In this episode of the Dementia Researcher - Xxplored Women’s Brain Health podcast, host Dr Laura Stankeviciute speaks with Professor Claudia Barth from Charite University and Dr Gillian Coughlan from Harvard Medical School to examine the midlife transition, menopause and its significance for women’s brain health.
Together they outline what the menopause truly involves across the early, late, and post stages, and explain how hormonal change affects brain structure, energy use, mood, and cognition. They also explore why this period may coincide with greater vulnerability to later Alzheimer’s disease and discuss the role of early or surgical menopause, symptom severity, and gaps in existing research cohorts.
The episode highlights the need for richer reproductive data, real time biomarker studies, and closer collaboration with digital health tools to better capture women’s lived experiences. It reflects a growing wave of research and public interest aimed at improving understanding, support, and evidence based care during this important life stage.
Takeaways
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- [Voice Over] Welcome to
XXplored, Women's Brain Health,
Speaker:a dementia researcher podcast
exploring the many factors
Speaker:that shape women's brain
health across the lifespan.
Speaker:(upbeat music)
Speaker:- Hello and welcome to another episode
Speaker:of XXplored, Women's Brain Health.
Speaker:Today we're diving into very important,
Speaker:yet often misunderstood
reproductive stage in women's life,
Speaker:which is the midlife transition,
Speaker:also known as the menopause.
Speaker:(upbeat music)
Speaker:I'm your host Dr. Laura Stankeviciute
Speaker:and today we are talking about menopause.
Speaker:In the world, over one billion women
Speaker:are going through this stage
Speaker:or are already post-menopausal,
Speaker:and this number is expected to rise
Speaker:up to 1.2 billion in five years time.
Speaker:There was a recent study
conducted in the UK
Speaker:which found that nearly one
in four women aged 40 to 60,
Speaker:covering this post-menopausal
Speaker:and per menopausal period
that are considering
Speaker:to quit the work due to
the menopausal symptoms
Speaker:and there 14% of those who
are actually considering
Speaker:to do so if not have done yet.
Speaker:So women make up nearly half
Speaker:of the global workforce population
Speaker:and many will spend a huge amount
Speaker:of time in the post reductive years.
Speaker:Yet our research, support systems
Speaker:and clinical care still remains patchy,
Speaker:but perhaps it's not all that grey.
Speaker:And in the past years indeed,
Speaker:we have seen a huge
proliferation and a boom
Speaker:towards the topic of
menopause, both in research
Speaker:but also in the in the societal campaigns
Speaker:such as Let's Talk About Menopause
Speaker:to global celebrities
sharing their navigation
Speaker:through this difficult and
sometimes daunting period.
Speaker:But menopause is still only
framed around the topics
Speaker:of vasomotor symptoms such as hot flashes
Speaker:or night sweats, hormonal therapy,
Speaker:or also sometimes mentioned
Speaker:as the reproductive
ageing, while the brain
Speaker:is still left out of the picture.
Speaker:That's why today's episode will explore
Speaker:how menopause might act not merely
Speaker:as an endocrine transition,
Speaker:but rather an neuroendocrine tipping point
Speaker:and will help us understand
through this conversation
Speaker:and move menopause from the sidelines
Speaker:into the scientific
and societal spotlight.
Speaker:And I'm joined today by
two great researchers
Speaker:in this field of women's brain health,
Speaker:but also specifically working
on the menopause transition.
Speaker:So they're gonna help and
unpack these questions.
Speaker:So it's my honour to
introduce Dr. Claudia Barth
Speaker:who holds a professorship
for the neurobiology
Speaker:of hormonal transitions at the Department
Speaker:of Psychiatry in neurosciences
Speaker:and the research unit gender in medicine,
Speaker:university of Berlin in Germany.
Speaker:She's a biologist
Speaker:and also neuroscientist by training
Speaker:with a strong background
in neuroendocrinology.
Speaker:And another speaker of today,
Speaker:our guest in the series
is Dr. Gillian Coughlan.
Speaker:She's a junior researcher faculty
Speaker:at Harvard Medical School MGH.
Speaker:And her research projects
Speaker:focus on elucidated
personalised risk factors
Speaker:associated with the changes
Speaker:in Alzheimer's disease biomarkers,
Speaker:but also she's extremely
interested in understanding
Speaker:how factors such as sex differences
Speaker:may shape different trajectories
in AD pathophysiology
Speaker:and cognitive decline, so welcome.
Speaker:- Thank you very much for the invitation.
Speaker:- Very happy to be here.
Speaker:- Thank you for that introduction Laura.
Speaker:That was great.
Speaker:(upbeat music)
Speaker:- So just before we diving
into our main themes of today,
Speaker:I would like to ask just
a very simple question.
Speaker:Can you tell in a few sentences
what are you actually doing?
Speaker:'Cause obviously your
biographies are so, so rich,
Speaker:but if you can distil
it very, very shortly
Speaker:for our listeners, Claudia,
maybe you can go first.
Speaker:You've been thinking for
some time, you want go first.
Speaker:- So my research kind of as the title
Speaker:of the professor where I was lucky
Speaker:just got two months ago, kind of covers it
Speaker:really how hormonal transition
periods impact the brain
Speaker:with relevance to health and disease.
Speaker:We broadly focus on depression
and Alzheimer's disease risk,
Speaker:but thereby we focus on
diverse hormonal transitions
Speaker:if it's just menstrual cycle
Speaker:but also pregnancy and menopause.
Speaker:In the last years,
Speaker:the focus has been very much
shifted towards menopause
Speaker:and perimenopause specifically.
Speaker:I recently got a grant from
the European Research Council
Speaker:to really tap into what's happening
Speaker:during perimenopause transition.
Speaker:So that's what I am doing
Speaker:as I just started in my new
position like two months ago.
Speaker:What I'm actually doing right
now is setting up a big study.
Speaker:- Congratulations,
Speaker:This is amazing and thank you so much
Speaker:for doing the work
Speaker:that you're doing
specifically in this area
Speaker:that we know have been historically
Speaker:really difficult to get funding.
Speaker:So kudos definitely for this huge grant.
Speaker:- Thank you very much.
Speaker:- Yeah, so hi, so I'm Gillian Coughlan,
Speaker:I'm junior research faculty
at Harvard Medical School
Speaker:and I'm part of a grant
that kind of sets me up
Speaker:to start off a lab the
start of: Speaker:So pretty soon, I'm mostly interested
Speaker:in preclinical Alzheimer's disease
Speaker:and I look specifically at,
you know, sex differences
Speaker:in order to understand disease processes,
Speaker:you know, kind of to a greater degree.
Speaker:So coming at it for more of this
Speaker:kind of personalised medicine approach
Speaker:and then to understand why women
Speaker:are disproportionately affected
by Alzheimer's disease,
Speaker:I also look at things
like age at menopause,
Speaker:specifically premature and early menopause
Speaker:and the use of hormone therapy.
Speaker:And I kind of investigate
Speaker:how those two things are
associated with AD biomarkers,
Speaker:primarily amyloid and tau pet,
Speaker:but also plasma biomarkers
like 217, et cetera.
Speaker:So we have a number
Speaker:of different grants now both from the NIH
Speaker:and different kind of foundation entities
Speaker:as well as private funding
Speaker:to look at women's brain health
Speaker:and how it can potentially increase risk
Speaker:for Alzheimer's disease in
that post-menopausal stage.
Speaker:So I think at the moment,
Speaker:there's actually so much interest
Speaker:it seems on a global level in
terms of women's brain health
Speaker:and Alzheimer's disease risk
Speaker:and there's a lot of research being done
Speaker:but I'm sure as we'll
discuss today, there's a lot
Speaker:of research that we can also do I think
Speaker:over the next three to five years.
Speaker:- Well this is a very
rich portfolio of topics
Speaker:that you are covering.
Speaker:Jillian, I think there's so many research
Speaker:that's gonna come up in the upcoming years
Speaker:from both of your labs and
congratulations to both of you.
Speaker:- Thank you.
Speaker:(upbeat music)
Speaker:So to start, I would like to go actually
Speaker:into the very, very basics
Speaker:of the question of what
is actually menopause.
Speaker:'Cause sometimes I feel like
it's a very confusing topic
Speaker:in terms of its terminology
Speaker:because you know, sometimes we may think
Speaker:or we can hear menopause being described
Speaker:as this one point in
women's reproductive life
Speaker:when a woman hasn't had
her menstrual period
Speaker:for 12 consecutive months.
Speaker:But of course that's more
Speaker:of an oversimplification than the reality
Speaker:because rather it's not just one point
Speaker:but a culmination of biological changes
Speaker:that have been preceding over the years.
Speaker:So Claudia, could you clarify to us
Speaker:what menopause really is?
Speaker:And then obviously you
have mentioned already
Speaker:the terminology of perimenopause,
Speaker:so can you also touch
Speaker:upon that and let us
clarify these two concepts.
Speaker:- Of course.
Speaker:- You kind of already hinted towards this.
Speaker:So it's kind of actually a lengthy
Speaker:endocrine transition period which starts
Speaker:with the like progressive
failure of ovarian function.
Speaker:So I like to compare it like,
Speaker:or I always like to say to students,
Speaker:so adolescence is when the
hormonal systems go online
Speaker:after they went already went online once
Speaker:during foetal development and mini purity.
Speaker:But then menopause is
kind of the delayed stage
Speaker:where systems slowly go offline.
Speaker:But it's not that you turn a switch
Speaker:and everything is offline
and you stop having cycles.
Speaker:The system goes slightly offline
Speaker:because it's regulated via the HPG axis.
Speaker:I hope I don't mix up the German
Speaker:and the English observation,
Speaker:but basically the brain
regulates the ovaries
Speaker:and this kind of little
dance gets interrupted
Speaker:more and more and more, which leads
Speaker:to erratic hormonal fluctuations,
Speaker:which then eventually cease.
Speaker:And that's the end of the
menopausal transition.
Speaker:And as you nicely said,
menopause by definition
Speaker:is actually just one time point
Speaker:after you haven't had a
menstrual cycle for 12 months.
Speaker:But preceding that, that's
what we call perimenopause,
Speaker:which are years of increasing like levels
Speaker:of fluctuation.
Speaker:Normally in the early
perimenopausal stages,
Speaker:you get slightly more variations
Speaker:in menstrual cycle length,
Speaker:tentatively more towards shorter cycles.
Speaker:You don't really have symptoms yet
Speaker:but your menstrual cycle length varies
Speaker:and there's some hormonal markers
Speaker:which slightly start changing.
Speaker:Then in the late per menopausal stage,
Speaker:which tends to on average we
between one to three years,
Speaker:but they're varying accounts
Speaker:when it comes to the
actual length of that,
Speaker:that's where the cycle variations
Speaker:become a much more
pronounced, late perimenopause
Speaker:after the straw criteria
Speaker:are defined by like not having
a cycle for 60 plus days.
Speaker:And then that's when also symptoms
Speaker:start to emerge in the majority of women.
Speaker:And that can be sleep
disturbances, night sweats,
Speaker:hot flashes, but also
cognitive disturbances
Speaker:and depressive symptoms.
Speaker:And then menopause again, this is one day
Speaker:and then post menopause is kind of starts
Speaker:after one year of not having had
Speaker:a menstrual cycle for 12 months.
Speaker:So actually there's one point
Speaker:of menopause which is often used
Speaker:to name the whole transition
Speaker:is really assessed retrospectively
Speaker:when you can say, okay, no,
Speaker:after now I haven't had
a cycle for 12 months.
Speaker:But also again for a lot of women,
Speaker:this might not be textbook,
Speaker:like they might not have a cycle
Speaker:for one year but then it comes back.
Speaker:So this system kind of
trying to compensate,
Speaker:just having another cycle
and eventually it stops
Speaker:and then hormonal fluctuation
stabilise and are stably low.
Speaker:- Well I hope our listeners can appreciate
Speaker:just how complex this whole continuum
Speaker:of pre, peri and post menopause is.
Speaker:And obviously each stage is accompanied
Speaker:by different symptoms
Speaker:and you mentioned obviously
the vasomotor symptoms,
Speaker:which are those that are
related to hot flashes,
Speaker:night sweats, but also you didn't leave
Speaker:outside these cognitive symptoms
Speaker:that sometimes kind of
are pushed under the rug.
Speaker:And I would actually like to go
Speaker:a little bit into those ones.
Speaker:So what is the actual
neurobiological explanation
Speaker:behind those symptoms?
Speaker:'Cause obviously it varies.
Speaker:We have different centres in the brain
Speaker:that orchestrate different functions.
Speaker:So we have the hypothalamus
perhaps more related
Speaker:to this thermo regulation.
Speaker:So vasomotor symptoms.
Speaker:But what about these cognitive symptoms.
Speaker:And also we hear that a lot of women
Speaker:are experiencing really huge differences
Speaker:in their mood from what they used to be
Speaker:to how their mood or like even
their personality changes.
Speaker:So what do we know about that Claudia,
Speaker:in terms of the brain specifics?
Speaker:- Well we know the most, you
already kind of hinted at,
Speaker:is like the changes in firm of regulation
Speaker:due to kind of changes
in the hypothalamus.
Speaker:So that's also the most studied symptoms,
Speaker:when it comes to the cognitive symptoms
Speaker:and the repressive symptoms,
we don't know that much yet.
Speaker:We know that declining
Speaker:and especially volatility
like this volatile
Speaker:decline in oestrogen,
Speaker:it's not just like linearly declining.
Speaker:It's like really fluctuating erratically
Speaker:and oestrogen has multiple
functions in the brain
Speaker:but it's also a very potent modulator
Speaker:of neurotransmitter systems
which are very important
Speaker:for your mood but also
your cognitive function.
Speaker:So that would be one potential mechanism
Speaker:which could like explain disturbances.
Speaker:Then also this oestrogen
is neuroprotective
Speaker:and with its declining level
this like neuroprotection
Speaker:might be lifted and in some women,
Speaker:which then also can contribute
to more accelerated ageing
Speaker:but also kind of neurological decline
Speaker:due to structural changes,
mainly from animal work
Speaker:but also for some human studies.
Speaker:And I think Gillian might
say more about that later,
Speaker:but there are hint
stories like grey matter,
Speaker:white matter changes,
Speaker:Print was the first ones postulating.
Speaker:There might be this
bioenergetic shift in the brain
Speaker:that kind of what the brain uses
Speaker:as an energy source might shift.
Speaker:And because glucose metabolism changes,
Speaker:then there's this theory
Speaker:that away from glucose metabolism,
Speaker:it shifts to ketone body,
Speaker:like metabolising ketone bodies
Speaker:which are part of the white matter.
Speaker:And so it's like it's
a very complex system
Speaker:which is likely very tightly interlinked.
Speaker:And then any of these
changes might then contribute
Speaker:to mood disturbance
Speaker:and cognitive changes,
Speaker:especially if you already
are potentially genetically
Speaker:at risk if you have a certain lifestyle.
Speaker:So which might not provide resilience
Speaker:against these shifts
Speaker:and especially also when you already
Speaker:have a history of depressive disorders.
Speaker:Depression has been postulated
Speaker:as a very well established risk factor
Speaker:of Alzheimer's disease later in life.
Speaker:So it's very much tightly connected.
Speaker:But my main statement in this regard
Speaker:would be really structural changes,
Speaker:functional changes
Speaker:and particularly also changes
Speaker:in neurotransmitter functioning.
Speaker:- Wow, so all of these changes obviously
Speaker:expose that women's brain
to be more vulnerable
Speaker:to later life conditions and
neurodegenerative diseases
Speaker:because of these fluctuations in hormones
Speaker:that you mentioned and obviously
Speaker:the critical glucose
consumption hypothesis
Speaker:that has been presented by Brenton.
Speaker:So now I'd like to shift the microphone
Speaker:and give the floor to Gillian
Speaker:because I would like
Speaker:to talk about probably the
research area that we work in
Speaker:and the research area
that has been receiving
Speaker:so much interest in the
greatest scheme of menopause,
Speaker:which is Alzheimer's disease.
Speaker:So obviously we know that
women make roughly 2/3
Speaker:of all Alzheimer's disease cases,
Speaker:but obviously it's not just the longevity
Speaker:that explains all of
these staggering numbers,
Speaker:but it's actually the underlying biology
Speaker:and the also cognitive
trajectories that we see in women.
Speaker:And in the past decades we
have had this hypothesis
Speaker:of menopause really breaching through
Speaker:and suggesting that this
is due to the menopausal
Speaker:hormonal fluctuation, specifically due
Speaker:to the decrease in in oestrogen levels.
Speaker:So I would like
Speaker:to ask Gillian if you
could share some evidence
Speaker:specifically advocated
Speaker:for menopause being this
critical inflexion point
Speaker:in women's life that exposes her
Speaker:to increased susceptibility
for Alzheimer's disease.
Speaker:- Yeah, so just as Claudia
had beautifully taken us
Speaker:to there, we have this whole
like of events that happen
Speaker:around menopause and then you know,
Speaker:we as Alzheimer's disease researchers,
Speaker:we're studying women usually
in their kind of mid seventies
Speaker:and looking at levels of
these neurotoxic proteins
Speaker:that cause Alzheimer's
disease essentially.
Speaker:And so what we do is
we look at these women,
Speaker:we image them for these
neurotoxic proteins
Speaker:and then we look back to see
Speaker:how they experience menopause basically.
Speaker:Now typically we don't have data sets
Speaker:that can look at the fluctuations
Speaker:in the hormones around menopause
Speaker:and link them to later AD biomarkers
Speaker:like these neurotoxic proteins.
Speaker:But what we can do is we can look
Speaker:at how women experience menopause
Speaker:in terms of their menopausal
symptoms which will be proxy
Speaker:for those hormonal fluctuations.
Speaker:We can also ask them, you
know, when did they have
Speaker:their last period,
Speaker:which would be their age at menopause
Speaker:and then we can also
ask them whether or not
Speaker:they were treated for
menopausal symptoms with HRT.
Speaker:And so I guess one of the
things we've learned so far
Speaker:is that if women move into
this kind of menopausal
Speaker:or perimenopausal state
earlier than expected,
Speaker:so particularly before the age of 40
Speaker:or maybe between 40 and 45,
Speaker:those women seem to be at a higher risk
Speaker:for depositing these neurotoxic proteins,
Speaker:amyloid and tau later in life.
Speaker:So that association has been
shown in neural imaging studies
Speaker:but also shown in these, you
know, epidemiological studies
Speaker:that show that the age of menopause
Speaker:is associated with Alzheimer's
disease prevalence.
Speaker:Right, so then we look at the biology
Speaker:of what that link could be.
Speaker:In terms of hormonal fluctuations,
Speaker:we are writing grants at the moment
Speaker:and I do know a couple of
other scientists in the US
Speaker:who are writing grants to look
at how all of those events
Speaker:during perimenopause change
the women's brain structure
Speaker:and function in real time.
Speaker:So not necessarily
looking at women's brains
Speaker:down the line like we currently are doing,
Speaker:but in real time
Speaker:as the fluctuations in the
hormones are occurring.
Speaker:So some of the leading scientists
Speaker:in that area right now
would be Roberta Briton,
Speaker:but also, you know, Emily
Jacobs, they have a grant
Speaker:kind of basically looking
at exactly these questions.
Speaker:Also Caitlyn Castello,
Speaker:she's another scientist
who's very prominent
Speaker:in this area and then ourselves.
Speaker:So me and Rachel Buckley,
we're also proposing
Speaker:a grant to look at perimenopausal effects
Speaker:and how that implicates the brain.
Speaker:In terms of what we look at in the brain
Speaker:in menopausal women, we don't look
Speaker:for the proteins of Alzheimer's disease
Speaker:because it's very unlikely that they exist
Speaker:at that stage, right?
Speaker:So typically, if menopause
is going to increase
Speaker:women's risk of Alzheimer's
disease, we won't know
Speaker:that will have officially
happened until they are at the age
Speaker:where they can actually start
depositing these proteins.
Speaker:So what we instead look at
is these other risk factors
Speaker:that might suggest that
women are on the road
Speaker:to preclinical Alzheimer's disease.
Speaker:And so some of those things
Speaker:would be like more the plasma biomarkers.
Speaker:Also things like inflammatory
pathways, vascular pathways,
Speaker:looking at brain structure
and function of course
Speaker:and brain structure,
particularly in subfields
Speaker:of the hippocampus like the CA3,
Speaker:that would be a kind of region
Speaker:we'd be particularly interested in
Speaker:in these menopausal women.
Speaker:And then looking at, you
know, the structural integrity
Speaker:of white matter tracts,
those kind of things.
Speaker:So those biomarkers are
more likely to change
Speaker:due to menopausal changes.
Speaker:And then if they do change,
Speaker:that kind of puts the brain
in a more vulnerable state
Speaker:to deposit these neurotoxic
proteins later down the line.
Speaker:And it's really the proteins
Speaker:that underlie the actual onset of symptoms
Speaker:related to Alzheimer's disease, at least,
Speaker:of course there are other dementias
Speaker:but we focus mostly on Alzheimer's,
Speaker:so there's a lot to unpack.
Speaker:Basically the way we're
doing at the moment
Speaker:is, as I said, we're looking at,
Speaker:we have this big space of time
Speaker:between when women report menopause,
Speaker:menopausal symptoms and
their menopausal age
Speaker:and then we get pet scans
on them 15 years later.
Speaker:Whereas the way the field is moving
Speaker:is to actually do those imaging studies
Speaker:as the women are actually
going through menopause
Speaker:and that will be able to,
Speaker:that will tell us a lot more
basically about how menopause
Speaker:leads women at risk, potentially
could leave women at risk
Speaker:of cognitive decline later in life.
Speaker:- So we are seeing that definitely
Speaker:a lot of retrospective studies
Speaker:have laid this foundation
Speaker:where we are now knowing or
learning about how menopausal
Speaker:or menopausal related
factors are associated
Speaker:with later accumulation
of these toxic proteins
Speaker:but also of structural changes
that then also as you said,
Speaker:kind of lead the brain to
become more vulnerable later on.
Speaker:And you mentioned one
of the risk practises
Speaker:that you have done in
your research is actually
Speaker:the earlier age of menopause
Speaker:and most of the people
probably think of menopause
Speaker:as a natural process
as it comes to ageing,
Speaker:but obviously we have
different types of menopause
Speaker:such as surgical menopause.
Speaker:So could you maybe comment a bit on that?
Speaker:- Yeah, so I think the original hypothesis
Speaker:was that it was probably
surgical menopause
Speaker:that would be women at risk
and we're seeing in our data
Speaker:or at least the data sets we work with,
Speaker:if not so much the fact
Speaker:that it was a surgically
induced menopause,
Speaker:it's more just that the
menopause was early, right?
Speaker:So you get this earlier than expected
Speaker:deprivation in circulating
estrogens, et cetera.
Speaker:And then the fact
Speaker:that this happens earlier than it should
Speaker:is kind of having the detrimental effect,
Speaker:as opposed to it being
surgically induced as such.
Speaker:At least that's what we're seeing
Speaker:in the data we look at
Speaker:from the Alzheimer's disease perspective.
Speaker:But just by nature of having a
surgically induced menopause,
Speaker:then that is likely happening
earlier than the average age
Speaker:of menopause, which is 50, right?
Speaker:It it's probably happening
before the age of 45
Speaker:if not before the age of 40.
Speaker:So I think, you know, when we do
Speaker:kind of interviews we also say
Speaker:it is important for women
Speaker:to always kind of know what's happening
Speaker:with their reproductive health
Speaker:and know if they're getting, you know,
Speaker:surgically induced menopause
that that is happening
Speaker:for the right reasons
Speaker:or at least it's really
necessary in their case
Speaker:'cause it can have implications
for women brain health
Speaker:and then you know, the brain
health later down the line.
Speaker:- Okay, so obviously that
becomes less clear then,
Speaker:it's not just again
Speaker:the type but maybe the age
Speaker:but then again maybe there
is something behind that
Speaker:that we don't know yet
Speaker:and probably we don't know how to quantify
Speaker:because historically the data
sets that we are working on,
Speaker:they don't collect that data
Speaker:or if they collect, it's not to the extent
Speaker:that we would like to.
Speaker:So I would like to now move a
little bit from what we know
Speaker:to what we will know
based on both of the work
Speaker:that you are doing and
specifically maybe talking
Speaker:a little bit about the
historical blind spots
Speaker:in terms of the methodologies,
these ageing cohorts
Speaker:or Alzheimer's disease
cohorts have been using.
Speaker:So obviously like we know like ADNI
Speaker:which is Alzheimer's Disease
Neuroimaging Initiative,
Speaker:but we also have more huge data sets
Speaker:that are looking specifically
Speaker:into how individuals
Speaker:develop Alzheimer's
disease from preclinical.
Speaker:So this asymptomatic stage
where the proteins start
Speaker:to accumulate but yet in the absence
Speaker:of any cognitive symptoms,
Speaker:but none of these data
sets have considered
Speaker:sex specific variables
Speaker:or perhaps to a very, very brief extent.
Speaker:And why do you think that
was the case potentially,
Speaker:and then the follow up
question, what would be
Speaker:your kind of perfect list
of reproductive variables
Speaker:that you would like to
include in your studies?
Speaker:Because I know both of you
are spinning big brands now.
Speaker:So let's start with Claudia
Speaker:and then go to you Gillian
with your wishlists.
Speaker:- So yeah, that's a good question
Speaker:because like I've in the past
mainly used like UK Biobank
Speaker:which is a big UK based population sample
Speaker:covering 500,000 individuals
Speaker:and the nice thing of the UK
Biobank it started collecting,
Speaker:so inclusion ranges
between like 40 and 70,
Speaker:which again is already
like actually a bit younger
Speaker:than the most ageing cohorts,
Speaker:which normally starts at the age of 65
Speaker:historically rooted into
based on the retirement age
Speaker:in most countries.
Speaker:And the UK Biobank
Speaker:actually does cover the
menopause transition,
Speaker:but it has surprisingly little variables
Speaker:on this particular aspect
Speaker:and has no variables about symptoms.
Speaker:And also it's really hard,
we tried multiple times
Speaker:to varying degrees of success,
Speaker:to really establish if women in this court
Speaker:perimenopausal.
Speaker:So yeah, simply knowing
if women have symptoms,
Speaker:if they had symptoms as Gillian said
Speaker:and that they ask retrospectively,
how did you experience
Speaker:the menopause transition
is super important
Speaker:'cause that varies a lot
and, and there is more
Speaker:and more indication that
the severity of symptoms,
Speaker:the number of co-occurring symptoms,
Speaker:what kind of co-occurring symptoms,
Speaker:how long they last
might really be critical
Speaker:for how women might age later in life.
Speaker:So like questions around that
are really, really important.
Speaker:Then past reproductive history
we have found associations
Speaker:between a number of life births
Speaker:and the ageing brain later in life.
Speaker:So these kind of variables
are really important
Speaker:if women have used hormonal contraception,
Speaker:can be very insightful to
know for later brain ageing.
Speaker:And so there's like, yeah,
Speaker:like now that I'm starting acquiring data
Speaker:across perimenopause,
Speaker:like I'm setting up this like
massive baseline questionnaire
Speaker:about reproductive factors
Speaker:and past histories and aged menarchy
Speaker:and like trying to really kind of map out
Speaker:all the reproductive years
Speaker:as kind of comprehensively as
possible to really kind of see
Speaker:what we found in the UK
Biobank, if that replicates
Speaker:but also how that informs
how women actively life
Speaker:as Gillian said earlier,
experience perimenopause.
Speaker:So my grant really also
kind of has a strong focus
Speaker:on like symptom mapping.
Speaker:So we are using an industry partnership
Speaker:to have an app really for
the participants to be able
Speaker:to on a daily basis record
their their symptoms
Speaker:and their experiences
Speaker:because I think that's a
really big, big missing part
Speaker:in all of these cohorts.
Speaker:It's first of all that symptoms
are not really acknowledged
Speaker:but also it's mainly you have one,
Speaker:two, three maybe time points.
Speaker:So having also more densely sample data
Speaker:across these critical inflexion points
Speaker:is really, really needed.
Speaker:And I'm really happy to see the trend
Speaker:towards like focusing on perimenopause
Speaker:and then focusing on longitudinal studies
Speaker:during perimenopause
Speaker:because I got money to do my part
Speaker:but we need like
comparable samples globally
Speaker:so we can really look
for robustness of effects
Speaker:and generalizability of effects
Speaker:and also to be able to tap
into biopsychosocial aspects.
Speaker:How does it differ between countries?
Speaker:Does it differ between healthcare systems?
Speaker:How kind of the experience
of perimenopause,
Speaker:transition impacts ageing later on life.
Speaker:And there are already
kind of some indication
Speaker:not from imaging studies
Speaker:but more also from when it comes
Speaker:to attitudes towards
menopause and mental health
Speaker:because of attitudes towards might differ
Speaker:between societies and
between societal structures
Speaker:and between potentially the western
Speaker:and kind of the global
north and the global south
Speaker:and all these kind of differentiation.
Speaker:So it's nice we are
going in this direction
Speaker:of having more varied approaches
Speaker:although it is still kind of clustered
Speaker:to the global north I have to admit.
Speaker:But yeah, that's more symptoms,
Speaker:more dense sampling
Speaker:and ideally in the long run,
also much more diverse samples
Speaker:which is not just white women.
Speaker:- Thank you so much for
sharing your study as well
Speaker:and what you're gonna be doing
Speaker:with this highly phenotyped cohort.
Speaker:And you were obviously saying
Speaker:that this is the global north
Speaker:but since we were talking about Germany
Speaker:and European perspectives
because of your study
Speaker:and my curiosity is what is
the situation on the other side
Speaker:of that Atlantic ocean and
how are you gonna measure
Speaker:and quantify your participants Jillian?
Speaker:- Yeah, so where to start really?
Speaker:So I think, well when
it comes to you know,
Speaker:what we would ask women,
Speaker:Emily Jacobs is actually putting together
Speaker:this standardised questionnaire,
you guys know about it.
Speaker:It's where all researchers
in, you know women's health
Speaker:can basically use the
standardised questionnaire
Speaker:which really covers the scope
Speaker:of things related menopause,
timing, symptoms, et cetera,
Speaker:but also hormone therapy type
of hormone therapy dosage,
Speaker:you know, et cetera.
Speaker:So I think that will probably
be incredibly valuable
Speaker:to the field at large
Speaker:and probably also using a global scale,
Speaker:not just necessarily in North
America I wouldn't think.
Speaker:And so the interesting
thing about women's health
Speaker:is that, you know, in maybe 10 minutes,
Speaker:we can acquire a huge amount
Speaker:of data on women's reproductive health,
Speaker:at least by participant self-report,
Speaker:which has some limitations
Speaker:but it still would be an awful lot better
Speaker:than kind of the relatively sparse amount
Speaker:of data we have on Women's
Healths from these big data sets
Speaker:that we work on at the moment.
Speaker:So there's been a big push for, you know,
Speaker:studies like a acne,
the Wisconsin Registry
Speaker:of Alzheimer's Prevention, the
Harvard Ageing Brain Study,
Speaker:all of these kind of open access data sets
Speaker:to start including these questionnaires
Speaker:as part of their screening processes.
Speaker:And so I think there is
a shift towards that now.
Speaker:So in the next five years in particular,
Speaker:I think we'll have a whole
host of kind of new data
Speaker:that we can work with
from those data sets.
Speaker:In terms of new studies that
we're doing, a lot of it
Speaker:is collecting blood samples from the women
Speaker:as they go through perimenopause.
Speaker:So these are more focused studies
Speaker:on you know, menopause AD link
Speaker:and then also using those blood samples
Speaker:to run new, which can basically allow us
Speaker:to capture all of these
kind of inflammatory
Speaker:and vascular pathways
Speaker:and potentially cope
apologies too like TBD 43,
Speaker:and things beyond just
Alzheimer's disease.
Speaker:So I think the studies
that we're designing now
Speaker:specifically to look at menopause,
Speaker:we'll be relying heavily on blood samples
Speaker:and looking at hormone levels
Speaker:and all of these other biomarkers.
Speaker:But you know, when we
think about these current
Speaker:big scale data sets that are out there,
Speaker:just bringing in these
women's questionnaires
Speaker:will also open us up to
a whole kind of new field
Speaker:of data analysis.
Speaker:- Thank you so much and
obviously your wishlist
Speaker:allows, you know, all of our listeners
Speaker:who are also potentially thinking
Speaker:about conducting such studies,
pay attention to variables
Speaker:that you have mentioned today.
Speaker:I also thought about
something that Claudia,
Speaker:you mentioned about the
industry collaboration.
Speaker:This is not still a common practise
Speaker:in research environments.
Speaker:Could you tell us how is your journey
Speaker:with establishing that collaboration
Speaker:and how that collaboration will help you
Speaker:and how you using those industry supports?
Speaker:- I kind of used to say when
people ask me about that
Speaker:that I'm just lazy
Speaker:because I don't need to reinvent the wheel
Speaker:or if they're much people out there
Speaker:already kind of doing the work,
Speaker:'cause for my study, like
we have repeated imaging,
Speaker:we have repeated blood samples
Speaker:and we have like all
the standards we've done
Speaker:in previous studies but
then I was like, okay,
Speaker:how do we actually like
really tap into symptom
Speaker:and experiences and there is already
Speaker:apps out there doing that.
Speaker:And so I reached out to Clue,
Speaker:which is a Berlin based menstrual cycle
Speaker:tracking app startup.
Speaker:And finally when I wrote my grant in 2023,
Speaker:like they just released a
perimenopause mode in September
Speaker:and my deadline was in November
Speaker:and then I just texted them
Speaker:and said like I'm preparing this grant,
Speaker:I just saw you release this board,
Speaker:I would love to use
that in my participants.
Speaker:Would that be like,
Speaker:are you interested in
collaborating and so on so forth.
Speaker:And they were super open
so it was like very easy
Speaker:and gave me a letter of support.
Speaker:I budgeted for that.
Speaker:And so it was like a nice story
Speaker:and now we are kind of going back
Speaker:and forth also how we could
use already acquired data
Speaker:and other kind of angles to really using
Speaker:the data these EmTech startup,
digital EmTech startups
Speaker:already collecting based
on their user base.
Speaker:And Clue has a very nice kind of setup
Speaker:where like in app you also already use
Speaker:if you like already ask if you want
Speaker:to participate in
scientific research studies.
Speaker:So that was really reassuring
Speaker:so that they already have
Speaker:very strict pipelines for research
Speaker:and also very pragmatically
for my context being in Europe
Speaker:because it's a Europe based startup,
Speaker:it also follows all the kind of GDPR,
Speaker:which is like privacy
law regulations in EU.
Speaker:So that was also very
attractive for me personally,
Speaker:knowing that they would follow
Speaker:the data protection standards
we would need for research.
Speaker:So for me that was a win-win.
Speaker:- That's really inspiring to hear
Speaker:that you have had a
really positive experience
Speaker:and obviously since we are talking
Speaker:about really highly dense
sampling methodologies
Speaker:for our symptoms and
potentially biomarkers,
Speaker:I think also the future
Speaker:of research and especially
women's health research
Speaker:should move from just
laboratory based studies
Speaker:to more remote settings.
Speaker:And these platforms, these
collaborations would allow us
Speaker:to collect the data,
whether it's symptoms,
Speaker:whether it's some type
Speaker:of sleep measures from the wearable device
Speaker:or even like blood-based biomarkers
Speaker:that obviously could be done
through the health providers
Speaker:and then they could put the information
Speaker:related to the sampling
time on their application.
Speaker:So I think there's
definitely way more bridges
Speaker:that need to be billed between industry
Speaker:and research in order to
propel what we are doing.
Speaker:And maybe fast track a little
bit more in the future.
Speaker:So our time is running away today,
Speaker:but it's been a really rich
Speaker:and great conversation about the menopause
Speaker:and why this midlife transition
has been really important.
Speaker:(upbeat music)
Speaker:Before we close, I would really like
Speaker:to just bring one personal
question to each of our speakers.
Speaker:What does women's brain health mean to you
Speaker:briefly in one sentence?
Speaker:Personal Claudia.
Speaker:- It means ageing gracefully
and as best as possible
Speaker:and by more research we can do that.
Speaker:- Beautiful, Gillian.
Speaker:- I think women's brain health for me
Speaker:means sort of the forefront of research
Speaker:and really coming out of the rug
Speaker:and understanding everything there is
Speaker:to understand about women's brains.
Speaker:- Thank you, so that's
it for the second episode
Speaker:of XXplored, a huge thank
you to both Dr. Claudia
Speaker:and Dr. Gillian for your insights
Speaker:and really taking us through
this difficult period
Speaker:in women's life.
Speaker:But hopefully it's just
brought a bit more light
Speaker:and a little bit more understanding.
Speaker:And as I reflect on the things
that we have discussed today,
Speaker:there are a few points
Speaker:that kind of really struck a chord in me.
Speaker:And one of them is both your research
Speaker:and what you're doing on
opposite sides of the world,
Speaker:trying to bring the woman's brain health
Speaker:and specifically during that
critical vulnerable period
Speaker:where it coincides with
Alzheimer's, preclinical stages
Speaker:of the disease and the
multitude of methodologies
Speaker:that you are using and trying
to navigate the questions
Speaker:that you are posing from multiple angles.
Speaker:And I think that just kind of highlights
Speaker:how still under researched this area is,
Speaker:but with having such work
coming up in the future,
Speaker:I'm definitely feeling a bit more assured
Speaker:about my own brain health
Speaker:and also the health of
our parents hopefully.
Speaker:And then another also
aspect that probably also
Speaker:our listeners are gonna leave with
Speaker:is that it's not just that one time
Speaker:during the women's reproductive phase
Speaker:and it's not just the menopause,
Speaker:it's not just the stop
in the menstrual cycle,
Speaker:it's not just the drop in oestrogen,
Speaker:but it's actually the
lifetime exposure of oestrogen
Speaker:through variables such
as number of children
Speaker:also the age at Menarchy,
different pregnancy complications,
Speaker:and as well as other
risk factors that happen
Speaker:during the whole life
that all kind of shape
Speaker:a woman's brain and may
increase ones' risk.
Speaker:So thank you once again for
this great conversation.
Speaker:I really hope that both of you
can reconnect in conferences
Speaker:and also we can bring more research
Speaker:from these great ideas.
Speaker:- Thank you very much for
this nice conversation.
Speaker:- Thank you Laura.
Speaker:- So I'm Dr Laura Stankeviciute
Speaker:and you have been listening
Speaker:to XXplored, Women's Brain Health
Speaker:on the Dementia Researcher Podcast.
Speaker:(upbeat music)
Speaker:- [Voice Over] Thank you
for listening to Xxplored,
Speaker:Women's Brain Health podcast
from Dementia Researcher,
Speaker:with generous support from the
National Institute for Health
Speaker:and Care Research,
Alzheimer's Association,
Speaker:Alzheimer's Research
UK, Alzheimer's Society,
Speaker:and Race Against Dementia.
Speaker:From hormones to cognition,
from risk to prevention,
Speaker:we feature conversations
with researchers, clinicians
Speaker:and change makers working
to challenge assumptions
Speaker:and close the gaps in how we understand
Speaker:and support the female brain.