[laughs]

Yes.

So we are now following our patients over time, and the results are not published yet, but what we do find, and this is until peer review allows publication, um, we do find at least descriptively that it depends.

So after menopause, there can be different outcomes.

For some women, cognition rebounds.

In other studies, clinical studies have shown that, that after the final menstrual period, there's still the early post-menopausal phase where the brain is kind of settling down.

It's trying to adjust.

Okay, so-

How are puberty and pregnancy relevant to menopause?

Yes, and I find this so important to talk about it.

So puberty, pregnancy, and perimenopause are all neuroendocrine transition states, which is a mouthful, but it's really, it's, it, it means that the brain and the hormonal systems are changing at the same time.

And it's the same system.

The women are born with a neuroendocrine system that directly connects the brain with the ovaries, and this is one of the most important systems that we have in our entire bodies.

And this system is turned on at puberty with the arrival of sex hormones, and then it's really boosted during pregnancy, should the woman get pregnant.

It crashes after, um, pregnancy, during the postpartum phase, and the brain needs to adjust another time.

Why is that?

Mm-hmm

... as scientists.

It was only in the '70s that scientists found that the same hormones actually had a lot of functions in the brain.

So they're not just sex hormones.

They're actual hormones that have...

They're brain hormones, you know? And it, especially estrogen, um, is called, what we call it, the master regulator in the female brain because it's in charge of a number of functions from, uh, immunity.

It really boosts your immune system inside the brain.

so where would you begin with that?

So

women seem to be more vulnerable to stress, and I think one connection is that stress is basically just this hormone, cortisol, which is the main stress hormone, that works in tandem with your estrogens.

So if your cortisol goes up, your estrogens go down.

If your cortisol goes down, your estrogens go back up.

So if you're constantly under stress, the body will try to steal the precursor to both cortisol and estrogen, which is called pregnenolone.

and shift the metabolism towards cortisol production.

So it sinks your estrogens to make more of the stress hormone, which is fine as long as the stress is temporary.

right

But

medicine has been historically gender biased.

So a lot of the information we have really derived from studies in men.

So the recommendations that we give patients and the guidelines that we use to diagnose certain diseases are really based on symptoms that are more prevalent in men than in women.

Cardiology is a good analogy from a different field.

We know that women are seven times more likely to be discharged in the middle of a heart attack as compared to a man having a heart attack.

And that is because doctors are trained to recognize the male symptoms of a heart attack, which is the very sudden chest pain and the pain shooting down the left arm.

So when we're thinking about those foundational pillars, where do we start?

Like you go to a sushi restaurant and see salmon roe?

Yes, perfect.

Salmon roe is fantastic.

It basically mirrors the nutritional composition of the brain.

It's very rich in polyunsaturated fatty acids, especially the omega-3 fatty acids that your brain needs on a daily basis.

It contains a good amount of essential protein.

So all the amino acids that the brain has gates for are in there.

affecting us and our children.

So walk everybody through the images.

Yes.

So these are three brain scans of three different women.

One is premenopausal, one is perimenopausal in the middle, and the last one is postmenopausal, early postmenopausal, 52.

And what we're looking at is the way that the estrogen tracer binds to estrogen receptors in the brain.

What's important to know is that estrogen receptors are everywhere....

in the brain, but they're more abundant in some regions than others.

And what is the question you're trying to answer?

So your grandmother took on the caretaking?

Yes.

Effectively, I was almost always with my grandmother.

And I remember her just being my grandmother, and then at some point, when I was about to graduate from university and start my PhD, um, she started showing signs of cognitive decline.

That was shocking because she was always as sharp as a tack.

But that led to at least a decade of dealing with progressive cognitive decline, Alzheimer's symptoms, dementia symptoms, like you mentioned, hallucinations, which is usually a sign of mixed dementia with some Lewy body components, which was the case for my grandmother as well, and she ended up spending at least years, her final years, in bed, clearly not enjoying her life, and that was the most heartbreaking part, you know, the, the helplessness.

And for my mother, who was the primary caregiver, I was already in the United States at that point.

who's-sitting at home right now listening to this and, and feel scared, what do you wanna say to her about her health, her brain health and, and moving forward?

Carvana.

Delivery fees may apply.

[mellow music] This brings us to this moment where we're talking a lot about the physiological changes and psychological, because as you've described in your research for so long, this affects the brain, too.

And I think a lot of times, you know, initially the thought was, well, this is a change that happens in hormones, in, uh, reproductive systems.

And what you're really saying here is this is actually neurological, this is neuroendocrine.

This is, like, both...

The, the brain is deeply affected.

Give me some context here.

Would you agree with that way to think about them, and how do you think of the suite of different radiographic studies that can be used?

Yes, I think what's most important is what you're measuring.

You can use different tools to measure different things, and the really good definition is whether you're looking for structure information, for functional information, for biochemical or pathological information.

With MRI scans, what you can do is look at the anatomy of the brain for sure.... is to look at volumetrics.

You want to make sure that some parts of your brain are really nice and dense with neurons, whereas if we find signs of atrophy, that could be a risk factor for future dementia.

Like, there's one part of the brain that we always look at, is the medial temporal lobe, which is a combination of structures that are quite primitive, if you will, and that are highly involved in memory function and also emotional regulation.

And there's one structure in particular, the hippocampus, which is considered a biomarker for Alzheimer's risk, because the hippocampus, you really want it to be as big as possible.

Yeah.

And that may be when men would start experiencing hot flashes, a lot of those vasomotor symptoms, brain fog, etc., What are you seeing on these scans that are kind of reinforcing this progression neurologically and physiologically as we're navigating into menopause?

What we're seeing is that menopause is a neurologically active state.

where many different functionalities of the brain are subject to change.

And by doing brain scans in women who are either at different stages of the menopause transition, or by following the same woman over time, which I find fascinating, we're able to map out changes that are associated with the menopause transition.

And what we have found is that number one, yes, menopause clearly has an impact.

on many different functionalities inside the brain, chiefly synaptic volume or gray matter volume, white matter volume as well, metabolic activity, which we measure in different ways.

And I'll tell you more about it because I think it's relevant to your line of work as well.

And then we go to Women's Health Initiative and things shifted quite extraordinarily.

is it about women's brains that are so unique that this seems to be a problem more for women than for men?

Yes, there are many things that make women's brains really unique.

And I think a big determining factor is really hormonal health.

Because I think it's very helpful to think of brain health as impacted by a number of factors.

Like you have your genes, you have your DNA, you have your lifestyle, you have your medical health, you have your environment, you have your hormones.

And all these factors really act synergistically to determine a person's risk of Alzheimer's.

But at the same time, a person comes with allies.

How important for women is working out for brain health?

Mm-hmm

...

in women's brains.

It's involved in a number of functionalities that have nothing to do with having kids and everything to do with having a healthy brain.

That's endogenous estrogen.

It's the estrogen your body makes for a reason.

The reason being that the system, the neuroendocrine system, is active and responds to estrogen.

Mm-hmm.