54. New insights into dementia risk reduction
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CORDIScovery podcast- Episode #54 - New insights into dementia risk reduction
This is an AI transcription.
00:00:16:05 - 00:00:35:22
Abigail Acton
Hello and welcome to this episode of CODIScovery with me, Abigail Acton. There are advances being made in the area of dementia and cognitive aging. The European Commission has granted the EU marketing authorisation for Kisunla, a medicine to treat mild cognitive impairment, including mild dementia, in the early stages of Alzheimer's disease.
00:00:36:01 - 00:00:58:14
Abigail Acton
Alongside pharmacological advances, we're also gaining insights into why some people may be more impacted than others and the role socioeconomics play in the overall picture. But sometimes it feels like a race against time. Worldwide, it is estimated that there are more than 50 million people living with Alzheimer's disease and related disorders. The most common class of neurodegenerative diseases.
00:00:58:16 - 00:01:21:01
Abigail Acton
This figure is expected to double every 20 years as the population ages. Evidence based solutions may help to foster better coordination between health and social care systems across the EU. So let's turn to our three guests, whose projects benefited from research and innovation funding, for an idea of what is being discovered.
00:01:21:03 - 00:01:39:03
Abigail Acton
Alina Solomon is professor of Neuroepidemiology at the University of Eastern Finland, visiting professor at Imperial College London and senior researcher at the Karolinska Institute. She's particularly interested in dementia risk detection and therapeutic approaches for dementia risk reduction. Hello.
00:01:39:09 - 00:01:40:03
Alina Solomon
Hello.
00:01:40:05 - 00:01:58:08
Abigail Acton
Welcome to join us today. Julia Neitzel is assistant professor at the Department of Radiology and Nuclear Medicine at the Erasmus University Medical Center in Rotterdam, the Netherlands. She uses brain scans in large population studies to discover what protects and hurts brain health. Hello, Julia.
00:01:58:10 - 00:01:59:05
Julia Neitzel
Hello.
00:01:59:07 - 00:02:07:06
Abigail Acton
Hi. Currently professor at the University of Luxembourg, Anja Leist will soon be taking up a professorship at the University of Heidelberg.
00:02:07:08 - 00:02:16:24
Abigail Acton
Her research focuses on sex and gender differences, socio-economic inequalities and risk reduction in cognitive aging and dementia. Hello.
00:02:17:01 - 00:02:17:20
Anja Leist
Hello.
00:02:17:22 - 00:02:31:15
Abigail Acton
Alina, I'm going to turn to you. The Brain Health Toolbox set out to create a strategy to develop accurate dementia prediction and effective prevention. There's been a lot of work done in this area. So what is the gap in our knowledge that the Brain Health Project sought to fill?
00:02:31:15 - 00:02:33:07
Abigail Acton
Please.
00:02:33:09 - 00:02:58:10
Alina Solomon
There are two main gaps. One was the gap between identifying dementia risk and the actual interventions to reduce the risk. And risk and prevention potential are two sides of the same coin, but they're not identical. For example, do people with high dementia risk also have high prevention potential? Who is most likely to benefit from what interventions and at what risk or disease stage?
00:02:58:12 - 00:03:24:18
Alina Solomon
And then there was also the gap between pharmacological and non-pharmacological interventions. That is new drugs for Alzheimer's disease. They're being tested in people in early risk or disease stages, people without dementia. And as I saw it, both drug and non-drug interventions had the same main goal to reduce the risk of dementia. And at the time, we had just finished the FINGER trial.
00:03:24:20 - 00:03:33:21
Alina Solomon
And that is the Finnish Geriatric Intervention Study to prevent cognitive impairment and disability. And that was a great basis for the project.
00:03:33:23 - 00:03:39:23
Abigail Acton
Okay. Super. So when it comes to risk prevention and mitigation, what intervention strategies were you considering?
00:03:40:00 - 00:04:02:17
Alina Solomon
I wanted to do precision prevention. So the Brain Health Toolbox focused on and developing the kinds of tools that researchers and clinicians would need for this, for getting the right interventions to the right people at the right time. We did work on disease models and risk prediction algorithms, but this time also tested them in actual intervention studies using the FINGER model.
00:04:02:19 - 00:04:37:03
Alina Solomon
And the FINGER is what we call a multimodal lifestyle intervention model. It combines nutrition advice, for the purpose of having a healthy, balanced diet. It's not about weight loss unless medical indicated. And then there was also an exercise program, cognitive training, social activities, and managing cardiovascular metabolic risk factors. It's a structured model, but it also has room for individual adaptations because one size is not going to fit.
00:04:37:05 - 00:04:38:04
Alina Solomon
Everyone.
00:04:38:06 - 00:04:52:14
Abigail Acton
So when you see a structured model, you know, these various components that you've just outlined would be set before, the people participating in the trial, but then more of one or less of another, depending on the relevance to a particular participant. Is that what you mean?
00:04:52:19 - 00:05:10:00
Alina Solomon
Yes. Depending on where each participant was at, for example, how much healthy lifestyle changes are needed in someone's current diet, because they will vary a lot. The same with exercise. Also depending on their own, let's say physical abilities and so on.
00:05:10:02 - 00:05:19:07
Abigail Acton
Of course. Absolutely. And when you said, I believe you said social activities and so on, can you give us some idea of the sort of activities that you were thinking mattered?
00:05:19:09 - 00:05:41:08
Alina Solomon
They were group activities that were embedded into the other domains of the intervention. For example, for nutrition advice. We also had group sessions where people can discuss with their nutritionist and ask questions and so on. More on in a group setting. Talk to each other. And so on. Same for the exercise program was in groups at the gym.
00:05:41:10 - 00:05:57:10
Alina Solomon
We also had group sessions for cognitive training, for the cognitive part, where they would also get to ask questions about aging, memory and cognition: what happens over time, what else can they do to improve things and so on.
00:05:57:15 - 00:06:05:22
Abigail Acton
Right. Because I understand that social interaction is actually one of the things that does help as a factor for mitigation. So you were combining two things there.
00:06:05:23 - 00:06:14:13
Alina Solomon
Yes. And it was also, many of the participants said that that was the one of the most appreciated components of the intervention.
00:06:14:15 - 00:06:34:10
Abigail Acton
Yeah, people do like being with people and it's important for their brain health to interact. Yes, indeed. Okay. So when you refer to the part of the project's title as toolbox, this, this is a notion then that you would be putting forward to health care providers, elements that could be used, as you say, at the right time with the right people.
00:06:34:12 - 00:06:37:16
Abigail Acton
So how are you actually envisaging that this could be used in practice?
00:06:37:18 - 00:07:05:03
Alina Solomon
The tools were primarily for researchers with the aim of eventually being used by clinicians as well, and for the research part one important thing was that I wanted relevance and effectiveness across different populations with very different contexts economic, cultural, geographical and so on. And part of the work was for example, how do we translate, adapt and optimise the FINGER model outside of Finland where it was developed?
00:07:05:05 - 00:07:28:22
Alina Solomon
How do we do all this testing in a harmonised way? We don't want these trials to be just scattered, separate pieces. We want them to to work like the pieces of a puzzle. We want to be able to fit them together. And when we do that, we're able to see, bigger and more, informative picture. And this project was a bit like a scientific engine for what we call the world wide FINGERs.
00:07:28:24 - 00:07:33:11
Alina Solomon
That's the first global network of multimodal dementia prevention trials.
00:07:33:11 - 00:07:33:19
Abigail Acton
Right.
00:07:33:19 - 00:07:34:05
Abigail Acton
Super.
00:07:34:05 - 00:07:40:03
Alina Solomon
And we started with maybe 4 or 5 countries, but now it's grown to over 70 member countries.
00:07:40:08 - 00:07:46:05
Abigail Acton
Oh, that's fantastic. That's super. That must give you a great feeling of satisfaction to see that there's uptake and real interest in this.
00:07:46:07 - 00:07:51:09
Alina Solomon
Yes. That was a big surprise. How much it grew, a lot more than we expected.
00:07:51:09 - 00:07:59:16
Abigail Acton
Yeah that's encouraging. Super. And do you have any findings that you can share with this? Are there any results or any key takeaways from the project that are worth considering?
00:07:59:16 - 00:08:24:05
Alina Solomon
If I were to pick one of the more significant findings, at least for me, was that people with genetic susceptibility for dementia can clearly benefit from lifestyle interventions and for example, people who are carriers of the APOE-ε4 allelel, which is the main genetic risk factor for Alzheimer's disease. They may even benefit more than non carriers.
00:08:24:07 - 00:08:40:04
Alina Solomon
And one exploratory finding. So still exploratory we still need to test. But I think it's very very important was that women with a certain genetic susceptibility may also benefit more than men. But again that's something we still need to test.
00:08:40:04 - 00:08:56:14
Abigail Acton
Right. Yeah. So you're still testing that hypothesis. But yeah that's interesting okay. Well that's fabulous. And could you just wind up maybe by just giving us some idea of the sort of interventions that you think we're probably going to be the most productive when you talk about the intervention of lifestyle choices and behavior, what sort of things are you thinking of?
00:08:56:16 - 00:09:27:23
Alina Solomon
Yeah, what we started doing already during the project, and we're continuing now in, in other EU funded projects is, what I call combination therapies. So FINGER was a multimodal intervention. It already combined multiple lifestyle domains. And now we're combining that with, pharmacological interventions. And I think this is this is a very, very important direction to go in because there's not only one magic pill that is going to sort it all out.
00:09:28:00 - 00:09:36:17
Abigail Acton
Sure it's a combination of things. But when you say lifestyle interventions, can you give us some ideas of the lifestyle interventions that you think are the best for people to consider, the most useful?
00:09:36:22 - 00:09:42:13
Alina Solomon
I wouldn't say, there is one intervention that's going to work there either.
00:09:42:13 - 00:09:43:04
Abigail Acton
Of course.
00:09:43:05 - 00:09:55:20
Alina Solomon
It's this multimodal approach that I think is... the concept, the idea is to try to address multiple risk lifestyle risk factors and multiple lifestyle domains at the same.
00:09:55:20 - 00:09:58:05
Abigail Acton
Such as exercise and diet.
00:09:58:07 - 00:10:23:22
Alina Solomon
Yes, these are the main ones. And we started with those because they are also known to be important for cardiovascular disease prevention, diabetes prevention and so on. And then of course there's the cognitive part and the social activities and certainly other domains as well. There's a long list of modifiable risk factors that have been associated with dementia. So lots of possibilities
00:10:23:24 - 00:10:24:10
Abigail Acton
Okay.
00:10:24:11 - 00:10:32:16
Abigail Acton
Fantastic. Thank you so much. You explained that very well I appreciate it. Does anyone have any questions at all for Alina? Anja. Yes. What would you like to ask?
00:10:32:18 - 00:10:52:05
Anja Leist
It was would be super interesting to hear your thoughts around adherence. So from an ethical perspective, we need to understand how much we can, kind of, ask people to do. Right. They have care obligations. They may need to be still in the workplace. So what would you recommend a sort of a minimal, standard?
00:10:52:07 - 00:11:19:06
Alina Solomon
Yeah, that's a good question. There are two questions there I'm hearing rolled into one. One is about the adherence and the other one is about how intensive should this intervention be. So they are both very important points. One thing we got already out of the original thing at trial was that this combination model, people did not find it too burdensome.
00:11:19:08 - 00:11:43:02
Alina Solomon
So it's a structured intervention is quite intensive because with prevention or risk reduction, it's about doing the right things but also doing enough of that. So but most people didn't find it too burdensome. Almost half of the control group thought that they were in the intervention group. Yes. So it's a good format.
00:11:43:02 - 00:11:59:00
Alina Solomon
It's possible. And it's also sustainable over the longer, a longer period of time, because we now have data from 7 to 11 years after the intervention. And it seems that a lot of that is quite sustainable over time.
00:11:59:05 - 00:12:00:13
Abigail Acton
Fantastic. Thank you.
00:12:00:15 - 00:12:07:14
Alina Solomon
And then the intensity of the intervention. That is something that we're still looking into that.
00:12:07:16 - 00:12:14:16
Abigail Acton
Have to get the right level. Yeah. That people actually adhere to it. Absolutely. Thank you. Any other observations or comments. Yes please. Julia.
00:12:14:20 - 00:12:38:22
Julia Neitzel
Yes. Thank you. Alina. The FINGER's work is absolutely amazing and the world FINGERs will be so important to move the field forward. So, my question is, and I love to you made this comment about or you pick the results of the genetic risk. So I wonder where do you see here the future. So I see more and more young people know actually their genetic risk
00:12:38:22 - 00:12:50:02
Anja Leist
via different companies. So do you think it is effective to target intervention based on genetic risk? For example APOE-ε4?
00:12:50:04 - 00:13:14:19
Alina Solomon
Oh thank you. And that's a very good question and one that we are now testing in a new FINGER based trial, a combination therapy, a FINGER plus drug, where we do enrichment of the population, that means about 50% of the participants are APOE-ε4 for carriers, because that's the kind of question we want to address.
00:13:14:19 - 00:13:21:19
Alina Solomon
Yeah. Is that, how important is it to target based on genetic profiling? We don't know at this point.
00:13:21:22 - 00:13:23:08
Anja Leist
Looking forward.
00:13:23:10 - 00:13:41:09
Abigail Acton
Yeah. Something to be looked into. Very good. Thank you very much, Julia. Actually thanks for that question. And I'm going to turn to you now actually preventing or delaying late life cognitive impairment and dementia through lifestyle interventions is one of the greatest global challenges. So what was your long term vision when you started the DIVERT-AD project, please?
00:13:41:13 - 00:14:07:15
Julia Neitzel
Yeah. I would like to talk about really a long term future vision. And I would love to see at one day that we are taking care of our brain as we do, for example, for brushing our thighs. So I think right now we all know we should exercise more, we should sleep more, eat healthier. But honestly, I think it's very hard to stay motivated when the consequences feel so far away.
00:14:07:17 - 00:14:31:02
Julia Neitzel
So what I envision is a future where you go for regular brain health checkups like people do, visits to dentists and, here is why it matters. We know when you have a broken tooth, you can replace it. But, well, it's not possible for our brains. Once it's damaged, it cannot be repaired. So prevention is here everything.
00:14:31:04 - 00:14:54:15
Julia Neitzel
So people might be afraid to learn about brain health. But I think if we combine this with personalized advice, not just generic advice, but really like something that's happening in your brain and what you can do about it, then I think it's really worth for people to know. And this is what I call precision prevention. And I'm working to make this vision true.
00:14:54:15 - 00:14:59:18
Julia Neitzel
Maybe for my grandchildren and to really motivate people to make those changes.
00:14:59:18 - 00:15:15:06
Abigail Acton
It sounds like an absolutely excellent idea. And actually, if I could be use a pun slightly here, a no brainer meaning it seems very clear and obvious that this would be something that would be desirable to do. We do take enormous care of various parts of our body, but we kind of bleed the brains just to get on with it, don't we?
00:15:15:06 - 00:15:20:22
Abigail Acton
So yes, indeed. So what did the project do to try and make this goal a little bit closer? Bring it a little closer.
00:15:20:24 - 00:15:44:08
Julia Neitzel
Yeah. So we are taking, of course, tiny steps here. I started a research line where I focus on this question of how we can measure actually brain health. And for that we need to look at the people's brain while they are still alive. So in one project we are using something which is called PET imaging. So PET is the abbreviation for Positron Emission Tomography.
00:15:44:10 - 00:16:12:19
Julia Neitzel
And this is a very fancy, very specialized brain scan, which, uses a tiny amount of radioactive tracer to light up specific regions in your brain. For example, we can use a tracer to light up Alzheimer's disease. Now, this technique is very expensive. While most studies using healthy participants have like 50 or 100 scans, we managed to scan more than 600 cognitively healthy people.
00:16:12:20 - 00:16:16:02
Abigail Acton
Well that's excellent. That's much higher number than usual. Yeah, yeah. Cool.
00:16:16:04 - 00:16:20:02
Julia Neitzel
Yeah. This makes it one of the largest single center study of its kind in Europe.
00:16:20:03 - 00:16:24:12
Abigail Acton
Brilliant. Bravo. Okay. Super. And what sort of things did you find?
00:16:24:15 - 00:16:32:11
Julia Neitzel
So the findings were really surprising to me. So maybe let's first explain a little bit what we're looking for. So. Alzheimer's.
00:16:32:16 - 00:16:33:15
Abigail Acton
Sure. Good idea.
00:16:33:18 - 00:16:56:03
Anja Leist
So Alzheimer's disease is the leading cause of dementia. And in Alzheimer's, you have a particular protein called amyloid that builds up sticky plaques in the brain. So before I analyzed the data, I thought that the risk factors which we know increase your dementia risk should also increase those plaques because they are the leading cause of the dementia.
00:16:56:03 - 00:17:12:12
Julia Neitzel
But actually we found something different. So I looked at 12 of the major risk factors for dementia. And I only found diabetes to be associated with amyloid. So people who had diabetes, they showed more amyloid in their brain about 12 years later.
00:17:12:16 - 00:17:16:05
Abigail Acton
Okay. So that was actually something that you were predicting probably would be the case.
00:17:16:05 - 00:17:16:24
Julia Neitzel
Yes.
00:17:17:01 - 00:17:19:02
Abigail Acton
And in other situations, in other cases.
00:17:19:02 - 00:17:41:17
Julia Neitzel
Well, all the other risk factors we looked at, we did not find an association. But it's very important to know that there are still incredibly important for brain health, but they work through other different, pathways. They're protecting your brain by improving your cardiovascular health, which means that more blood can flow to your brain. And they also directly improve the brain's blood vessels.
00:17:41:21 - 00:17:44:02
Julia Neitzel
So I could, for example, give an example.
00:17:44:04 - 00:17:44:24
Abigail Acton
Please.
00:17:45:01 - 00:18:13:12
Anja Leist
When I looked at people who wear a fitness watch, for seven days and we combined the data with our PET scans where we could see the plaques, then we found the people who were more active, showed the same amount of amyloid plaques than inactive people. However, the overall shape of their brain looked much better, so they had, for example, better blood flow in their brain, but also fewer tiny bleeds in their brain, which is an indication of vascular brain health.
00:18:13:14 - 00:18:21:11
Abigail Acton
So it's almost as if the amyloid plaques may come, but the brain is more robust and able to deal with the impact of those.
00:18:21:16 - 00:18:36:16
Julia Neitzel
Yeah, you can say it like that. So the overall health of the brain, especially if the blood vessels is better when you're, for example, more physically active. And you also prevent vascular disease of the brain. This is also very important.
00:18:36:19 - 00:18:38:08
Abigail Acton
Well, obviously highly desirable.
00:18:38:10 - 00:18:42:05
Julia Neitzel
Another cause which can also lead to cognitive decline and dementia.
00:18:42:09 - 00:18:55:03
Abigail Acton
All of this is absolutely fascinating. Thank you very much for sharing it. What is the one key piece of information you think is an important takeaway, either for future research by others or future research indeed by yourself?
00:18:55:05 - 00:19:20:11
Julia Neitzel
I think what is very important is to understand that there are many pathways to dementia, and that's why, as Alina said, that we need multimodal prevention in order to tackle all the pathways. It would be very important to find something for the Alzheimer pathway to really prevent Alzheimer built up. And we actually had one study where we showed sleep could be one tool.
00:19:20:13 - 00:19:38:16
Julia Neitzel
In one study, we showed that people had a fragmented sleep wake pattern. They do have more amyloid plaques in their brain later. So this could be a tool or a pathway where we need more research to see whether this could be really leading to prevention of Alzheimer's disease.
00:19:38:22 - 00:19:45:19
Abigail Acton
Excellent. Thank you very much. Super. Does anyone have any observations or questions to pose to Julia, please, Alina. Yes, please.
00:19:45:21 - 00:20:11:22
Alina Solomon
Yeah, that's a great observational study with so many people with brain imaging. I'm curious, what do you think your results say about one of the current hot potato questions. If you see amyloid accumulation or you see something on amyloid PET in people who don't have cognitive symptoms... well, what does that mean?
00:20:11:24 - 00:20:38:24
Julia Neitzel
So I, I think amyloid per se might not be the crucial point, but amyloid plaques build up has a lot of negative consequences afterwards. Inflammation, Tau Tangle pathology and so forth. That's why I think it's the starting point of a disease. A starting point is often not. It's just a trigger. It's not the full cause, but something we want to intervene. If we want to
00:20:38:24 - 00:20:43:09
Julia Neitzel
intervene early probably. Yeah. Preventing distorted endpoint could help.
00:20:43:11 - 00:20:56:04
Alina Solomon
Yeah. Or we could see if there's a risk factor also. Right. Because that's how I see it. Someone without symptoms so has amyloid might be regarded as having a risk factor for dementia in a sense.
00:20:56:04 - 00:20:56:24
Julia Neitzel
Yeah.
00:20:57:01 - 00:20:57:24
Abigail Acton
Like a red flag.
00:20:58:05 - 00:21:02:13
Alina Solomon
Yeah. Dementia may or may not happen but there's a risk there.
00:21:02:15 - 00:21:23:24
Abigail Acton
Excellent. Thank you very much. Yeah that's clear. And the I'm going to turn to you now the CRISP project considered contextual influences on cognitive aging with a focus on inequalities related to educational opportunities and also gender inequalities. So slightly a different angle here, more of a contextual concept I think. I know the gender difference obviously is a factor that you considered.
00:21:23:24 - 00:21:26:16
Abigail Acton
So what did you want to better understand? Please.
00:21:26:16 - 00:21:46:11
Anja Leist
Thanks so much for the question. Yeah. So when I wrote the proposal for the CRISP, we just didn't have a lot of studies really interested in sex-gender differences. So many of the studies I looked into when I wanted to understand cognitive aging better, were not making a difference between men and women, in analyzing the data.
00:21:46:11 - 00:22:05:13
Anja Leist
And I was just really trying to understand better how men and women differ in terms of risk burden, and also in the relationships between the risk and, well, cognitive aging and dementia. So would women and men benefit differently from different advice, for example, in the end.
00:22:05:15 - 00:22:15:12
Abigail Acton
Okay. Super. So no much work done on looking at the difference between the genders. Can you tell me a little bit about what you did a to get a better understanding, a better insight?
00:22:15:18 - 00:22:38:10
Anja Leist
Yeah. First thing was to describe the differential risk burden of men and women. Have a look at what individual risk factors are, more or less prevalent in men and women in different cohorts of different ages and different countries. So that was sort of red thread through the publications.
00:22:38:12 - 00:23:04:05
Anja Leist
And I also wanted to understand better on a contextual level, what different opportunities men and women have throughout their lives. And so, this question of gender equality, really, was something that I felt, okay, this is not considered at all at the moment. And from, sociological research, we can systematically disentangle the schooling opportunities for boys and girls.
00:23:04:05 - 00:23:32:10
Anja Leist
So, inequality of educational opportunity can explain a lot in people's life courses. And then in turn, explain how people are doing at the end of their lives. So, what we did was, in terms of methodology, to contextually have a sample of people in different European countries born at different times and then exploit that variation in inequality of educational opportunity.
00:23:32:12 - 00:23:36:11
Anja Leist
So how much does it matter what parents I have.
00:23:36:13 - 00:23:37:07
Abigail Acton
Right.
00:23:37:09 - 00:24:06:04
Julia Neitzel
To receive higher levels of schooling? Yeah. And there we found that, for one thing, inequality of educational opportunity matters a lot. Also, that women from more disadvantaged backgrounds were more vulnerable to higher inequality levels. So there was really this sort of multi factual explanation of cognitive aging. And there's this joke that, well, if you want to age healthily, you need to choose your parents wisely.
00:24:06:06 - 00:24:07:08
Abigail Acton
Very pertinent
00:24:07:10 - 00:24:16:07
Anja Leist
Yeah. And very modifiable. So this is, something that was really interesting for me. So I was a project and still is.
00:24:16:12 - 00:24:31:10
Abigail Acton
Yeah. No, it's absolutely fascinating. One thing to clarify, though, is what is the relationship do you think, even approximately, what is the connection between cognitive aging and perhaps a worse socioeconomic outlook? What was the connection there?
00:24:31:12 - 00:24:35:07
Anja Leist
So in terms of modifiability of risk factors...
00:24:35:07 - 00:24:35:16
Abigail Acton
For example.
00:24:35:16 - 00:24:59:02
Julia Neitzel
Education really matters a lot. So it's one of the most important modifiable risk factors. And there's also a lot of simulation research showing, well, actual research with children in school, showing that there's a dose response relationship, between education and cognitive functioning. And this can at least partially translate into explaining cognitive levels at older ages.
00:24:59:04 - 00:25:05:10
Abigail Acton
I see. Okay, great. So I've heard the term cognitive reserve being used quite frequently. Is this the sort of thing that we're talking about here?
00:25:05:16 - 00:25:09:07
Anja Leist
Yeah. Cognitive reserve is kind of the catch all term.
00:25:09:07 - 00:25:12:24
Abigail Acton
It is at the moment. Can you tell us what that means? Actually, what do we mean by this?
00:25:13:02 - 00:25:34:20
Anja Leist
It's supposed to explain the disconnect between brain pathology and cognitive performance at older ages. So we still don't have a biomarker, right, to tell us how, well, is somebody cognitively impaired or not? Somebody is showing good scores on memory tests or not. So but this disconnect is not really an explanation. Right? It's not a mechanism.
00:25:34:20 - 00:26:00:20
Anja Leist
So we are thinking about something like, processing of information, more complexity of the neural networks. But for the moment we cannot really capture it empirically. So I'm still super convinced that education plays a big role. And we can translate this into cognitive and social stimulation. Right. Prolonged exposure to cognitively stimulating tasks. And we have this similar associations when it comes to occupational complexity.
00:26:00:20 - 00:26:30:17
Anja Leist
So what we are doing throughout the life course, in terms of work, matters a lot for cognitive functioning and aging. And here we also looked into what men and women have done over the life courses. So women and men born in the 1920s and 1930s, 40s, 50s, they had very different work family biographies. So, there's also so much interesting research showing that it matters how you combine your work career and your family career.
00:26:30:17 - 00:26:32:13
Anja Leist
For those who were parents.
00:26:32:15 - 00:26:48:16
Abigail Acton
Okay. I see that's interesting. So basically was saying that the, or Anja correct me if I'm wrong, are we saying that the more cognitively stimulating and challenging and demanding life you have, the more robust your brain is going into old age? Is that the sort of parallel that you were drawing?
00:26:48:18 - 00:26:51:06
Anja Leist
That's the idea of the cognitive reserve.
00:26:51:08 - 00:26:51:18
Abigail Acton
Right?
00:26:51:19 - 00:27:01:00
Anja Leist
Concept. Yes. It it's not applicable on any... on the individual level. But when we look at these large population level datasets, then we find these associations.
00:27:01:03 - 00:27:02:14
Abigail Acton
Sort of patterns going through.
00:27:02:14 - 00:27:02:19
Anja Leist
Yeah.
00:27:02:19 - 00:27:11:08
Abigail Acton
Yes. I see okay. Super. So considering all the work that you've done, what would you feel would be the most important thing for people to understand from your results.
00:27:11:10 - 00:27:34:11
Anja Leist
From my results, well, we ask a lot of questions in the publications then. I'm a researcher, so, as everybody, I complain about a lack of data on certain things. And, when it comes to sex-gender differences, we still don't know very much, for example, about how menopause or dysregulation of the glucose metabolism, for example, after menopause, impacts our dementia risk.
00:27:34:17 - 00:27:57:16
Anja Leist
So there's much much more to be done. But we also have a lot of knowledge. And Julia and Alina have pointed out very nicely that, it matters a lot, for example, to manage our cardiovascular health. And I would just always recommend for people to go and have a health checkup. I know so many people who never visit a doctor, and this applies to men and to women. Beyond,
00:27:57:18 - 00:28:20:07
Anja Leist
and of course, physical activity and moving more, protecting ears and eyes. We see in our surveys that, people really don't do these sort of very, let's say, basic brain health-friendly behaviors, like wearing a helmet when going skiing or going cycling. So we have a whole project now on this just to get the word out there.
00:28:20:09 - 00:28:38:16
Anja Leist
People are afraid of dementia. They are worried about the brain health. But at the same time don't know much about how to modify their risk for impaired brain health. So the getbrainhealthy.org website really collects this and makes it accessible for everybody.
00:28:38:22 - 00:28:57:21
Abigail Acton
That's a wonderful wonderful note upon which to end that, there is actually a resource out there that you can consult to get better understanding. And when you say health checkups, it's also for blood sugar and things like cholesterol and blood pressure, and so on. Your 'protect your eyes and ears' is very interesting too, you know, the correct prescription glasses or perhaps a hearing aid.
00:28:58:01 - 00:29:04:12
Abigail Acton
Why is that important? What is the relationship between how well our eyes and ears are stimulated and our brain? What's going on there?
00:29:04:14 - 00:29:35:18
Anja Leist
Yeah, we have, looked into particularly hearing loss and hearing aids. And this is actually a publication with Alina where we use the UK Biobank, to understand... does it make a difference to wear a hearing aid? And the idea, the supposed mechanism, is that we have little social and cognitive stimulation when there's hearing loss, simply because people withdraw from their usual social activities, because they cannot meaningfully participate in conversations anymore.
00:29:35:22 - 00:29:45:01
Abigail Acton
So there we go. And then we're going back to this notion of social interaction being so very important to brain health. Well thank you. Does anyone have any comments for any, any observations? Alina? Yes.
00:29:45:01 - 00:30:12:06
Alina Solomon
Yes. Anja, going back to this paper we worked on together. There's something else in there that I think is also very very important, especially now, because there was a lot about real world data in there, real world health data. And I think one of the things that paper showed was the limits of real world data.
00:30:12:08 - 00:30:34:16
Alina Solomon
There's a lot of emphasis on this now. It's very, of course, it's very important to have real world data and big data and so on and so forth, but it's not going to fix everything. And sometimes it even tells us things that are, either not correct or not very useful.
00:30:34:21 - 00:30:36:10
Abigail Acton
And might actually be misleading.
00:30:36:12 - 00:30:46:16
Alina Solomon
Yeah. Might actually be misleading. Yes. So that is for me one other thing that came out of that study that we did.
00:30:46:18 - 00:30:48:04
Anja Leist
Yeah, I fully agree.
00:30:48:06 - 00:31:03:19
Alina Solomon
We still need the kinds of studies we've all been doing. We still need the observational studies. We still need the intervention studies. We can't, we won't be able to just rely on real world health data. It's not going to be enough.
00:31:03:21 - 00:31:33:09
Anja Leist
To fully agree 100%. But I'm actually, just right now, writing, a review article on this problem of missing data, for, I mean, also for many, it's not just about, health care data, but it's all data possible, right? For people who are less willing to participate in studies, who may have less trust in researchers, who may also not just be in the places that we, the researchers, look for.
00:31:33:09 - 00:31:52:15
Anja Leist
So, there's really much to know. And so when it comes to really drawing clear medical implications from our research, we need to be even more careful here. So health care algorithms will learn what's happening in the real world and with all the biases in the real world at the moment.
00:31:52:17 - 00:32:13:24
Abigail Acton
Yes. The whole notion of bias and algorithms is another can of worms. Okay. Well, listen, I want to thank the three of you for sharing your time with us today. It was really interesting and also encouraging because you know, sometimes you look at this and you just think panic. But it's clear that there are pathways opening up and that the work being done is going to make a substantial difference going forward.
00:32:13:24 - 00:32:25:04
Abigail Acton
I particularly like the idea of your various health checkups. Go for them, get them done. Because yeah, it'll help your brain as well as the rest of your body. I think that's excellent. Thank you very much for your time.
00:32:25:06 - 00:32:26:17
Anja Leist
Thank you. Bye.
00:32:26:19 - 00:32:28:00
Julia Neitzel
Thank you. Bye.
00:32:28:00 - 00:32:28:17
Alina Solomon
Thank you. Bye.
00:32:28:18 - 00:32:34:01
Abigail Acton
Bye bye. Good luck with your work.
00:32:34:03 - 00:32:48:08
Abigail Acton
If you've enjoyed this podcast, follow us on Spotify or Apple or wherever it is that you get your podcasts. Or check out the podcast homepage on the CORDIS website. Subscribe to make sure that the hottest research and EU funded science isn't passing you by.
00:32:48:10 - 00:33:07:13
Abigail Acton
And if you're enjoying listening, why not spread the word? We've talked about the pressure democracy is under and how to meet the challenges. What hell might have smelt like to the medieval mind. Yes, you heard that correctly. And the work being done to deflect asteroids in our last 53 episodes. There will be something there to tweak your curiosity.
00:33:07:15 - 00:33:29:19
Abigail Acton
Maybe you're involved in a project or would like to apply for funding. Take a look at the CORDIS website to see what others are doing in your domain. So come and check out the research that's revealing what makes our world tick. We're always happy to hear from you. Drop us a line editorial@cordis.europa.eu. Until next time!
This is an AI transcription.
00:00:16:05 - 00:00:35:22
Abigail Acton
Hello and welcome to this episode of CODIScovery with me, Abigail Acton. There are advances being made in the area of dementia and cognitive aging. The European Commission has granted the EU marketing authorisation for Kisunla, a medicine to treat mild cognitive impairment, including mild dementia, in the early stages of Alzheimer's disease.
00:00:36:01 - 00:00:58:14
Abigail Acton
Alongside pharmacological advances, we're also gaining insights into why some people may be more impacted than others and the role socioeconomics play in the overall picture. But sometimes it feels like a race against time. Worldwide, it is estimated that there are more than 50 million people living with Alzheimer's disease and related disorders. The most common class of neurodegenerative diseases.
00:00:58:16 - 00:01:21:01
Abigail Acton
This figure is expected to double every 20 years as the population ages. Evidence based solutions may help to foster better coordination between health and social care systems across the EU. So let's turn to our three guests, whose projects benefited from research and innovation funding, for an idea of what is being discovered.
00:01:21:03 - 00:01:39:03
Abigail Acton
Alina Solomon is professor of Neuroepidemiology at the University of Eastern Finland, visiting professor at Imperial College London and senior researcher at the Karolinska Institute. She's particularly interested in dementia risk detection and therapeutic approaches for dementia risk reduction. Hello.
00:01:39:09 - 00:01:40:03
Alina Solomon
Hello.
00:01:40:05 - 00:01:58:08
Abigail Acton
Welcome to join us today. Julia Neitzel is assistant professor at the Department of Radiology and Nuclear Medicine at the Erasmus University Medical Center in Rotterdam, the Netherlands. She uses brain scans in large population studies to discover what protects and hurts brain health. Hello, Julia.
00:01:58:10 - 00:01:59:05
Julia Neitzel
Hello.
00:01:59:07 - 00:02:07:06
Abigail Acton
Hi. Currently professor at the University of Luxembourg, Anja Leist will soon be taking up a professorship at the University of Heidelberg.
00:02:07:08 - 00:02:16:24
Abigail Acton
Her research focuses on sex and gender differences, socio-economic inequalities and risk reduction in cognitive aging and dementia. Hello.
00:02:17:01 - 00:02:17:20
Anja Leist
Hello.
00:02:17:22 - 00:02:31:15
Abigail Acton
Alina, I'm going to turn to you. The Brain Health Toolbox set out to create a strategy to develop accurate dementia prediction and effective prevention. There's been a lot of work done in this area. So what is the gap in our knowledge that the Brain Health Project sought to fill?
00:02:31:15 - 00:02:33:07
Abigail Acton
Please.
00:02:33:09 - 00:02:58:10
Alina Solomon
There are two main gaps. One was the gap between identifying dementia risk and the actual interventions to reduce the risk. And risk and prevention potential are two sides of the same coin, but they're not identical. For example, do people with high dementia risk also have high prevention potential? Who is most likely to benefit from what interventions and at what risk or disease stage?
00:02:58:12 - 00:03:24:18
Alina Solomon
And then there was also the gap between pharmacological and non-pharmacological interventions. That is new drugs for Alzheimer's disease. They're being tested in people in early risk or disease stages, people without dementia. And as I saw it, both drug and non-drug interventions had the same main goal to reduce the risk of dementia. And at the time, we had just finished the FINGER trial.
00:03:24:20 - 00:03:33:21
Alina Solomon
And that is the Finnish Geriatric Intervention Study to prevent cognitive impairment and disability. And that was a great basis for the project.
00:03:33:23 - 00:03:39:23
Abigail Acton
Okay. Super. So when it comes to risk prevention and mitigation, what intervention strategies were you considering?
00:03:40:00 - 00:04:02:17
Alina Solomon
I wanted to do precision prevention. So the Brain Health Toolbox focused on and developing the kinds of tools that researchers and clinicians would need for this, for getting the right interventions to the right people at the right time. We did work on disease models and risk prediction algorithms, but this time also tested them in actual intervention studies using the FINGER model.
00:04:02:19 - 00:04:37:03
Alina Solomon
And the FINGER is what we call a multimodal lifestyle intervention model. It combines nutrition advice, for the purpose of having a healthy, balanced diet. It's not about weight loss unless medical indicated. And then there was also an exercise program, cognitive training, social activities, and managing cardiovascular metabolic risk factors. It's a structured model, but it also has room for individual adaptations because one size is not going to fit.
00:04:37:05 - 00:04:38:04
Alina Solomon
Everyone.
00:04:38:06 - 00:04:52:14
Abigail Acton
So when you see a structured model, you know, these various components that you've just outlined would be set before, the people participating in the trial, but then more of one or less of another, depending on the relevance to a particular participant. Is that what you mean?
00:04:52:19 - 00:05:10:00
Alina Solomon
Yes. Depending on where each participant was at, for example, how much healthy lifestyle changes are needed in someone's current diet, because they will vary a lot. The same with exercise. Also depending on their own, let's say physical abilities and so on.
00:05:10:02 - 00:05:19:07
Abigail Acton
Of course. Absolutely. And when you said, I believe you said social activities and so on, can you give us some idea of the sort of activities that you were thinking mattered?
00:05:19:09 - 00:05:41:08
Alina Solomon
They were group activities that were embedded into the other domains of the intervention. For example, for nutrition advice. We also had group sessions where people can discuss with their nutritionist and ask questions and so on. More on in a group setting. Talk to each other. And so on. Same for the exercise program was in groups at the gym.
00:05:41:10 - 00:05:57:10
Alina Solomon
We also had group sessions for cognitive training, for the cognitive part, where they would also get to ask questions about aging, memory and cognition: what happens over time, what else can they do to improve things and so on.
00:05:57:15 - 00:06:05:22
Abigail Acton
Right. Because I understand that social interaction is actually one of the things that does help as a factor for mitigation. So you were combining two things there.
00:06:05:23 - 00:06:14:13
Alina Solomon
Yes. And it was also, many of the participants said that that was the one of the most appreciated components of the intervention.
00:06:14:15 - 00:06:34:10
Abigail Acton
Yeah, people do like being with people and it's important for their brain health to interact. Yes, indeed. Okay. So when you refer to the part of the project's title as toolbox, this, this is a notion then that you would be putting forward to health care providers, elements that could be used, as you say, at the right time with the right people.
00:06:34:12 - 00:06:37:16
Abigail Acton
So how are you actually envisaging that this could be used in practice?
00:06:37:18 - 00:07:05:03
Alina Solomon
The tools were primarily for researchers with the aim of eventually being used by clinicians as well, and for the research part one important thing was that I wanted relevance and effectiveness across different populations with very different contexts economic, cultural, geographical and so on. And part of the work was for example, how do we translate, adapt and optimise the FINGER model outside of Finland where it was developed?
00:07:05:05 - 00:07:28:22
Alina Solomon
How do we do all this testing in a harmonised way? We don't want these trials to be just scattered, separate pieces. We want them to to work like the pieces of a puzzle. We want to be able to fit them together. And when we do that, we're able to see, bigger and more, informative picture. And this project was a bit like a scientific engine for what we call the world wide FINGERs.
00:07:28:24 - 00:07:33:11
Alina Solomon
That's the first global network of multimodal dementia prevention trials.
00:07:33:11 - 00:07:33:19
Abigail Acton
Right.
00:07:33:19 - 00:07:34:05
Abigail Acton
Super.
00:07:34:05 - 00:07:40:03
Alina Solomon
And we started with maybe 4 or 5 countries, but now it's grown to over 70 member countries.
00:07:40:08 - 00:07:46:05
Abigail Acton
Oh, that's fantastic. That's super. That must give you a great feeling of satisfaction to see that there's uptake and real interest in this.
00:07:46:07 - 00:07:51:09
Alina Solomon
Yes. That was a big surprise. How much it grew, a lot more than we expected.
00:07:51:09 - 00:07:59:16
Abigail Acton
Yeah that's encouraging. Super. And do you have any findings that you can share with this? Are there any results or any key takeaways from the project that are worth considering?
00:07:59:16 - 00:08:24:05
Alina Solomon
If I were to pick one of the more significant findings, at least for me, was that people with genetic susceptibility for dementia can clearly benefit from lifestyle interventions and for example, people who are carriers of the APOE-ε4 allelel, which is the main genetic risk factor for Alzheimer's disease. They may even benefit more than non carriers.
00:08:24:07 - 00:08:40:04
Alina Solomon
And one exploratory finding. So still exploratory we still need to test. But I think it's very very important was that women with a certain genetic susceptibility may also benefit more than men. But again that's something we still need to test.
00:08:40:04 - 00:08:56:14
Abigail Acton
Right. Yeah. So you're still testing that hypothesis. But yeah that's interesting okay. Well that's fabulous. And could you just wind up maybe by just giving us some idea of the sort of interventions that you think we're probably going to be the most productive when you talk about the intervention of lifestyle choices and behavior, what sort of things are you thinking of?
00:08:56:16 - 00:09:27:23
Alina Solomon
Yeah, what we started doing already during the project, and we're continuing now in, in other EU funded projects is, what I call combination therapies. So FINGER was a multimodal intervention. It already combined multiple lifestyle domains. And now we're combining that with, pharmacological interventions. And I think this is this is a very, very important direction to go in because there's not only one magic pill that is going to sort it all out.
00:09:28:00 - 00:09:36:17
Abigail Acton
Sure it's a combination of things. But when you say lifestyle interventions, can you give us some ideas of the lifestyle interventions that you think are the best for people to consider, the most useful?
00:09:36:22 - 00:09:42:13
Alina Solomon
I wouldn't say, there is one intervention that's going to work there either.
00:09:42:13 - 00:09:43:04
Abigail Acton
Of course.
00:09:43:05 - 00:09:55:20
Alina Solomon
It's this multimodal approach that I think is... the concept, the idea is to try to address multiple risk lifestyle risk factors and multiple lifestyle domains at the same.
00:09:55:20 - 00:09:58:05
Abigail Acton
Such as exercise and diet.
00:09:58:07 - 00:10:23:22
Alina Solomon
Yes, these are the main ones. And we started with those because they are also known to be important for cardiovascular disease prevention, diabetes prevention and so on. And then of course there's the cognitive part and the social activities and certainly other domains as well. There's a long list of modifiable risk factors that have been associated with dementia. So lots of possibilities
00:10:23:24 - 00:10:24:10
Abigail Acton
Okay.
00:10:24:11 - 00:10:32:16
Abigail Acton
Fantastic. Thank you so much. You explained that very well I appreciate it. Does anyone have any questions at all for Alina? Anja. Yes. What would you like to ask?
00:10:32:18 - 00:10:52:05
Anja Leist
It was would be super interesting to hear your thoughts around adherence. So from an ethical perspective, we need to understand how much we can, kind of, ask people to do. Right. They have care obligations. They may need to be still in the workplace. So what would you recommend a sort of a minimal, standard?
00:10:52:07 - 00:11:19:06
Alina Solomon
Yeah, that's a good question. There are two questions there I'm hearing rolled into one. One is about the adherence and the other one is about how intensive should this intervention be. So they are both very important points. One thing we got already out of the original thing at trial was that this combination model, people did not find it too burdensome.
00:11:19:08 - 00:11:43:02
Alina Solomon
So it's a structured intervention is quite intensive because with prevention or risk reduction, it's about doing the right things but also doing enough of that. So but most people didn't find it too burdensome. Almost half of the control group thought that they were in the intervention group. Yes. So it's a good format.
00:11:43:02 - 00:11:59:00
Alina Solomon
It's possible. And it's also sustainable over the longer, a longer period of time, because we now have data from 7 to 11 years after the intervention. And it seems that a lot of that is quite sustainable over time.
00:11:59:05 - 00:12:00:13
Abigail Acton
Fantastic. Thank you.
00:12:00:15 - 00:12:07:14
Alina Solomon
And then the intensity of the intervention. That is something that we're still looking into that.
00:12:07:16 - 00:12:14:16
Abigail Acton
Have to get the right level. Yeah. That people actually adhere to it. Absolutely. Thank you. Any other observations or comments. Yes please. Julia.
00:12:14:20 - 00:12:38:22
Julia Neitzel
Yes. Thank you. Alina. The FINGER's work is absolutely amazing and the world FINGERs will be so important to move the field forward. So, my question is, and I love to you made this comment about or you pick the results of the genetic risk. So I wonder where do you see here the future. So I see more and more young people know actually their genetic risk
00:12:38:22 - 00:12:50:02
Anja Leist
via different companies. So do you think it is effective to target intervention based on genetic risk? For example APOE-ε4?
00:12:50:04 - 00:13:14:19
Alina Solomon
Oh thank you. And that's a very good question and one that we are now testing in a new FINGER based trial, a combination therapy, a FINGER plus drug, where we do enrichment of the population, that means about 50% of the participants are APOE-ε4 for carriers, because that's the kind of question we want to address.
00:13:14:19 - 00:13:21:19
Alina Solomon
Yeah. Is that, how important is it to target based on genetic profiling? We don't know at this point.
00:13:21:22 - 00:13:23:08
Anja Leist
Looking forward.
00:13:23:10 - 00:13:41:09
Abigail Acton
Yeah. Something to be looked into. Very good. Thank you very much, Julia. Actually thanks for that question. And I'm going to turn to you now actually preventing or delaying late life cognitive impairment and dementia through lifestyle interventions is one of the greatest global challenges. So what was your long term vision when you started the DIVERT-AD project, please?
00:13:41:13 - 00:14:07:15
Julia Neitzel
Yeah. I would like to talk about really a long term future vision. And I would love to see at one day that we are taking care of our brain as we do, for example, for brushing our thighs. So I think right now we all know we should exercise more, we should sleep more, eat healthier. But honestly, I think it's very hard to stay motivated when the consequences feel so far away.
00:14:07:17 - 00:14:31:02
Julia Neitzel
So what I envision is a future where you go for regular brain health checkups like people do, visits to dentists and, here is why it matters. We know when you have a broken tooth, you can replace it. But, well, it's not possible for our brains. Once it's damaged, it cannot be repaired. So prevention is here everything.
00:14:31:04 - 00:14:54:15
Julia Neitzel
So people might be afraid to learn about brain health. But I think if we combine this with personalized advice, not just generic advice, but really like something that's happening in your brain and what you can do about it, then I think it's really worth for people to know. And this is what I call precision prevention. And I'm working to make this vision true.
00:14:54:15 - 00:14:59:18
Julia Neitzel
Maybe for my grandchildren and to really motivate people to make those changes.
00:14:59:18 - 00:15:15:06
Abigail Acton
It sounds like an absolutely excellent idea. And actually, if I could be use a pun slightly here, a no brainer meaning it seems very clear and obvious that this would be something that would be desirable to do. We do take enormous care of various parts of our body, but we kind of bleed the brains just to get on with it, don't we?
00:15:15:06 - 00:15:20:22
Abigail Acton
So yes, indeed. So what did the project do to try and make this goal a little bit closer? Bring it a little closer.
00:15:20:24 - 00:15:44:08
Julia Neitzel
Yeah. So we are taking, of course, tiny steps here. I started a research line where I focus on this question of how we can measure actually brain health. And for that we need to look at the people's brain while they are still alive. So in one project we are using something which is called PET imaging. So PET is the abbreviation for Positron Emission Tomography.
00:15:44:10 - 00:16:12:19
Julia Neitzel
And this is a very fancy, very specialized brain scan, which, uses a tiny amount of radioactive tracer to light up specific regions in your brain. For example, we can use a tracer to light up Alzheimer's disease. Now, this technique is very expensive. While most studies using healthy participants have like 50 or 100 scans, we managed to scan more than 600 cognitively healthy people.
00:16:12:20 - 00:16:16:02
Abigail Acton
Well that's excellent. That's much higher number than usual. Yeah, yeah. Cool.
00:16:16:04 - 00:16:20:02
Julia Neitzel
Yeah. This makes it one of the largest single center study of its kind in Europe.
00:16:20:03 - 00:16:24:12
Abigail Acton
Brilliant. Bravo. Okay. Super. And what sort of things did you find?
00:16:24:15 - 00:16:32:11
Julia Neitzel
So the findings were really surprising to me. So maybe let's first explain a little bit what we're looking for. So. Alzheimer's.
00:16:32:16 - 00:16:33:15
Abigail Acton
Sure. Good idea.
00:16:33:18 - 00:16:56:03
Anja Leist
So Alzheimer's disease is the leading cause of dementia. And in Alzheimer's, you have a particular protein called amyloid that builds up sticky plaques in the brain. So before I analyzed the data, I thought that the risk factors which we know increase your dementia risk should also increase those plaques because they are the leading cause of the dementia.
00:16:56:03 - 00:17:12:12
Julia Neitzel
But actually we found something different. So I looked at 12 of the major risk factors for dementia. And I only found diabetes to be associated with amyloid. So people who had diabetes, they showed more amyloid in their brain about 12 years later.
00:17:12:16 - 00:17:16:05
Abigail Acton
Okay. So that was actually something that you were predicting probably would be the case.
00:17:16:05 - 00:17:16:24
Julia Neitzel
Yes.
00:17:17:01 - 00:17:19:02
Abigail Acton
And in other situations, in other cases.
00:17:19:02 - 00:17:41:17
Julia Neitzel
Well, all the other risk factors we looked at, we did not find an association. But it's very important to know that there are still incredibly important for brain health, but they work through other different, pathways. They're protecting your brain by improving your cardiovascular health, which means that more blood can flow to your brain. And they also directly improve the brain's blood vessels.
00:17:41:21 - 00:17:44:02
Julia Neitzel
So I could, for example, give an example.
00:17:44:04 - 00:17:44:24
Abigail Acton
Please.
00:17:45:01 - 00:18:13:12
Anja Leist
When I looked at people who wear a fitness watch, for seven days and we combined the data with our PET scans where we could see the plaques, then we found the people who were more active, showed the same amount of amyloid plaques than inactive people. However, the overall shape of their brain looked much better, so they had, for example, better blood flow in their brain, but also fewer tiny bleeds in their brain, which is an indication of vascular brain health.
00:18:13:14 - 00:18:21:11
Abigail Acton
So it's almost as if the amyloid plaques may come, but the brain is more robust and able to deal with the impact of those.
00:18:21:16 - 00:18:36:16
Julia Neitzel
Yeah, you can say it like that. So the overall health of the brain, especially if the blood vessels is better when you're, for example, more physically active. And you also prevent vascular disease of the brain. This is also very important.
00:18:36:19 - 00:18:38:08
Abigail Acton
Well, obviously highly desirable.
00:18:38:10 - 00:18:42:05
Julia Neitzel
Another cause which can also lead to cognitive decline and dementia.
00:18:42:09 - 00:18:55:03
Abigail Acton
All of this is absolutely fascinating. Thank you very much for sharing it. What is the one key piece of information you think is an important takeaway, either for future research by others or future research indeed by yourself?
00:18:55:05 - 00:19:20:11
Julia Neitzel
I think what is very important is to understand that there are many pathways to dementia, and that's why, as Alina said, that we need multimodal prevention in order to tackle all the pathways. It would be very important to find something for the Alzheimer pathway to really prevent Alzheimer built up. And we actually had one study where we showed sleep could be one tool.
00:19:20:13 - 00:19:38:16
Julia Neitzel
In one study, we showed that people had a fragmented sleep wake pattern. They do have more amyloid plaques in their brain later. So this could be a tool or a pathway where we need more research to see whether this could be really leading to prevention of Alzheimer's disease.
00:19:38:22 - 00:19:45:19
Abigail Acton
Excellent. Thank you very much. Super. Does anyone have any observations or questions to pose to Julia, please, Alina. Yes, please.
00:19:45:21 - 00:20:11:22
Alina Solomon
Yeah, that's a great observational study with so many people with brain imaging. I'm curious, what do you think your results say about one of the current hot potato questions. If you see amyloid accumulation or you see something on amyloid PET in people who don't have cognitive symptoms... well, what does that mean?
00:20:11:24 - 00:20:38:24
Julia Neitzel
So I, I think amyloid per se might not be the crucial point, but amyloid plaques build up has a lot of negative consequences afterwards. Inflammation, Tau Tangle pathology and so forth. That's why I think it's the starting point of a disease. A starting point is often not. It's just a trigger. It's not the full cause, but something we want to intervene. If we want to
00:20:38:24 - 00:20:43:09
Julia Neitzel
intervene early probably. Yeah. Preventing distorted endpoint could help.
00:20:43:11 - 00:20:56:04
Alina Solomon
Yeah. Or we could see if there's a risk factor also. Right. Because that's how I see it. Someone without symptoms so has amyloid might be regarded as having a risk factor for dementia in a sense.
00:20:56:04 - 00:20:56:24
Julia Neitzel
Yeah.
00:20:57:01 - 00:20:57:24
Abigail Acton
Like a red flag.
00:20:58:05 - 00:21:02:13
Alina Solomon
Yeah. Dementia may or may not happen but there's a risk there.
00:21:02:15 - 00:21:23:24
Abigail Acton
Excellent. Thank you very much. Yeah that's clear. And the I'm going to turn to you now the CRISP project considered contextual influences on cognitive aging with a focus on inequalities related to educational opportunities and also gender inequalities. So slightly a different angle here, more of a contextual concept I think. I know the gender difference obviously is a factor that you considered.
00:21:23:24 - 00:21:26:16
Abigail Acton
So what did you want to better understand? Please.
00:21:26:16 - 00:21:46:11
Anja Leist
Thanks so much for the question. Yeah. So when I wrote the proposal for the CRISP, we just didn't have a lot of studies really interested in sex-gender differences. So many of the studies I looked into when I wanted to understand cognitive aging better, were not making a difference between men and women, in analyzing the data.
00:21:46:11 - 00:22:05:13
Anja Leist
And I was just really trying to understand better how men and women differ in terms of risk burden, and also in the relationships between the risk and, well, cognitive aging and dementia. So would women and men benefit differently from different advice, for example, in the end.
00:22:05:15 - 00:22:15:12
Abigail Acton
Okay. Super. So no much work done on looking at the difference between the genders. Can you tell me a little bit about what you did a to get a better understanding, a better insight?
00:22:15:18 - 00:22:38:10
Anja Leist
Yeah. First thing was to describe the differential risk burden of men and women. Have a look at what individual risk factors are, more or less prevalent in men and women in different cohorts of different ages and different countries. So that was sort of red thread through the publications.
00:22:38:12 - 00:23:04:05
Anja Leist
And I also wanted to understand better on a contextual level, what different opportunities men and women have throughout their lives. And so, this question of gender equality, really, was something that I felt, okay, this is not considered at all at the moment. And from, sociological research, we can systematically disentangle the schooling opportunities for boys and girls.
00:23:04:05 - 00:23:32:10
Anja Leist
So, inequality of educational opportunity can explain a lot in people's life courses. And then in turn, explain how people are doing at the end of their lives. So, what we did was, in terms of methodology, to contextually have a sample of people in different European countries born at different times and then exploit that variation in inequality of educational opportunity.
00:23:32:12 - 00:23:36:11
Anja Leist
So how much does it matter what parents I have.
00:23:36:13 - 00:23:37:07
Abigail Acton
Right.
00:23:37:09 - 00:24:06:04
Julia Neitzel
To receive higher levels of schooling? Yeah. And there we found that, for one thing, inequality of educational opportunity matters a lot. Also, that women from more disadvantaged backgrounds were more vulnerable to higher inequality levels. So there was really this sort of multi factual explanation of cognitive aging. And there's this joke that, well, if you want to age healthily, you need to choose your parents wisely.
00:24:06:06 - 00:24:07:08
Abigail Acton
Very pertinent
00:24:07:10 - 00:24:16:07
Anja Leist
Yeah. And very modifiable. So this is, something that was really interesting for me. So I was a project and still is.
00:24:16:12 - 00:24:31:10
Abigail Acton
Yeah. No, it's absolutely fascinating. One thing to clarify, though, is what is the relationship do you think, even approximately, what is the connection between cognitive aging and perhaps a worse socioeconomic outlook? What was the connection there?
00:24:31:12 - 00:24:35:07
Anja Leist
So in terms of modifiability of risk factors...
00:24:35:07 - 00:24:35:16
Abigail Acton
For example.
00:24:35:16 - 00:24:59:02
Julia Neitzel
Education really matters a lot. So it's one of the most important modifiable risk factors. And there's also a lot of simulation research showing, well, actual research with children in school, showing that there's a dose response relationship, between education and cognitive functioning. And this can at least partially translate into explaining cognitive levels at older ages.
00:24:59:04 - 00:25:05:10
Abigail Acton
I see. Okay, great. So I've heard the term cognitive reserve being used quite frequently. Is this the sort of thing that we're talking about here?
00:25:05:16 - 00:25:09:07
Anja Leist
Yeah. Cognitive reserve is kind of the catch all term.
00:25:09:07 - 00:25:12:24
Abigail Acton
It is at the moment. Can you tell us what that means? Actually, what do we mean by this?
00:25:13:02 - 00:25:34:20
Anja Leist
It's supposed to explain the disconnect between brain pathology and cognitive performance at older ages. So we still don't have a biomarker, right, to tell us how, well, is somebody cognitively impaired or not? Somebody is showing good scores on memory tests or not. So but this disconnect is not really an explanation. Right? It's not a mechanism.
00:25:34:20 - 00:26:00:20
Anja Leist
So we are thinking about something like, processing of information, more complexity of the neural networks. But for the moment we cannot really capture it empirically. So I'm still super convinced that education plays a big role. And we can translate this into cognitive and social stimulation. Right. Prolonged exposure to cognitively stimulating tasks. And we have this similar associations when it comes to occupational complexity.
00:26:00:20 - 00:26:30:17
Anja Leist
So what we are doing throughout the life course, in terms of work, matters a lot for cognitive functioning and aging. And here we also looked into what men and women have done over the life courses. So women and men born in the 1920s and 1930s, 40s, 50s, they had very different work family biographies. So, there's also so much interesting research showing that it matters how you combine your work career and your family career.
00:26:30:17 - 00:26:32:13
Anja Leist
For those who were parents.
00:26:32:15 - 00:26:48:16
Abigail Acton
Okay. I see that's interesting. So basically was saying that the, or Anja correct me if I'm wrong, are we saying that the more cognitively stimulating and challenging and demanding life you have, the more robust your brain is going into old age? Is that the sort of parallel that you were drawing?
00:26:48:18 - 00:26:51:06
Anja Leist
That's the idea of the cognitive reserve.
00:26:51:08 - 00:26:51:18
Abigail Acton
Right?
00:26:51:19 - 00:27:01:00
Anja Leist
Concept. Yes. It it's not applicable on any... on the individual level. But when we look at these large population level datasets, then we find these associations.
00:27:01:03 - 00:27:02:14
Abigail Acton
Sort of patterns going through.
00:27:02:14 - 00:27:02:19
Anja Leist
Yeah.
00:27:02:19 - 00:27:11:08
Abigail Acton
Yes. I see okay. Super. So considering all the work that you've done, what would you feel would be the most important thing for people to understand from your results.
00:27:11:10 - 00:27:34:11
Anja Leist
From my results, well, we ask a lot of questions in the publications then. I'm a researcher, so, as everybody, I complain about a lack of data on certain things. And, when it comes to sex-gender differences, we still don't know very much, for example, about how menopause or dysregulation of the glucose metabolism, for example, after menopause, impacts our dementia risk.
00:27:34:17 - 00:27:57:16
Anja Leist
So there's much much more to be done. But we also have a lot of knowledge. And Julia and Alina have pointed out very nicely that, it matters a lot, for example, to manage our cardiovascular health. And I would just always recommend for people to go and have a health checkup. I know so many people who never visit a doctor, and this applies to men and to women. Beyond,
00:27:57:18 - 00:28:20:07
Anja Leist
and of course, physical activity and moving more, protecting ears and eyes. We see in our surveys that, people really don't do these sort of very, let's say, basic brain health-friendly behaviors, like wearing a helmet when going skiing or going cycling. So we have a whole project now on this just to get the word out there.
00:28:20:09 - 00:28:38:16
Anja Leist
People are afraid of dementia. They are worried about the brain health. But at the same time don't know much about how to modify their risk for impaired brain health. So the getbrainhealthy.org website really collects this and makes it accessible for everybody.
00:28:38:22 - 00:28:57:21
Abigail Acton
That's a wonderful wonderful note upon which to end that, there is actually a resource out there that you can consult to get better understanding. And when you say health checkups, it's also for blood sugar and things like cholesterol and blood pressure, and so on. Your 'protect your eyes and ears' is very interesting too, you know, the correct prescription glasses or perhaps a hearing aid.
00:28:58:01 - 00:29:04:12
Abigail Acton
Why is that important? What is the relationship between how well our eyes and ears are stimulated and our brain? What's going on there?
00:29:04:14 - 00:29:35:18
Anja Leist
Yeah, we have, looked into particularly hearing loss and hearing aids. And this is actually a publication with Alina where we use the UK Biobank, to understand... does it make a difference to wear a hearing aid? And the idea, the supposed mechanism, is that we have little social and cognitive stimulation when there's hearing loss, simply because people withdraw from their usual social activities, because they cannot meaningfully participate in conversations anymore.
00:29:35:22 - 00:29:45:01
Abigail Acton
So there we go. And then we're going back to this notion of social interaction being so very important to brain health. Well thank you. Does anyone have any comments for any, any observations? Alina? Yes.
00:29:45:01 - 00:30:12:06
Alina Solomon
Yes. Anja, going back to this paper we worked on together. There's something else in there that I think is also very very important, especially now, because there was a lot about real world data in there, real world health data. And I think one of the things that paper showed was the limits of real world data.
00:30:12:08 - 00:30:34:16
Alina Solomon
There's a lot of emphasis on this now. It's very, of course, it's very important to have real world data and big data and so on and so forth, but it's not going to fix everything. And sometimes it even tells us things that are, either not correct or not very useful.
00:30:34:21 - 00:30:36:10
Abigail Acton
And might actually be misleading.
00:30:36:12 - 00:30:46:16
Alina Solomon
Yeah. Might actually be misleading. Yes. So that is for me one other thing that came out of that study that we did.
00:30:46:18 - 00:30:48:04
Anja Leist
Yeah, I fully agree.
00:30:48:06 - 00:31:03:19
Alina Solomon
We still need the kinds of studies we've all been doing. We still need the observational studies. We still need the intervention studies. We can't, we won't be able to just rely on real world health data. It's not going to be enough.
00:31:03:21 - 00:31:33:09
Anja Leist
To fully agree 100%. But I'm actually, just right now, writing, a review article on this problem of missing data, for, I mean, also for many, it's not just about, health care data, but it's all data possible, right? For people who are less willing to participate in studies, who may have less trust in researchers, who may also not just be in the places that we, the researchers, look for.
00:31:33:09 - 00:31:52:15
Anja Leist
So, there's really much to know. And so when it comes to really drawing clear medical implications from our research, we need to be even more careful here. So health care algorithms will learn what's happening in the real world and with all the biases in the real world at the moment.
00:31:52:17 - 00:32:13:24
Abigail Acton
Yes. The whole notion of bias and algorithms is another can of worms. Okay. Well, listen, I want to thank the three of you for sharing your time with us today. It was really interesting and also encouraging because you know, sometimes you look at this and you just think panic. But it's clear that there are pathways opening up and that the work being done is going to make a substantial difference going forward.
00:32:13:24 - 00:32:25:04
Abigail Acton
I particularly like the idea of your various health checkups. Go for them, get them done. Because yeah, it'll help your brain as well as the rest of your body. I think that's excellent. Thank you very much for your time.
00:32:25:06 - 00:32:26:17
Anja Leist
Thank you. Bye.
00:32:26:19 - 00:32:28:00
Julia Neitzel
Thank you. Bye.
00:32:28:00 - 00:32:28:17
Alina Solomon
Thank you. Bye.
00:32:28:18 - 00:32:34:01
Abigail Acton
Bye bye. Good luck with your work.
00:32:34:03 - 00:32:48:08
Abigail Acton
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Abigail Acton
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Evidence-based solutions reduce the risk and improve the treatment of dementia
The European Commission has granted EU marketing authorisation for Kisunla(opens in new window), a medicine for treating mild cognitive impairment, including mild dementia in the early stages of Alzheimer’s disease – such monoclonal antibodies are showing potential. Alongside pharmacological advances, we are also gaining insights into why some people may be more impacted than others, and the role socio-economics plays in the overall picture. Worldwide, it is estimated(opens in new window) that there are more than 50 million people living with Alzheimer’s disease and related disorders, making these the most common class of neurodegenerative diseases. This figure is expected to double every 20 years as the population ages. Evidence-based solutions may help to foster better coordination between health and social care systems across the EU. Our three guests, whose projects benefited from research and innovation funding, are helping to make a complex picture, clearer. Alina Solomon(opens in new window) is professor of Neuroepidemiology at the University of Eastern Finland, visiting professor at Imperial College London, and senior researcher at the Karolinska Institute. She is particularly interested in dementia risk detection and therapeutic approaches for dementia risk reduction, which she explored through the Brain Health Toolbox project. Julia Neitzel(opens in new window) is assistant professor at the Department of Radiology and Nuclear Medicine at the Erasmus University Medical Centre(opens in new window) in Rotterdam, the Netherlands. Coordinator of the DIVERT-AD project, Neitzel uses brain scans in large population studies to discover what protects and hurts brain health. Currently professor at the University of Luxembourg, Anja Leist(opens in new window) will soon be taking up a professorship at the University of Heidelberg. Her research focuses on sex and gender differences, socio-economic inequalities, and risk reduction in cognitive ageing and dementia. Leist coordinated the CRISP project.
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