Podcast – Detecting UTIs Early in Dementia

Voice Over:

The Dementia Researcher Podcast, talking careers, research, conference highlights, and so much more.

Adam Smith:

Hello, and welcome to the Dementia Researcher Podcast. Today we're talking about urinary tract infections in dementia, why they're so difficult to detect, and why getting this wrong has serious consequences for people and services. We'll also explore a new approach to early detection that could change how UTIs are identified and managed in dementia care.

Hello, I'm Adam Smith, and in today's episode, we're focusing on something that sounds simple, but in practise, is anything but. Urinary tract infections are one of the most common causes of hospital admissions for people living with dementia. They're often linked to delirium, sudden changes in cognition, distress, and sometimes life-threatening complications. And yet, diagnosing them accurately often relies upon symptom reporting, which does not work well when communication is impaired or when presentations are atypical.

This creates a difficult situation for clinicians and carers. Decisions made with limited information. Antibiotics are sometimes prescribed without clear evidence, and people end up in hospital when they might not need to be.

Something that caught my attention recently was a piece of work approaching this problem from a completely different angle. Instead of asking how someone feels, it asks whether we can detect infection directly, quickly, and closer to where care actually happens.

With me today are two people behind that work. We have Tom Adam, who is a researcher and engineer at the UK Dementia Research Institute at Imperial College, London, where he's been developing a rapid point of care diagnostic device designed specifically for people living with dementia.

And alongside Tom, we have Professor Paul Freemont, who also from Imperial College London and the DRI, who's working in structural synthetic biology and leads work on biological and automated systems that make innovations like this possible. Hi, Paul. Hi, Tom.

Tom Adam:

Hello.

Adam Smith:

Thanks very much for joining us.

Professor Paul Freemont:

Hi, Adam. Yeah, thanks for having us.

Adam Smith:

I gave a bit of an introduction there, but Tom, why don't you introduce yourself in your own words, first of all?

Tom Adam:

Yeah, sure. So, my name's Tom. I'm a biomedical engineer by background and currently a researcher at Imperial in Paul's group and been in charge of the engineering side of building this diagnostic device to detect UTIs for people living with dementia, but in the comfort of their own home. So, looking at the design and development of that whole process and pathway.

Adam Smith:

Thank you, Tom. And Paul.

Professor Paul Freemont:

Yeah. Hi, I'm Paul Freeman, professor at Imperial College. From the context of this podcast, I'm a PI, if you like, in the UK Dementia Research Institute Care and Research Technology Centre at Imperial College.

And part of our programme within the CRT, the Care and Research Technology Centre is to think about urinary tract infections and how we can better identify them early on in participants or in people living with dementia. Because it is, as you pointed out, Adam, it's a massive, massive problem.

To the extent that a lot of hospital beds are occupied by people with dementia that have these very basic infections, and of course they're caught too late and the results can be very, very, very damaging and they get huge cognitive decline and delirium and agitation. And of course, they don't actually come back to where they were before the infection.

So, it is a massive problem on the health burden side and also on a personal side, because my father had one of these, and so I became very interested in them, and that's why we spent a lot of time working with other colleagues on this area.

Adam Smith:

Thank you, both. And it's brilliant that the DRI isn't just focused entirely on the disease itself, but on these other conditions, these comorbidities that affect people and that can then impact on the disease. Well, let's get into it.

Okay. We're going to start by setting with Dean and talking about why UTIs matter in dementia. So, before we talk about devices or diagnostics, I want to stay with this UTI problem. Paul, UTIs are often treated as routine infections in dementia, but they can be anything but routine, as you've just alluded to. Can you explain why UTIs are such a serious issue for people living with dementia and why they're so difficult to diagnose?

Professor Paul Freemont:

Yeah, no, it's a complicated question actually. And when you start guiding into urinary tract infections, you suddenly realise the problems you have in diagnosing them correctly for people, elderly people, and particularly people in dementia. And there are a couple of factors that affect that.

One, I think you alluded to earlier, which is the cognitive decline aspect of people with dementia. They don't communicate properly. They don't actually necessarily feel the symptoms that you would have with a urinary tract infection, and therefore it's very difficult to get a sense of the infection from them communicating that they feel unwell or they have some urinary problem. So that's the first problem.

And then the second problem is that as you get older, elderly people tend to have what they call colonisation, bacteria colonisation within their urinary tract, which is normal. Asymptomatic does not give rise to a urinary tract infection.

But of course, there is bacteria there present. And therefore, when we go and we'll dive a bit more into detail about how you detect that, but the detection of the asymptomatic environment, if you like, the people that don't have infection, but have a lot of bacteria, from those that have a lot of bacteria and have a pathogenic kind of bacteria that will give rise to urinary tract, is actually very, very difficult to discriminate between both of those clinical situations.

But essentially the urinary... This is very interesting. The urine, or the urinary tract, is actually a microbiome. And what I mean by that is that there are organisms living in that environment, microorganisms, similar to the gut, similar to the skin, similar to all of the enormous sort of microbiomes that we actually have on our bodies, and we're carrying millions of organisms around with us every day.

And within the urinary tract and the bladder system, there are organisms living there and they have certain characteristics. And I think it's a natural environment, if you like, for organisms to colonise.

And as I said earlier, when you get older, you get more colonisation and you get more bacteria present, but something triggers, something happens where you end up getting one sort of what they call a uropathogen, E. Coli is one, proteos, klebsiella, EDGE con. These bacteria suddenly become very dominant within the urinary tract, and that results in a clinical present infection presentation within the urinary tract.

And then what happens is that the body detects that and quite rightly says, "Oh gosh, I've got an infection. I better turn on all my kind of innate immune systems, all my response systems and, to try and get rid of that." And that means it releases a lot of these small chemicals called interleukins or cytokines.

And these chemicals are really very potent in terms of activating other cells to do different things. And so, you end up with this, what they call a sort of a pro inflammatory response. You get this big inflammatory response when you have this infection in the urinary tract, and then that results in a kind of more systemic response. And there's still a little bit of mechanistic lack of detail about why an infection in a urinary tract would affect the brain. So, there's a lot of work to be done on the actual mechanism of that.

But essentially what happens is that there's a sort of systemic response to the infection, and a lot of the cytokines and all of the pro inflammatory markers, flood through into the brain and they activate the brain immune cells, what they call microglia cells. And these cells get activated. And when you're living with dementia, you have a slightly impaired neuronal environment.

And when you have this massive inflammatory, you have essentially had a neuroinflammatory brain already. And when you have this massive response to the infection in the body, then of course you end up with these sort of cognitive behavioural changes that happen.

And so, it is a natural event, if you like, to an infection, but within obviously this subpopulation of people, and it's a lot of people, the brain is almost primed, ready to start to receive these signals and to get this sort of massive amplification of inflammatory responses. And that results in the outcomes we see physiologically.

Adam Smith:

So, we talked before that quite often diagnosis relies upon people communicating symptoms. What typically are those symptoms? And is there anything that makes people living with dementia particularly more prone? What are those symptoms that we're usually relying upon that I guess people with dementia can't communicate?

Professor Paul Freemont:

Yeah.

Adam Smith:

Obviously, temperature, is it a burning-

Professor Paul Freemont:

Yeah, burning sensation, frequency of urination and discomfort around the bladder region. Yeah. I mean, obviously when you start getting towards high temperatures and fevers, you've got a full-blown infection then, but there is certain sort of pre areas, discomfort and all these sorts of things, which you would normally report to your GP.

And actually, urinary tract infections in the female population are a real massive problem. And there's a very, very, very common in females to get urinary tract infections. So, they can be treated because you're reporting symptoms, the doctor can then get a sample and then send it off to the path lab. And this is where it gets sort of biochemically interesting. And if you like, I'll just explain a bit about the actual tests that we currently use in the NHS and in our health system, which is following the NICE guidelines.

And that is that the sample goes off the path lab and then they will streak it out and grow bacteria. Any bacteria in there, they will grow up. Then they will count the number of colonies on the bacterial plate. And if you have a colony forming unit count of greater than 100,000, that ticks a box to say, okay, there is a lot of bacteria here in this urine sample.

Then they'll do a kind of analysis, what they call a kind of dipstick analysis. They'll measure a whole other bunch of biochemical markers. One of them is nitrite in the urine. And the reason that that's important is that only gramme-negative bacteria like E. Coli and others can convert nitrate, which is normal. In your urine, you will have nitrates because of plants, foods, and other things. It's a kind of natural metabolic product, if you like, from your diet. But those nitrates in the urine, of course, the bacteria will use that as a kind of substrate and the E. Coli bacteria will convert that to nitrite. So, they try and detect that, the presence of that.

And then another marker is the presence of white cells, white blood cells, which are obviously kind of immune cells, to try and deal with the infection and kill the bacteria. And there's an enzyme called an esterase, which occurs on the surface in these white blood cells. And so, they measure this enzyme, which is indicative of the presence of white blood cells. So, you've got white blood cells, nitrites, and high colonies. So those are the three kind of major markers, if you like, of a urinary tract infection.

But the problem comes is that there are sets, not all bacteria convert nitrate to nitrite. So, for example, I think it's entococcus or one of the bacterias, I can't remember which one, does not do that, but can give rise to urinary tract infection. So, it could be a false positive there if you like, or a false negative.

Then there are other problems that you can have colonisation, like a lot of bacteria there. And also, when you get elderly, you can have a kind of inflammatory... We do all develop a more pro inflammatory environment, unfortunately, in the body. And there could be other kind of parts of the body which are producing inflammatory responses that your kind of picking up. And so, then that indicates that it may not be a complete urinary tract thing.

So, you have this really difficult problem if you're a clinician and a doctor or GP to know what to do. Do you give antibiotics? Do you just say, right, I think there's enough criteria to suggest we give antibiotics. And of course, a lot of clinicians would probably err on the caution side if you're living with dementia, such a serious problem.

But then the problem comes is that you're then getting a lot of potential prophylactic antibiotic treatments, and therefore you're building up antimicrobial resistance. And of course, this is a big no-no, obviously, for the system. So, it's a real dilemma, and, to know when you don't have a younger adult saying, "I can't go to the toilet. I can't. It's very hurting. I feel a bit rough. I feel it's very, very difficult."

And so that's the sort of basis of what we're trying to do. We're trying to work out what are the bacterial changes that happen in the urine over time as with people living with dementia just normally. And then when they have a urinary tract event, we can follow that. We can also follow the resetting of the bacteria culture once they've been treated with antibiotics. So, trying to get that, and we're trying to build out other biomarkers that would give us a hint of presymptomatic, can we detect something that's just before they get the kind of infection?

And that's the golden nirvana, if you like, what we're all desperately keen for, because we want to monitor people more routinely and we want to say, "Okay, they have this marker and that is really high probability they're going to get a urinary tract within the next week," I don't know, whatever. And that would be enormously helpful, but very difficult problem.

Adam Smith:

So, I can see this. So particularly as people's dementia progresses and they become less communicative, that spotting those early signs or communicating it means that they don't get identified until such time as the-

Professor Paul Freemont:

Full-blown infection.

Adam Smith:

... [inaudible 00:14:30] temperature or there's really something wrong.

Professor Paul Freemont:

Serious. Yeah.

Adam Smith:

Or if they monitor urine output clearly, they kind of start notice through that, which is a problem. So having a test that could spot this earlier is clearly beneficial. Is there anything that makes people living with dementia more susceptible to getting UTIs in the first place? What's the underlying cause?

Professor Paul Freemont:

Really good question. Yeah, really. I mean, that is like the 60... Whatever, $4,000 question. I mean, that is a really difficult question. I mean, there are some arguments that as you get older, your immune system becomes less effective. And that's this sort of colonisation that you're getting of non-pathogenic bacteria, has been argued that that will produce an inflammatory response. The body will detect; you've got a lot of bacteria. There are not harmful bacteria, but it will detect you've got a lot of bacteria in your urinary tract. And there is a thought that that may lead to further cognitive... It's very difficult to know specifically.

I haven't seen anything saying that people will, live in dementia have a greater probability of developing a urinary tract infection. I don't think that data exists as far as I know, and I could be wrong there, but as far as I know, I think what it's indicating-

Adam Smith:

[inaudible 00:15:51] In itself.

Professor Paul Freemont:

Well, I mean, that is true. And I'm going to have to rapidly go and look at the clinical literature to see if I've got that wrong, but I haven't been made aware of that. And I think what generally happens is that they're just very primed and prone to, if they have an infection, then the whole system is really primed to be very disrupted.

Adam Smith:

I already touched on this already, but what is it about infection and inflammation and the ageing brain, if you like, that makes UTIs particularly destabilising for somebody who already has dementia? Because I think if you didn't have dementia, for example, and you had a UTI, the effects of that are... Well, what are the effects of that? They can...

Professor Paul Freemont:

Yeah. I mean, if you don't have dementia, you can get quite ill, but you're probably not going to go into a cognitive decline situation or delirium situation.

Adam Smith:

It's like delirium, isn't there.

Professor Paul Freemont:

Yeah. There are delirium and cognitive decline. There's a kind of not... Agitation, all of the sort of not knowing where you are, all sort of things that are very cognitive or brain driven, if you like. And I suppose the problem with dementia, still quite a lot of debate on the real cause of it all. But it is a kind of pro inflammatory environment already because you have neuronal death, you have the kind of microbial cells already activated in some way. So, you have this sort of neuroinflammatory baseline system. And what you're doing is you're just like 10X-ing it, if you like. I mean, that's just a descriptive thing.

Adam Smith:

Yeah, you take those symptoms that you may have already had and then stack on top of that.

Professor Paul Freemont:

You're stacking on that big time. Exactly. Yeah. And then physiologically, you have the outcomes, as we all observe, which are very debilitating, very difficult for carers, very, very difficult, obviously for the person themselves and it's just a horrendous situation. And then of course, they end up often in hospital. And of course, unfortunately, my father, he never came out of hospital. So it can be, depending on what stage you're at, it can be a very difficult problem.

Adam Smith:

Which you could see that. And particularly when we collect people living with dementia at that later stages, particularly into care home environments and other places, where, I mean, I don't know, I suppose it depends on the care home as to how much focus or whether somebody's so...

Professor Paul Freemont:

You're right.

Adam Smith:

It doesn't shift in just recognising a difference in personality or when somebody's different is different to if somebody's living at home, for example, and they have their partner as their care impact.

Okay. So, I think we've learned quite a lot there about urinary traction infections. Tom, I'm just going to bring you in there. From your perspective, why do you think issues like infection detection have not necessarily received the same attention in dementia research as memory and cognition?

Tom Adam:

Yeah. So, I guess one of the main reasons that infections aren't perceived, and given that same level of attention, well, especially compared to memory or cognition is that I kind of think they're not really perceived or reported in the same way. And I think cognitive and memory-based symptoms, they're deeply associated with dementia anyway. If I ask friends or family that aren't in it, that's what people immediately think of.

And I think as symptoms, they're quite universally feared that they really fundamentally alter a person's identity and independence and relationship if those functions are impaired. And yeah, the prospect of losing agency over your own lifestyle and your social connections is just a really distressing idea. And I think public opinion, and then research as a result as well, it's drawn to these symptoms.

But I guess then, yeah, in contrast, infections like UTIs, they're viewed as treatable. And so, if UTIs, in particular as well, are normalised, because as Paul was mentioning, they're common in younger populations, especially women. I think that maybe just leads to a misunderstanding of their impact in older adults, especially people living with dementia. And yeah, as a result, they're just not offered the same level of concern or urgency, I suppose.

Adam Smith:

It's interesting. I know the NYHRs recently had a big push on looking at multiple conditions, and you feel like this is one of those kind of areas that could be looked at, that these other infections, that particularly people are more susceptible, that this could... Really, it's great that you're focusing on this because it clearly...

I'm not aware of a great deal of research going on in urinary traction infections in dementia as a whole, but we've looked a lot on gut microbiome recently, and I haven't been aware on... This is a great area to focus on.

Well, let's move on now to talk a little bit more about how you're bridging from problem to approach. So, Paul has helped us understand why UTIs are such a difficult and high-risk issue in dementia. Tom, before we get into the details of the technology that you... This amazing technology you've created, could you talk about how you approached this problem as a researcher, and what you were trying to answer when you first started working on this?

Tom Adam:

Yeah. So, I mean, for me, the initial question was, it was very fundamental. It was simply just, could I build a device that was capable of triggering this amplification process? I think Paul touched on it earlier. So, am I able to trigger this amplification process, which requires a heating element, and then am I able to measure the output that's coming from these samples, which in our case a thrust and output? And that was just posed to me at the early stages, and it was just an engineering problem of could this be done?

And then as time went on, and we quickly realised we can do that. So, we did do that. From a research perspective, it then became more about feasibility, and trying to reproduce things that we'd found in literature, and understand what work people had already done, and how we could apply that to our situation.

And yeah, for me as well, understanding how the technology and these systems actually function. And I don't think I had particularly clear view of the broader clinical context, I suppose, at that point. And the focus was much more on just developing a confidence around the methodology and the hardware, just proving to me and the rest of the team that we could get it going on that first sort of device.

But once we had researched the point where we answered this question that it does work, it was shifting the focus more as to how it's actually going to be applied to someone who's in primary care and living with dementia, what it looks like as that real world context. And yeah, that was where I had to move beyond the purely technical problem, I suppose, and start thinking about the design and particularly co-design of including people who we saw using this product. So that was workshops and integrating co-design into the actual development of the device.

Adam Smith:

So, if I understand this rightly, Tom, at the beginning, were you trying to improve the existing test, or address that obviously the issue that Paul mentioned earlier on, which is trying to detect much earlier. So, were you trying to rethink the pathway entirely, or just recreate the existing test in a more home usable format?

Tom Adam:

So, I think that the vision with building the device was that it would design its own pathway. And my first few steps were just finding other literature and other projects that had used technology in a similar way but then repurposing it for our specific needs. Yeah, so extracting bits from projects, people who had built more basic devices or devices that were testing for something else, and then just reapplying that into our instance.

And then once we had got that building block of what the device is probably going to look like and that it was possible to heat the sample in a certain way and collect this for us and signal, from there, we could then be like, "Okay, well, how do we actually see this sitting in a care pathway? Is it going to be in someone's home? Who's going to be taking these tests? What level of communication of the result is going to be given to the user?" Yeah, all of those questions then start to form afterwards.

Adam Smith:

So was that first then the idea, was it to create a rapid testing device that could be placed at point of care, not necessarily jumping ahead to think that that's in healthcare or in home. Or did you go straight down that kind of route of thinking this is something that could be used that people could use for themselves, like diabetes tests done at home and things like that?

Tom Adam:

I think initially it was that, can we design a device which will rapidly give us a result and be at point of care. So not needing a healthcare professional to operate the device, it can just be done in the comfort of someone's home. And I think in a lot of senses, the benefit of COVID was that people became very familiar with conducting these tests in their home and became very comfortable with the sort of testing process that we almost needed people to be able to adopt to be able to use this device.

Adam Smith:

There are already other devices that exist, not necessarily for UTIs, but that do provide a point of care urine test for other things, for other conditions.

Tom Adam:

Yeah, there's definitely devices on the market that are detecting for UTIs or tests urine. Some people have done this, and it would be the ideal for us is like a device that's mounted in a toilet that you then would pee on and then it naturally collects data in that sense, and gives you results in a bit more of a passive method of collection rather than this hands-on testing process.

But what is useful about ours is that it's specific bacteria detection that can be done in someone's home. So a lot of devices on the market that are kind of either used LAMP, so the same amplification process, they are doing similar things and they can detect bacteria specifically, but you need pipettes, you need lab space, you need to conduct these typically in laboratories rather than being able to conduct it in a home.

Adam Smith:

Yeah. So, I don't know if you answered the question, apologies if you already did and I missed it. So, was it trying to replicate that same test that a GP would send off, but using newer technologies that could be done differently, or were you trying to detect things differently or both, I guess?

Tom Adam:

So, I think when the GP sends off their sample or diagnosis, as Paul mentioned earlier, it goes through this colony counting process, which is pretty laborious and requires a technician to be present and plating and then counting and monitoring these plates.

Another option is PCR, but that's more expensive. And so, we're trying to use a similar technology to PCR, so a more expensive form of testing that's more accurate. But in our case, we're not using PCR, we're using LAMP and that was our aim. So, a more technologically evolved-

Adam Smith:

To get the same result, but using a different, just taking a-

Tom Adam:

Exactly. Exactly.

Adam Smith:

... [inaudible 00:29:24] the same result. And you both talk to this now, but the idea was then was to not just replicate this, which is when symptoms have necessarily appeared, because you're fixing a problem we already kind of have a solution to, but it's to also be more sensitive, a bit like we've seen with the blood biomarker test these days to make this even more sensitive that you can do this.

Are you thinking that this could be something that could just be routine, something you would do... Like you say, if it was attached to a toilet, it would test every time you went to the toilet. But if it Was the idea as well to make this something that's so sensitive that you could make it routine to spot that earlier?

Tom Adam:

Yeah. I mean, I definitely envisage it as being an appliance you have in your home. I mean, it's small, it's the same as a portable speaker or something. But an appliance you have in your home that you can run weekly, fortnightly tests through this device, and it mitigates that need for symptom recognition that we discussed earlier.

I think in this age where wearables and people's watches and people's aura rings, people are so health conscious, and also happy to do the legwork, on finding out what's wrong with them and monitoring themselves. I think it's a good time to be...

Adam Smith:

I'm one of those people. Anything that comes out. I don't have high blood pressure, but I have a high blood pressure monitor because I hate that Apple, obviously other brands are available, that Apple has this thing to measure my blood pressure and there's no number in there. And I want there to be a number in there.

So, I get that, that I guess the potential consumers of such a product will be people who want to keep an eye on this themselves. Well, I guess sports people. You mentioned before, women are particularly more susceptible to UTIs. If you've got a history, you know this is, you can see that those.

So, whilst people... It's great that the underlying aim here is to help people living with dementia, but there's the broad potential applications of this are huge, aren't they?

Paul, I mean, obviously, are you one of those people that was drawn to this because it's a problem and you like to fix problems? Or you mentioned your father, obviously.

Professor Paul Freemont:

Yeah, I think mainly my dad actually, to be honest, because... Excuse me. I think when you see it firsthand, it's quite impactful. I think that a lot of people have to care for people with dementia. It's a very, very impactful problem. Effects, as Tom said, it's very difficult for families and for elderly care. If it's a partner and you're looking after your other partner, it's a very debilitating condition and disease.

And so, when you see it happen firsthand, it really brings it home to you. And then when you delve into it a bit and you say, "Well, actually, is there anything... How do we deal with this problem?" Then I suddenly thought, crikey, this is crazy. We are not really dealing with... Well, I mean, we're not... Technologically, I meant. I mean, obviously clinically, we're obviously dealing with it. But why can't we think about early interventions, trying to catch people early in their infection progression, if you like, so that we can treat them quicker and ideally prevent hospitalisation.

So, it's a bit of a personal journey, but the more I get into it, the more I realise that this is a really exciting area as well, because there's a lot you could do outside of just people living with dementia.

But urine monitoring, it's a very key area, because a lot of people are interested in diet, for example. Because a lot of your diet metabolites end up in your urine. So, you can monitor people's diets. There are other types of markers you can monitor within the urinary microbiome. And of course, for women, it's extremely problematic throughout their whole lives.

So, it's an area that I think right for biomarker discovery, we need to... So, part of our programme is that we want to not only use a device to detect particular bacteria, but we actually can then use the device to detect whether those bacteria are multi-drug antibiotic resistant.

We can do all sorts of other kind of refinements on version two, version three, if you like, as we understand the genetic profiles of the bacteria in these people living in dementia, and that's part of the programme. So, we have all of the genetic profiles of all the organisms that exist within these urine samples over time.

So, we can look to see if there's any genetic changes within the bacteria that we could be attributable to some kind of activation point for the disease progression of the growth of the bacteria, some kind of what they call dysbiosis, some disorganisation of the urinary microbiome.

Because what's interesting in microbiomes is the organisms are all living together in communities, including your gut. And there's sort of like... That's not quite an equilibrium, but they're all set up and they're all set in different kind of environments, all working, living happily together, if you like.

And then you do some in your diet or you have an antibiotic treatment, and that just wipes out a whole bunch of the microbes. And then, you get resetting and all sorts of things. And I think that whole idea of what allows the pathogenic E. Coli to suddenly become extraordinarily dominant within the microbial flora, if you like, within the urinary tract, it's a really super interesting scientific question, and there are lots of things that one can analyse to try and get at that.

Adam Smith:

Absolutely. And the exciting potential is not just as a device that can help people immediately, but as you highlighted as well, we've done a podcast on this before, about the potential for collecting data, longitudinal data from this as well, and how that information can be applied in so many different ways is really, really exciting.

Professor Paul Freemont:

I agree. And I guess the future for... The future, I imagine, and obviously it depends on lots of technological breakthroughs, but is kind of monitoring, standard urine monitoring constantly with people living with dementia, even elderly people, if you like, but certainly people with dementia, and just having a constant monitoring of their urine samples every day, if possible. And we would have enough longitudinal data and enough analysis, and we could use AI to build up models of changes within the urine and hopefully build out a very detailed profile to say that actually there's a high probability that this person is close to maybe getting a urinary tract. That's kind of the future.

And then we'd alert the clinical teams or the carer teams or whatever, and they would come in and decide what to do at that point. But of course, one of the problems we've got is that there's a huge problem with prophylactic antibiotic treatments and, i.e. Giving antibiotics before disease, before symptoms. And this is a huge problem because we would then introduce antibiotics into the system, we'd introduce antimicrobial resistance into the person, into the whole population of organisms.

So, there are some very deep issues there that we would need to discuss and work out. But hopefully with data, AI, model-driven, zillions of data points, we hope to come to a point where we can say, "That's going to be a UTI, let's treat them."

Adam Smith:

Many underlying potential benefits.

Professor Paul Freemont:

Yeah. That's what I'm hoping.

Adam Smith:

So far, we've asked about why UTIs are so difficult to diagnose, the high-risk issue in dementia, how that shaped this problem, and how it was approached.

I want to move on to thinking more about practise and your research. And I still, for anybody who hasn't yet got a picture for this, Tom, could you describe exactly what it is you've developed? So, this isn't a COVID test that somebody, or the kind of stick that you might pee on at home. Paint me a picture of what this looks like, what's actually in it, and how it... I mean, we've talked a lot already about how it differs in its detection, but what are the kind of outputs? Paint me a picture for what this looks like.

Tom Adam:

Yeah. Yeah. I guess I've kind of chopped and changed with different descriptions as I've gone through. So yeah, I mean, what I've developed is this home-based UTI detection device, and it's specifically designed for people living with dementia. We co-designed it with people living with dementia through workshops, specifically with the Helix Centre, which is a design group associated with our centre groups of designers who are amazing and they help us orchestrate these workshops that led the design.

And so, the intention of the device is that it functions as an appliance at home and allows for early and easy testing without the need of going into hospital. So, in practical terms, the user takes a urine sample and transfers a small amount into a pre-prepared test tube, that's quite similar to when we all did those PCR tests. So, it's a tube with some liquid already inside-

Adam Smith:

[inaudible 00:39:20].

Tom Adam:

Filled with various chemicals. And we tried to make this deliberately similar. But so, once you then transfer the urine into this tube, you put the tube lid on, and then you put it in the device, click go, and it runs a test. And so, what's actually happening, is that the device is heating the sample to a specific temperature, and that triggers an amplification process called LAMP. I mentioned it earlier. And so, that is enabling very small amounts of bacterial DNA to be rapidly amplified to a detectable quantity.

And so, in our case, we're detecting E. Coli at this stage, we do plan on expanding to different bacterias, but E. Coli is the most common cause of UTIs. And then so alongside this amplification, as it amplifies the DNA, it's measuring a fluorescent signal because a dye, a fluorescent interclating dye binds to the E. Coli bacteria. And so, as this amplification occurs, we get a bigger signal, this bigger fluorescent signal.

And what we specifically want to see, if we are detecting positive, is we'll get a bigger signal quicker. So, we test for 30 minutes, and if the signal comes up in say 15 minutes, that is indicative of there being a high portion of E. Coli in that sample.

Adam Smith:

Is this a big box? Is this the size of a shoebox?

Professor Paul Freemont:

What's the object? Have you got one, Tom?

Tom Adam:

I've actually got it right here.

Adam Smith:

Well, those who are watching the video version of this podcast will benefit from this, I'll describe it.

Tom Adam:

Yeah, yeah. I've done a bad job of describing it, but it can sit on one hand. It's the size of the portable speaker is normally what I say. So, the urine sits in a little tube in there.

Adam Smith:

So, what Tom's holding up now is a ops, which is about the size of a portal. Much, much smaller than a shoebox. And it has a slot that opens up on the top, two buttons, couple of buttons. What's the arrow from it? I mean, does this connect to a computer? Does it print something out?

Tom Adam:

Yeah.

Adam Smith:

How do you get the result from that?

Tom Adam:

Yeah. So currently all we have on it is like you saw a button and then two lights, and that is purely to tell the user what stage in the test you're in. So, there's a heating stage, then there's a stage that tells you to put the sample in, and all of this. In the workshops mentioned earlier that the level of data communicated to the user is actually quite important, and almost quite a sensitive thing to handle because you don't want to just say you've got a huge amount of E. Coli in your urine.

So, we have it so that the device runs off a little setup of electronics that can be connected to the Wi-Fi, and then therefore can communicate with, send the reports to your GP. And, we are also looking at introducing a screen, but as I said, working out what amount of information to communicate is tricky. And when we've done workshops before, a lot of the users said, "We don't really like having all the bells and whistles that you would maybe expect from other devices," because considering the demographic we're working with, technological and digital literacy-

Adam Smith:

Not as high?

Tom Adam:

Yeah. Is not necessarily as abundant as you could assume in other populations.

Adam Smith:

But you can see how you could have different kind of levels of output, can't you? What the kind of carer needs in terms of their information is different to what you then might give a GP.

Tom Adam:

Exactly. Yeah. Yeah. And sorry, so you asked what the output was, specifically. So, when I'm running a test and I'm interpreting the data, I'm interpreting this data, which is a fluorescent signal. And I suppose that raw data can be exported, but then also we have various tools to interpret that data.

Adam Smith:

And could you potentially, wirelessly remotely collect this as well? Is that something you've looked at in... I'm assuming you've got these, have you had any of these? We're jumping ahead a little bit, I think, to my next bit, but have you given somebody one of these devices to take home and try yet? No.

Tom Adam:

Not yet. Not yet. So, we are in this process of setting up an experiment actually in next month with David Wingfield, who's a GP associated with our centre. And in that, we're going to be deploying the device in a GP setting and be collecting...

So, in that GP, they already collect urine samples and run tests, and they get sent actually to our lab. But what we're going to be doing in parallel to that is running tests through the device.

And this will be very telling, because currently it's me running these tests and validating them with all the clinical samples, actually getting people to use it specifically for the testing. It still won't be in the exact intended environment, which would be in someone's home with carers using it, but it's going to be a good bridging step, where it'll be out of my hands in a professional clinical environment.

But yeah, that'll be really interesting data to see how that works and also get feedback for me, in terms of a design, from design perspective of actually seeing how people do it.

Adam Smith:

Yeah. And I can't imagine you're going to be short of volunteers often to get involved in testing. It's such a cool thing. And Paul, from your perspective, how does this piece of work reflect the kind of broader shift on how diagnostics have been designed and deployed? It's a very smart looking thing.

Professor Paul Freemont:

Yeah. I mean, I think there's been a lot of work done over the last many years on point-of-care or point-of-use devices, and people have explored many different things, and there aren't that many on the markets. And not many have actually made it through the whole translational pipeline to get actually products into the market.

And there are lots of people working on that, and actually not necessarily for disease, but mainly for younger people or people who want to monitor their health, their health, the wellbeing community, that's the community that's driving the kind of point-of-care testing systems, which is interesting because they just want to see whether they're... How am I feeling this morning? What are my biomarkers looking like? And therefore, that will then drive more innovation into the real diagnostics.

I mean, clearly at the moment, diagnostic testing is going through a bit of a revolution, if you like, because traditionally it was very much the GP and then the path lab. And then the path lab would send the results back to the GP, and then the GP would get the patient to come back in and discuss the results and all the rest of it.

And I think there is a big move to de-localise that and actually have it much more localised into where the patients are, where they come. And the initial step, I think, would have a lot of diagnostics done within the GP clinical environment so that the person comes in, has a quick test, get the result quickly, hopefully doesn't go home, but could maybe hang around a little bit and then, that kind of thing.

Adam Smith:

To interrupt you there, we know from the new NHS 10-year plan, you tick the box on their three core ends, which is from hospital to community, from analogue to digital, and from sickness to prevention. You tick all three boxes for that, which...

Professor Paul Freemont:

Yeah. I think it's a super important area, and the technology is now allowing that to happen. And the reason I know that is that during the SARS-CoV-2 epidemic, there was a all hands to the deck kind of attitude, for the country in terms of the scientific community. It was an incredible mobilisation of all of the amazing science and research we have in this country, which is incredible. And we were part of that.

Adam Smith:

I suppose you can see, I mean, whilst the drive within the infrastructure isn't quite there in the same way to fast track things in the same way, all the, the great thing is that the connections you made at that time, and your experience of doing that puts you in a great position to take what is clearly a much needed product right through from-

Professor Paul Freemont:

Hopefully.

Adam Smith:

... from development through to delivery. You mentioned both there that you've obviously moving on to testing this at the point of care. So have you been able to validate so far on real samples that this is... So, it works?

Professor Paul Freemont:

Yeah. Oh, yeah. No, the beauty of our programme... Sorry, Tom, interrupting you, but the beauty of our programme is that we have all these urine samples. So, we have essentially mimicked what they do in a path lab in my own lab here in South Kensington at Imperial College, because that's what we call the clinical gold standard, if you like, for UTI decision making. So, we have that, all the same kind of stuff, the same test that they do. So, we're doing that.

So, we've got all these samples coming in as part of our study. And then, what we do in addition to what they do is that we biobank all the clinical strains. So, we have all these, we have well over a thousand E. Coli strains by a bank. And then what we're doing is we're sequencing them all, genetic sequencing. So, we'll have the genetic sequences of all of these strains.

And then the beauty of it is it will have them longitudinally as well, which is super interesting if you're interested in microbial evolution and adaptation and things. So, there's lots of hardcore scientific interesting microbiological questions there. And therefore, the samples are so thoroughly analysed.

Then, Tom's machine or device can take advantage of those samples and can then test them. And so, we have all the detail of what's in the sample, negative, positive, different organisms. We know everything about them. So, we've tested a lot of urine samples from our cohort in our lab, but that's not the same as going out into the field.

Adam Smith:

So, we've talked about the problem, the research, what your early findings show. I just want to finish by really looking at the barriers. So, we're now at the point where you've got some final testing to do, but what are the barriers to now bring this technology into people's homes? Tom, why don't you start?

Tom Adam:

So, I think for me, the big barriers, I would say, of taking into the home, the UK... Well, on a broader sense, the UK is very risk averse too when it comes into investment in these sectors and especially in spinouts if they're coming from universities, and that kind of startup pathway is suffocated quite a lot.

And I guess the other big barrier is that sadly, the NHS is very hard to penetrate with diagnostic technologies like this for obvious reasons, the sort of financial strain and everything that they're going through.

Adam Smith:

So, there's the regulatory side of things. And then, I mean, we hear, don't we, all the time that there are... Well, we hear about them. Whether they work in reality is these fast-track systems to get ideas through. And obviously, Paul, you talked about how that was so much.

Professor Paul Freemont:

In the COVID, it worked.

Adam Smith:

Easier to do. What about from your perspective, Paul?

Professor Paul Freemont:

Yeah, I mean, I think Tom alluded to some of the issues. I mean, I think where we work, Imperial College is quite forward-thinking in some of these areas, in the sense that the big problem with UK startup companies coming out of spinouts, if you like, out of universities, is that the universities themselves have always overvalued the IP and have taken too much of equity stake in the companies. And there's a realisation that it's just not the right thing to do on day one when you've got a small startup.

But those are kind of structural issues which I think are being addressed. And Imperial is very at the forefront of that, and realises that it's not like the US, but its certainly Imperial's model is certainly a lot better than many other UK institutions, but there's still problematic problems there.

Tom alluded to the NHS. I think they're very aware of new innovation tenure. How do we get new innovations into the NHS as quickly as possible? And they have set up a lot of schemes and pathways, but I've also heard on the other hand that the procurement process by the NHS to procure... So, say you have a new technology or a new device, and that you would need an offtake agreement in order to get investment in to order, to manufacture it. All of those kind of normal commercial things that might happen in the commercial world are extremely difficult, I think, in the NHS system.

So, I mean, I think everyone's aware of that. And if they can make money and solve a huge problem, it's amazing.

Adam Smith:

Connecting into the likes of the UKRI's Innovate UK programme, which we've done podcasts on before, because we've had a couple of our guests before. We had Sam Moxon who's joined us and hosted some podcasts for us talking about his nanotechnology that was developed out of 3D bioprinting that came on to be a high temperature substance.

And we had Zeke Steer from Milbotics that's created super socks that have socks with lots of sensors in for measuring things. We know that that can be done, but it's definitely tough. But I think underlying this, you've got this great product. So, for anybody, what would you like our listeners to do with this information that they've got today? Is there anything that they can do to get involved or to support the work in any way, or do we just need them to keep watching and be ready when you are?

Professor Paul Freemont:

Well, to be honest, I think Tom, I mean, this is Tom's activity really, but I'm very supportive of it. I think Tom eventually will want to talk to people who are interested in investing in this kind of product, if we were to form a company or a spinout or something out of that. So, I think anyone who's interested in helping an early-stage translation journey with a seed around, or anything. Or just interested in wanting to learn more, they should talk to Tom. I mean, that's one obvious area that would be helpful.

The other thing for me is to just make more people aware of the problem of urinary tract infections in people living with dementia and just make sure that people understand it. We didn't talk a little bit about some of the aspects of diet and things with people living with dementia, and especially hydration and water and drinking.

And I think obviously that is really important, I think, as well. So, there are some, I think just awareness that this is a really serious problem. And to be very, very on it if you're a carer, and try and find out as much as possible about it, talk to GP, find out, are there anything I can do to try and monitor this or whatever? I mean...

Adam Smith:

Yeah. And if anybody who's listening to this who is a funder or an investor or thinks, "Hey, this sounds brilliant. I've got some money." [inaudible 00:56:03] Tom, are you looking for investors, do you...?

Tom Adam:

Yeah, that'd be nice. Yeah, thank you, if anyone can. Yeah, I think just pushing the project forward is definitely what we want from this. And I guess for the listeners, I think spreading the word and doing your best to know other people about the effect that UTIs have. I think with that awareness, and it creates an area where people would want to use these kind of products.

Adam Smith:

And this isn't research for research’s sake. This has got real people at the heart of it, which actually I think is a good point to wrap up.

So, we're out of time, but to reflect on today's show, I think what we've heard today is not really even about a device or technology. It's about noticing where systems quietly fail people and taking time to redesign them with real care and intent.

Progress in dementia care rarely drives through some dramatic breakthrough. More often it comes through careful thinking, thoughtful design, underlying research, and a willingness to question assumptions that have gone unchallenged for years. And the potential here lies not only in what this work might become, but what makes it possible. And a shift towards either certainty or karma decisions, and care that happens closer to home. It's a reminder that when research pays attention to everyday realities, even small changes as to how we can detect and respond can quietly reshape lives, and as Paul talked to with his father.

And thank you. I think that's all we've got time for today. Thank you to the incredible Professor Paul Freemont, the amazing Tom Adam, and for all of you for joining us today, and thank you for listening.

You can find more information and links to resources on our website. We'll also include some important links about UTIs, supporting those infections and how you can combat those. We'll include any links as well that we've got to papers and things that have already been published for the team, and contact details for Tom, should you be a research funder.

Tom Adam:

Thanks, Adam.

Adam Smith:

You can find all that information at dementiaresearcher.nihr.ac.uk. Do also visit our community app where we continue the conversations and where we share new events, blogs, and podcasts. I'm Adam Smith, and you've been listening to the Dementia Researcher Podcast. Thank you, everybody.

Professor Paul Freemont:

Thanks, Adam.

Tom Adam:

Thanks, Adam.

Voice Over:

The Dementia Researcher Podcast was brought to you by University College London, with generous funding from the UK National Institute for Health Research, Alzheimer's Research UK, Alzheimer's Society, Alzheimer's Association, and Race Against Dementia. Please subscribe, leave us a review, and register on our website for full access to all our great resources, dementiaresearcher.nihr.ac.uk.