alzheimer's disease,

and you compared them to people who didn't, the people with Alzheimer's were more likely to have viral infection in their brains than people who didn't have dementia. And that was where this sort of modern-day viral association started. How revolutionary was that? It was...

Not very widely accepted at first. So mainstream, we thought that dementia and Alzheimer's disease, especially, which is the most common cause, was caused by neurons dying, which is true, and that the biggest contributors were these pathological proteins in the brain, which is still well-subscribed. But we didn't really know that the immune system plays such a role in the sort of genesis of Alzheimer's disease.

Been proven right, though. Yeah, the data has gotten more and more compelling. I was one of those sceptics at the beginning, but as more data were accumulated, I do think that this is playing a role. It may not be the biggest contributor to risk, but I think it's definitely one of them. So Tara, we were chatting to Pascal earlier about shingles, but there are other viruses that have been implicated to things like the cold sore virus or herpes simplex virus. How do these get to the brain?

these viruses can get into the brain through multiple routes one is they can infect your peripheral nervous system and so those are the nerves for example that innervate your face and your mouth so that that's the ones that would be infected when you have cold sores i believe they can also some viruses can get into your brain through

your nasal epithelium. So if you have a head cold, The connection between your sensory receptors in your nose and your brain is one of the real weak points in the blood-brain barrier because you've got nerves that go all the way down that actually have their processes in your nose and they project into your brain so that if you get infection...

into those cells in your nose, they can get up into your brain as well. When I saw this emerging data, I thought the most likely explanation is that there's more virus in the brain because When you have dementia, your blood brain barrier is disrupted. And if your blood brain barrier is disrupted, then it's just more likely that that virus, which is already in your body, is going to get into your brain cells because it can infect brain cells.

But I think the data are changing. And my view now is that there is evidence that viral infection is likely associated with increasing risk of dementia. It's certainly not the only factor, but I think it's one of the many factors that plays into your dementia risk. So what was the evidence that changed your mind, Tara?

The first is this epidemiology. So studying large cohorts of people, the evidence is getting stronger and stronger that viral infections are associated with increased risk of dementia. So particularly herpes simplex virus one, but also flu and COVID are associated with increased risk.

The second is that vaccination is associated with decreased risk, particularly for shingles virus. And the third is the emerging neuroscience. So the biology linking infection of particularly HSV-1 in brain cells with the biological. causes of Alzheimer's disease dementia. It sounds to me like we're kind of getting to the point where we're kind of there in thinking that vaccines are protecting against dementia.

At least in part. I mean, we don't know for sure all of the causes of dementia and we don't know for sure yet the best ways to prevent. But one of the things that's really clear. is that age is the biggest risk factor for most types of dementia. One of the best supported parts of why we think age is doing this is because your brain has more inflammation as you age.

And so I think the evidence is there that there's definitely some association and that vaccination, if it's preventing this kind of infection, might be reducing that really big risk factor of brain inflammation. Tara, thank you so much for coming on. Professor Tara Spires-Jones there. At the BBC, we go further so you see clearer. With a subscription to BBC.com... Thank you.

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You're listening to Inside Health with me, James Gallagher. And let's turn now to the sexually transmitted infection, gonorrhea, because there's so much going on at the moment. This month, the UK has become the first in the world to roll out a vaccine. We're seeing historically...

high levels of the bacterial infection and we're running out of effective antibiotics with the emergence of resistant super gonorrhea. So let's talk to Sunita Soni who's a consultant physician in sexual health based in Brighton.

Sunita, welcome to Inside Health. Thank you. Sunita, there's so many things to talk about, about gonorrhea. I want to come on to, like, drug resistance in a minute. But can I start with the number of cases we're getting? Because the numbers are huge by historical levels now, aren't they?

Yes, they are. So we've got good epidemiological data and you can see the graphs are just going up and up. And that's for a number of reasons. And we can see from studies how sexual behaviour has changed over time. And we know that people are having more sexual... They are changing their sexual partner more frequently and probably less likely to use condoms. We've also been doing a lot more testing over the last 10 years or so because we know that STIs are a problem so we therefore are testing.

more and picking up more infections. But I don't want to get away from the fact that we've seen changes in sexual behaviour that are probably accounting for more infections. And we're seeing quite different rates of infection in different groups. Yeah, so it's not across the board, you're right. And we would be more likely to diagnose gonorrhea infections in gay and bisexual men who have sex with men, people who are living in more socially deprived areas.

certain ethnicities as well. But it's always important to stress that anybody can catch this. Anyone can catch gonorrhea, absolutely. And are we seeing those increases across the board or is it... in specific groups that's driving that overall incidence? Historically, the rises have mainly been in gay and bisexual men who have sex with men. But it's fair to say that it's crossing over into other risk groups and we are starting to see more heterosexual.

individuals being affected by gonorrhea. And on top of that we are getting to a point where it's getting harder to treat isn't it gonorrhea? Yeah, so you will have heard about super gonorrhea and multi-drug resistant gonorrhea and lots of different terms get used. I think I may have written the first headline that included the phrase super gonorrhea. Yeah, super, super bug, super gonorrhea.

makes it sound like a good thing doesn't it a terrific gonorrhea um but yes what you're referring to there is is a an organism or a bacteria that has developed resistance to different classes of antibiotics and is therefore becoming more difficult to treat. How many different antibiotics has gonorrhea evolved resistance to now? Several. Seven to ten.

And we're currently on an antibiotic called Keftriaxone, which is an injection. You have to actually come in to the clinic or, you know, be given an injection by a nurse or a doctor. And, you know, that's our last, our remaining. efficacious antibiotics so it's the one that works really well but

Even now with the data that we've got from the resistance surveillance data that we've been collecting, we can see that that effectiveness is waning slightly and we have even seen some actual resistance. So when people say things like gonorrhea is getting... close to becoming untreatable is that for real or is that a bit of scaremongering to try to make his practice safer sex

It's not scaremongering. It's just it's a fear, I think, of what is to come. Because once we've lost the antibiotics and once multi-drug resistant gonorrhea is much more widespread and even more difficult to treat, there's no coming back.

Do we understand what it is about gonorrhea that makes it so good at becoming resistant to all those different types of antibiotics? Because things like syphilis or chlamydia and, you know, there is some resistance, but nothing like what we're seeing with gonorrhea. Yeah, we do. know that gonorrhea uses lots of different mechanisms to

develop resistance against antibiotics and you know we've actually seen gonorrhea pushing antibiotics out of itself so that they don't work. We know that gonorrhea can pick up genetic material from neighbouring organisms, from other organisms. that are lying around that are resistant. So it's got lots of tricks up its sleeves and more so than other more stable organisms like Chlamydia.

I suppose that's the background then to where we are now with the rollout of the world's first vaccine for gonorrhea. It's not designed for gonorrhea, it's a meningitis vaccine, but it's working in gonorrhea. Yeah, and that's important. It's an important distinction to make because it wasn't developed for gonorrhoea. It was very much developed for meningitis. the protection that that vaccine confers is not as much as you would see for meningitis. How big an impact do we think it's going to have?

In gonorrhea. Yeah, so that depends on a lot of things. We know that, well, we think that the effectiveness is going to be about 30 to 40%.

But the overall effect that that will have on instant or new cases of gonorrhea will depend on the uptake. So, you know, you need to vaccinate enough people and enough at-risk people. How much demand has there been so far? Because I remember... not that long ago when there was the mpox outbreak and people were queuing around the block yeah for that vaccine yeah and it's not the same it's very different this time around so mpox there was an urgency there was a lot of

panic almost about it, whereas this is different. We are... opportunistically vaccinating people as they come in for care, routine care, routine appointments, we're offering the vaccine if they're at risk. Does it tell us something that we're using a vaccine that's maybe... 30 40 effective which isn't a sky high effectiveness number does it tell us something about the kind of pickle we're in with gonorrhea at the moment

Yeah, I mean, we very much like a gonorrhea-specific vaccine. There doesn't appear to be anything in the pipeline for that, you know, for lots of reasons. But yes, we spoke at the beginning about... The case is rising and year on year seeing more and more gonorrhea and the presentation of it is becoming a bit more complicated as well. So we're seeing eye infections and joint infections.

We need something. We do need to intervene and find some way of reducing the number of cases. So 40% is not ideal, but it's certainly better than nothing. I'm sorry, Sunita, I was going to let you go and then you raised...

Gonorrhea infections in the eye and your joints. And I was like, come again? Yeah, yeah. So that's a lot rarer. It's rare, but it's a serious presentation. Gonorrhea, you know, most of the time, gonorrhea doesn't cause any symptoms. The usual symptoms would be... a discharge from either the penis or the vagina, some bleeding, vaginal bleeding.

pain pelvic pain it can cause serious reproductive health consequences but but you know it can also cause joint infections and quite a serious eye infections which need to be treated quite promptly and i say again That's rare, but it's a sign that we're seeing those things and that must be a signal that there are more infections and there are more serious infections going on. Sunita, thank you so much for coming on. That's all right. I thought that was...

worrying and fascinating in equal measure there but now a little bit different because right at the beginning of the program i did promise you a wallace and gromit moment that I'm going to go try on some robotic trousers and see how I get on, all with the aim of trying to understand how technology can help us preserve our independence and live in our own homes for longer into old age. So let's hear how I got on. the Bristol Robotics Laboratory.

You can tell that I've come to the right place because instead of lampposts on the approach, there's a whole load of those mechanical arms that you get in a car assembly plant and they've all got giant light bulbs on the end of them. Let's go inside because we're actually going to see if you can engineer a new type of... clothing that can make everyday living easier.

Hello, James. Good to meet you. Hello. I'm Jonathan Roster. I'm Professor of Robotics at Bristol Robotics Laboratory. And welcome to our lab. Thanks for having me in. This is the Vivo hub for enhanced independent living. I'll take you inside the lab and you can see some of the interesting... stuff that we've got. Do you want to come this way? Please lead on.

So as you can see, our work here is focused on trying to help people to be as independent and as happy as possible as they live their independent lives. And we like to consider the activities of daily living that people need to undertake. to be able to dress in the morning, to go down to the kitchen to make a cup of tea, to be able to walk up and down stairs, even to go out into the garden.

As you get older, these things become a little bit more difficult. Muscles become weaker, people suffer from frailty. But instead of using... care, the idea is to use technology so that people keep their independence for longer. Yeah, that's right. We know that the UK is facing a crisis of care. I think one of the estimates is that over the next 10 years or so, we need half a million.

new care workers. That's not practical. What is the solution? Well, we think that robots can help, but these aren't the kind of robots that we typically think of in terms of robots. These are wearable robots. That means that instead of thinking of a robot as a different device, it becomes part of your body. Clothing, for example.

Okay, as soon as we're in the lab, can you show me some stuff? Yeah, yeah, come this way and I will show you some of our artificial muscles. So instead of using an exoskeleton, which uses motors and gearboxes and very rigid metals, here we think that... We need to put muscles into our clothing to help us to move. Those are not based on motors, they're not based on gearboxes, they're based on softer materials. Okay, is this a muscle?

This is a muscle, yes. Come and have a look. It doesn't look like a muscle. Well, this is a piece of textile. Why don't you hold it and you can see what it is. Okay, so it is, it's a, what is it, a bit of black tubing with some... metal ringlets that's exactly what it is so it's a piece of tube made out of polyurethane textile so it's like nylon it's an artificial textile and what we've done is we've sealed it and we've made this tube and then we've inserted these rings along it and what we do

is to put air inside this. And if you push air inside this structure, it becomes shorter. So it contracts like a muscle? It contracts like a muscle. Shall we have a go? Shall we have a go? Yes. I'm just going to press the button and you should hear it and you should feel it contracting. Oh, hello. Yep. Thank you. And now you're going to relax it and then you can pour out again. Okay, so it's a bit like an accordion.

going in and out in and out it's a little bit like an accordion so you can feel the force i'll do it again so i'm pulling on both ends of this tube it's a bit like if you've done resistance band training or something at the gym like that you can really feel yeah you have to work quite hard How practically can you use this then? Okay, so what you've got there is the simple artificial muscle that we've made. It's very lightweight. It's very low cost. You know, this only takes a few pence to make.

But we are taking those muscles and then we're putting them into devices to help people to move. And that's a real challenge. So instead of trying to get people to move in all possible ways. Straight away what we've done is to focus on some key activities and the first one is to get people out of a chair So that's what we've done. We've taken a whole series of these artificial muscles and we've turned them into a knee support device. When you need to get out of a chair, it will detect.

that you are starting to get out of the chair and then apply the power to help with the rest of the way. So you just need to initiate the movement. And it does that by sensing your body movement. You know, when you get out of a chair, you kind of lean forward a bit and then you start pushing. It detects that and automatically...

applies the appropriate amount of power to lift you up. Can we give it a go? Yeah. Do I just stand on the button? We've got a little switch on the floor here which will deliver energy into the device. Here we go. And up she comes. So that kind of creaking and wrinkling sound there is the bubble muscles activating. And it's quite thick textile, so it's quite loud.

And then when you release it, down it goes. You need an air supply everywhere you go, though. So if we take this, which is a pump, and the bubble muscles, which is the artificial muscle, put the two together, you apply electricity to this pump, and then it drives the muscles, and then you're done.

And you switch this off and it relaxes. My eye keeps getting drawn to something in the corner of the lab, Jonathan. What are you looking at, James? The suit. The suit. Are you keen to put on the suit now? I can't resist. If it's... Am I allowed if you've agreed not to? So Lele is going to help you put on the suit now. Hi Lele. It takes about 10 minutes. And then what we're going to do is we're going to run it in two different modes. One is...

The assistive mode to help give you a little bit of an extra boost as you're walking. Well, that's helping your muscles if they're weak. And then we will turn it into a resistive mode. And you say, why would you want a resistive mode? Well... If you're getting older and you want to build your muscles up again, you want to keep them as strong as possible, you don't just want to assist. You have to provide a bit of resistance so that the muscles themselves get stronger. Okay, let's do this.

So we've got the trousers on now, Lele. I'm all plumbed in. So you've got sensors in the shoes. So yes, you've got sensors on the soles of your shoes. It tells the suit where in the gait cycle you are, so where in the walking cycle you are. Got some of these bubble muscles above and below the knee, more straps around the leg.

Lots of tubes. Yes, those are for the air to get in. I look like a hospital patient. Yeah, you do. Okay, so I'll get you to a comfortable walking speed, so not too fast and not too slow. It's a very weird sensation on your legs. I can feel them inflating as I walk on my legs. Should we try it the other way? Yeah, we can try the resistance. To me, it feels like when my son grabs hold of my ankles and I'm trying to walk around the kitchen and he's just holding on and everything's ten times harder.

What the objective was with this is that even though we're implementing resistance, we don't want to change the way people walk, right? We want the suit to work with their gait. Could that help with like physiotherapy and all those programs that we're often... given but we don't always pay a lot of attention to yeah one of our targets is physiotherapy and if you can make physiotherapy transparent so that you don't even have to think about it because the

clothing is providing the resistance when it's needed and the assistance when it's needed, then people are much more likely to do the physiotherapy. We know that when a physiotherapist prescribes a course of treatment and then you go home with your piece of paper. Here's your resistance band. And a piece of A4. Do these things. It's really hard. I've had to do that. And it is so hard to keep motivated.

But if you don't have to worry about the motivation because it's all in the trousers. You're just wearing a T-shirt. You're wearing a T-shirt and it's resisting you. You're wearing trousers and they're resisting you when needed. You don't notice. Thank you everyone for having me in and yeah, I'll come back in five years time for my suit fitting. Looking forward to it James, thanks.

Well, that's Inside Health 2030 sorted. But before that, next week, we're going to see the impact a new generation of drugs has been making to the lives of people living with cystic fibrosis. You've been listening to Inside Health with me, James Gallagher, the producers. were Debbie Kilbride, Minnie Harrop and Tom Bonnet. The editor was Ilan Goodman. Technical production by Tim Heffer. The show was made by the BBC's Audio Science Unit in collaboration with The Open University. See you next time.

At the BBC, we go further so you see clearer. With a subscription to bbc.com, you get unlimited articles and videos, hundreds of ad-free podcasts and the BBC News Channel streaming live 24-7. From less than a dollar a week for your first year, read, watch and listen to trusted, independent journalism and storytelling. Find out more at