XXplored Podcast – The Midlife Transition: Menopause and the Brain

Voice Over:

Welcome to Xxplored, Women's Brain Health, a Dementia Researcher Podcast exploring the many factors that shape women's brain health across the lifespan.

Dr Laura Stankeviciute:

Hello, and welcome to another episode of Xxplored, Women's Brain Health. Today, we're diving into very important, yet often misunderstood reproductive stage in women's life, which is the midlife transition, also known as the menopause.

I'm your host, Dr. Laura Stankeviciute, and today, we are talking about menopause. In the world, over one billion women are going through the stage are already postmenopausal. And this number is expected to rise up to 1.2 billion in five years' time. There was a recent study conducted in the UK, which found that nearly one in four women aged 40 to 60, covering this postmenopausal and perimenopausal period that are considering to quit the work due to their menopausal symptoms, and there are 14% of those who are actually considering to do so, if not have done yet. So, women make up nearly half of the global workforce population, and many will spend a huge amount of time in the post-reproductive years. Yet, our research support systems and clinical care still remain patchy, but perhaps it's not all that grey. And in the past years indeed, we have seen a huge proliferation and a boom towards the topic of menopause, both in research, but also in the societal campaigns such as Let's Talk About Menopause, to global celebrities sharing their navigation through this difficult and sometimes daunting period.

But menopause is still only framed around the topics of vasomotor symptoms such as hot flashes or night sweats, hormonal therapy, or also sometimes mentioned as the reproductive ageing, while the brain is still left out of the picture. That's why today's episode will explore how menopause might act not as merely as an endocrine transition, but rather a neuroendocrine tipping point and will help us understand through this conversation and move menopause from the sidelines, into the scientific and societal spotlight.

And I'm joined today by two great researchers in this field of women's brain health, but also specifically working on the menopause transition. So, they're going to help and unpack these questions. So, it's my honour to introduce Dr. Claudia Barth, who holds a professorship for the Neurobiology of Hormonal Transitions at the Department of Psychiatry and Neurosciences and the research unit gender in medicine at Charité University of Berlin in Germany. She's a biologist and also a neuroscientist by training, with a strong background in Neuroendocrinology.

And another speaker of today, our guest in the series is Dr. Gillian Coughlan. She's a junior researcher faculty at Harvard Medical School MGH. And her research project is focused on elucidated personalised risk factors associated with the changes in Alzheimer's disease biomarkers. But also, she's extremely interested in understanding how factors such as sex differences may shape different trajectories in a deep pathophysiology and cognitive decline. So welcome.

Professor Claudia Barth:

Thank you very much for the invitation. I'm very happy to be here.

Dr Gillian Coughlan:

Thank you for that introduction, Laura. That was great.

Dr Laura Stankeviciute:

So just before we are diving into our main themes of today, I would like to ask just a very simple question. Can you tell in a few sentences what are you actually doing? Because obviously, your biographies are so, so rich, but if you can distil it very, very shortly for our listeners. Claudia, maybe you can go first. You've been thinking for some time.

Professor Claudia Barth:

If you want, I go first. My research as the title of professor where I was luckily just got two months ago, kind of covers it really how hormonal transition periods impact the brain with relevance to health and disease. We broadly focus on depression and Alzheimer's disease risk. Thereby, we focus on diverse hormonal transitions if it's just menstrual cycle, but also pregnancy and menopause. In the last years, the focus has been very much shifted towards menopause and perimenopause specifically. I recently got a grant from the European Research Council to really tap into what's happening during perimenopause transition. So that's what I am doing as I just started in a new position two months ago. What I'm actually doing right now is setting up a big study.

Dr Laura Stankeviciute:

Congratulations.

Professor Claudia Barth:

Thank you.

Dr Laura Stankeviciute:

This is amazing. And thank you so much for doing the work that you're doing specifically in this area that we know have been historically really difficult to get funding. So, kudos definitely for this huge grant.

Professor Claudia Barth:

Thank you very much.

Dr Gillian Coughlan:

Hi. So, I'm Gillian Coughlan. I'm junior research faculty at Harvard Medical School. And I'm part of a grant that kind of sets me up to start off a lab, start of 2026 actually. So pretty soon. I'm mostly interested in preclinical Alzheimer's disease, and I look specifically at sex differences in order to understand disease processes to a greater degree. So, coming at it from more of this kind of personalised medicine approach, and then to understand why women are disproportionately affected by Alzheimer's disease. I also look at things like age at menopause, specifically premature and early menopause, and the use of hormone therapy. And I kind of investigate how those two things are associated with AD biomarkers, primarily amyloid and Tau PET, but also plasma biomarkers like p-tau217, et cetera.

So, we have a number of different grants now both from the NIH and different foundation entities, as well as private funding to look at women's brain health and how it can potentially increase risk for Alzheimer's disease in that postmenopausal stage. So, I think at the moment, there's actually so much interest it seems, on a global level, in terms of women's brain health and Alzheimer's disease risk. And there's a lot of research being done, but I'm sure as we'll discuss today, there's a lot of research that we can also do, I think, over the next three to five years.

Dr Laura Stankeviciute:

Well, this is a very rich portfolio of topics that you are covering, Gillian. I think there's so much research that's going to come up in the upcoming years from both of your labs. And congratulations to both of you.

So, to start, I would like to go actually into the very, very basics of the question of, what is actually menopause? Because sometimes I feel like it's a very confusing topic in terms of its terminology, because sometimes we may think or we can hear menopause being described as this one point in women's reproductive life when a woman hasn't had her menstrual period for 12 consecutive months. But of course, that's more of an oversimplification than the reality because rather, it's not just one point but a culmination of biological changes that have been preceding over the years. So, Claudia, could you clarify to us what menopause really is? And then obviously, you have mentioned already the terminology of perimenopause. So, can you also touch upon that and let us clarify these two concepts?

Professor Claudia Barth:

Of course. You already hinted towards this. So, it's kind of actually a lengthy endocrine transition period, which starts with the progressive failure of ovarian function. So, I like to compare it, or I always like to say it to students, so adolescence is when the hormonal systems go online after they already went online once during foetal development and mini puberty. But then menopause is kind of the delayed stage where systems slowly go offline, but it's not that you turn the switch and everything is offline and you stop having cycles. The system goes slightly offline because it's regulated via the HPG access. I hope I don't mix up the German and the English abbreviation. But basically, the brain regulates the ovaries, and this little dance gets interrupted more and more and more, which leads to erratic hormonal fluctuations, which then eventually cease, and that's the end of the menopausal transition.

And as you nicely said, menopause by definition is actually just one time point after you haven't had a menstrual cycle for 12 months. But preceding that, that's what we call perimenopause, which are years of increasing levels of erratic fluctuation. Normally in the early perimenopausal stages, you get slightly more variations in menstrual cycle length and tentatively more towards shorter cycles. You don't really have symptoms yet, but your menstrual cycle length varies and there are some hormonal markers which slightly start changing. Then in the late perimenopausal stage, which just tends to on average, be between one to three years, but there are varying accounts when it comes to the actual length of that, that's where the cycle variations become much more pronounced, late perimenopause after the STRAW criteria are defined by not having a cycle for 60 plus days. And then that's when also symptoms start to emerge in the majority of women. And that can be sleep disturbances, night sweats, hot flashes, but also cognitive disturbances and depressive symptoms.

And then menopause again, is this one day, and then post menopause kind of starts after one year of not having had a menstrual cycle for 12 months. So actually, there's one point of menopause which is often used to name the whole transition, is really assess retrospectively when you can say, "Okay, now I haven't had a cycle for 12 months." But also again, for a lot of women, this might not be textbook. They might not have a cycle for one year, but then it comes back. So, this system kind of trying to compensate just having another cycle and eventually, it stops, and then hormonal fluctuations stabilise and are stably low.

Dr Laura Stankeviciute:

Well, I hope our listeners can appreciate just how complex this whole continuum of pre, peri and post menopause is. And obviously, each stage is accompanied by different symptoms. And you mentioned obviously, the vasomotor symptoms, which are those that are related to hot flashes, night sweats. But also, you didn't leave outside these cognitive symptoms that sometimes are pushed under the rug. And I would actually like to go a little bit into those ones. So, what is the actual neurobiological explanation behind those symptoms? Because obviously, it varies. We have different centres in the brain that orchestrate different functions. So, we have the hypothalamus perhaps more related to this thermoregulation, so vasomotor symptoms. But what about these cognitive symptoms? And also, we hear that a lot of women are experiencing really huge differences in their mood from what they used to be, to how their mood or even their personality changes. So, what do we know about that, Claudia, in terms of the brain specifics?

Professor Claudia Barth:

What we know the most, you already kind of hinted at, is changes in thermoregulation due to changes in the hypothalamus. So that's also the most studied symptoms. When it comes to the cognitive symptoms and the repressive symptoms, we don't know that much yet. We know that declining and especially volatility, this volatile decline in oestrogen, it's not just linearly declining. It's really fluctuating erratically. And oestrogen has multiple functions in the brain, but it's also a very potent modulator of neurotransmitter systems, which are very important for your mood, but also your cognitive function. So that would be one potential mechanism which could explain disturbances. Then also, this oestrogen is neuroprotective and with its declining level, this neuroprotection might be lifted in some women, which then also can contribute to more accelerated ageing, but also neurological decline due to structural changes mainly from animal work, but also for some human studies. And I think Gillian might say more about that later, but there are hints towards like grey matter, white matter changes that...

And Brinton, Roberta Brinton was the first one postulating there might be this bio-energetic shift in the brain that what the brain uses as an energy source might shift. And because glucose metabolism changes, then there's this theory that away from glucose metabolism, it shifts to metabolising ketone bodies which are part of the white matter. And so, it's a very complex system which is likely very tightly interlinked. And then any of these changes might then contribute to mood disturbance and cognitive changes, especially if you already are potentially, genetically at risk, if you have a certain lifestyle which might not provide resilience against these shifts. And especially also, when you already have a history of depressive disorders, depression has been postulated as a very well-established risk factor of Alzheimer's disease later in life. So, it's very much tightly connected. But my main statement in this regard would be really, structural changes, functional changes, and particularly, also changes in neurotransmitter functioning.

Dr Laura Stankeviciute:

Wow. So, all of these changes obviously, expose then women's brain to be more vulnerable to later life conditions and your degenerative diseases, because of these fluctuations in hormones that you mentioned, and obviously, the critical glucose consumption hypothesis that has been presented by Brinton. So now, I'd like to shift the microphone and give the floor to Gillian, because I would like to talk about probably the research area that we work in and the research area that has been receiving so much interest in the greatest scheme of menopause, which is Alzheimer's disease.

So obviously, we know that women make roughly two thirds of all Alzheimer's disease cases, but obviously, it's not just the longevity that explains all of these staggering numbers, but it's actually the underlying biology and also, cognitive trajectories that we see in women. And in the past decades, we have had this hypothesis of menopause really breaching through and suggesting that this is due to the menopausal hormonal fluctuations, specifically due to the decrease in oestrogen levels. So, I would like to ask Gillian if you could share some evidence specifically advocated for menopause being this critical infliction point in women's life that exposes her to increased susceptibility for Alzheimer's disease?

Dr Gillian Coughlan:

Yeah. So just as Claudia had beautifully taken us too there, we have this whole flurry of events that happen around menopause. And then we as Alzheimer's disease researchers, we're studying women usually in their mid-70s and looking at levels of these neurotoxic proteins that cause Alzheimer's disease essentially. And so, what we do is we look at these women, we image them for these neurotoxic proteins, and then we look back to see how they experience menopause basically. Now, typically, we don't have data sets that can look at the fluctuations in the hormones around menopause and link them to later AD biomarkers, like these neurotoxic proteins. But what we can do is we can look at how women experience menopause in terms of their menopausal symptoms, which will be a proxy for those hormonal fluctuations. We can also ask them, when did they have their last period, which would be their say, age of menopause. And then we can also ask them whether or not they were treated for menopausal symptoms with HRT.

And so I guess one of the things we learned so far is that if women move into this kind of menopausal or perimenopausal state earlier than expected, so particularly before the age of 40 or maybe between 40 and 45, those women seem to be at a higher risk for depositing these neurotoxic proteins, amyloid and tau, later in life. So that association has been shown in our neuroimaging studies but also shown in these epidemiological studies that show that the age of menopause is associated with Alzheimer's disease prevalence. Right? So then, we look at the biology of what that link could be. In terms of hormonal fluctuations, we are writing grants at the moment, and I do know a couple of other scientists in the US who are writing grants to look at how all of those events during perimenopause change the women's brain structure and function in real time.

So not necessarily looking at women's brain down the line like we currently are doing, but in real time as the fluctuations in the hormones are occurring. So, some of the leading scientists in that area right now would be Roberta Brinton, but also, Emily Jacobs. They have a grant basically looking at exactly these questions. Also, Caitlin Costello, she's another scientist who's very prominent in this area, and then ourselves. So, me and Rachel Buckley, we're also proposing a grant to look at perimenopausal effects and how that implicates the brain. In terms of what we look at in the brain in menopausal women, we don't look for the proteins of Alzheimer's disease because it's very unlikely that they exist at that stage. Right? So typically, if menopause is going to increase women's risk of Alzheimer's disease, we won't know that will have officially happened until they are at the age where they can actually start depositing these proteins.

So, what we instead look at, is these other risk factors that might suggest that women are on the road to preclinical Alzheimer's disease. And so, some of those things would be more the plasma biomarkers. Also, things like inflammatory pathways, vascular pathways, looking at brain structure and function of course, and brain structure, particularly in some fields of the hippocampus, like the CA3. That would be a region we'd be particularly interested in, in these menopausal women. And then looking at the structural integrity of white matter tracts, those kinds of things.

So those biomarkers are more likely to change due to menopausal changes. And then if they do change, that puts the brain in a more vulnerable state to deposit these neurotoxic proteins later down the line. And it's really the proteins that underlie the actual onset of symptoms related to Alzheimer's disease, at least. Of course, there are other dementias, but we focus mostly on Alzheimer's.

So, there's a lot to unpack. Basically, the way we're doing at the moment is, as I said, we had this big space of time between when women report menopause, menopausal symptoms, and their menopausal age, and then we get PET scans on them 15 years later. Whereas the way the field is moving, is to actually do those imaging studies as women are actually going through menopause. And that will tell us a lot more basically, about how menopause leaves women at risk, potentially could leave women at risk of cognitive decline later in life.

Dr Laura Stankeviciute:

So we're seeing that definitely, a lot of retrospective studies have laid this foundation where we are now knowing or learning about how menopausal or menopause related factors are associated with later accumulation of these toxic proteins, but also of structural changes that then also, as you said, kind of lead the brain to become more vulnerable later on. And you mentioned one of the risk factors that you have done in your research, is actually the earlier age of menopause. And most of the people probably think of menopause as a natural process as it comes to ageing, but obviously, we have different types of menopause, such as surgical menopause. So, could you maybe comment a bit on that?

Dr Gillian Coughlan:

Yeah. So, I think the original hypothesis was that it was probably surgical menopause that would be women at risk. And we're seeing in our data, or at least the data sets we work with, not so much the fact that it was a surgically induced menopause. It's more just that the menopause was early. Right? So, you get this earlier than expected deprivation in circulating estrogens, et cetera. And then the fact that this happens earlier than it should, is kind of having the detrimental effect, as opposed to it being surgically induced as such. At least that's what we're seeing in the data we look at from the Alzheimer's disease perspective. But just by nature of having a surgically induced menopause, then that is likely happening earlier than the average age of menopause, which is 50. Right? It's probably happening before the age of 45, if not before the age of 40.

So, I think when we do interviews, we also say it is important for women to always know what's happening with their reproductive health and know if they're getting surgically induced menopause, that that is happening for the right reasons, or at least it's really necessary in their case. Because it can have implications for women's brain health, and then the brain health later down the line.

Dr Laura Stankeviciute:

Okay. So obviously, that becomes less clear then. It's not just again, the type, but maybe the age. But then again, maybe there is something behind that that we don't know yet, and probably, we don't know how to quantify. Because historically, the data sets that we are working on, they don't collect that data, or if they collect it, it's not to the extent that we would like to.

So, I would like to now move a little bit from what we know, to what we will know based on both of the work that you are doing. And specifically, maybe talking a little bit about the historical blind spots in terms of the methodologies that these ageing cohorts or Alzheimer's disease cohorts have been using. So obviously, we know like ADNI, which is Alzheimer's Disease Neuroimaging Initiative, but we also have more huge data sets that are looking specifically into how individuals develop Alzheimer's disease from preclinical. So, this asymptomatic stage where the proteins start to accumulate, but yet, in the absence of any cognitive symptoms. But none of these data sets have considered sex specific variables or perhaps to a very, very brief extent. And why do you think that was the case potentially? And then the follow-up question, what would be your kind of perfect list of reproductive variables that you would like to include in your studies? Because I know both of you are spinning big brands now. So, let's start with Claudia, and then go to you, Gillian, with your wish lists.

Professor Claudia Barth:

So yeah, that's a good question. Because I've in the past, mainly used UK Biobank, which is a big UK-based population sample covering 500,000 individuals. And the nice thing with UK Biobank, it's started collecting... So, age inclusion ranges between 40 and 70, which again, is already actually a bit younger than the most ageing cohorts, which normally starts at the age of 65, historically rooted into based on the retirement age in most countries. And UK Biobank actually does cover the menopause transition, but it has surprisingly little variables on this particular aspect and has no variables about symptoms. We tried multiple times to varying degrees of success, to really establish a woman in this cohort, perimenopausal. So yeah, simply knowing if women have symptoms, if they had symptoms, as Gillian said, and that they ask retrospectively, how did your experience? The menopause transition is super important because that varies a lot.

And there is more and more indication that the severity of symptoms, the number of co-occurring symptoms, what kind of co-occurring symptoms, how long they last, might really be critical for how women might age later in life. So, questions around that are really, really important. Then past reproductive history, we have found associations between a number of live births and the ageing brain later in life. So, these kinds of variables are really important if women have used hormonal contraception. It can be very insightful to know for later, brain ageing. Yeah. Now that I'm starting acquiring data across perimenopause, I'm setting up this massive baseline questionnaire about reproductive factors and past histories and age at menarche, and trying to really map out all the reproductive years as comprehensively as possible to really kind of see what we found in the UK Biobank if that replicates, but also, how that informs how women's actively life, as Gillian said earlier, experience perimenopause.

So, my grant also has a strong focus on symptom mapping. So, we are using an industry partnership to have an app really for the participants to be able to on a daily basis, record their symptoms and their experiences. Because I think that's a really big, big missing part in all of these cohorts. It's first of all, that symptoms are not really acknowledged, but also, it's mainly you have one, two, three, maybe time points. So having also more densely sample data across these critical inflexion points is really, really needed. And I'm really happy to see this trend towards focusing on perimenopause and then focusing on longitudinal studies during perimenopause. Because I got money to do my part, but we need comparable samples globally, so we can really look for robustness of effects and generalizability of effects. And also, to be able to tap into biopsychosocial aspects. Does it differ between countries? Does it differ between healthcare systems how the experience of perimenopause and the menopause transition impacts ageing later in life?

And there is already some indication not from imaging studies, but more also from when it comes to attitudes towards menopause and mental health. Because of attitude too, it might differ between societies and between societal structures and between potentially, the western and the global north and the global south, and all these differentiations. So, it's nice we are going in this direction of having more varied approaches, although it is still kind of clustered to the global north, I have to admit. But yeah, that's more symptoms, more dense sampling. And ideally in the long run, also much more diverse samples, which is not just white women.

Dr Laura Stankeviciute:

Thank you so much for sharing your study as well, and what you're going to be doing with this highly phenotype cohort. And you were obviously saying that this is the global north, but since we're talking about Germany and European perspectives because of your study, my curiosity is, what is the situation on the other side of that Atlantic Ocean and how are you going to measure and quantify your participants, Gillian?

Dr Gillian Coughlan:

Yeah. So where to start really? So, I think, well, when it comes to what we would ask women, Emily Jacobs is actually putting together this standardised questionnaire. You know about it. It's where all researchers in women's health can basically use the standardised questionnaire, which really covers the scope of things related to menopause timing, symptoms, et cetera, but also hormone therapy, type of hormone therapy dosage, et cetera. So, I think that will probably be incredibly valuable to the field at large, and probably also used in a global scale, not just necessarily in North America, I wouldn't think. And so the interesting thing about women's health is that in maybe 10 minutes, we can acquire a huge amount of data on women's reproductive health, at least by participant self-report, which has some limitations, but it still would be an awful lot better than the relatively sparse amount of data we have on women's health from these big data sets that we work on at the moment.

So, there's been a big push for studies like the Wisconsin Registry of Alzheimer's Prevention, the Harvard [inaudible 00:33:33]. So, all of these open access data sets to start including these questionnaires as part of their screening processes. And so, I think there is a shift towards that now. So, in the next five years in particular, I think we'll have a whole host of new data that we can work with from those data sets.

In terms of new studies that we're doing, a lot of it is collecting blood samples from the women as they go through perimenopause. So, these are more focused studies on menopause, AD link. And then also using those blood samples to run ELISA, which can basically allow us to capture all of these kinds of inflammatory and vascular pathways, and potentially copathologies too, like [inaudible 00:34:20] and eosinophilia, and things beyond just Alzheimer's disease. So, I think the studies that we're designing now, specifically to look at menopause, will be relying heavily on blood samples and looking at hormone levels and all of these other biomarkers. But when we think about these current big scale data sets that are out there, just bringing in these women's questionnaires will also open us up to a whole new field of data analysis.

Dr Laura Stankeviciute:

Thank you so much. And obviously, your Wishlist allows all of our listeners who are also potentially thinking about conducting such studies, pay attention to variables that you have mentioned today. I also thought about something that Claudia, you mentioned about the industry collaboration. This is not still a common practise in research environments. Could you tell us how was your journey with that, establishing that collaboration, and how does that collaboration will help you and how you're using those industry supports?

Professor Claudia Barth:

I used to say when people ask me about that, that I'm just lazy because I don't need to reinvent the wheel if there are much smarter people out there already doing the work. Because for my study, we have repeated imaging, we have repeated blood samples, and we have all the standards we've done in previous studies. But then I was like, "Okay, how do we actually really tap into symptom and experiences?" And there were already apps out there doing that. And so, I reached out to Clue, which is a Berlin-based menstrual cycle tracking app startup. And finally, when I wrote my grant in 2023, they just released a perimenopause mode in September, and my deadline was in November. And then I just texted them and said, "I'm preparing this grant. I just saw you release this mode. I would love to use that in my participants. Are you interested in collaborating?" And so on and so forth. And they were super open.

So, it was very easy and gave me a letter of support. I budgeted for that, and so it was a nice story. And now, we are kind of going back and forth also on how we could use already acquired data and other angles to really using the data. These digital FemTech startups are already collecting based on their user base. And Clue has a very nice setup where in app, you also already used, like already asked if you want to participate in scientific research studies. So that was really reassuring, so that they already have very strict pipelines for research. And also, very pragmatically for my context being in Europe, because it's Europe-based and startup, it also follows all the GDPR, which is like privacy law regulations in the EU. So that was also very attractive for me personally, knowing that they would follow the data protection standards we would need for research. So, for me, that was a win-win.

Dr Laura Stankeviciute:

That's really inspiring to hear, that you have had a really positive experience. And obviously, since we are talking about really highly dense sampling methodologies for our symptoms and potentially, biomarkers, I also think the future of research, and especially women's health research, should move from just laboratory-based studies to more remote settings. And these platforms, these collaborations would allow us to collect the data, whether it's symptoms, whether it's some type of sleep measures from the wearable device or even blood-based biomarkers that obviously, could be done through the health providers. And then they could put the information related to the sampling time on their application. So, I think there's definitely way more bridges that need to be built between industry and research, in order to propel what we are doing and maybe fast track a little bit more in the future.

So, our time is running away today, but it's been a really rich and great conversation about the menopause and why this midlife transition has been really important. Before we close, I would really like to just bring one personal question to each of our speakers. What does women's brain health mean to you briefly in one sentence, personal? Claudia?

Professor Claudia Barth:

It means, ageing gracefully and as best as possible. And by more research, we can do that.

Dr Laura Stankeviciute:

Beautiful. Gillian?

Dr Gillian Coughlan:

I think women's brain health for me, means sort of the forefront of research and really coming out of the rug and understanding everything there is to understand about women's brains.

Dr Laura Stankeviciute:

Thank you. So that's it for the second episode of Xxplored. A huge thank you to both Dr. Claudia and Dr. Gillian, for your insights and really taking us through this difficult period in women's life. But hopefully, it has just brought a bit lighter and a little bit more understanding. And as I reflect on the things that we have discussed today, there are a few points that kind of really stroke a chord in me. And one of them is both your research and what you're doing on opposite sides of the world, trying to bring the women's brain health and specifically, during that critical vulnerable period where it coincides with Alzheimer's preclinical stages of the disease and the multitude of methodologies that you're using, and trying to navigate the questions that you're posing from multiple angles. And I think that just highlights how still under-researched this area is. But with having such work coming up in the future, I'm definitely feeling a bit more assured about my own brain health, and also the health of our parents hopefully.

And then another also aspect that's probably also our listeners are going to leave with, is that it's not just that one time during the woman's reproductive phase, and it's not just the menopause, it's not just the stop in the menstrual cycle. It's not just the drop in oestrogen, but it's actually the lifetime exposure of oestrogen through variables, such as number of children, also the age at menarche, different pregnancy complications, as well as other risk factors that happen during the whole life that all kind of shape a woman's brain and may increase one's risk. So, thank you once again for this great conversation. I really hope that both of you can reconnect in conferences. And also, we can bring more research from these great ideas.

Professor Claudia Barth:

Thank you very much for this nice conversation. Thank you, Laura.

Dr Laura Stankeviciute:

I'm Dr. Dr Laura Stankeviciute, and you have been listening to Xxplored, Women's Brain Health on the Dementia Researcher Podcast.

Voice Over:

Thank you for listening to Xxplored, Women's Brain Health Podcast from Dementia Researcher, with generous support from the National Institute for Health and Care Research, Alzheimer's Association, Alzheimer's Research UK, Alzheimer's Society, and Race Against Dementia. From hormones to cognition, from risk to prevention, we feature conversations with researchers, clinicians, and change makers working to challenge assumptions and close the gaps in how we understand and support the female brain.