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Why Women Suffer More from Brain Diseases: Alzheimer's, Dementia, Migrane, Multiple Sclerosis: Dr. Antonella Santuccione Chadha, Women's Brain Project

April 27, 2023 Alex: interviewing visionaries of healthcare innovation
X-Health.show - meet the future of healthcare
Why Women Suffer More from Brain Diseases: Alzheimer's, Dementia, Migrane, Multiple Sclerosis: Dr. Antonella Santuccione Chadha, Women's Brain Project
Show Notes Transcript

Overlooked.
Disregarded.
Biologically and culturally predisposed.

Backed by volumes of scientific research and her experience as a medical doctor, Dr. Antonella Santuccione Chadha set out on a journey to improve the way brain diseases are diagnosed, drugs are developed, and personalised medicine does its job.

To save our brains from degenerating. 

You’ll hear about the world of Alzheimer’s disease, Alzheimer symptoms, Alzheimer treatment and diagnosis. How scary it looks today and what hopes are there in the future.

You’ll also hear about 

  • the role of sex and gender in clinical trials
  • the impact of hormonal cycle on drug efficacy
  • Bruce Willis and dementia he suffers from
  • digital biomarkers that may change it all 
  • the future of brain healthcare.

Trigger warning: this interview contains content about suicide.


Dr. Antonella Santuccione Chadha is a medical doctor passionately speaking about clinical pathology, neuroscience, and psychiatric disorders. She is a pro bono CEO of Women’s Brain Project, currently transforming into a foundation to promote research in Sex and Gender Precision Medicine.

She studied novel immunotherapies for Alzheimer’s disease in the laboratory of Roger Nitsch and Christoph Hock at the University of Zurich.

She is also Chief Scientific Officer of Altoida, a startup developing non-invasive brain health diagnostics using AI and augmented reality.

Her career paths crossed with Biogen, Swiss Agency for Therapeutic Products Roche Diagnostics and Roche Pharmaceuticals the EU Commission Directorate for Health and Food Safety the OECD and several other Alzheimer’s Disease organizations.


Here are some links for you if you want to explore more: 

https://www.womensbrainproject.com

http://altoida.com

Economist Impact paper: Sex gender and the brain: Towards an inclusive research agenda  https://econ.st/3lluJLA

The Lancet covering the Economist Impact paper: https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(23)00120-5/fulltext

Twitter https://twitter.com/womensbrainpro

LI https://www.linkedin.com/company/womensbrainproject/

YT https://www.youtube.com/channel/UCBeR85u3RbgXaGEm2T2iJkQ

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The information in this podcast is for informational purposes only and should not be considered medical advice. If you have any medical questions, please consult your healthcare practitioner. The opinions on the show are Alex's or her guests. The podcast does not make any responsibility or warranties about guests statements or credibility. While the podcast makes every effort to ensure that the information shared is accurate, please let us know if you have any comments, suggestions or corrections.

Dr. Antonella Santuccione Chadha:

Now it's the turn of women to rewrite medical books

Alex X-Health.show:

Hi, I'm Alex and welcome to the X-Health.show, where I talk to visionaries behind the latest innovations in healthcare. For the eXtra Health of the future. We're in Zurich, Switzerland, among the morning crowd grabbing a coffee in their crisp white shirts. Caught between a call with Tokyo and one with New York. Dr. Antonella Santuccione Chadha is a CEO and co-founder of women's Brain Project, and the Chief Medical Officer at Altoida. A physician and passionate expert in clinical pathology, neurological and psychiatric diseases. Just wait to hear her comparing a microscope image of brain cells to a Picasso painting. Women's Brain Project's mission is to address sex and gender differences in brain diseases and foster more diversified clinical trials. Altoida develops a 10-minute AI-powered augmented reality brain health diagnostics tool. You'll hear today if you're more prone to dementia, depression, anxiety, multiple sclerosis, migraine, Alzheimer's disease, or Parkinson's, whether you are a woman or a man, beware, it will turn emotional times. Antonella, three out of five women would not benefit from prescribed drug. That's what Women's Brain Project recent paper at the Economist Impact called 'Sex, gender and the brain towards an inclusive research agenda' says. Have you noticed that in your experience in psychiatry?

Dr. Antonella Santuccione Chadha:

Well, certainly I did. And we can start quoting an article that has been published in 2015 in'Nature', which described that, for example, Abilify, which is an antipsychotic, would have been beneficial only in one person out of five who received this medication. Now, this is not only valid for women, but also for males. And this goes right to the direction of what we define today shallow medicine. So shallow medicine, it is an approach that medicine has been used until now, to develop drugs considering that one side, one size will fit all. But we know that this is not the case and sex and gender is the first component to bring what we define personalised medicine or precision medicine on the table. There are also other factors beyond sex and gender that play a role like for example, ethnicity, race, even the wealth of an individual plays a role on how a patient adhere to a treatment, respond to a treatment and, and we know that, you know, people who have higher wealth status will be healthier, for example. So I think that in an era of modern medicine, or let's say, the medicine of the future will be more precise, will be the medicine where the cure, the medication will be given to the right patient at the right time at the right moment for the right reason. And this is where we have to move forward. And this is what the Women's Brain Project is advocating for providing the science behind generating the habit and science behind it. Because we need to be factual we need to be evidence-based. And yes, that's what we think.

Alex X-Health.show:

How did that look for you, like, patients came and said, it doesn't work or, you know, they didn't take drugs? Yeah. How did you experience that?

Dr. Antonella Santuccione Chadha:

You know, in psychiatry, this is a known phenomenon. I mean, I've been practising psychiatry for several years and the adherence in psychiatry, it's a major issue. That's because very often side effects of this drugs are very severe for the person receiving the drug while the effects might be there, but the side effects are very much invalidating. So, to gain adherence, it's not that easy. What we know is that in general, women adhere better than men to treatment. And this is certainly due to factors like education, cultural upbringing, and... But is it something that we have to certainly solve, because we need to bring on the market better drugs more efficient and with less safety issues, such as that the patient is content and remain adherent to the treatment.

Alex X-Health.show:

Why they're not content? You said, you mentioned the...

Dr. Antonella Santuccione Chadha:

I can tell you that there are some side effects... for example, we mentioned antipsychotics, they give side effects such as increase of prolactin which induces production of milk in the in the mammalian gland, both of men and women and you can understand how unpleasant this might be or there is the...

Alex X-Health.show:

Just out of the blue, I mean, we're not speaking about pregnant people?

Dr. Antonella Santuccione Chadha:

It's not about pregnant people, and it can happen also in the male population. And this is very, very unpleasant as you can imagine. The same is true for the gain of weight. This is another side effect very common of this type of drugs, which, of course, it's not pleasant for the patient. And so, it is what it is, we have to improve. As I said, the discovery overall for neurology and psychiatry indication, we need to include more women in the clinical pipeline development, because it's also a big issue. And such as better drug can be brought to the market. The main problem is that at the moment, we treat symptoms of neurological and psychiatry condition in general. Of course, I'm generalising. But we can say that we mainly focus on treating symptoms. We should aim for a medicine that is trying to treat the underlying cause, that it's curing eventually, and not removing a symptom only. Because that's not the solution, especially not in psychiatry, and neurology, because those symptoms stay. I mean, they're chronic, and then you need a chronic treatment with the chronic side effects that we mentioned. So the ideal world of the future will be to really treat the underlying cause of these diseases, understanding, of course, which are the reasons because we're not there yet, we still don't know for many of these diseases, which is the real cause the real main factor that it is provoking these diseases. It's not like it's a viral infection, you know, it was the virus, right? Or cancer, you know, that it's one bad cell that get mutated and then become, you know, spreading etc. In brain and mental diseases, the underlying mechanism needs to be still well characterised. And only in this way we can bring precise solution that treats the cause of the disease and not just the symptom.

Alex X-Health.show:

So let's go back to the current clinical trials. So the drug development basically. Who's an average clinical trials patient.

Dr. Antonella Santuccione Chadha:

Well, I have to say that, based on what we know, today, the majority of the participants in a clinical trial tend to be Caucasian, meaning white skin people. It's going to be male and especially in phase one, phase two, the first phase of characterising how a drug might work in terms of pharmacokinetic and pharmacodynamic. This is really preponderant male. And that's a problem because we miss important information that might be generated in different type of population, meaning the female population, meaning different ethnicity, and races. And that's very, very important because we know that there is a profound difference in the way we metabolise drugs, and in the way they might act on our body based on several factors, man, women, whether we have a Caucasian background, or maybe an Asian background. I can just tell you that, for example, if we look at the black population, barely 5% of them is included clinical trials worldwide, which is basically nothing.

Alex X-Health.show:

Wow, it's shocking.

Dr. Antonella Santuccione Chadha:

It's shocking. And it's even worse for the Asian population.

Alex X-Health.show:

Even worse than 5%?

Dr. Antonella Santuccione Chadha:

I don't remember exactly the number and please forgive me, but it is what it is. And we need to change this. The smart folks were Japanese. Japanese people implemented a legislation that says that if you want to bring on the Japanese market any type of drug that has been developed in another race or in another ethnicity group, you have to make a sub-study with Japanese people to see how it works on Japanese people. And they know that this is important because they have differences in metabolising drugs which is not just for Japanese. I'm sure that... I mean, I know that also, for instance, Asian people have different way of metabolising drugs, and it's not yet addressed, what is the impact on them. So I think we need to change the way we do drug development, we need to be more inclusive, we need to bring diversity on the table. And we need to have actors main actors that represent this under represented groups. Meaning if you want to change something, well, I can talk as much as I want, and maybe someone will liste, but if someone of my community tells me that's needed, there are higher chances that I will be listened to. So the general trend is that we should have more researchers, more doctors coming from this underserved community to educate to, to bring this issue up and solve the problem.

Alex X-Health.show:

Now, FDA has announced that they will soon,"soon" - that's what they say - require researchers and companies seeking approval for late-stage clinical trials to submit a plan for ensuring diversity among trial participants. Now, how to address this imbalance in research? You know, I spoke on the other podcast with Dr. Colleen Fogarty Draper about her PhD research and what she said was that, you know, it was decided in a room that we will do men, because they don't have menstrual cycle. So they don't have all that variability.

Dr. Antonella Santuccione Chadha:

Well, which is also not fully true because it's true that they don't have the menstrual cycle but they have nevertheless hormonal cycles. It's just this is a pre-concept and sometimes we stick to an idea and we just move on with this idea and plan accordingly, which it's a missed opportunity. I mean, it's undeniable that there are fluctuations in the hormonal cycle of a woman and luckily so but this has to be, again, taken seriously into account when we want to develop a drug. I can give you examples that come straightforward from patients I've talked with. There are now new and worrying phenomenon of having young women, younger women experiencing Parkinson disease. And if you speak with these patients, what they will tell you is that often the therapy that they are receiving might have differences in the efficacy based on the menstrual cycle, phase they are they are going through.

Alex X-Health.show:

So, say, they take a pill on a daily basis, and it works or doesn't work.

Dr. Antonella Santuccione Chadha:

Exactly. And the same is true for other conditions like... There is an interesting work done by a patient with Myasthenia and she will tell you the same thing. So now what we're doing, we're trying to get this cluster of women under this type of treatment who are still young, and try to study the impact of the hormonal cycle on the efficacy of the drugs. And this has to be absolutely taken into account for several reasons. First of all, for the patient, which is the priority,

Alex X-Health.show:

Yeah, that's obvious.

Dr. Antonella Santuccione Chadha:

But also, if you want to have a good drug, I mean, you need to know how to adjust the dosage based on which lifecycle of the patient you are or hormonal cycle of the patients you are and metabolism or BMI. I mean, there's so many components. So that's what we mean with precision medicine, we need to really optimise drug development to make better drugs, and consider all this peculiarity that might have an impact on the way the patient respond. And if you bring a better drug on the market, you get better return, economical return as a drug developer, so in the interest is for everyone. And in the end, for them shall be a meaningful interest because as I said, revenues will be higher, people will be more content and the final mission of benefiting life of people would be achieved fully.

Alex X-Health.show:

So are we speaking now, I'm just thinking aloud, like, are we speaking about, like, for example, taking different dosages of a drug, during different phases of menstrual cycle, or are we speaking about the medicines that will actually work for all menstrual cycle phases.

Dr. Antonella Santuccione Chadha:

I cannot answer to this question because this question, it's a very good one, but speaks about the future. We still don't know. So this is going to be highly likely a possibility what you're describing, but we still don't know if we're going to get there or elsewhere. Certainly, what we know is that this things needs to be started. And maybe the medicine of the future will be a pink or a blue pill. Or maybe it will differ in the dosage based on the phase of hormonal cycle you're in. I don't know. But we need to learn if this is needed. And maybe we will learn that that's not needed at all. But still, this research deserves to be done because these are scientifically relevant questions that cannot remain unsolved. It's unethically not acceptable to deny that there is an impact and not to study this impact on alpha, the worldwide population.

Alex X-Health.show:

So let's speak about what we know and about the Economist Impact paper. So the research behind it. What neurological diseases have higher prevalence among women, and which among men?

Dr. Antonella Santuccione Chadha:

I have to say that overall, brain and mental diseases impact more the female population then the male one. I can start with some of those. Dementia is female 70% if not more of patients are women. Depression - 80%. Anxiety- 80%. Multiple sclerosis, migraine... Well, it's a long list. When it's about the male population, what we know is that Parkinson's tend to be more in the male population as well as ILS. But, you know, the reason why are currently studied and analysed. And it's not only about numbers, it's not only about incidence and prevalence of those diseases, but profound differences exist in the symptoms, those disease manifest.

Alex X-Health.show:

So the different symptoms for men and women,

Dr. Antonella Santuccione Chadha:

Exactly. There are differences in the way the disease progress, there are differences in the treatment response, we just spoke about it. There are differences in the way patients adhere to the treatment, we already spoke about it. So it's really important to consider all these differences, because it's not only about numbers, it's beyond. Even biomarkers. We know that biomarkers of given disease might change between men and women. And when you want to diagnose, when you want to manage a patient it'ss a very important information that doctor has to take into account. So there is a lot to be done. And it's a great opportunity. And we hope that, what I always say is that I hope that now it's the turn of women to rewrite medical books. With their own hands. Because if you think about it, till now, it has been mainly males writing medical books, right. I mean, majority of the medical doctors worldwide and scientists worldwide till yesterday had been made. And it's not their fault if, if some symptoms or some concepts around diseases were not very much well characterised for the female population. Because imagine also the, the... what happened to my grandmother. I mean, my grandmother used to go to the doctor when she was allowed to go to the doctor with either the husband or the brother sitting in the same room and speaking with an unknown man. How she will feel comfortable in describing symptoms of her disease, fully. You know, I myself as a doctor, still, when I sit in front of a male colleague, I might have some feeling of shame or, you know, you feel not to share the whole thing. And so what I'm trying to tell you is that it's nobody's fault but now that we will have more women sitting, you know, on the other side of a patient, and the patient being a woman, I think that we will have higher opportunity of sharing on symptoms that before maybe we're not fully transparently disclosed or reported. And now that's why it's the time that women rewrite the history of medicine or the history of diseases that mainly impact women.

Alex X-Health.show:

So the paper speaks about five diseases. So that's multiple sclerosis, migraine, Alzheimer's disease, Parkinson's disease, and stroke. So you already spoke about Parkinson's disease. How about multiple sclerosis, migraine, Alzheimer's disease, stroke? These are, I assume, these are also more prevalent in women?

Dr. Antonella Santuccione Chadha:

Yes, so when we talk about dementia, migraine, multiple sclerosis, certainly. One about stroke, what we know is that stroke impacts women more severely in terms of clinical outcomes. So a woman that will have a stroke has higher chances of mortality, but also of surviving with major consequences due to the stroke. So it's about the severity and morbidity and... of the disease overall. And, again, this needs to be carefully addressed, both from diagnostic perspective, clinical development perspective, patient management perspective, and family care.

Alex X-Health.show:

So the paper says that these brain diseases are influenced by sex but also by gender.

Dr. Antonella Santuccione Chadha:

Oh, yes.

Alex X-Health.show:

Meaning, also by some sociological, cultural and economical... There are some influences like that. Why gender, could you could you say?

Dr. Antonella Santuccione Chadha:

Well, you know, let's first of all define what we mean with gender and what we mean with sex. So the sex of the individual refers to the DNA, what it's embedded in your chromosomes and what your chromosomes, actually, express in a human body. Whereas about gender, we refer to a social construct that an individual might have or might not have within a given society. Or might choose to have within a given society. And we know that our society is heavily gendered. Certain jobs are more female, certain jobs are more male. I can give you some practical example. For example, being a caregiver, it's mainly a female responsibility both as paid caregiver, as well as unpaid caregiver. Now to be a caregiver poses you at risk of depression and in the late phase of your life, poses you at risk of even dementia. Why? Because being a caregiver 24/7 puts you under the burden of social isolation. And social isolation is a specific risk factor for depression, and even dementia, according to the literature. So just to tell you how important the impact of gender might be on disease and disease outcomes. Another example, it is the exposure to certain type of environmental factors based on your job. And this goes more direction for example of men. Let's take the example of mesothelioma, which is a known tumour that was caused mainly by asbestos and exposure to this toxic agent. This was mainly in the male population because they were doing the job of dealing with construction sites where this asbestos was ever represented. So these are just two very simple examples to explain how gender has an impact and of course it goes beyond this. Another one it is education. Education is known to be a preventive factor for dementia. So the higher you study, the higher you are educated, the less chances you'll have to develop dementia when you're an old person. And again, worldwide women are less educated than men. This could be one reason why more women have dementia. And the question that remains to be addressed, are we speaking about education to university or is it long life education? Again, women have a lot less long life education simply because they are belonging less to the workforce. And if you work usually you will receive trainings, you keep on learning, you keep on being with an active brain. Women who do not work they don't have this continuous, let's call it, education. Does this have an impact then on the way your brain will stay healthy for the rest of your life? We need to answer these questions. And this is another example of gender.

Alex X-Health.show:

You specialise in Alzheimer's disease. Could you, before we dive into that, could you say why you chose that as your specialisation? Was there any any particular reason for this?

Dr. Antonella Santuccione Chadha:

This is about my personal story. What I can tell about myself is that I am a person driven by challenges. I love to do what it is almost impossible to do. And that's what keeps my energy high, my spirit high and my curiosity high. So when I finished medical school, which was, by the way, a challenge with myself because I said when I finished my high school, which is the most impossible discipline for me to study. And I said it's going to be medicine, not because of the content, but because of the length of the study and the amount of study. I said, OK, let's take the challenge. And that was my first challenge. Then when I graduated, what really fascinated me was, absolutely, the brain. I mean, the brain remains still the most mysterious organ.

Alex X-Health.show:

Yeah, that's what I wanted to say, like, we don't know so much about brain.

Dr. Antonella Santuccione Chadha:

Exactly. So that was my challenge. I wanted to understand how the brain function works or might get diseased. And this was my choice of doing neuroscience and becoming a scientist, and working for several years in a research setting to really understand the beauty of our brain and how neurons interact. And, well, it's really a fascinating discipline that I have to describe as a piece of art. or me to sit in front of a confocal microscope and take a picture on an oligodendrocyte on how two proteins will interact with one another based on fluorescence colour was like a Picasso painting. And I could have spent hours just getting the perfect picture but not for me, for people who would have looked at the picture outside to see exactly what I was seeing in that moment. Because that is the difficulty. You have to translate what you see in that moment for the... for the person that will look at that picture outside of that room where you are with a microscope. And that was the beauty. Then why Alzheimer. Because in all this neuroscience passion I've had, I realised that Alzheimer's was certainly one of those most mysterious disease affecting a huge number of the worldwide population. And... and that's it. I mean, I was doing a lot of research. And I told myself I want to see now, finally, patients. So I started to work in a ward, with people living with dementia, and other brain diseases, mainly acute psychiatry, and I have to say that this had been one of the most beautiful experiences of my entire life. And when I do what I do today, I own it to the eyes, the view, the gaze of the people that I met. And that we're hoping I could have done something for them or for their beloved one. And that's my... my... that's why I do what I do.

Alex X-Health.show:

What's the beauty in it? Let me and also, you know, people who listen to us, understand that.

Dr. Antonella Santuccione Chadha:

I can talk about the beauty for myself, of course. I mean, what is beautiful for me in it, because I think that each of us will find something else beautiful. I mean, if you ask my child they will tell you that what is beautiful for him it is to build something with his hands, cut wood and... and so for another person might be something else. For me what it's beautiful into it, is that you help people, at least you try to help the best possible way you can. You do something very meaningful with a lot of purpose, and it explains why we are alive, at least for me. It gives me a reason to wake up every morning and say, I'm alive because that's what I do, I... I really like to do it and I want to improve the world. I want to improve life of people. I want to.. I believe in good. I want that the good counts, you know, that's my main driver. I'm a very positive person, motivated by the good of this planet. And I want to believe that the more we apply ourself, and we work hard, the more the good will come out.

Alex X-Health.show:

Now, so why women are more susceptible to Alzheimers? What do we know at least right? Because we don't know everything, I can imagine.

Dr. Antonella Santuccione Chadha:

That's right. And actually, we go back to Alzheimer's indeed, and women. We don't really know exactly why more women are impacted by this condition. Certainly, the changes that we experience with the menopause phase might have an impact. Because what we know is that oestrogen are protective for our brain. And when there is a drop in oestrogen then more neurodegenerative diseases, inflammation in the brain, at cetera, might impact the female brain. Profound research is ongoing in this direction. We also know that women who have more Alzheimer, for example, might have higher predisposition of certain oestrogen receptor that are mutated in a certain way. And so just to say that there are several reasons there is the hormonal component, there might be some genetic reason underlying, and still to be fully characterised. And there is the gender factor that we discussed. It's also about the education, the role that the woman has in a given society, the job we do, et cetera, et cetera.

Alex X-Health.show:

Could you tell us a bit more about zombie cells? There is something I read about zombie cells that may have influence on Alzheimer's disease?

Dr. Antonella Santuccione Chadha:

I don't think I have an answer on this. I apologise. But I can tell you that if we speak about zombie, Alzheimer's certainly had zombie that capture our brain. There are those amyloid plaque of proteins that are toxic and accumulate and they basically progress over time, and the brain shrinks, and... I don't want to be taken wrong but the word you use now resonates well in my mind as... we become a zombie to ourself when we get Alzheimer's, because we don't know anymore who we are or where we are. It's a devastating disease. And, and again, you asked me why I am into this. Because I don't wish this to anyone and I don't want anyone to have this. And I define it as one of the..., at least for me, one of the most severe disease that mankind have to face?

Alex X-Health.show:

What are the symptoms? Like, how can we notice it's starting or it's happening.

Dr. Antonella Santuccione Chadha:

Alzheimer's is a very unfair type of disease. Well, like many actually, if you think about it, all diseases start decades before the symptoms become manifested. There are... in oncology and cancer now there is early detection, prevention. But before you would find out there is a tumour just maybe three months before you die. And it's a bit the same with Alzheimer. The disease starts two decades before the symptoms become manifested. And symptoms also become to be noticed in a very subtile way. So at the beginning, there are just slight changes in maybe memory, or the person changed personality. We go back to women. Very often women are diagnosed with depression. And after a couple of years it turns out this is Alzheimer's, it's not a depression. Man, for example, start with symptoms of being more aggressive or drinking more alcohol. And that's because alcohol represents a comfort zone where to hide the fears of starting to notice that something is wrong with your brain, with your memory, with your behaviour. Because patients at the beginning notice that something is changing and it is very frightening. So these are the first symptoms. Very difficult to be recognised and diagnosed because they refer a lot to changes in personality and how we function on a daily basis. And so sometimes the caregiver or the husband or the daughter says my mom is changing and noticing something strange but it's difficult to bring into right away Alzheimer's disease..

Alex X-Health.show:

It can be blamed on the perimenopause.

Dr. Antonella Santuccione Chadha:

Exactly. For example, or, you know, it can also be that you're really depressed or there is a difficult phase in your life or your lack of sleep. I mean, there are many reasons. But the truth is that we need to have a much better awareness of those type of symptoms and not to, let's say... not not to ignore them. What we have found also the Women's Brain Project, we have started that it's the first of its kind where we look at sex and gender difference in the patient journey for Alzheimer's disease. So how a journey for a woman or a man differ in the history of Alzheimer from the first symptoms up to the end of their.. of their history. And what we've learned, for example, is that very often, women are underdiagnosed or overlooked, and they usually go to the attention of the general practitioner first versus male who've seen directly straightforward with a specialist. Now, the reason might we've multifactorial, one of them goes back to gender. Often the man has a wife or a daughter that proactively brings the father taking care of, to the visit of a specialised doctor. Women are very often widows or less wealthy, they have less money so they access less specialised care. And you know, there is a trend of believing that a woman who displayed this kind of symptoms like changing behaviour or a bit forgetful maybe she's stressed or she fought with the husband or she fought with the daughter, or you know, come back in six months. And then it goes on and on till things are too late and she develops a full dementia. And we have to change this we need to bring more education to GPs, to general practitioner, to specialise doctor that also women deserve the same attention that men do and this is not true only for Alzheimer's. This is for cardiovascular diseases. This is for, you know, for many, many diseases. I mean, even multiple sclerosis very often in young patients because multiple sclerosis... It's referring to often women who are in their 40s it might take up two years. I mean, I had one friend, I can give a clear example in a highly specialised healthcare system, highly educated family. She took five years to understand that she had a multiple sclerosis rather than labyrinthitis or depression, or anxiety. She's been diagnosed with anything, hospitalised and no one have a total doing an MRI. After five years she got an MRI and it was not about, as I said, being depressed or having labyrinthitis. It was about having symptoms of MS, multiple sclerosis, and now she's on treatment and she's doing fine but this should not be a norm and it happened not in healthcare system which are coming from low and middle income countries. It happened here, in highly specialised healthcare systems.

Alex X-Health.show:

That brings to my mind Sofia's story one published on Women's Brain Project's blog, you know.

Dr. Antonella Santuccione Chadha:

Exactly.

Alex X-Health.show:

She was going from one doctor to another, and you know, there was no diagnosis for her even so, she said that her father died of dementia caused by Alzheimer's disease. Same for her grandmother. And actually, she was diagnosed at the age of 39.

Dr. Antonella Santuccione Chadha:

Yes, yes, we're speaking about a familial form of Alzheimer's disease where a gene is mutated. And unfortunately, if you belong to the offspring that got the mutated gene, your likelihood of having Alzheimer's is almost certain. And that's Sofia's story. And when you're mentioned her name, I get skin bumps. I mean, Sofia is a dear person to my heart. And her disease advanced a lot at the moment. And yeah, she started her journey when she was, I think, around 37, or even younger, because she has noticed that something was changing in her and she says it very clearly in the blog on our website. At that time, she could still write, now she has difficulties. She used to say, for me, the problem when I was tested for Alzheimer's, using the scales that existed at the time, and it still are used routinely for diagnosing patients. Was not to design a lane from A to B or calculate 100 minus 7. But my symptoms were much more subtile. And it was about how high I was feeling I was not functioning as before. So... and she had to struggle. Finally, she had to reach out to highly specialised centre in Sweden. And she met one of the key opinion leader in the Alzheimer’s field, they did a genetic testing, and they could confirm that unfortunately she was carrier one of the mutated form of the protein underlying the familal form of Alzheimer's disease, the genetic form of Alzheimer's disease. And yeah, I mean, then the story started and... yeah, we should have not allowed to lose brain cells from Sofia's brain. I mean, this is very tough for me. And I wish we will have another story to discuss this morning rather than this one.

Alex X-Health.show:

Sorry, sorry to bring that up.

Dr. Antonella Santuccione Chadha:

No, it's just, you know, what we do is also in her name, and to avoid that anyone else like Sofia will have to face the same. And she has daughters and... and there are other patients because we hear these stories very often, you know. There are very..., there are many patients with early Alzheimer disease due to these mutations, and it's just devastating for them, for the family members, for us. And it's a defeat, if you can't help someone. It's a defeat for each medical doctor and researcher in the world. And as far as we can have these people we are defeated.

Alex X-Health.show:

Also, she wanted to help. She wanted to get into clinical trials and she was too young.

Dr. Antonella Santuccione Chadha:

It was also the paradox of this... that we have this age limit of 50 in majority of the clinical trials for Alzheimer's disease. And when you ask around those who just develop this, this guideline why, they will tell you, well, we don't really know. Maybe just to exclude the early onset form of Alzheimer's disease but that's not an issue because the diseases are very much resembling one another. The sporadic and, and early onset so... And for her it was really a struggle to be admitted into a clinical trial. Then we finally succeeded in supporting her unfortunately, she was on an arm of a clinical trial of a drug that showed major side effects on the liver of patients. So that arm of the trial was terminated and she was out of the trial with removed our hopes. It's difficult and she has been a fighter. She has been a strong fighter all her life. She's still fighting. And yeah, I wish as I said, that we will not speak... We want to say Sofia is cured, but we're not there yet.

Alex X-Health.show:

I wish, I wish we her that, definitely, I wish her that. What's the current standard for diagnosing Alzheimer's disease?

Dr. Antonella Santuccione Chadha:

Well, actually, we can diagnose Alzheimer's and we also can recognise a symptom pretty early. It's just that the infrastructures are very scattered. So not all the patients around the world but even in healthcare systems which are highly specialised as the Swiss one, for example, can access this highly... let's say, highly refined way of diagnosing Alzheimer's. So, in general, it's about the patient going to the doctor describing the symptoms or the caregiver, bringing the patients to the doctor and describing the symptoms, when the symptoms are already manifested and obvious to everyone. And then what happens is that the doctor will do some neuroimaging, will analyse those results, and we'll start to understand what's going on. If you're in a specialised healthcare infrastructure, you might have done neuropsychological assessments where you will do lots of tests, they last up to three hours. And the neuropsychologist will tell you, in which cognitive domain you might function, not function, and we'll start to help the doctors towards a diagnosis of mild cognitive impairment, Alzheimer's disease, etc. In addition to this, and based on our latest discovery and very important, we can also do diagnosis based on those toxic protein concentration that are measured either in the cerebral spinal fluid, or that could be quantified or semi quantified in the brain, thanks to amyloid PET imaging, so there is radiotracers that goes in the brain, stick to this toxic protein and you can see with neuroimaging where they are and more or less how much there is of this. The same is true for CSF, it's a quantitative test, that gives you an indication of how much toxic protein it's in your liquor, which is the fluid that circulates in our brain. And that's a way to be certain that there is what we define amyloid pathology. And there are disease modifying treatment or let's say antiamyloid agents that are already approved in the United States and hopefully will be approved also in Europe, but many more are under development that target exactly this amyloid. So why it's important to make a CSF diagnosis or amyloid PET of the brain? Because if you're considered positive for this type of proteins, that's the way the drug can be prescribed. So your doctor can prescribe you those anti amyloid agents that will remove the plaque will clean the plaques out of your brain and will slow down the progression of the disease. And that's quite important. Now, I hope that those drugs will show to have also preventive effect, which means the earlier you give them, the higher the likelihood of functioning and not allowing this block to be formed, saving the neurons. Because when you have a plaque forming, it means neurons are dead, they are not coming back. So there is nothing to do about it. And it's a bit like with the antilipid or anticholesterol agents, or, you know, other type of diseases which are chronic, you start to measure some biomarkers early enough, even before the disease manifests, so the symptom manifests, so you can prescribe a given therapy and prevent those events to happen. So let's hope that for Alzheimer's in the future it will be the same with the new drugs under development and which will be further characterised in a real world setting.

Alex X-Health.show:

How long can it take to get diagnosed with Alzheimer's disease.

Dr. Antonella Santuccione Chadha:

In fact, we go back to where you live and how rich you are. If you are wealthy and you're lucky to live next to the best neurologist in town, it might take, maybe, one or two months, from the moment you start till... if the symptoms are clear, and if the results are easy to be interpreted. If you don't access this infrastructure and that's the majority of the people worldwide, it might take up to two years. I mean, you know, the average to diagnose one of those brain diseases we mentioned even earlier, it's up to two to three years, even in the best health care system. And again, this is a trajectory that has to be changed, absolutely. Because time is brain brain is time. And the more we wait, the more damage is significant and more there is nothing to do about it. Because as I said, you can imagine a brain that shrinks, a brain that is full of plaques you just need a miracle than to to reverse the narrative. You really need a magic stick. There is nothing much you can do if not having a magic, which I think we're far from that.

Alex X-Health.show:

And speaking of access to the best healthcare systems, you know, it brings the case of Bruce Willis, who's I mean, he's not Alzheimer's disease patient but he has dementia. And it also... it wasn't obvious from the beginning. It started with aphasia, right, and then, you know, the family just announced that he has frontotemporal dementia. which is yeah, like how that differs from from Alzheimer's.

Dr. Antonella Santuccione Chadha:

So let's start saying that there are several types of dementia and Alzheimer represent the majority of the cases. But then there is Frontotemporal dementia, Lewy Body disease, I mean, there are several of those. The differential diagnosis is very complex. It's not an easy task for a neurologist or a psychiatrist, or a geriatrician to make a precise diagnosis. Above all, at the beginning of the disease manifestation. And that's true for the majority of brain disorders or brain diseases. Because symptoms tend to resemble one another, the eye, the naked eye of a doctor might have difficulties in understanding what type of disease is observing. I can give you some examples that occurred directly to me. I had that very dear patient that we all believed she would have had corticobasal degeneration. This is another type of neurodegenerative disease with some symptoms of dementia. She also had problem in finding words, she would have falled, down she had the so called Person syndrome where the body hangs on one side, she couldn't recognise her right arm as her own, which is called the ghost limb syndrome. Now, this was all pointing to corticobasal degeneration. She had a bride gait, so she was walking in a special way with large gait. And when... she donated the brain for research, so the family decided to donate the brain for research. I received the brain, I sent the brain to be analysed by the best histopathologist in the world. So you know, it's not that they missed it. And the result was, like, pure Alzheimer's disease. So to my biggest surprise and... so in the pathology that I was seeing we had clearly signs of Alzheimer, but the symptoms were completely different. Now, still, it could be that there is a mixed pathology, that we might have missed something, that's always possible in medicine. But what I wanted to tell you at the end of the story is that symptoms resemble frontotemporal dementia back to what you asked me. It is a disease where majority of the changes occur in the way you behave. And it's about suddenly a person being disinhibited or doing things that would have never done before, like wasting a fortune in... family money that were saved in a bank account or suddenly gifting all his property to a new person coming in their life, because maybe they fall in love. So do things that are completely absurd. And you say, I don't recognise this person. It can become aggressive sometimes. Actually, frontotemporal dementia has a very strong component of aggressivity. So... and it's mainly due to changes in the frontal part of our cortex, there are some specific proteins that are suspected to play a major role for this disease. And as I said, it's one of the many types of dementia. It's certainly and luckily rare as compared to what Alzheimer's. Not that one is better or the other is worse, they're both terrible diseases. But frontotemporal is even more complicated to manage from the caregiver perspective. Because as I said, the behavioural changes impact not only the patient, but also the surrounding, the family, friends and... Usually those diseases impact not only the individual, but the whole family and surrounding, which is also something to take into account.

Alex X-Health.show:

Now, you joined a startup Altoida as the Chief Medical Officer and an interim interim CEO. They develop digital medical application, and they claim that this diagnosis period, I mean, can be shortened to 10 minutes. So 10 minutes with an app and you're diagnosed

Dr. Antonella Santuccione Chadha:

Let me tell you... So basically, this is going to be hopefully the future of medicine. And this is why I joined because I believe in the best way to predict the future and it's not my quote, it is to build it. So I said, I want to build my future, and the future, my future as a doctor, you know. And why that? Because when I worked at the Swiss regulatory agency for therapeutic products approval and I was analysing the data of new medications to be approved for the Swiss market and deciding whether this would have been working, whether this will they'd been safe. And therefore authorising it or not. I have noticed that very often drugs might have not shown the effect that they could have brought on the table. Because the scales that were used to measure those effect were not, appropriate, not accurate. Imagine also that now we're discovering that... you know, as we said in Alzheimer's, for example, the disease starts 20 years before there is accumulation of these toxic proteins. And this is what we're learning lately. But the scales that we use to measure Alzheimer's disease were scales that were mainly designed for later phases of the diseases where dementia symptoms were more obvious. And we didn't know that, you know, it sytook 20 years to arrive to that symptom. So I want to say, and please allow me to say so that most of the scales are obsolete. They were developed in the 60s. And you know, 60s is... I wasn't born, you weren't born. So it's a long time ago, and medicine has advanced. So why the future of medicine, why digital biomarkers. Digital biomarkers have the potential of objectifying measurements that the naked eyes of the doctor, which I mentioned earlier, are not capable to recognise or to see. And what for example, the test that Altoida does is to measure more than 800 features, multimodal, on how our brain, while taking certain type of tasks to be accomplished, function in terms of motoric, executive function, cognition, memory. And the machine learning behind it, when it's trained on how a healthy brain is functioning, and how Alzheimer's brain or mild cognitive impairment brain, or any other type of brain is functioning, will start to distinguish and recognise, oh-oh, this is healthy, good, oh-oh, this is a brain which has problems. And that's how we bring this assessment of cognition thanks to Altoida. So we assess cognition, based on exercises that are taken between 10 and maybe 15 minutes, of course, then depends on the individual. And based on the results, we can determine if the brain is functioning well, or if it has problems in the way it moves in space and time, execute a given task, remembers about it, et cetera, et cetera. And the beauty of it is that it measurs these micro errors and micro tremors and this is measured by sensors that are embedded in our portable devices, like a smartphone or an iPad. And that's the magic about it. You know...

Alex X-Health.show:

That's fascinating. That's really fascinating.

Dr. Antonella Santuccione Chadha:

It is fascinating. It is, anyhow, apparently easy to be done. And this is, again, the future of medicine. So this is just an example of what will be in the future. And I really hope so because for, as I said, majority of brain and mental disorders, the scales we use are too subjective to biases of the doctor, to how the patient is feeling in that moment. They are not objective measures and they are not also measuring the patient at this crisis time. I mean, now the same is true for depression. I used to ask to my patients, do you have suicidal thoughts? Now, I tell you all the patients who unfortunately committed a suicide, and I've lost them, they were the ones who would tell me "No".

Alex X-Health.show:

Are you saying a useless question or..

Dr. Antonella Santuccione Chadha:

It's an intimate thing. And some people might respond honestly, others not. What we know is that those type of taboo, like suicidal thoughts or others are asked more to Google than to a doctor. So just to tell you that there is an intimacy as fear of what I mean is, why should I tell an unknown doctor showing up in front of me what I really think. I mean, with objective measures, and thanks to digital biomarkers to this type of solutions, we will learn I think, much more than we can do today based on our ability as humans to judge other humans or to evaluate other humans, judge in terms of disease judgement.

Alex X-Health.show:

How far into the future are we speaking now?

Dr. Antonella Santuccione Chadha:

I want to believe that it's going to be... 10 years from now, not longer. We have no time. I mean, people have told me, ah, you are very impatient. Yes, of course. I mean, it's about life of people and the way they feel. It's not about changing the colour of the building next door or buying a new dress.

Alex X-Health.show:

And then, what to do after such a self-diagnosis. So you make this 10-15-minute test...

Dr. Antonella Santuccione Chadha:

This has to be prescribed by a doctor, it's a medical device. I requires a prescription from a healthcare provider. So you're not alone. You'll do the test, and you will have someone guiding you through the results of the test. And then, this will inform a doctor on what to do eventually next, whether you need an MRI or whether you need the cerebral spinal fluid lumbar puncture, we spoke about. I mean, what to do next, right, I mean, it's an aid for a doctor to take an informed decision on where your condition is, and what to do about it.

Alex X-Health.show:

Let's round up back to Women's Brain Project, and the fact that it's called a project. So is there a timeline, you know, towards, like, when do you want to bring this equality in research, in clinical trials?

Dr. Antonella Santuccione Chadha:

So Aleksandra, let me tell you, when we decided the name, Women's Brain Project, we had a lot of discussions about it because people didn't like the fact that there was "women" there, people didn't like the fact that there was "project" there, and they really had to struggle.

Alex X-Health.show:

Brain was OK, right?

Dr. Antonella Santuccione Chadha:

Brain was OK. Brain was OK. But"women's" and "project"? Mhm. And you know, I really had to struggle. I remember I really took a strong position on that. First of all, because I thought, why not "women"? I mean, we have I don't know, the word "man" is used almost in any type of association or organisation. Why shouldn't we use now for"women", even for a scientific organisation. And it's about women, it's about improving the health of women, the drug development for women, the research for women, etc. But I have to admit, and this is, of course, an observation I have, it's not supported by large statistics, but very often when people have to spell out Women's Brain Project, they still have problem. They go Women man brain project. So the word women still creates a certain difficulty in articulating the whole length of the three words together. I don't know why. But it's an interesting phenomenon that I observed very, very often. And"project"... I remember there was a member of the team Żaneta, she said, Antonella, why do you want to call it "project", I mean, a project has a beginning and an end, it doesn't give continuty... And I said, exactly because of this. I want that it begins with us and hopefully, it''ll end with us because we have finished the job and the topic of sex and gender medicine will become obsolete, because we've solved the issue. And now we have to speak about something else. So to your question, why Women's Brain Project? "Women", because it's about women's brain and understanding all this features and characteristics, and problems we discussed during this hour. "Brain" because it's about the brain. And "project" because we want to have a beginning and an end. And that's my legacy to the world. I really hope that we will solve the issue and in 15 years from now, we will speak about something else to solve in medicine.

Alex X-Health.show:

I wish you that, Antonella, I want to see that.

Dr. Antonella Santuccione Chadha:

Yes, me too.

Alex X-Health.show:

Thank you very much the conversation we've had. And if you want to learn more about Women's Brain Project head to www.womensbrainproject.com. And if you want to learn more about Altoida, you'll find it at altoida.com . Thank you so much. Thank you so much.