Podcast – International Lewy Body Dementia Conference Highlights 2025 – Part Two

Voice Over:

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

Dr Sterre de Boer:

Hello everyone and welcome to the Dementia Researcher Podcast. We're here in Amsterdam at the International Lewy Body Dementia Conference and it's my honour and pleasure to sit with this brilliant scientist who have attended the conference. I'm super happy that the conference is here in my hometown in Amsterdam.

I am Sterre de Boer. I'm a postdoctoral researcher at the Alzheimer's Centre Amsterdam, and my research focus is actually on front temple dementia. But for my clinical work, I also see patients with Lewy body dementia and other types of dementia. So, this conference is also very relevant for me and that's why I was super happy that it was very nearby my house and that I could attend this year.

Enough about me, there were a lot of highlights to discuss, and I would like to introduce our speakers. First, I would like to start with Salomón Salazar Maybe you can introduce yourself and what your work is and what your interest is.

Salomón Salazar-Londoño:

Thank you Sterre. So, I'm Salomón. I'm from Colombia, med student at Xavierian University in Bogota, so I'm also an ISTAART ambassador. And my main interest in research is around the DLB Consortium in Colombia that works in collaboration with King's College London at the Stavanger University Hospital. I also like some things around geriatric assessments, frailty markers, unconventional biomarkers in dementia, and that's what I do in clinical and research side.

Dr Sterre de Boer:

Super interesting. Thank you. Next to you is Lauren Walker.

Dr Lauren Walker:

Yeah, so hi, I'm Lauren Walker. I'm an Alzheimer's research UK fellow based in Newcastle in the UK. So, my focus is mainly neuropathology. So, I'm interested in Dementia with Lewy bodies that's been at this conference. More specifically common and pathologies in particular, how AD-related pathology can influence the clinical and the neuropathological phenotype of patients with Lewy body dementia.

Dr Sterre de Boer:

Thank you so much. Then next to you we have Felipe Botero Rodriguez.

Dr Felipe Botero Rodriguez:

Hi, I'm Felipe Botero. I'm from Colombia too. I'm psychiatrist and my focus are on neuropsychiatric symptoms related with dementia. I just moved to Norway at SESAM to Stavanger University Hospital to work at a Professor Dag Aarsland Labs.

Dr Sterre de Boer:

Right, thank you and great for everyone here to being part of the podcast. So yeah, this is actually the second part of a two-part special on a podcast on the conference. So, if you already, for instance, the first part you're listening, please also check out the first part and then rush back to this podcast because we also have some interesting highlights to discuss. That actually brings me back to you. I think you've all been presenters at this conference being either talk on the podium or a poster. So maybe we can start with you, what was your poster about? What was your...

Salomón Salazar-Londoño:

Yes, so I presented today my poster. It is a review that we built around the Colombian DLB Consortium, about DLB research in Latin America. In our consumption we have different steps, and the first step is to know what the gaps and opportunities for DLB research in our continent are. And as a brief resume, Brazil has an enormous lead in publications compared to the other countries. So, there is an under-representation within the under-represented, there is a very limited number of clinical trials and also most research is cross-sectional. So really, we are not assessing causality in Latin America related to LBD research.

Also, there was almost no neuroimaging or biomarkers research, so that's also important. Most research was clinical focus, which makes sense because it's the cheapest one to make and also the one that is more accessible based on memory clinics. So yeah, we have a lot of work to do. And the second part of the consortium will be told by Felipe, can't wait for that.

Dr Sterre de Boer:

Well maybe then that's a nice way to go to your poster. That's-

Dr Felipe Botero Rodriguez:

Great. Well, my poster was about the prevalence of DLB, prevalence and associated related factors. We found anything I think very important and very highlighted. There is a very low prevalence, 0.6%. So that give us a space for a lot of hypotheses. For example, it can be misdiagnosed under diagnosed I think a bit. But also, regarding your research about FTD, there are some papers about the ancestry, genetic ancestry in Colombia that tell or that explain a high prevalence of FTD because of that.

It also can be a high related factor to that low prevalence, but I really don't think that the reality or the real prevalence be as low as we see. So, there is a lot of things to prove and to study. This is the second step. In cold DLB are working in the third one to make our prospective study based on the E-DLB protocol.

Dr Sterre de Boer:

Well, very interesting.

Salomón Salazar-Londoño:

Just to add up on that prevalence that Felipe said was in our own clinic. So, it is some prevalence for a tertiary centre that you would expect to be higher, but it wasn't. We actually have one of the largest memory clinic for Latin America. Our database has more than 5,000 patients, but very few DLB patients. So, we really need to dig on that to see how percentage it is because of underdiagnosis, what percentage it is because of misdiagnosis and what percentage it is of something very different that we have not found about DLB in Latin America.

Dr Lauren Walker:

Yeah, so the DLB obviously the diagnosis that you do, does that involve, is that neuropathological confirmed or is that purely based on the clinical symptoms?

Salomón Salazar-Londoño:

Purely based on clinical symptoms. Yeah, so we use, of course, the McKeith criteria, but we cannot confirm the diagnosis based on neuropathology or maybe use a DBO markers we need or can see if there is co-pathology or maybe a misdiagnosis with AD we can't, that's our problem. Or maybe we can go further into the podcast about dementia clinical practise in Latin America.

Yeah, we are good clinicians because we have to because we don't have other tools. So yeah, it's really clinical.

Dr Sterre de Boer:

Yeah, I think it's super important that we bring that awareness as well to an international conference like this. I think there were 32 countries attending this conference and DLB goes beyond borders of course. I think it's very important that you bring that awareness to this international conference, but it also raises questions for me. How are you going to investigate where the cases with Lewy body dementia are in maybe more remote areas, maybe not in an academic hospital? Do you have any already protocol or plan or methods how you're going to find it?

Salomón Salazar-Londoño:

We have a few ideas. We want to collaborate with other centres in Colombia. One of the centres is the group on your resident you can't imagine, which is the group that follows the largest kindred of patients with autosomal dominant AD, which is the well-known Colombian families with AD. So, they have a lot of experience of dealing with patients with the disease and how to find patients in small towns or in zones that are more rural. We also will collaborate with a group in Cali, which is called Fundación Valle de Lili. Cali is another city in Colombia. That also has experience in tracking patients, but more into movement disorder’s part. They have a very strong research in PD. They belong to large PD and other research consortium. So, we are working together.

Also, I want to mention that our collaboration with Professor Aarsland, like Felipe said, is because we want to have blood samples and CSF samples from the patient, but to send them to King's College London or to Norway to have their analysis of biomarkers because that's the way of starting. It's super time brain hunted technology. That's the idea.

Dr Sterre de Boer:

It's very nice that the collaboration is already ongoing and that there are these opportunities to share expertise and equipment all over the world to do this research. How does it then, if you go to this conference, because like you said, we use the McKeith criteria, but we can't use all the maybe biomarker tools that other sites are using. Then how is it to attend to a conference that you see that that's starting to become such an important part also of clinical practise that maybe you can't already bring back to your clinic? I'm always very curious to ask how is that?

Salomón Salazar-Londoño:

It's like little kid to see a candy that have a... Will put it like that. I have talked a lot to Felipe about this because personally I love biomarkers. I really read the papers about biomarkers when I can't use them. But I think it's great that we see the conference and learn how to biologically define disease because once they arrive, we're going to be ready to apply it.

But I also think that we need to be cautious because biomarkers won't behave the same way in Latin America that they do in Europe for a lot of reasons. So maybe we have different cut off points, maybe we have other factors that can change how biomarkers behave. But also, I think that for example in Europe or North America, biomarkers arrive in a certain order. So, you have CSF, you have PET, now you have blood. We will have blood before all of that. So that will change how you apply biomarkers. If you read a guideline about AD biomarkers that you use the blood biomarkers and then confirm diagnosis with PET, that doesn't apply to us because how do we confirm with you if you don't have PET but only the blood biomarker.

So that will be a crucial topic I think in next years for dementia research.

Dr Sterre de Boer:

I think that's super interesting you're bringing this up. So, I think that like you said, the orders kind of reversed actually. So, I think it would be super interesting to see the effect as well in the clinic, but also the research. Maybe that also brings down a question to your field, Lauren. Do you actually see the difference in the pathological confirmation or mismatches maybe from one in the clinic and what you see on a microscope? Did you see that change over the years with all these biomarkers coming available?

Dr Lauren Walker:

Neuropathologically when we get the tissue into the brain bank, obviously we go through a load of neuropathological tests and this, sorry, a load of neuropathological experiments to confirm or understand what the mismatch and diagnosis was. This is some of the things that I was talking about on Wednesday. So, I had to talk on Wednesday looking at how AD related pathology can affect the neuropathological phenotype and how we may be able to relate that back to the clinical symptoms that we see in patients during lab.

Because a lot of the time patients with DLB get misdiagnosed as Alzheimer's disease and up to 30% of patients with DLB will have enough Alzheimer's related pathology to also categorise as a full diagnosis of Alzheimer's disease. And when we look at these cases under the microscope, these particular cases have a different distribution pattern of pathology.

So DLB cases that have very high tau tango loads look very different to the cases that have very low tau tango loads. In more specifically it's the amygdala that seems to have a lot more, excuse me, a lot more alpha-synuclein pathology. It has a lot more tau pathology, more so that it's affected than any other brain region that we've studied.

We use a tissue microarray system so we can look at 15 different brain regions on one slide so we can get a whole load of information. What we found in our study is I said the amygdala is very highly affected. It seems like it's a bit of a hotspot for pathology for both tau and A beta they co-localise within the same cells. In addition to co-localising in the same cells, they co-localise in different subcellular compartments. So, we think there could be a potential interaction between these two proteins that could be driving the diseases forward. We just don't really fully understand these relationships yet.

It's difficult to do that with post-mortem tissue obviously, but there's a lot of animal research and in vivo models to show that these potential, these protein interactions could potentially drive the disease forward both neuropathologically and clinically as well.

Dr Sterre de Boer:

Very interesting. Yeah. So, I think there's more, like you said, when this information becomes available, of course we'll also get more information about how to translate into what we actually see in the brain happening and vice versa as well. Because I also know you also correlate all the pathology back to the clinical symptoms.

Dr Lauren Walker:

Yeah, we do.

Dr Sterre de Boer:

Was there anything particularly striking that you saw in this more amygdala hot spot cases, was it even possible to disentangle all that information and symptoms?

Dr Lauren Walker:

I don't have that information yet. So that's something that I'm now going back to. Excuse me. So, we take all of the... We have research nurses that do clinical tests annually on all of these patients and it's just starting to dig back through that data to see if we can correlate anything with these cases that particularly will have a lot of pathology within the amygdala. And I think this is something that we're going to talk about more in the brain first, body first hypothesis, which is obviously one of the talks that was given at this conference.

Dr Sterre de Boer:

So, I'm already curious and interested in what you're going to find in your ongoing research on that topic as well. Especially because I think we have also clinicians here on the couch, so we're always curious to see how that relates back to what we see as a phenotype and how that can help also with our diagnostics.

So, you've talked a little bit about what we've presented and also about what you've presented. Were there specific highlights during the conference that you would like to talk a bit more about?

Dr Felipe Botero Rodriguez:

Well, I would like to highlight the debate between body first mind first because of course it is very important, but in the clinical practise it could be almost the same, in the clinical practise. What I mean is that the patients have a lot of clinical manifestations and here it opens the doors through neuropsychiatric symptoms.

Neuropsychiatric symptoms are very important because it is related with burden disease, burden of caregiver, and it affects quality of life and wellness. So, in this moment that we already... or we don't have yet any treatment, any cure to these diseases. I think it's very important quality of life; to mitigate the symptoms and we can see it in neuropsychiatric symptoms in one hand. In other hand, I think broader what we can see at the clinics, for example, it's not only movement disorders that is very important but is another option, the effect psychosis [inaudible 00:15:31], anyway. So, I think it's very important this debate especially for that, for it open our eyes, open our minds and be aware of other manifestations.

Dr Sterre de Boer:

So, you're referring to the plenary, right, from Per Borghammer of body or minds first, I think you were saying, yes. Maybe I'm just going to ask you, but if you don't have an answer that's also okay, but what do you think is first then, the body or the minds?

Dr Felipe Botero Rodriguez:

Well, my response depends on the site, on my world location, because if we talk here because of my biomarkers, I could say boys first, but in Colombia, in Latin America, I will say my first clinical manifestations first. It also opens the door to a non-conventional or atypical biomarkers. Why can't we say that neuropsychiatric symptoms, for example, mild behaviour impairment checklist, why this can't be a biomarker, a non-conventional biomarker. Of course, it's very different and under sensibility specificity will be very different than CSF biomarkers, but we have to work with the thing that we have. So, it's our first approach.

Dr Sterre de Boer:

And maybe I can ask this. I think it would be interesting to also ask you the same question. What do you think as more from the pathology side, what do you think is first?

Dr Lauren Walker:

I say I really enjoyed Per Borghammer's talk earlier today and the amount of data that he presented that was clinical, that was neuroimaging and the neuropathology data sets that he looked at, plus the animal models as well was... I really love his work. I really appreciate reading his papers. I think both. As the short answer, I think both will play a role.

In terms of neuropathology, we have cases in our brain bank that have amygdala-only Lewy bodies that don't have any other involvement. We've just been, these are normally incidental Lewy body cases, whether they will go on them to develop a clinical syndrome, who knows. But certainly, we have cases that are amygdala predominant, amygdala only and olfactory bulb only. So, there's definitely a strong case for brain first and body first hypothesis.

I think what surprises me the most is... because when I start thinking about this, my opinion would be, well, DLB is obviously going to be brain first all of the time because obviously the one-year rule they have the cognitive symptom, but in his data, he showed that 66% of DLB cases were body first. So, it's still something that I'm trying to wrap my head around. What he's saying makes a lot of sense that a lot of these DLB cases will have an abnormal DaT scan, but we'll have a normal MIBG, and some will have a normal MIBG and have a completely normal DaT scan.

So, I can see how both mechanisms will play a role and as I said, the post-mortem data sets that he's been using, the number of cases that he's got, which I think is really important to look at. I think what we struggle in a lot of these data sets is looking at diversity, which is a problem that I have with our cohorts as well, 99.9% of the people that come into our brain bank, are white Caucasian. I've got a feeling a lot of the bigger data sets that he uses as well probably don't have that much diversity. So, it'll be interesting to see how that actually translates into larger data sets and more diverse data sets.

What I also find interesting is the animal models as well. When you inoculate in different injection sites, they show the different distribution patterns. So, I definitely think there's something going on there and something I'm particularly interested in is how the contribution of different pathologies, obviously the brain has Alzheimer's pathology, it has TDP-43, there's vascular lesions, probably are the things that we don't know about yet and how that could play a role. I think it's a lot more complicated and adds to the heterogeneity that we see in Lewy body diseases.

Salomón Salazar-Londoño:

I'm talking about TDP-43, if I say a lot about that, for example, I don't know if you remember the talk about, in the session about pathologic assessments. There was a talk that says about patients with early onset DLB versus late onset DLB. When one of the almost last slide was comparing the pathology between groups. I was expected to find a lot of more TDP-43 pathology in the younger patients. Why not because of a differential diagnosis with FTD or would they have a different version? But they had not. It even didn't... In the older patient didn't even have more AD pathology. So, it's rare that co-pathology. It's a really interesting topic.

Dr Sterre de Boer:

It is.

Salomón Salazar-Londoño:

And yes, and TDP-43 is really underrepresented. People need to talk more about it, other than late also how it behaves with the other pathology.

Dr Sterre de Boer:

Yeah, and I think you were already saying about the order of biomarkers coming available. I think maybe I'm not a pathologist in any way, so please correct me if I'm wrong, but I also understand that when we found out more of the pathology types and more of different staining, and it's quite also... you had to go back to the old cases and maybe you already back in the day it would stop if you find AD pathology, it was like, "Oh, it's AD," and then you wouldn't do all the other staining.

But now I know people do all the stainings just to see whether what the co-pathology is a co-pathology. I think when we get more knowledge of what's there throughout all these decades of research, we also have to do more work to see what the co-pathology is actually and not just the first pathology we found back in the day.

Dr Lauren Walker:

We did that recently with TDP-43. So, in the last, I think we published a paper in 2020/2021 just after latency, it being defined. But we went back through our pathological cohort that had an AD diagnosis for controls and with DLB just to get the prevalence of what TDP-43 looked like in these cases, but the stainers hadn't been done because we weren't aware of that. So, we're probably going to get more of that in the next-

Salomón Salazar-Londoño:

Yes. I think dementia can be as complicated as you want it to be. For me, dementia has always been an umbrella term. So, you have neurocognitive disorder, MCI, dementia, and then you can have Lewy body dementia, but you can have Lewy body dementia with AD, Lewy body dementia with vascular and so go on, go on, go on, go on, go on.

So, in theory of personalised medicine, we will have to have a debate of how much personalised we will want to be because in one point being more personalised won't change patient's outcome. That will be the important part. It would be more expensive to be more personalised, but at the end, what's the goal of it?

Dr Sterre de Boer:

Yeah, yeah, enough challenges ahead. Salomón, I have to of course also ask you the question what your body or mind, but would you answer, I know it's a very difficult question.

Salomón Salazar-Londoño:

I will dodge the curveball and say it depends. Patients can have both, I think. Yeah, as you say, 66% of the patients with can have the other way around. So, it depends on up to the patient and it's a spectrum as you can have PDD and DLB. You can have DLB body first, DLB mind first. It is an important topic because it changed clinical trial [inaudible 00:23:05] of patients and it changed how they need to make some priorities regarding their clinical care, caregiver, all of that. So, both.

Dr Sterre de Boer:

Yeah. I think also very nice what Lauren said as well, right? It's not like the mind is separate from the body at all. It's all intertwined, it's all affecting each other, and the body is the minds and vice versa. I think it's also really nice that we also have this interdisciplinary couch today. So, we have people, I think a psychiatrist if I'm correct.

Salomón Salazar-Londoño:

Yes.

Dr Sterre de Boer:

You have someone working in pathology, you work in neurology and biomarkers. I work in neurology. So, we are already showing that it's not just one discipline that's going to fix all these challenges. We really have to work together. But I think it's nice that this was such a provocative plenary that was there during the conference.

I also think there was a highlights mentioned of another debate that was today. Maybe Lauren you can share a bit of the debate that was happening. I think this was the, I will say the statements, the house belief that DLB and PDD are still useful concepts. How was the debate?

Dr Lauren Walker:

It's always an interest. It's one of the highlights of this conference that we always have a debate, and it's always very well attended and it's always good-humoured. Yeah, so it's always on an important topic. Things like the one-year rule and this year DLB and PDD still useful terminologies?

I voted yes, I do think it's useful looking in terms of different disease types, but what I will say is that things like treat and pathologies, individual pathologies will help all of these patients regardless of what the label is.

Dr Sterre de Boer:

Yeah. And Felipe, you also mentioned it that you enjoyed the debate. Do you want to share what your standpoint of view was on this?

Dr Felipe Botero Rodriguez:

Well, I really like the pragmatic point of view that it could be the same and I mean maybe that microscope and is very important. It could be different, but when assessing the patient, it could be the same and even the treatments are very similar, and the responses are very similar to. So, it could be a last name if he's only Parkinson's or dementia with Lewy body. So maybe it could be the same and we can go forward to manage the same entity or to manage it like the same and get it.

Dr Sterre de Boer:

Yeah. Do you think where we are right now that would also benefit the patients, or do you think it's more benefiting research if we come to that consensus?

Dr Felipe Botero Rodriguez:

I think it's more beneficial for research. For patients, maybe it is the same because it could be another variable to confuse them to patients and family. So, for clinical I think it's almost the same.

Dr Sterre de Boer:

Yeah. And what is your point of view on that?

Salomón Salazar-Londoño:

I have a difficult point of view because at the beginning of the debate, I vote that it was different and at the end I didn't vote. I agree with what they say that in the prodromal stage it is very similar. At the end is very similar. I completely agree. But patients don't really care about both ends. They care about the middle part, which that's where is different. That's where patients have different clinical trajectories and that's where we need to really take good care of them.

So, I understand the pragmatic approach, it may be easier, but during the clinical trajectories excluding the prodromal at the end age, that's where we're going to fight the difference. So, I think for the moment I will use the DLB PDD approach. Maybe if we have widely available alpha-synuclein assay that we change maybe the scope. Because some people at the debate said that we are treating patients not with DLB, not with PDD, but with alpha-synucleinopathy. But I don't agree totally with that statement, but maybe in the future with widely availability of biomarkers, I can change my answer. I have the right to.

Dr Sterre de Boer:

Salomón, I think it's also really nice to see that throughout the debate you didn't change your mind, but you did get maybe a different few points and you'll take that into account of course.

Salomón Salazar-Londoño:

It's great to change what you think. If everyone is thinking the same, someone is not thinking.

Dr Sterre de Boer:

No, no. I'll ask all of you the same question in the next conference, see how we go. I also remember before we were starting the podcast, you also said you also really like the plenary or debate as well on how we can use the biological framework that's currently really starting to emerge within the Alzheimer's field. What can we learn from that in the DLB field?

I was wondering, so you already mentioned it, I really like biomarkers. How was that for you to be part of that talk and how did you find it useful, maybe also for your research already now?

Salomón Salazar-Londoño:

It was an excellent research session all yesterday afternoon from the plenaries to the debate, they were great. I also liked that they had Dr. Shelton to have the AD perspective because I think we can learn a lot from AD, we have that advantage. The AD folks didn't have an example. We have an example.

I think the bigger question is not where to see if the synergy approach or other approach is whether we want to say that DLB is a solely biological entity, or we want to have a biological and clinical approach. So, bringing that to Alzheimer's disease is Alzheimer's Association criteria versus the International Working Group criteria. I think that's the main thing that we need to discuss. It was discussed, I remember Professor Lang talking about. What for me is one of the biggest arguments is that not all patients with neuropathology will develop symptoms. I think you know that as a pathologist.

Dr Sterre de Boer:

Yeah.

Salomón Salazar-Londoño:

If a patient one develops symptoms, why you want him to treat him or to do a disease-modifying therapy that maybe won't do good for him. For me, that's key. That perspective paper that Professor Lang highlighted about disentangling clinical trajectories from Professor Villain in France, because French people are the most about the clinical, [inaudible 00:29:34] clinical framework. It's really, really great to see how they show all the different trajectories that a patient can have.

We also need to agree on how we are going to call those patients with a positive biomarkers but without clinical symptoms because the Alzheimer's Association criteria says that they are already with the diseases, they are not ill, but they have the disease. The International Working Group says that they are at risk of AD and can't have a lot of implications, social implications, health implications. It's not the same to say a patient, you are at risk of an idea, saying you have Alzheimer's disease.

If someone says, stop to me at, I don't know, 65 years old, what am I going to do? I will be scared. Maybe I will develop symptoms. But maybe yes. So, I also understand the other side of if I have a disease morphine therapy and I can give it to the patient very early, of course I would like to know. I think that in the next DB conference we need to have that discussion about is it going to be at risk of LBD with alpha-synuclein or is it going to be with alpha-synucleinopathy? Because that's the other thing. You have the Alzheimer's staging criteria, you are talking about Alzheimer's disease, you are at risk of Alzheimer's disease.

Here you're going to say you're at risk of multiple system atrophy. You are at risk of Lewy body dementia; you're at risk of Parkinson's disease. Or maybe that's where you need to make them the same and say only Lewy body disease. We have another debate to do, that's an excellent session.

Dr Lauren Walker:

No, I really appreciated the fact that they had, it was Tanya Simuni from Chicago, Anthony Lang from Toronto. So, the two lead offers of those two papers and then obviously they have Philip Shelton's on the ATN perspective and then David Byrne from a movement disorders perspective. So, it was a very nice conversation, and I think what I really appreciated, they went through the pros and the cons of each of the staging criteria.

I think what I appreciated the most is the fact that both authors said this is version one. So, I remember reading the papers thinking this isn't going to work for DLB right now. So, there's a lot of things that I think that they're obviously aware that we still need to progress, but you've got to start from somewhere and we do need to take lessons from movement disorders and the Alzheimer's field.

You're right, people with incidental Lewy body diseases, what does that staging system mean for them? They might not ever go on to develop a clinical syndrome and by the same token, 50% of Alzheimer's patients will have synuclein in the amygdala. What does it mean for them if they've been labelled with this? You've got Lewy body disease as well. It might never manifest clinically; it might never affect their Alzheimer's disease. So yeah, I really appreciated the fact that this is version one. Version two will incorporate co-pathologies or incorporate quantitative seed amplification assays.

Salomón Salazar-Londoño:

Just to say one small thing. One thing that is important is the effect of treatments. So, for example, we always have the comparison with the cancer field and the cardiovascular field saying that for example, if a patient has ovarian cancer and you hey take a biomarker of say CA-125, you can take out the ovary or you can give... But in dementia you can't take out the brain.

Or if you talk about cardiovascular disease, you take a blood test and the low-density lipoprotein is high, you can give the patient a statin. But here, yes, you can give the lidocaine up and we are making huge progress, but it's not the same thing to give patients atorvastatin versus infusion therapy with all that is in implied.

So, I think that as this is modified therapies will advance also the biological definition of the disease will advance at the same time. In DLB have an event that in Alzheimer's the definition has changed around the availability of this is modified therapies. In DLB we are not at that point yet. So, we have the chance to do a definition of disease without the pressure of those treatments. So that also will be very, very important.

Dr Sterre de Boer:

Yeah. Yeah. And Felipe, we always compare what the Alzheimer field to DLB. I've noticed this of course also in the FCD field and like you said, I think it's very nice how you say, we have an example so we have to use it, but what can actually the Alzheimer field learn from DLB research you think?

Dr Felipe Botero Rodriguez:

Well, I think that is very important that the DLB field maybe has been a little underestimated. So, in work or being that second layer works to go ahead without pressure or with less pressure from one hand and looking another kind of symptoms. At the beginning, Alzheimer was only forgetting things, memory, we were talking about this cognitive homogeneity, the ammonia. But in Lewy it's very different. Indeed, I think that memory is not the main concern in the DLB or LVD game, of both. So, what can the AD file learn about DLB file? I think that look not only the cognitive status is of course very important, but all the domains.

Dr Sterre de Boer:

Yeah, I think that's what I also really appreciate from the conference. I'm coming from a different focus maybe within dementia, but I really enjoyed that there were so many ways of phenotyping all the patients in a very high-level well-thought test. Different viewpoint going from the phenotype all the way to pathology and back using not just biomarkers of phenotype but also really good clinical assessments. That's what I really took home as well for myself at this conference. So really mindset.

You also point this out and I think it's so important as well. All the clinicians we're mentioning it a few times, but never to forget what you actually see on the outside. And then we're so lucky to have pathologists working on how we can actually translate that and correlate that, what's happening in the brain.

Dr Lauren Walker:

To add to that, actually I think something that we can learn from the field of DLB that we can apply to other neurodegenerative diseases is because DLB is so heterogeneous, we can't just look for the protein aggregates. We've known for a long time that alpha-synuclein in the brain doesn't correlate well with clinical symptoms. So, we need to look further around that.

An example of that at this conference is one of the posters that I looked at by David Koss's group in Dundee and he's looking at DNA damage and how that can influence clinical symptoms and disease progression in dementia with Lewy bodies. So, what they did is they've looked at post-mortem tissue and found that alpha-synuclein is present in the nucleus. They found that this alpha-synuclein is also seed competent, so it gives a possible amplification assay result and they're starting to take this further. So, to look at different DNA markers and how that affects the different neurodegenerative pathologies in the brain.

They've also looked at different proteomic analysis as well. And its DNA damage enzymes that are up regulated in this brain tissue. So, it's taken a more holistic approach that it's not necessarily just about the proteins that we see, but it's specifically other mechanisms that could be influenced in the disease progression as well. And I think that could... Because we've had to do that in DLB, I think this is something else we can take to different fields as well.

Dr Sterre de Boer:

Yeah, you really almost embracing the heterogeneity. It's not like something we trying to tackle down all the time. It's really trying to, okay, how can we then approach this disease in the most holistic way like you're saying. Yeah.

Dr Lauren Walker:

And for example, this can lead on to repurposing therapies that we've never usually considered if we're trying to target alpha-synuclein all of the time where missing chances to repurpose different existing therapies that could be promising.

Salomón Salazar-Londoño:

Thesis.

Dr Sterre de Boer:

Yeah. Yeah, very nice.

Salomón Salazar-Londoño:

Then breaks out a point and maybe at the conference we didn't have the chance to address and that is cognitive reserve and resilience to clinical symptoms because that complicates landscape of a lot. You include potentially modified risk factors and why some patients develop symptoms and why other not that brings another variable to the heterogeneity, which is very important, but it's the hardest to assess because why is this patient with alpha-synuclein will develop symptoms and this one will not.

Dr Sterre de Boer:

Yeah. Were there any other highlights that we didn't discuss that you feel like we should really share with the audience?

Dr Lauren Walker:

Well, I, not surprisingly, really love the pathology sessions. So yeah, there was a few talks in that, but in particular it was Liisa Myllykangas discuss from Helsinki in Finland and she's a neuropathologist and looks at... in Finland they've got some massive post-mortem cohorts which are fabulous. It's hundreds of cases. She is specifically looking at the endo-diagnosis of diagnosis of Lewy body disease, which we've known for a long time. It's very endo-diagnosed unless it's pathologically confirmed, and it's misdiagnosed as Alzheimer's disease a lot of the time.

What she found is in, I think she had 500 in, it's Vantaa 85 study and it was over 500 cases that she was looking at and she'd stained the post-mortem tissue for alpha-synuclein. It was brainstem regions, and it was the hippocampus, and it was from ages 19 up to I think it was 94, and found the youngest person to have an alpha-synuclein positive immunohistochemistry in the brainstem was aged 54. So, a long time before we start to see the clinical symptoms.

So, I think she'd estimated, I think people over the age of 50, there's Lewy body pathology in about 9% of that population. So, it's a population-based cohort, so obviously not hospital-based. So, it's very representative of the environment. I think it's important that... Obviously biomarkers will help us to take these when we have a good biomarker or when we have a good blood biomarker or a good neuroimaging scan, which unfortunately we don't have any of these.

This is where we struggle, a lot of the time, at neuropathology because we get very end-stage tissue. So, a lot has already gone on in the brain, but I think that's due to really highlighted that we need biomarkers, and we need them pretty quickly for at least alpha-synuclein so we can start and track this disease in midlife and get a better representation and better diagnostics for patients.

Salomón Salazar-Londoño:

I completely agree with you, and I remember really well the session. It really made me to ask if that pathology is present that many years ago, how many years ago a biomarker will be positive. Because in AD we already have evidence that remember that during the Journal of Amazing Paper that shows how clinical surgery is on patient decades before the symptoms can have a positive AD biomarker.

That brings us to the same question that many before is why you will do that biomarker in an asymptomatic patients. Here is the same thing. You have pathology in patients that are that young. Why will you do a biomarker? I wish I could do it to give a perfect treatment and that the patient didn't have the disease, but in this moment, it is not possible. As people yesterday say, "We need more that." That's the conclusion of the course; we need more data.

Dr Sterre de Boer:

Yeah, well I think that was also... That's always very clear after ever conference we've come, right? We need more research; we need more data. But I also felt like this was the first time for me attending this conference, but I really felt this really motivated group, very enthusiastic who are very willing to collaborate. I think it's very, like you said, maybe the field is underestimated, but I felt like when I was sitting in the audience, you're the one to watch, I think.

I think stuff was going really quickly and it was nice to immediately compare also the conference from two years ago when they showed after the conference, we did this, we found this. So, I think it's moving very quickly and hopefully note all the things we were wishing for and hoping that I think in two years they will actually already be there. But I actually think, like you say, I think it's underestimated, but we shouldn't.

Salomón Salazar-Londoño:

Yeah, I completely agree with you. It's also my first time in this conference and you can see the community is really closed. Really open to having a conversation about something. And I also want to highlight the work that they're doing with early career researchers like us. That's incredible. They really want to be good mentors to really want more people in the DLB fields. Multiple times they say we need early career researchers; we need people to take over our position when we are retired. So that's also great that they are thinking about early career researchers and including them in the conference.

Dr Sterre de Boer:

In the next generation. Yeah-

Salomón Salazar-Londoño:

That's important.

Dr Sterre de Boer:

... super important.

Salomón Salazar-Londoño:

Agree.

Dr Sterre de Boer:

Well, we already touched on the pathological session as well. Was there any other session or plenary or talk that you thought I have to mention is before we end our podcast?

Salomón Salazar-Londoño:

We can talk about the McKeith, the Ian McKeith Prize. That was great. Yeah, a good recognition for-

Dr Sterre de Boer:

Can explain it to the audience.

Salomón Salazar-Londoño:

So, the first thing that happened at the conference after it was started, they handed to Dr. Ian McKeith is the one that wrote the criteria for DLB diagnosis and a prize name after him. So, the Ian McKeith criteria was given to Ian McKeith, and they asked to highlight the work of seniors’ researchers in the field, and I think it is important, and it has a good name for the prize.

We'll see who gets it next year.

Dr Sterre de Boer:

Or maybe one of you on the couch who knows.

Salomón Salazar-Londoño:

In a few years. But yeah, that was important. Also, his talk after the prize was great to see all the work during all these 30 years and also the prodroma diagnostic criteria is really, really important. They are up-to-date and they have the clinical biological perspectives. They don't have yet the only biological definition piece, that's great.

Dr Sterre de Boer:

Yeah, he gave a really nice, I think, overview and also almost a history lesson, but in a way to really inspire and motivate, I think everyone who was sitting in the room and to... Like you said, if you know where you came from, then you also know where you're going and where you were going ahead. So, I really enjoyed that talk as well. Yeah, it was very good.

I think lovely prize of course, and I'm very keen to see who the next recipient of it will be.

Dr Lauren Walker:

I just have one more highlight to throw in there. So, in terms of the biomarkers, I'm interested in AD co-pathologies in DLB and how we're starting to use pTau-181 and 231 to identify co-pathologies in Lewy body disease because obviously once we have a good idea of co-pathology, if and when disease modifying therapies come through, we can give it to the patients that need it.

There's been a few posters in, it was on day one and obviously it was a biomarker session. I think something that we're really struggling with right now is that DLB patients, that it was a post by Leonidas Chouliaras from Cambridge, and he specifically looked at patients that had a diagnosis of DLB and patients that had a diagnosis of AD and he looked at pTau, I think it was 217 and 231. At the minute there's very little difference to separate the two conditions, which I think something that we're going to need to work on.

So, I don't think it's going to be one biomarker that will differentiate between AD and DLB because they all have a certain amount of pathology. So, there was no clear definition. So, I think what I'm taking from that is that we need... it's going to be a panel of biomarkers that will be able to hopefully in the future give us a more definitive diagnosis in patients that have DLB, but with also additional Alzheimer's related pathology.

Salomón Salazar-Londoño:

I want to do a comment on that because eventually maybe people will start thinking of what if we try disease modifying therapies from Alzheimer's disease in patient DLB? That's whereby biomarkers will play a very important role seeing if patients will have the same clinical progression or it would change. But third, it will be also an important factor that is vascular pathology.

That is also forgotten in DLB, but is also very, very important because if we are thinking of giving patients with DLB disease, modifying therapies with AD based on co-pathology, also need to assess if this patient had a big burden of vascular pathology because that will forbid us to use that treatment based of the risk of ARIA. So, I think if we see AD co-pathology in DLB, we also think to see vascular co-pathology in DLB.

Dr Felipe Botero Rodriguez:

And to note eventually, indeed that is happening now.

Salomón Salazar-Londoño:

Yes.

Dr Felipe Botero Rodriguez:

You see the pipeline of treatment of clinical trials saying most of them are related or has been tried for Alzheimer's.

Salomón Salazar-Londoño:

Yeah, I agree. The group from Karolinska as detected from Dr. Ferreira with Ana Renyi, she's a PhD year student, has a lot of work related to vascular pathology in DLB. They have evidence that supports the vascular pathology is common in DLB and you can see it in the MRIs. You don't need to go to the pathology in vivo, you can say see it. So, it is really important to take that into account.

Dr Sterre de Boer:

Yeah, and I think also really what you're saying, we probably need a panel. I also think that during the biomarker session also, [inaudible 00:47:25] was also mentioning that she is trying different panels on different types of assays to really see what the best combination is. Not just to differentiate DLB from controls, but also from AD and what does co-pathology do. And I think once we are there, then the next step will be what does vascular co-pathology do? Well, maybe it's also thrown TDP in the mix.

So, it's going to be, yeah, like you say, it's going to be a lot of steps ahead and even more challenges. But it's, I think also excited that we can already think of these challenges and see them coming and getting prepared. I think that's really... It's very clear in a DLB field that everybody is prepared, everybody ready if its wherever people are, if it's here in Amsterdam or in Newcastle or in Columbia, everyone is getting prepared for what's happening. So that's I think, very nice to see.

I think I also saw the same poster by the way I even took a photo of, and I hope that's allowed, but because I thought it was nice that is actually being done and shown what is working, what is not working. Especially because the blood-based biomarkers are getting so much attention, of course, which makes sense. It's going to be great if we can use them in the clinic as well and for research, but also clinical trials. But that also means we have to know what they do in other clinical diagnosis and clinical phenotypes.

Felipe, did you have any other last highlights to add?

Dr Felipe Botero Rodriguez:

In the same vein of clinical trials, there's a lot to work. Results are not so promising as I wanted, but it's a first step. Since the pathology to this trial, these clinical trials, that are totally necessary. But let's work on this. Let's wait in which moment we'll have something to help more our patients.

Dr Sterre de Boer:

So, you're referring to the trial that was presented I think today, right? Yeah, yeah.

Salomón Salazar-Londoño:

Yeah. It's a complicated pipeline and a small pipeline compared to AD as Felipe said. So, I think we really need to see what treatments we are choosing and really what treatment can we take from the others. For example, I would love to see a trial of GLP-1 analogues in DLB. We already have some trials on Parkinson's disease with distance results, but maybe for DLB that will be important. We don't the part of brain health, that's another topic about the other will be great to see what we can learn from other diseases.

Dr Sterre de Boer:

And probably also when people, let's hope it's not going to take a long time when people maybe come to autopsy that actually had a treatment, we can also learn more about what that actually did on the pathology. I think to wrap it up, because I think we can go on for hours, but maybe to wrap it up, maybe give a little bit of a message to people listening at home, what you're bringing back from this conference.

Salomón Salazar-Londoño:

No, it was an outstanding conference. I learned a lot. I met a lot of people. I saw people that I saw in other conferences. I think the DLB field is growing in a very interesting way, and it is a field that has something for everyone. If you like motor symptoms, if you like neuropsychiatric symptoms, if you like pathology, if you like treatment, if you like [inaudible 00:50:53], it has it all and it really needs more people involved with it.

Dr Sterre de Boer:

Lauren, what are you taking home?

Dr Lauren Walker:

For me, it's the increase of interdisciplinary research. There are clinicians, there's people that work in neuropathology like me. We're starting to get more fundamental science at this conference, which I really like. So, getting a lot of different aspects fed into DLB that we've not really considered before. So, I'm really positive about that.

Yes, we didn't get the results from some of the clinical trials, but I think they will come in time. I think one thing that hasn't been mentioned, and I don't know if it was mentioned in the previous podcast, but the formalisation of an international consensus to really drive that's being discussed today. So hopefully the start of an international consensus. A more formalised society that will hopefully, anyone who's interested in DLB and was to contribute can also... We need as many different minds as possible to come up with solutions and better diagnostics and better treatments and more understanding of the diseases that we're studying.

So, I think that was a big positive, that we're becoming a better group, and we'll become a more cohesive...

Salomón Salazar-Londoño:

And we work for our patients. That's the final goal of all of this.

Dr Sterre de Boer:

Felipe?

Dr Felipe Botero Rodriguez:

Well, it was great. It was very nice. There is passion for learn, work, work for our patients, and my main message is the importance of teamwork. There is a lot of people that is working for the same goal, each of one from... it's a lot of expertise, but there is a teamwork that we have to keep doing.

Dr Sterre de Boer:

Yeah, thanks. Well, those were all beautiful messages and words to end this podcast. As we're running out of time. I want to thank of course our brilliant guests for today. Thank you so much for taking the time after probably already quite exhausting days and a lot of information that you still probably want to grasp while travelling home. So, thank you so much.

If you want to know more about Lewy body dementia or about the conference, you can still visit the website ILBDC2025.com. I'm Sterre de Boer, thank you so much for listening to the Dementia Researcher Podcast and we hope to see you next time. Bye.

Dr Felipe Botero Rodriguez:

Bye.

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.

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