December 2, 2025 • 52 mins
Almost two-thirds of people diagnosed with Alzheimer’s are women. Shifting hormones make us especially vulnerable. But what if there were ways to lower your risk? Preventive neurologist Dr. Richard Isaacson believes nearly half of dementia cases can be avoided. He shares how to know if you’re at risk for Alzheimer’s and what steps to take for better long-term brain health.
Links to resources mentioned in this episode:
Individualized clinical management of patients at risk for Alzheimer’s dementia
Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function
Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission
Clinical Application of APOE in Alzheimer's Prevention: A Precision Medicine Approach
Association of Reproductive History With Brain MRI Biomarkers of Dementia Risk in Midlife
Sex-driven modifiers of Alzheimer risk: A multimodality brain imaging study
The Institute for Neurodegenerative Diseases (IND)
Note: In this show, we use “women” as shorthand for people with XX chromosomes. We understand sex and gender are more complex, and acknowledge the experiences we describe reach beyond that word.
See omnystudio.com/listener for privacy information.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:17):
Pushkin. Hi everyone, Doctor Poyter here, I'm popping in to
let you know that we're working on a special episode
of Decoding Women's Health. We're i'll be answering your questions
about one of my favorite topics, hormone therapy. If you've
been wondering about the different types of therapy, when it
(00:39):
might make sense to start possible side effects are really
anything else? This is your chance to ask. You can
leave us a voicemail at four FI five two one
three three eight five, or send an email to Decodingwomen's
Health at Pushkin dot fm and let us know if
you'd like to stay anonymous, or if you're up for
(00:59):
having your voice featured on the show. I'm so excited
for this one. Hormone support is such a misunderstood area
of medicine, and there's a ton of new and fascinating
research to talk about together. I can't wait to hear
what you're curious about.
Speaker 2 (01:16):
This show is not a substitute for professional medical advice, diagnosis,
or treatment. It is for informational purposes. Please consult your
healthcare professional with any medical questions.
Speaker 3 (01:32):
Genes are not our destiny. The field of Alzheimer's disease
is changing so rapidly, the things that I can talk
about now like I couldn't even dream about ten years ago.
Speaker 1 (01:42):
Welcome back to Decoding Women's Health. I'm doctor Elizabeth Poynter.
Today on the show. We're talking about dementia prevention and
long term brain health. If you've ever cared for a
loved one with Alzheimer's, you know the emotional toll. You
watch someone you care about lose memories, abilities, and pieces
of who they are, and somewhere in the back of
(02:05):
your mind, a quiet fear grows, what if this happens
to me? For women, that fear is statistically grounded nearly
two thirds of people diagnosed with Alzheimer's or female. One
of the most frustrating realities of the disease is that
there is no cure, but what if prevention were possible?
(02:27):
Doctor Richard Isaacson has devoted his career to answering that
very question and to helping people understand what they can
do right now to reduce their risk. Doctor Isaacson is
a preventive neurologist at the Atria Health and Research Institute,
and he is also the director of the Institute for
neurodegenerative diseases, where he is doing groundbreaking research studying brain
(02:52):
biomarkers for Alzheimer's and dementia. He is also the founder
of the first ever dementia prevention program at wild Cornell.
He has been a pioneer in this area for a
long time, and I'm so excited to talk with him
today about something we both care so deeply about brain health.
Speaker 3 (03:13):
So I'm a preventive neurologist, and most people haven't heard
that term because it's not a common term. It's like
a handful of us. We need an army of preventive
neurologists because most neurological diseases, brain diseases start silently decades
before symptoms, and that's kind of when we should intervene.
And just like you know, when a person has a
heart attack or a stroke, that problem, the vascular problems
(03:35):
and the atherosclerosis and all that it built up over decades,
and it's the same thing with brain disease. So I think,
you know, instead of being a reactive neurologist, I want
to be a proactive neurologist, and that's what preventative neurology
is all about.
Speaker 1 (03:47):
I first heard about doctor Richard Isaacson, and when I
came across his research on how nutrition and lifestyle interventions
could help protect the brain against Alzheimer's disease. He had
a strong personal motivation. Several of his close relatives had
developed Alzheimer's and he was determined to find a way
to prevent its development. I was immediately intrigued. For the
(04:09):
first time, felt like there might be real hope to
offer my patients who had a family history of the disease.
I reached out and we soon began collaborating. We were
both early believers in the potential protective role that hormone
therapy could play for the brain, and today we're colleagues.
His approach to dementia prevention has gained significant recognition in
(04:31):
recent years, but when he began it was anything but mainstream.
Many in the medical community were, let's just say skeptical.
So you started the first Alzheimer's prevention clinic and preventive
brain health clinic. That was revolutionary at the time. It
still is a concept that a lot of people don't
(04:52):
speak about enough. How did you come up with that idea?
Where did that come from?
Speaker 3 (04:56):
Yeah, so you know, you said revolutionary. I thought the
first word you were going to say it was controversial
or that was.
Speaker 1 (05:03):
My next sentence. Yeah, I was like, why was it
so controversy? That's my next question.
Speaker 4 (05:06):
Okay, gotcha.
Speaker 3 (05:07):
So yeah, what I would say is two thousand and
nine was when I saw my first, like my first
Alzheimer's prevention patient. And you know, I see people with
dementia and I see family members sitting next to them.
And one of these family members was a physician, and
he said, hey, Doc, this is tough, and I know
(05:27):
you've been affected by this, Like is there anything, like
what can we do? Because he knew that I have
a family history and obviously he has a family history.
And I spoke with forty five minutes in the hallway
about things that, you know, maybe he could do. Talked
about exercise, and talked about nutrition, and talked about Omega
three fatty acids, and you know, there was like a
list of things, and that conversation just turned into you
(05:49):
know what, why don't you come back and maybe we
can check some labs and maybe I can help you
through this. And then I saw that person's sister. And
then later that same week, doctor Arthur Agatson, who was
one of the first preventive cardiologists. You know, people know
his name because of the South Beach diet. And he
referred me a patient whose father had Alzheimer's disease and
he didn't want to get it. And that's when everything
(06:11):
kind of clicked, you know, three times in one week.
I was talking to a person about how to protect
themselves potentially from developing Alzheimer's, and I said, this is
what I need to do.
Speaker 1 (06:21):
How do your colleagues react to this? We work in
a system of you know, sick care and reactive care
and trade a disease, and you're preventing something that we
were taught isn't necessarily preventable at the time.
Speaker 3 (06:33):
Yeah, I mean one person called it hogwash. One person
who I love, a really nice guy, like, you know,
Isaac's I don't get you, man. You know you're a
good guy, But why are you trying to peddle this stuff?
Like what are you trying to sell?
Speaker 1 (06:48):
Man?
Speaker 3 (06:48):
This is snake oil. You're selling empty promises. And I
was like, but I really believe it. And then he said, well,
go study it and.
Speaker 4 (06:56):
Go prove it.
Speaker 3 (06:56):
And I said, h call the action. Better go study
it and go prove it. And that's when I kind
of went on this road show to figure out, like
where could I go to prove it? Because when I
was at the University of Miami, I wasn't able to
build a practice for prevention and do all the things
that I needed to do. So that's when I started interviewing,
and I interviewed in Boston and New York and the Midwest,
and honestly, the only place that would allow me to
(07:17):
put my kind of flag in the ground with an
announcement to say Alzheimer's prevention clinic was at a wild
Cornell in New York Presbyterian.
Speaker 1 (07:24):
So how long did it take you to say I'm
really onto something here with what I'm doing.
Speaker 3 (07:28):
Well, I'll start by saying the fact that people could
come to see a doctor and talk to someone that
was a net positive for a lot of people. They
felt like they had agency, they felt like they had
some control. Now, you know, I have a saying that
I say a lot promise, not to overpromise. Back then,
(07:51):
you know, I made no promises, But what I said is,
you know, if we can improve your heart health, improve
your vascular health, improve your metabolic health, and later down
the road turns into better brain health, than that's worth it.
And back then I didn't have blood tests biological markers
like we do now. We had cognitive tests, and these
were early days, and you know, took us a long
(08:12):
time to prove that these cognitive tests were right. But
we were showing in like the late you know, twenty ten, nine, ten, eleven, twelve,
that people that took the baseline cognitive tests and then
came back after they controlled these risk factors actually had
improved cognitive function.
Speaker 4 (08:28):
And to me, that was it.
Speaker 3 (08:30):
That was the thing where I said, Aha, their blood
pressure is better, there's all these vascular measures that are better,
and their cognitive functions better. Maybe this is real. I
want to go try and study this improve it. Initially,
eighty percent had dementia and twenty percent of my clinic
was for prevention, and then little by little its switched.
Then it was twenty percent dimension, eighty percent prevention. Then
I switched to prevention full time in twenty thirteen.
Speaker 1 (08:52):
I sent you a lot of patients when you first opened.
Speaker 4 (08:54):
Co managing patient. I learned a lot from you.
Speaker 1 (08:56):
I was like a big believer. I'm gynecologist who loves
brain help and so appreciated your care of our patients.
Speaker 3 (09:04):
And honestly, if it wasn't for that, I wouldn't have
made a pivot. We did brain imaging in women. We
in a structure way, like focused on women's brain health.
And you know, women get Alzheimer's more likely than men. Right,
two out of three brains affected by Alzheimer's or women's brains.
Speaker 4 (09:19):
We don't know why.
Speaker 3 (09:20):
I always said it was age, women live longer, right, Well, no,
that was wrong. And basically because of all these questions,
half of my time was spent, which it should be
half the population, but half of my time more than yeah,
more than half of my time was spent on trying
to figure out the answers to these questions.
Speaker 1 (09:39):
Just for our listeners, let's talk a little bit about,
like what are the risk factors for dementia and Alzheimer's disease?
Speaker 3 (09:45):
Sure, so, the number one respector for Alzheimer's disease and
dementia's age advancing age and as we get older. You know,
it's not exactly like fine wine. Things do happen as
we age. Our brains age too, and when it comes
to women's brains, women's brains, age at I would say
different rates than men. I think that has to do
with in part this estrogen drops during the perimenopost transition.
(10:07):
I think that triggers accelerated brain aging. And I believe
that one of the most powerful things that we can
do during the perimenopaust transition for these women is to
consider hormone replacement therapy. I think that age and the
perimenopaust transition are the two biggest risk factors in some ways,
plus obviously having a gene that increases risk. Obviously you
(10:28):
can't change your genes, can't choose your parents necessarily, But
what you can do is you can change your lifestyle
when it comes to modifiable risk factors. I believe that
the majority of the negative effects of the life that
we live can overcome that risk, and genes are only
part of the story. The femal biological sex is only
(10:51):
part of that story. And I believe through living a
brain healthy lifestyle, we can attenuate or neutralize most of
those other risks.
Speaker 1 (10:57):
Actually, I want our listeners to understand a little bit
about apoe four, like what is apou four and who
should be tested? Should everybody be tested, or just if
you have a family history.
Speaker 3 (11:06):
Talk to us about that great question. So, for everyone
out there that has not heard about apo e, a
poe is a gene. You get either a two, a
number three, or a number four from Mom, and you
get a two, A three, or four from Dad. Apoe
three is neutral, Apoe two is protective, and a pox
four increases risk. So everyone out there, everyone is either
(11:29):
a most commonly three three, which is about fifty five
percent of the population. Three three is neutral risk. So
if a person has one copy of an eight POE
four variant from Mom or Dad, that increases risk a
little bit of Alzheimer's disease. If a person has two
copies of the a POI four variant, so one four
from Mom, one four from Dad, then that risk is higher.
(11:50):
But but, but please, genes are not our destiny. We
can win the tug of war against our genes. And
what I mean by that is this is not a
genetic combination that definitively leads to Alzheimer's. Does it increase risk?
Speaker 4 (12:04):
Sure?
Speaker 3 (12:04):
Can you neutralize or negate or you know, account for
a lot or most of that risk by doing brain
healthy things and living a brain healthy lifestyle. I absolutely
believe that to be the case, whether it's sixty percent,
seventy percent, eighty percent, or ninety percent of that dad
Apoi four risk. I think most of that risk can
be neutralized by brain healthy living, modifying risk factors. And
(12:28):
I believe that people with this genetic combination should kind
of follow a different path on the road against Alzheimer's disease.
You know, forty five percent of dementia cases may be
preventable if that person does everything right. And that's based
on the twenty twenty four Lancet Commission. So I believe passionately,
yet in a controversial you know, want to be clear
(12:48):
that this is not maybe the exact accepted you know framework.
I think it's really important for people that want to
know to know and to find out. And if a
person has an Apoi four, okay, let's do it, let's fight,
and let's go. For example, women with one or more
copies of the Apoi four variant, I start looking at
their estra dial levels or estrogen levels in the blood.
(13:09):
If that starts dipping even sometimes before perimenopausal symptoms, maybe
we need to start doing something about it. And then
do something about that. On the early side, if a
woman has perimenopausal symptoms and they have an Apoi four variant,
I'm really, really really gonna want to treat, and I'm
gonna obviously work very closely with uns or are there
treating clinicians to try to navigate that. Women or men
(13:31):
with apoe also need to drink alcohol in a much
less way like alcohol plus apoe is bad, Smoking plus
apoe is bad. A sedentary lifestyle plus apoe is bad.
There are so many things that I tell patients to
do differently if they have one or more copies of
the Apoe four variant of the gene. For example, Omega
(13:55):
three fatty acids, So Omega three fatty acids are a
brain healthy type of fat. If a woman wants to
reduce their risk of Alzheimer's disease and they have an
Apoi four variant and they're eating lots of fatty fish
or a couple times a week fatty fish like lake trout, mackerel, herring,
Alba cortuna, wild salmon, sardines, and they can't get the
(14:16):
Omega three fatty acid levels up from eating a brain healthy,
you know, fatty fish diet. Then potentially using an Omega
three fatty acid supplement is preferentially beneficial for people with
the APOI four variant. So the take on point with
APOE is, I believe it's important to be tested. I
believe it's important to then personalize a care plan based
on APOEE, and we've published on this. You know, the
(14:38):
instruction manual is at least there, But I would say
most doctors and most of the public are totally unaware.
I think the other thing is if there is someone
out there listening that's reluctant and doesn't want to know
because they think that if they find out that they
have an APOI four you know their life is going
to be ruined and they're going to be sad and anxious.
I'd first say, I don't agree that that's the case.
(15:00):
When you get a genetic result like that, it does
not mean you're going to get Alzheimer's disease. You can
have one or two copies of apo BE four and
never get Alzheimer's, and you cannot have any.
Speaker 4 (15:09):
Copies of apo BE four and still get Alzheimer's.
Speaker 3 (15:12):
So to me, getting tested for the APOI four variant
is something that can help personalize care, but not predict
if someone's going to get the disease.
Speaker 1 (15:20):
So the estimate is about forty five percent of dementia
cases can be prevented. What about the other fifty five percent.
Speaker 3 (15:26):
Some people can do everything right and still get Alzheimer's disease,
And in a very small number of cases, like a
few percent, there's a gene, an early onset gene where
if they get it, and these are usually people that
get Alzheimer's symptoms in their forties or fifties, we just
don't have the best tools for or many tools at all.
There are other people that have different genetics and different
(15:47):
lifestyle factors and different things that maybe we haven't figured
out yet, where maybe they do everything right and they
can delay Alzheimer's by six months here, two years, or
five years, but no matter what they do, they're still
going to develop. So what I would say is based
on the best available evidence, there's a reasonable number of
people that can get off the road to Alzheimer's, but
(16:07):
there's a lot of people that may only be able
to delay it. But to me, that's a glasses have
full thing. If we can delay Alzheimer's by six months,
a year, two years, or five years, and in that
time period, that new blockbuster drug comes and something comes.
Speaker 1 (16:20):
Out, right, figure it out.
Speaker 3 (16:21):
Then through the person's own you know, behavior change in
adopting brain healthier habits than that person was able to
make a difference. But no, I think within a few
years will be at fifty percent, fifty five percent, sixty
percent because the evidence will evolve. But I think we're
pretty close to the majority of people. And that's not
what I was taught in metopal.
Speaker 1 (16:40):
Yeah, that's just kind of like the cancer predisposition genes, right,
like ten percent is hereditary. So talk to us a
little bit about those imaging studies that you did, because
I thought they were so profoundly impactful.
Speaker 4 (16:51):
Yeah.
Speaker 3 (16:51):
So, and this is you know, led by doctor Lisa
Mosconi and Holly Hurstov at the Alzheimer's Prevention Clinic and
Women's Brain Initiative. And what we did was we looked
at basically brain imaging of women during various time periods,
so premenopause, perimenopause, and postmenopause, and we looked at women's
(17:11):
brains in terms of MRIs MRIZ or magnetic resonance imaging,
which is brain imaging that can look at the size
of the brain like if they're shrinkage or if it
looks normal. You could also look at something called white
matter disease, which is evidence of vascular issues and strokes
and mini strokes and silent strokes. And then we looked
at a type of imaging called the PET scan. We
use a marker that actually bound to amyloid amoloids, that
(17:34):
sticky protein, a plaque that builds up in the brain
of a person with Alzheimer's disease. And basically we tracked women.
We also then had a men's brain imaging study that
kind of tailed on later, and we tried to compare
the two. But women who were treated with hormone replacement
therapy had less amoloid accumulation and their brains looked better.
At least one or two, probably three of these women
(17:56):
were your patient, So you were a big part of this.
And I mean I had a sixty sixty one year
old woman who sho had two copies of the APRILI
four variant. She should have done worse. Her brain looked pristine.
Her brain looked like a fifty year old woman or
a four five year old woman. Why she had been
on harmone replacement therapy the whole time. And I remember
another woman was on harmone replacement therapy and it's seven
(18:19):
years because it was some magic number. They told her
to come off and the woman's like, but I don't
want to, but the doctor said, you have to because
this study and this research and you can't be on
it for more than seven years. And the woman came off,
and like, aside from feeling worse, her cognition got worse.
Speaker 1 (18:35):
Her hormones scary stuff.
Speaker 3 (18:36):
Clearly went down, her estrogen went down, her cholesterol went wackado,
I mean, everything got worse.
Speaker 4 (18:44):
And then she had to fight with her gyn to
go back on hormone.
Speaker 1 (18:48):
Replacement therapy an better education.
Speaker 3 (18:50):
Yeah, so she finally did, and she felt better, but
she probably lost like six months of I think brain
protection and she ended up okay. But you know, I
think where we are today, hopefully that happens less.
Speaker 1 (19:01):
I think it does happen last, but it's still happening.
Speaker 4 (19:04):
I there is so much, my gosh, just garbage out there.
Speaker 3 (19:07):
I'm worry about estrogen and it saddens me because estrogen
is what I believe to be among the most if
not the most protective like chemicals. A woman's brain can
be protected by we just see better brain outcomes, like
brain size is larger, amyloid is less or not there,
(19:27):
a cognitive function is better, memory function is better. So
to me, estrogen is a brain protective hormone.
Speaker 1 (19:34):
Late start estrogen women in their sixties. We're being told
kind of by our guideline makers, right, don't start after
sixty or after ten years of menopause. So talk to
us about that. Are we okay to use estrogen in
older women over sixty?
Speaker 4 (19:50):
Yeah?
Speaker 3 (19:51):
So I can tell you if we had this conversation
a few years ago, I would say I have no idea.
I would say that the best I could do is
women that were on estrogen for between seven to ten
years or greater than ten years in our cohort, and
what I saw had better brain outcomes. But I didn't
have like definitive evidence. Now and again I wouldn't say
(20:12):
this is definitive evidence. And we haven't fully published this.
We've presented this at a conference, but not published. We
have women between the ages of forty two and sixty
seven in our research coulport where we track brain biomarkers,
we track hormones, and we track Oh there is something
I want to talk to you about We've done six
blood draws during the menstrual cycle just to figure out
(20:33):
like what happens to these brain markers as estrogen and
progesterone change during the natural mentrol cycle. So between the
ages of forty two to sixty seven we've studied hormone
replacement therapy and on a whole on the women that
we've studied hormone replacement therapy with estrogen and or progesterone,
depending on with the gin and or primary care and
(20:53):
or endrocronologists we have helping too. We have shown significant
improvements reductions in tau protein, which is a bad protein
that builds up in the brain of Alzheimer's, and maybe
a little bit of familoid too, but more on the
TAW side, and women have higher baseline taws than men,
and that's a whole different discussion and we haven'tgured out
exactly why that is. But on the whole harm and
(21:13):
replacement therapy throughout, whether you're forty two, we have a
forty five year old, we have a forty seven year old,
we have a forty nine, multiple forty nine, fifty and
fifty one, so we have a cluster obviously, right around there.
And then we have a sixty year old woman and
a sixty seven year old woman. And in these individual women,
when we look at like how were their numbers, they
got more normal. Some of these women were borderline optimized yep,
(21:36):
and they got optimized it. But basically we're building up
a cohort of women to study this in and so
far in our IRB approved research study, we've shown better
brain protein outcomes after starting harmon replacement therapy, even in
women at age sixty and above.
Speaker 1 (21:53):
Coming up, when it comes to Alzheimer's, what are the
biggest risk factors outside of hormones and genetics and what
are the best possible actions we can take to mitigate them.
We'll be right back. Let's talk a little bit about
(22:20):
the other risk factors for women. Actually, we've talked about
hormonal risk factors. You hear a lot like heart health
is brain health, cardioc health is brain health. Talk to
me about the other risk factors for Alzheimer's STU sure.
Speaker 3 (22:33):
So you know, in terms of lifestyle factors, there's many
A hugely important bucket is vascular health and vascular brain health.
So things like diabetes. When a person has diabetes, they
have twice the risk of developing Alzheimer's disease. High blood pressure, hypertension,
Does it cause Alzheimer's, Well no, I don't think it
causes Alzheimer's, but it fast forwards cognitive decline. High cholesterol.
(22:54):
Oh boy, same sort of thing. You know, people say, oh,
your cholestero's borderline. Go you know, eat less this or
go exercise more. No, A lot of that's genetic and
like a lot of times, most of the time someone's
going to need a medicine if the general lifestyle things
don't work. So when I think about the big buckets
blood pressure management, cholesterol management, and diabetes management, what I
would say here is borderline is not normal and borderline cholesterol,
(23:20):
borderline blood pressure. You know all these numbers that are borderline.
See you back in a year. Like the difference between
normal and optimal and normal and borderline is a big
difference when it comes to preventive brain health. So what
I would say here is know your numbers. Everyone out
there should know what their blood pressure is. And there's
a study called the Sprint Mind Study. The Sprint Mind
(23:42):
study looked at two different blood pressure ranges and the
effects of these blood pressure targets on brain health. And
I would say a lot of doctors think that one
forty eighties is like okay, But this study looked at
how do people do one forties versus a lower target
of one twenties or below. And I actually stopped the
trial early. The results were so good. After three and
(24:04):
a half years of just lowering the blood pressure from
one forties to one twenties, not a big drop, people
were able to reduce their chances of developing the earliest
symptomatic phase of dementia called mild cognitive impairment by nineteen percent,
well nineteen percent, just by optimizing blood person. So again
the concept here is normal versus optimal. Same thing with cholesterol.
(24:26):
I see so many people out there with ldl's that's
you know, the bad cholesterol LDL cholesterols one thirties, one forties,
one fifties, on sixties, one seventies, And doctors will say, eh,
I don't know, let's.
Speaker 4 (24:38):
See it back in the year.
Speaker 3 (24:38):
Go eat less fast food and the person's like going
on any fast food. The take on point with cholesterol
is you can eat everything right and still a high cholesterol.
So what we try to do fundamentally is if a
person is doing everything right from a nutrition perspective and
their cholesterol is still high, then we may need to
use a pharmacologic agent, a drug, a prescription drug. And
(24:59):
when we don't know what to do, we may look
at the heart because the calcium score in the heart
basically predicts what your heart risk is for the following
ten years. And if person has elevated calcium in their
heart vessels, they are at a much higher risk of
vascular cognitive impairment or vascular dementia twenty years later. And
(25:19):
what we can look at in the heart potentially as
a proxy for brain is if a younger woman is
at risk and their calcium score is zero, but they
have soft plaque building up in their heart that hasn't
turned hard yet, and they're in their forties or fifties
or sixties, then that's someone If they have borderline cholesterol,
I'd rather treat them, and as a clue that we
(25:41):
should treat earlier rather than later. Now, there are some
women and some men that just their vessels are clean,
their brain looks clean, there's no soft plaque, there's no
hard plaque, and they have borderline or elevated cholesterol. And
maybe those cases are okay not to treat, but there's
so much nuance here, and you know it's an evolving story.
Speaker 1 (25:57):
Yeah, that's tough one. So talk to me about statins
a little bit, because you know, I have a few
patients that will come to me saying I'm not going
to take that statin because it actually causes dementia because
it impacts my mitochondria, the powerhouses of the cells.
Speaker 3 (26:09):
Yeah yeah, okay, my favorite topic, I'm so go advertised
is being recorded. Hop Yeah, it's the same, right, I'd
love to do this again. Don't get me wrong if
there's a glitch. But okay, let me start by saying
the totality of evidence is extremely strong, that the net
positive effects of statins are absolutely net positive and protective
(26:30):
on brain health, and the lion's share of studies, the
vast majority of studies where people have been on statins,
and these are epidemiological studies and they follow them over time.
People that take statins are at a lower risk of
dementia and Alzheimer's disease. That's what I would say. There
are certain cases. This goes back to the whole personalized
care and precision medicine there are certain cases, and I
(26:51):
would say this is a small number of cases, but
there's a lot of internet chatter about this where people
who take statins feel that they have brain fog. People
that have statins can also have muscle soreness, and there's
all sorts of things that can happen from statins. But
I would say, on the whole, the vast majority of
people that take statins will be most likely to benefit
from statins on the overall net effects. So I guess
(27:14):
what I would say is, I don't have all the answers.
I don't have the perfect answers, but the totality of
evidence suggests that statins are protective. You know, I don't
have the perfect answer for precision based cholesterol treatment, but
this is something we're studying in our research.
Speaker 1 (27:26):
Let's talk about sugar. Most people will go the doctor
and hemoglobin a one ce by point six, it's okay,
you don't have diabetes. By point eight it's okay, you
don't have diabetes. But it's insulin resistance absolutely, And so
talk to us about that. What should be our target
for our measurements of our glucose metabolism?
Speaker 5 (27:45):
Yes?
Speaker 1 (27:45):
Why?
Speaker 4 (27:46):
Yeah?
Speaker 3 (27:46):
So I think I mentioned earlier that people with diabetes,
and it's a frank diagnosis of diabetes where hemoglobin a
one cee as much higher, is two times the risk
of Alzheimer's. But insulin resistance just really fast forwards amyloid
accumulation and amyloid isn't that bad protein the pathological protein
that builds up in the brain of a person with
Alzheimer's disease and insulin resistance, I think fast forwards brain aging.
(28:10):
As the belly size gets larger, the memory center in
the brain gets smaller. Fat around the mid section, around
the visceral organs, especially for women, Women that have increased
belly fat are at an increased risk of dementia.
Speaker 1 (28:23):
That's huge because it's such a problem for perimen apostle women.
Speaker 4 (28:28):
Stubborn area to get rid of it.
Speaker 3 (28:29):
And women could do everything right and still have trouble
getting rid of that fat. And you know, there's some
you know stuff which I'm sure we're going to talk
about GLP ones, which is.
Speaker 4 (28:37):
A very interesting topic, hot button.
Speaker 3 (28:39):
That's our big hot button topic which you and I
have both talked about and implemented in our clinical practices.
But women and men need to gain muscle mass, and
the more muscle you have, the better your metabolism. Women
and men need to lose belly fat and that can
be hard, and that's you know, through a targeted exercise,
lower intensity zone to training that some people talk about.
(29:00):
Through nutrition changes obviously sometimes these new drugs that can help,
but yeah, insulin resistance, just fast forwards brain aging and
fast forwards amyloid and you know, as one of the
most critical things that we need to optimize in the
fight against Alzheimer's disease.
Speaker 1 (29:15):
Give us your exercise prescription. Is it zone two cardio?
Is it strength training? Three times a week? Like? What
is the exercise prescription to prevent dementia?
Speaker 3 (29:26):
Everyone that I see gets an individualized exercise prescription based
on what I would say are three factors. We call
it the ABC's of Alzheimer's Protection. My next question, so A,
is anthropometrics. Anthropometrics is a big fancy word for body composition.
Body composition is percent body fat and muscle mass, and
(29:50):
to me, the percent of lean mass is the most important.
And it's not just about what the percent body fat is,
but where it is in a woman that has stubborn
belly fat, especially perry or postmenopausal. We recommend really a
multi prong attack. So number one, zone two training, which
is about steady state cardio where a person is exercising
(30:11):
walking fast, for example, but the person can still carry
on a conversation. This is not, you know, high intensity
interval training, This is not sprinting. This is lower intensity
steady state or zone two means zone two of your
cardiovascular rate where you can take your maximum heart rate
and you multiply that by point six or point sixty five,
so at sixty to sixty five percent of what your
(30:34):
maximum heart rate is and try to stay in that
heart rate zone for forty five to sixty minutes to
burn the carbs that are in your blood and basically
lose body fat. And I think most people are unaware that.
Like high intensity interval training, for example, where someone's either
on a peloton bike at a hit class or an
orange theory or berries, that's a great way to get
(30:55):
a great workout and sweat a lot and make your
heart stronger. But a lot of the times you're just
not being efficient at burning body fat. You actually burn
body fat more efficiently when you're at a lower steady state.
The zone two cardio, where again this could be walking
fast with a weighted for forty five to sixty minutes
and you do that three times a week and if
your doctor says, okay, you know, I can't give anyone
(31:17):
individual medical advice here, but the doctor says, okay, even
doing it fasted in the morning, and that's another way
to jump start body fat loss. So if a woman
is trying to lose fat around the midsection, we recommend
at least a few times a week, two to three
times a week of Zone two training. We absolutely, absolutely,
absolutely recommend strength training. Strength training is tricky in women
(31:38):
during the peri and postmenopause because many women have trouble
gaining muscle mass after the perimenopause.
Speaker 1 (31:43):
You gotta lift heavy, yep.
Speaker 3 (31:44):
But like there are certain women that just cannot gain muscle,
And then what do you do? Is it protein? Is
it creatine? Is it testosterone?
Speaker 4 (31:52):
Hormones? Hormones and hormones exactly, And that's what I thought
you were going.
Speaker 1 (31:55):
To say, persistence, lift heavy yep, safely yep, and hormones
and hormones.
Speaker 3 (32:00):
And I agree with that, and I had to put
nutrition and protein and all that kind of stuff. But
you can't just do zone two, and you can't just
do strength training, and you can't just do high intense
interval training. If a woman is muscled, then you want
to do more strength training.
Speaker 1 (32:14):
For brain health, what should we aim for in terms
of percent body fat, percently muscle mass.
Speaker 3 (32:19):
These are tricky things, so we recommend dex's scans. So
DEXes are a little bit of radiation, but it's like
less than a chest X ray minimal, and you look
at body fat, muscle mass, and you look at bone density.
So to me, when I'm giving a woman recommendations for
brain health, I'm also very interested in their bone health.
And if a woman has osteoporosis or low bone mass,
(32:41):
I'm going to prioritize strength training, maybe more so than
would otherwise. You know, obviously I'm trying to prevent someone
from getting dementia, but when it comes to women, I
also want to prevent them from having like a fracture.
You know, my mom, when she was eighty two, fractured
her femur, her hip.
Speaker 4 (32:57):
She broke her hip.
Speaker 3 (32:58):
And like you learn in medical school that once a
woman breaks their hip, they usually die within six months.
And six months later, my mom passed away, So you
really taken the whole picture.
Speaker 1 (33:10):
Talk to me about other prevention maneuvers that you can do.
Social engagement, neuroplasticity, cognitive reserve, keeping your mind nimble, and
learning new things.
Speaker 3 (33:19):
Yeah, so if you don't use it, you lose it.
I mean, the list goes on and on. You know,
forty five percent of cases of dementia maybe preventable. There
are so many modifiable risk factors, you know. For example,
hearing loss is something that people just they hear and
they're like, wait, what what do you mean treating hearing loss?
At like eight percent of cases of dementia may be
attributable to hearing loss, And that's confusing, like why would
(33:42):
that be well, less socialization, less interaction, less verbal whatever.
So hearing loss is key. Vision screening is key. Socialization
is absolutely critical. Learning something new, a new language, musical instrument.
Stay engaged. It's not just you can do all the
sodoka you want and you're just going to get better
at sodoku, but learning something new, socializing with friends, staying engaged.
(34:06):
Stress reduction is key. Stress mitigation something called mindfulness based
stress reduction NBSR. It's tied to better brain health outcomes.
Speaker 1 (34:14):
So you do a lot of work in biomarkers. Oh yeah, right,
So tell us the utility of biomarkers, what they are
and when does Alzheimer's start? Does it start in our
forties and we just don't know that it's starting and
biomarkers can help us with that.
Speaker 4 (34:30):
Or talk to us. Yeah.
Speaker 3 (34:31):
So, you know, I've been talking about trying to develop
and create and prove a cholesterol test of the brain
to fruition. And what I mean by that is just
like everyone goes to their doctors and hopefully starting in
their thirties and forties, they get a cholesterol test where
you look at your total cholesterol, your HDL, your LDL
which is the bad cholesterol, and triglycerides, and then doctors
(34:52):
know how to treat it. There's going to be what
I colloquially call the cholesterol tests for the brain, and
instead of those markers, you're going to have the amyloid
and the TAO and this and the that. And currently
in our lab we have over one hundred and fifty
markers that we're looking at and that we're tracking over time.
So what I would say is, you know, it's still
early days. There are blood tests that are available today
(35:13):
that if a person has symptoms and the person's doctor
thinks that the symptoms could be related or due to
Alzheimer's disease, then there are blood tests out there today.
They can be used to basically say, aha, this is
a good screening test, these symptoms are probably due to Alzheimer's.
I think when it comes to prevention and risk reduction
and doing a risk assessment, our work has shown that
(35:34):
you can't just order one test. You can't just order
a handful of tests. You have to order a panel
of tests and really interpret them within the context of
each other. So I hope and I believe that people
in the coming years will go to their doctors in
their thirties, forties, fifties, sixties, seventies, eighties and beyond before
they have symptoms and get this cholesterol test for the brain,
(35:54):
this risk assessment panel to figure out are they at risk?
And then not just are they at risk, but based
on the markers, what you can do about it. If
a person has high tau before symptoms, what do you do.
If a person has high amyloid before symptoms, what do
you do? It's the same thing like what do you
do if you have an LDL cholesterol that's high, Well,
you take this medicine or that medicine, or you do
(36:15):
a scan. We kind of understand that for preventive cardiology.
We're just starting to understand that now for preventive neurology,
and you know, I hope that very soon we'll be
able to offer these tests to people. I think the
challenge with blood tests for Alzheimer's disease one, sometimes you
can have elevated levels and they're not really elevated. They
(36:37):
could be a false positive. What we've seen in our
in our work is that people with active viral illnesses.
I've seen people with you know, for example, herpes lesions
or herpes herpie simplex one. I've seen someone who just
had COVID and their markers were off the charts, and
then a few weeks later we retest and the markers
came down. I've seen people that looked like they had
elevated brain biomarkers worrisome for Alzheimer's disease triggered by things
(37:02):
that were transient. I had someone going through a divorce,
sleep deprived, terrible like situation, really rough, and one of
these brain markers was through the roof, came back six
months later. I was pretty worried about the person. Divorce
was over the person that slept. We repeated the markers
and everything was normal.
Speaker 1 (37:24):
It's time for a quick break. But when we return,
doctor Isaacson and I will get into some of the
biggest hot button issues around long term cognitive health, and
we get into what the future of diagnostics and treatment
will look like for Alzheimer's and dementia. Decoding women's health
will be right back. Let's do some hot button topic. Sure,
(37:56):
of course, talk to me about testosterone in women's brain health.
Speaker 3 (37:59):
So I was for both women and men a decade ago,
like I would say anti testosterone, I would say, what
are these people doing or reving up the system? Like
why are we using testosterone? That's my performance enhancing drugs?
Like I would say, that's the way I was a
decade ago. I was wrong what I've seen clinically, and
this is a shotal shift for me. I mean, there's
(38:21):
probably ten men and women that have started on testosterone
that I mean one more muscle mass or sustained muscle mass.
Two felt better clinically, you know, was tired yet.
Speaker 4 (38:35):
Yeah, exactly.
Speaker 3 (38:36):
People don't even realize how bad they feel until they
start taking testosterone, and like that was really surprising to me.
I didn't really understand that. And what I would say
is when I say estrogen replacement plus progesterone like slam dunk,
better brain outcomes on the whole. With testosterone, I would
say a lot of people on testosterone, I don't see
(38:59):
much of a brain health brain biomarker change, but some
people I do, it's just less robust of a change.
So please don't take this as fact. Then we haven't
studied this, but I've never seen brain biome marker worsening
in the ten or so people that have started on.
Speaker 1 (39:15):
Testosterroen important because yeah, some some women with lower testosterone
levels have fatigue. And it's interesting because we always asked
this question like how do you feel? And it really
speak could you feel better?
Speaker 4 (39:24):
Right?
Speaker 1 (39:25):
You know, let's get really controversial. Okay, I'm ready microdosing
GLP ones for brain help. Yeah, my favorite topic.
Speaker 4 (39:32):
Yeah, this is the whole.
Speaker 1 (39:32):
Thing lands me in hot water all the time.
Speaker 4 (39:35):
Oh you're telling me forget it? Okay.
Speaker 3 (39:38):
So I did not wake up one day and say
I'm gonna try to advance the narrative on microdosing. What
happened was I had a patient that needed a GLP
one for insulin resistance that did not seem to benefit
from lower carb diets, exercising out to wazoo, you know,
(40:00):
doing the zone two, doing the strength training, was still
insulin resistant eight POE four. Just too many risk factors
and I just did not feel comfortable. Was the person
diet No is this off label by the FDA? Yes,
but their doctor put them on tr zeppetide, which is,
you know, one of the GLP ones two point five milligrams,
(40:22):
and that person felt really sick, lost some body fat,
which is good, also lost a little muscle mass which
wasn't as good. And basically the recommendation was try half
of the dose. And in that one case, that's what
kind of like changed it for me. The person did better,
felt better, their insulin resistance went away, and their brain
biomarkers improved. And this was using less than the FDA
(40:44):
approved regular dose of the drug. So the drug companies
will say, oh, that's never been studied, you can't use it.
I mean people use drugs off label all the time,
like blood pressure medicine, can't tolerate it, get lightheaded. Use
less pain medications. Oh boy, getting lightheaded, but you're still
in pain. Use less some people it works for right.
So I think, you know, using drugs off label is controversial,
and I think you know, obviously the doctor has to
(41:06):
talk to their patient about this and make informed decisions.
But in our data set, you know, we have a
subset of people that have taken less than the lowest
dose recommended or FTA approved of glp ones, the injectables.
And also I want to say that there is twenty
years of data on glp ones, the oral ones that
(41:28):
show that people that are on these glp ones for
long periods of time have a lower likelihood of developing dementia.
It's not like we're trying these things willy nilly. I mean,
there's like many studies that have shown this. There's also
a study that's going to be published sometime later this
year to look at is the oral dose of semaglutide
and commercial name is Rabelsis, but semiglutide is the generic name,
(41:49):
and a fourteen milligram pill is being studied in two
studies called Evoke and Evoke plus and people with mild
cognitive impairment, which is the earliest symptomatic phase of Alzheimer's
to see. You know, does it improve symptoms? Does it
delay progression? Like?
Speaker 4 (42:02):
How do these people do?
Speaker 1 (42:03):
These are people without diabetes or without insulin resistance crack.
These are just like all comme. So how much of
the effect do you think is a direct effect of
the gl maybe as an anti implammatory And how much
of the effect of this microdose sing do you think?
Is it just change in body comp and decrease of
visceral fat.
Speaker 3 (42:19):
Yeah, I don't know. I think there's more to it
than just the body fat loss. I think there's some
sort of direct effect. I think something happens with inflammation.
I also am very you know, I'm an advocate that
if people are on glp ones and they're losing muscle
mass or losing a majority of their weight is due
(42:39):
to muscle mass, I tell their doctors or or I advocate,
because I'm not usually prescribing these, please stop, or please
go on a lower dose, like we don't want to
lose muscle mass. And you know, I guess what I
would say is in the right person, at the right
dose and for the right duration of time, as long
as the person's doing strength training, eating enough protein and
carbs around their workouts so they don't lose muscle mass,
(43:02):
and eating brain healthy and otherwise, I really think GLP
one's at lower doses if possible, when possible, maybe one
one of our most like helpful things for dementia.
Speaker 1 (43:14):
Prevention keytnes keto.
Speaker 4 (43:17):
Yeah.
Speaker 3 (43:19):
I spent a lot of my time earlier in my career,
like probably fifteen years ago on keytnes and ketosis, and
I really do think that there's something to this and
lower carbs and ketogenic diet, time restricted eating, intermittent fasting.
There's what I would say, is this The answer here
is personalized medicine and precision nutrition. And I haven't figured
out like the exact algorithm I think, but I'm not
(43:40):
certain that people without an apoe four variant may benefit
more from keytnes and ketosis.
Speaker 1 (43:47):
And that's because you can use them as an alternate
energy source for the brain. Right. This is like tapping
into the brain's energy production exactly.
Speaker 3 (43:53):
So the brain can only use two things as fuel. Sugar,
which is, you know, the stuff that we don't want
to overload the brain with because it causes inflammation, insulin
resistance and key tones. KEYTNES is like, you know, a
cleaner burning fuel. It's like the hybrid car model, Like
you have the hybrid battery, which is the KEYTNES, and
then you have the gasoline, which is the sugar. And
of course what do you want to do? You want
to use the keytones right if you can. I think
(44:14):
there is probably a role for ketogenic diet maybe and
if someone can handle it, but I don't fully have
it all worked out.
Speaker 1 (44:21):
Yet looking forward to that answer. And some of these interventions,
like lifestyle interventions impact women more than men. Actually, is
that correct or yeah?
Speaker 3 (44:30):
So you know, we actually published a paper on this.
We took our Alzheimer's Prevention Clinic cohort and we actually
showed that the interventions, the lifestyle interventions in our Alzheimer's
Prevention Clinic actually on the whole worked better in women
than in men.
Speaker 1 (44:44):
So like some good news for women.
Speaker 4 (44:46):
It's really good news. And you know, we're not powerless.
Speaker 3 (44:51):
And our data shows that while yes, on the whole
for everyone, it work, meaning lifestyle interventions and managing risk factors.
On average, the people in our study got twenty one
different interventions, so This wasn't like, you know, eat a
magic blueberry and think you can prevent Alzheimer's disease. But
between the synergies you have the exercise, the brain healthy nutrition,
the olive oil, omega three fatty a acids, the stress reduction,
(45:12):
the staying engaged and modifying your blood pressure, cholesterol, diabetes.
Like you do all of these things together, socialization making
sure someone gets adequate sleep. Doing all these things together works,
and it works better in women. And it worked regardless
if a woman had either one, zero or two copies
of the Apoi four variant.
Speaker 1 (45:33):
What have I not asked you about today? Do you
think is important for especially for midlife women, in their
brain health.
Speaker 3 (45:39):
I've seen so many women over the last fifteen years
that are concerned about their brain health, and women are
more likely to be affected. The Apoi four gene affects women,
you know, more in a negative way. There's so many
individual risk factors for women that are really confusing, complicated,
and I would say, in some way scary, and the
best thing that I could do is just tell women
(46:00):
to just just pause, take a deep breath, and it's
going to be okay. Genes are not our destiny. The
field of Alzheimer's disease is changing so rapidly. The things
that I can talk about now, like I couldn't even
dream about ten years ago. I went from like seeing
patients and you know, doing all these like cognitive tests
and some blood draws to now like running a comprehensive
(46:24):
blood biomarker lab where we have multiple pieces of equipment
and we like finger prick techt Like I have a
fingerprint card and my backpack over there, Like we're going
to be doing finger print card testing soon. It's not there,
it's not one drop of blood, but it's like with
nine drops of blood, we can detect one hundred and
twenty brain proteins. Like things are getting better. And what
I would say to women out there, regardless if you're premenopausal, perimenopausal,
(46:47):
or postmenopausal, there are things that you can do today
to improve your brain helth tomorrow. You know, we have agency.
We can take control of our brain health. Talk to
your doctor, get online, learn there are resources out there
we can win the fight against Alzheimer's disease.
Speaker 1 (47:02):
Where can we find information, Like because a lot of
doctors don't talk about this and it's not well recognized
but where can we get the real information?
Speaker 3 (47:09):
Yeah, so back in twenty fourteen, you know, we created
the first I believe kind of evidence based curriculum about
Alzheimer's prevention. We studied it in a randomized controlled trial,
and we published on it and we put coursework out there.
We've then updated that and now we have two different resources.
So one people can go to id dot org. I
in D stands for the Institute for Neurodegenerative Diseases i
(47:33):
ND dot org and if you go to the learn
page i ind dot org backslash learn, you can watch
video after video after video. There's over fifty videos interviews
about brain healthy nutrition and the latest on blood testing
and exercise and all sorts of information. It's all available
for free. The other website is also a randomized controlled
study that we've done. It was funded by the NIH
and National Students of Health, where people can go to
(47:55):
Retain your Brain dot com and basically using a software
platform that gets to know you from the comfort of
your own cell phone. You can do a risk assessment,
you can do cognitive activities and then the software will
learn about you. You can actually type in your APO
if you know it, if you checked it on twenty
three and meters and basically the SOFTWARELD then put you
(48:16):
on a kind of a risk education plan to try
to get you to adopt brain healthier habits. So what
we've tried to do is take everything we've learned in
our research studies, take everything that we've learned from other
people's research studies, and we've tried to put it out there.
Speaker 4 (48:31):
And I think that's going to be the way to
It's pretty cool.
Speaker 1 (48:34):
That's kind of a model for like a lot of
issues that we can prevent, right, not just brain health.
But it's like a great paradigm.
Speaker 3 (48:41):
Yeah, I mean, access to care is so difficult, and
you've said this before. We're a sick care system. Were
not a healthcare system. There's no diagnostic code that a
doctor can bill an insurance company for the term Alzheimer's prevention.
We lost so much money at the Alzheimer's Prevention Clinic.
It was like impossible. We were collecting twenty eight cents
on the dollar, and we had to get grant funding
and donations and all this kind of thing. Preventive care
(49:03):
is like it doesn't pay, doctors can't build for it.
So we've decided to just put it out there online
for free.
Speaker 1 (49:09):
Yeah, that's great. I mean to really focus on preventative care.
Thank you so much for joining us today. So appreciate it. It's,
like I said, such an honor to have you.
Speaker 4 (49:17):
I appreciate it. Thank you.
Speaker 1 (49:22):
The landscape of Alzheimer's prevention is changing. Leading neurologists like
doctor Isaacson are proving through robust research that evidence based
strategies can delay and even in some cases, prevent the
disease from ever taking hold. And there are meaningful steps
that you can start today. First, know your genetic risk.
(49:44):
A simple test can tell you which APOE variant that
you carry. Even if you have one or two copies
of the APOE for variant, it does not mean that
you're destined to develop Alzheimer's. Understanding your risk helps you
take action early. Talk to your doctor about hormone support.
Estrogen is a brain protective hormone. Beginning therapy around menopause
(50:08):
is ideal, but even later into your sixties and beyond
may still offer cognitive benefits, and I look forward to
that research in the future. Monitor your numbers, keep an
eye on blood pressure, cholesterol, and hemoglomina ONEC borderline isn't optimal,
and there is a big difference between optimal and borderline,
(50:31):
so it's not something to shrug off. Even small improvements
in metabolic and vascular health can positively affect brain function.
Understand your body composition. A DEXA scan can help you
track visceral fat, which is linked to cognitive decline, as
well as bone density and muscle mass. Zone two. Cardio
(50:51):
and strength training are really powerful tools for shifting body composition.
And if insulin resistance is severe, talk with your doctor
about whether a golp one medication might help protect your
mental well being. Chronic stress is neurotoxic. Find practices that
help you slow down, breathe, and enjoy your life, and finally,
(51:15):
stay hopeful. We are living in a moment of unprecedented progress.
Do what you can today, knowing that even more effective
tools are coming tomorrow. Coming up on the next episode
of Decoding Women's Health, I speak with a pioneer and
weight loss surgery about his own experiences not only as
a clinician, but also as a patient.
Speaker 5 (51:37):
Society, including a lot of doctors, think people are taking
the easy way out because there's this absolute myth and
it's a myth that you can do this sort of
weight loss on your own and keep it off.
Speaker 1 (51:55):
Decoding Women's Health is a production of Pushkin Industries and
the Adrea Health and Research Institute. This episode was produced
by Rebecca Lee Douglas. It was edited by Amy Gaines McQuaid,
mastering by Sarah Burguier. Our associate producer is Sonia Gerwitt.
Our executive producer is Alexandra Garreton. Our theme song was
(52:15):
composed by Hannes Brown. Concept creative development and fact checking
by Shavon O'Connor. A special thanks to Alan Tish, David Saltzman,
Sarah Nix, Eric Sandler, Morgan Rattner, Amy Hagdorn, Owen Miller,
Jordan McMillan, and Greta Cohne. If you have a question
(52:37):
about women's health in midlife, leave us a voicemail at
four f five two oh one three three eight five,
or send us a message at Decoding Women's Health at
Pushkin dot Fm. I'm doctor Elizabeth Pointer, and thanks for listening.
Until next time.
Pushkin. Hi everyone, Doctor Poyter here, I'm popping in to
let you know that we're working on a special episode
of Decoding Women's Health. We're i'll be answering your questions
about one of my favorite topics, hormone therapy. If you've
been wondering about the different types of therapy, when it
(00:39):
might make sense to start possible side effects are really
anything else? This is your chance to ask. You can
leave us a voicemail at four FI five two one
three three eight five, or send an email to Decodingwomen's
Health at Pushkin dot fm and let us know if
you'd like to stay anonymous, or if you're up for
(00:59):
having your voice featured on the show. I'm so excited
for this one. Hormone support is such a misunderstood area
of medicine, and there's a ton of new and fascinating
research to talk about together. I can't wait to hear
what you're curious about.
Speaker 2 (01:16):
This show is not a substitute for professional medical advice, diagnosis,
or treatment. It is for informational purposes. Please consult your
healthcare professional with any medical questions.
Speaker 3 (01:32):
Genes are not our destiny. The field of Alzheimer's disease
is changing so rapidly, the things that I can talk
about now like I couldn't even dream about ten years ago.
Speaker 1 (01:42):
Welcome back to Decoding Women's Health. I'm doctor Elizabeth Poynter.
Today on the show. We're talking about dementia prevention and
long term brain health. If you've ever cared for a
loved one with Alzheimer's, you know the emotional toll. You
watch someone you care about lose memories, abilities, and pieces
of who they are, and somewhere in the back of
(02:05):
your mind, a quiet fear grows, what if this happens
to me? For women, that fear is statistically grounded nearly
two thirds of people diagnosed with Alzheimer's or female. One
of the most frustrating realities of the disease is that
there is no cure, but what if prevention were possible?
(02:27):
Doctor Richard Isaacson has devoted his career to answering that
very question and to helping people understand what they can
do right now to reduce their risk. Doctor Isaacson is
a preventive neurologist at the Atria Health and Research Institute,
and he is also the director of the Institute for
neurodegenerative diseases, where he is doing groundbreaking research studying brain
(02:52):
biomarkers for Alzheimer's and dementia. He is also the founder
of the first ever dementia prevention program at wild Cornell.
He has been a pioneer in this area for a
long time, and I'm so excited to talk with him
today about something we both care so deeply about brain health.
Speaker 3 (03:13):
So I'm a preventive neurologist, and most people haven't heard
that term because it's not a common term. It's like
a handful of us. We need an army of preventive
neurologists because most neurological diseases, brain diseases start silently decades
before symptoms, and that's kind of when we should intervene.
And just like you know, when a person has a
heart attack or a stroke, that problem, the vascular problems
(03:35):
and the atherosclerosis and all that it built up over decades,
and it's the same thing with brain disease. So I think,
you know, instead of being a reactive neurologist, I want
to be a proactive neurologist, and that's what preventative neurology
is all about.
Speaker 1 (03:47):
I first heard about doctor Richard Isaacson, and when I
came across his research on how nutrition and lifestyle interventions
could help protect the brain against Alzheimer's disease. He had
a strong personal motivation. Several of his close relatives had
developed Alzheimer's and he was determined to find a way
to prevent its development. I was immediately intrigued. For the
(04:09):
first time, felt like there might be real hope to
offer my patients who had a family history of the disease.
I reached out and we soon began collaborating. We were
both early believers in the potential protective role that hormone
therapy could play for the brain, and today we're colleagues.
His approach to dementia prevention has gained significant recognition in
(04:31):
recent years, but when he began it was anything but mainstream.
Many in the medical community were, let's just say skeptical.
So you started the first Alzheimer's prevention clinic and preventive
brain health clinic. That was revolutionary at the time. It
still is a concept that a lot of people don't
(04:52):
speak about enough. How did you come up with that idea?
Where did that come from?
Speaker 3 (04:56):
Yeah, so you know, you said revolutionary. I thought the
first word you were going to say it was controversial
or that was.
Speaker 1 (05:03):
My next sentence. Yeah, I was like, why was it
so controversy? That's my next question.
Speaker 4 (05:06):
Okay, gotcha.
Speaker 3 (05:07):
So yeah, what I would say is two thousand and
nine was when I saw my first, like my first
Alzheimer's prevention patient. And you know, I see people with
dementia and I see family members sitting next to them.
And one of these family members was a physician, and
he said, hey, Doc, this is tough, and I know
(05:27):
you've been affected by this, Like is there anything, like
what can we do? Because he knew that I have
a family history and obviously he has a family history.
And I spoke with forty five minutes in the hallway
about things that, you know, maybe he could do. Talked
about exercise, and talked about nutrition, and talked about Omega
three fatty acids, and you know, there was like a
list of things, and that conversation just turned into you
(05:49):
know what, why don't you come back and maybe we
can check some labs and maybe I can help you
through this. And then I saw that person's sister. And
then later that same week, doctor Arthur Agatson, who was
one of the first preventive cardiologists. You know, people know
his name because of the South Beach diet. And he
referred me a patient whose father had Alzheimer's disease and
he didn't want to get it. And that's when everything
(06:11):
kind of clicked, you know, three times in one week.
I was talking to a person about how to protect
themselves potentially from developing Alzheimer's, and I said, this is
what I need to do.
Speaker 1 (06:21):
How do your colleagues react to this? We work in
a system of you know, sick care and reactive care
and trade a disease, and you're preventing something that we
were taught isn't necessarily preventable at the time.
Speaker 3 (06:33):
Yeah, I mean one person called it hogwash. One person
who I love, a really nice guy, like, you know,
Isaac's I don't get you, man. You know you're a
good guy, But why are you trying to peddle this stuff?
Like what are you trying to sell?
Speaker 1 (06:48):
Man?
Speaker 3 (06:48):
This is snake oil. You're selling empty promises. And I
was like, but I really believe it. And then he said, well,
go study it and.
Speaker 4 (06:56):
Go prove it.
Speaker 3 (06:56):
And I said, h call the action. Better go study
it and go prove it. And that's when I kind
of went on this road show to figure out, like
where could I go to prove it? Because when I
was at the University of Miami, I wasn't able to
build a practice for prevention and do all the things
that I needed to do. So that's when I started interviewing,
and I interviewed in Boston and New York and the Midwest,
and honestly, the only place that would allow me to
(07:17):
put my kind of flag in the ground with an
announcement to say Alzheimer's prevention clinic was at a wild
Cornell in New York Presbyterian.
Speaker 1 (07:24):
So how long did it take you to say I'm
really onto something here with what I'm doing.
Speaker 3 (07:28):
Well, I'll start by saying the fact that people could
come to see a doctor and talk to someone that
was a net positive for a lot of people. They
felt like they had agency, they felt like they had
some control. Now, you know, I have a saying that
I say a lot promise, not to overpromise. Back then,
(07:51):
you know, I made no promises, But what I said is,
you know, if we can improve your heart health, improve
your vascular health, improve your metabolic health, and later down
the road turns into better brain health, than that's worth it.
And back then I didn't have blood tests biological markers
like we do now. We had cognitive tests, and these
were early days, and you know, took us a long
(08:12):
time to prove that these cognitive tests were right. But
we were showing in like the late you know, twenty ten, nine, ten, eleven, twelve,
that people that took the baseline cognitive tests and then
came back after they controlled these risk factors actually had
improved cognitive function.
Speaker 4 (08:28):
And to me, that was it.
Speaker 3 (08:30):
That was the thing where I said, Aha, their blood
pressure is better, there's all these vascular measures that are better,
and their cognitive functions better. Maybe this is real. I
want to go try and study this improve it. Initially,
eighty percent had dementia and twenty percent of my clinic
was for prevention, and then little by little its switched.
Then it was twenty percent dimension, eighty percent prevention. Then
I switched to prevention full time in twenty thirteen.
Speaker 1 (08:52):
I sent you a lot of patients when you first opened.
Speaker 4 (08:54):
Co managing patient. I learned a lot from you.
Speaker 1 (08:56):
I was like a big believer. I'm gynecologist who loves
brain help and so appreciated your care of our patients.
Speaker 3 (09:04):
And honestly, if it wasn't for that, I wouldn't have
made a pivot. We did brain imaging in women. We
in a structure way, like focused on women's brain health.
And you know, women get Alzheimer's more likely than men. Right,
two out of three brains affected by Alzheimer's or women's brains.
Speaker 4 (09:19):
We don't know why.
Speaker 3 (09:20):
I always said it was age, women live longer, right, Well, no,
that was wrong. And basically because of all these questions,
half of my time was spent, which it should be
half the population, but half of my time more than yeah,
more than half of my time was spent on trying
to figure out the answers to these questions.
Speaker 1 (09:39):
Just for our listeners, let's talk a little bit about,
like what are the risk factors for dementia and Alzheimer's disease?
Speaker 3 (09:45):
Sure, so, the number one respector for Alzheimer's disease and
dementia's age advancing age and as we get older. You know,
it's not exactly like fine wine. Things do happen as
we age. Our brains age too, and when it comes
to women's brains, women's brains, age at I would say
different rates than men. I think that has to do
with in part this estrogen drops during the perimenopost transition.
(10:07):
I think that triggers accelerated brain aging. And I believe
that one of the most powerful things that we can
do during the perimenopaust transition for these women is to
consider hormone replacement therapy. I think that age and the
perimenopaust transition are the two biggest risk factors in some ways,
plus obviously having a gene that increases risk. Obviously you
(10:28):
can't change your genes, can't choose your parents necessarily, But
what you can do is you can change your lifestyle
when it comes to modifiable risk factors. I believe that
the majority of the negative effects of the life that
we live can overcome that risk, and genes are only
part of the story. The femal biological sex is only
(10:51):
part of that story. And I believe through living a
brain healthy lifestyle, we can attenuate or neutralize most of
those other risks.
Speaker 1 (10:57):
Actually, I want our listeners to understand a little bit
about apoe four, like what is apou four and who
should be tested? Should everybody be tested, or just if
you have a family history.
Speaker 3 (11:06):
Talk to us about that great question. So, for everyone
out there that has not heard about apo e, a
poe is a gene. You get either a two, a
number three, or a number four from Mom, and you
get a two, A three, or four from Dad. Apoe
three is neutral, Apoe two is protective, and a pox
four increases risk. So everyone out there, everyone is either
(11:29):
a most commonly three three, which is about fifty five
percent of the population. Three three is neutral risk. So
if a person has one copy of an eight POE
four variant from Mom or Dad, that increases risk a
little bit of Alzheimer's disease. If a person has two
copies of the a POI four variant, so one four
from Mom, one four from Dad, then that risk is higher.
(11:50):
But but, but please, genes are not our destiny. We
can win the tug of war against our genes. And
what I mean by that is this is not a
genetic combination that definitively leads to Alzheimer's. Does it increase risk?
Speaker 4 (12:04):
Sure?
Speaker 3 (12:04):
Can you neutralize or negate or you know, account for
a lot or most of that risk by doing brain
healthy things and living a brain healthy lifestyle. I absolutely
believe that to be the case, whether it's sixty percent,
seventy percent, eighty percent, or ninety percent of that dad
Apoi four risk. I think most of that risk can
be neutralized by brain healthy living, modifying risk factors. And
(12:28):
I believe that people with this genetic combination should kind
of follow a different path on the road against Alzheimer's disease.
You know, forty five percent of dementia cases may be
preventable if that person does everything right. And that's based
on the twenty twenty four Lancet Commission. So I believe passionately,
yet in a controversial you know, want to be clear
(12:48):
that this is not maybe the exact accepted you know framework.
I think it's really important for people that want to
know to know and to find out. And if a
person has an Apoi four, okay, let's do it, let's fight,
and let's go. For example, women with one or more
copies of the Apoi four variant, I start looking at
their estra dial levels or estrogen levels in the blood.
(13:09):
If that starts dipping even sometimes before perimenopausal symptoms, maybe
we need to start doing something about it. And then
do something about that. On the early side, if a
woman has perimenopausal symptoms and they have an Apoi four variant,
I'm really, really really gonna want to treat, and I'm
gonna obviously work very closely with uns or are there
treating clinicians to try to navigate that. Women or men
(13:31):
with apoe also need to drink alcohol in a much
less way like alcohol plus apoe is bad, Smoking plus
apoe is bad. A sedentary lifestyle plus apoe is bad.
There are so many things that I tell patients to
do differently if they have one or more copies of
the Apoe four variant of the gene. For example, Omega
(13:55):
three fatty acids, So Omega three fatty acids are a
brain healthy type of fat. If a woman wants to
reduce their risk of Alzheimer's disease and they have an
Apoi four variant and they're eating lots of fatty fish
or a couple times a week fatty fish like lake trout, mackerel, herring,
Alba cortuna, wild salmon, sardines, and they can't get the
(14:16):
Omega three fatty acid levels up from eating a brain healthy,
you know, fatty fish diet. Then potentially using an Omega
three fatty acid supplement is preferentially beneficial for people with
the APOI four variant. So the take on point with
APOE is, I believe it's important to be tested. I
believe it's important to then personalize a care plan based
on APOEE, and we've published on this. You know, the
(14:38):
instruction manual is at least there, But I would say
most doctors and most of the public are totally unaware.
I think the other thing is if there is someone
out there listening that's reluctant and doesn't want to know
because they think that if they find out that they
have an APOI four you know their life is going
to be ruined and they're going to be sad and anxious.
I'd first say, I don't agree that that's the case.
(15:00):
When you get a genetic result like that, it does
not mean you're going to get Alzheimer's disease. You can
have one or two copies of apo BE four and
never get Alzheimer's, and you cannot have any.
Speaker 4 (15:09):
Copies of apo BE four and still get Alzheimer's.
Speaker 3 (15:12):
So to me, getting tested for the APOI four variant
is something that can help personalize care, but not predict
if someone's going to get the disease.
Speaker 1 (15:20):
So the estimate is about forty five percent of dementia
cases can be prevented. What about the other fifty five percent.
Speaker 3 (15:26):
Some people can do everything right and still get Alzheimer's disease,
And in a very small number of cases, like a
few percent, there's a gene, an early onset gene where
if they get it, and these are usually people that
get Alzheimer's symptoms in their forties or fifties, we just
don't have the best tools for or many tools at all.
There are other people that have different genetics and different
(15:47):
lifestyle factors and different things that maybe we haven't figured
out yet, where maybe they do everything right and they
can delay Alzheimer's by six months here, two years, or
five years, but no matter what they do, they're still
going to develop. So what I would say is based
on the best available evidence, there's a reasonable number of
people that can get off the road to Alzheimer's, but
(16:07):
there's a lot of people that may only be able
to delay it. But to me, that's a glasses have
full thing. If we can delay Alzheimer's by six months,
a year, two years, or five years, and in that
time period, that new blockbuster drug comes and something comes.
Speaker 1 (16:20):
Out, right, figure it out.
Speaker 3 (16:21):
Then through the person's own you know, behavior change in
adopting brain healthier habits than that person was able to
make a difference. But no, I think within a few
years will be at fifty percent, fifty five percent, sixty
percent because the evidence will evolve. But I think we're
pretty close to the majority of people. And that's not
what I was taught in metopal.
Speaker 1 (16:40):
Yeah, that's just kind of like the cancer predisposition genes, right,
like ten percent is hereditary. So talk to us a
little bit about those imaging studies that you did, because
I thought they were so profoundly impactful.
Speaker 4 (16:51):
Yeah.
Speaker 3 (16:51):
So, and this is you know, led by doctor Lisa
Mosconi and Holly Hurstov at the Alzheimer's Prevention Clinic and
Women's Brain Initiative. And what we did was we looked
at basically brain imaging of women during various time periods,
so premenopause, perimenopause, and postmenopause, and we looked at women's
(17:11):
brains in terms of MRIs MRIZ or magnetic resonance imaging,
which is brain imaging that can look at the size
of the brain like if they're shrinkage or if it
looks normal. You could also look at something called white
matter disease, which is evidence of vascular issues and strokes
and mini strokes and silent strokes. And then we looked
at a type of imaging called the PET scan. We
use a marker that actually bound to amyloid amoloids, that
(17:34):
sticky protein, a plaque that builds up in the brain
of a person with Alzheimer's disease. And basically we tracked women.
We also then had a men's brain imaging study that
kind of tailed on later, and we tried to compare
the two. But women who were treated with hormone replacement
therapy had less amoloid accumulation and their brains looked better.
At least one or two, probably three of these women
(17:56):
were your patient, So you were a big part of this.
And I mean I had a sixty sixty one year
old woman who sho had two copies of the APRILI
four variant. She should have done worse. Her brain looked pristine.
Her brain looked like a fifty year old woman or
a four five year old woman. Why she had been
on harmone replacement therapy the whole time. And I remember
another woman was on harmone replacement therapy and it's seven
(18:19):
years because it was some magic number. They told her
to come off and the woman's like, but I don't
want to, but the doctor said, you have to because
this study and this research and you can't be on
it for more than seven years. And the woman came off,
and like, aside from feeling worse, her cognition got worse.
Speaker 1 (18:35):
Her hormones scary stuff.
Speaker 3 (18:36):
Clearly went down, her estrogen went down, her cholesterol went wackado,
I mean, everything got worse.
Speaker 4 (18:44):
And then she had to fight with her gyn to
go back on hormone.
Speaker 1 (18:48):
Replacement therapy an better education.
Speaker 3 (18:50):
Yeah, so she finally did, and she felt better, but
she probably lost like six months of I think brain
protection and she ended up okay. But you know, I
think where we are today, hopefully that happens less.
Speaker 1 (19:01):
I think it does happen last, but it's still happening.
Speaker 4 (19:04):
I there is so much, my gosh, just garbage out there.
Speaker 3 (19:07):
I'm worry about estrogen and it saddens me because estrogen
is what I believe to be among the most if
not the most protective like chemicals. A woman's brain can
be protected by we just see better brain outcomes, like
brain size is larger, amyloid is less or not there,
(19:27):
a cognitive function is better, memory function is better. So
to me, estrogen is a brain protective hormone.
Speaker 1 (19:34):
Late start estrogen women in their sixties. We're being told
kind of by our guideline makers, right, don't start after
sixty or after ten years of menopause. So talk to
us about that. Are we okay to use estrogen in
older women over sixty?
Speaker 4 (19:50):
Yeah?
Speaker 3 (19:51):
So I can tell you if we had this conversation
a few years ago, I would say I have no idea.
I would say that the best I could do is
women that were on estrogen for between seven to ten
years or greater than ten years in our cohort, and
what I saw had better brain outcomes. But I didn't
have like definitive evidence. Now and again I wouldn't say
(20:12):
this is definitive evidence. And we haven't fully published this.
We've presented this at a conference, but not published. We
have women between the ages of forty two and sixty
seven in our research coulport where we track brain biomarkers,
we track hormones, and we track Oh there is something
I want to talk to you about We've done six
blood draws during the menstrual cycle just to figure out
(20:33):
like what happens to these brain markers as estrogen and
progesterone change during the natural mentrol cycle. So between the
ages of forty two to sixty seven we've studied hormone
replacement therapy and on a whole on the women that
we've studied hormone replacement therapy with estrogen and or progesterone,
depending on with the gin and or primary care and
(20:53):
or endrocronologists we have helping too. We have shown significant
improvements reductions in tau protein, which is a bad protein
that builds up in the brain of Alzheimer's, and maybe
a little bit of familoid too, but more on the
TAW side, and women have higher baseline taws than men,
and that's a whole different discussion and we haven'tgured out
exactly why that is. But on the whole harm and
(21:13):
replacement therapy throughout, whether you're forty two, we have a
forty five year old, we have a forty seven year old,
we have a forty nine, multiple forty nine, fifty and
fifty one, so we have a cluster obviously, right around there.
And then we have a sixty year old woman and
a sixty seven year old woman. And in these individual women,
when we look at like how were their numbers, they
got more normal. Some of these women were borderline optimized yep,
(21:36):
and they got optimized it. But basically we're building up
a cohort of women to study this in and so
far in our IRB approved research study, we've shown better
brain protein outcomes after starting harmon replacement therapy, even in
women at age sixty and above.
Speaker 1 (21:53):
Coming up, when it comes to Alzheimer's, what are the
biggest risk factors outside of hormones and genetics and what
are the best possible actions we can take to mitigate them.
We'll be right back. Let's talk a little bit about
(22:20):
the other risk factors for women. Actually, we've talked about
hormonal risk factors. You hear a lot like heart health
is brain health, cardioc health is brain health. Talk to
me about the other risk factors for Alzheimer's STU sure.
Speaker 3 (22:33):
So you know, in terms of lifestyle factors, there's many
A hugely important bucket is vascular health and vascular brain health.
So things like diabetes. When a person has diabetes, they
have twice the risk of developing Alzheimer's disease. High blood pressure, hypertension,
Does it cause Alzheimer's, Well no, I don't think it
causes Alzheimer's, but it fast forwards cognitive decline. High cholesterol.
(22:54):
Oh boy, same sort of thing. You know, people say, oh,
your cholestero's borderline. Go you know, eat less this or
go exercise more. No, A lot of that's genetic and
like a lot of times, most of the time someone's
going to need a medicine if the general lifestyle things
don't work. So when I think about the big buckets
blood pressure management, cholesterol management, and diabetes management, what I
would say here is borderline is not normal and borderline cholesterol,
(23:20):
borderline blood pressure. You know all these numbers that are borderline.
See you back in a year. Like the difference between
normal and optimal and normal and borderline is a big
difference when it comes to preventive brain health. So what
I would say here is know your numbers. Everyone out
there should know what their blood pressure is. And there's
a study called the Sprint Mind Study. The Sprint Mind
(23:42):
study looked at two different blood pressure ranges and the
effects of these blood pressure targets on brain health. And
I would say a lot of doctors think that one
forty eighties is like okay, But this study looked at
how do people do one forties versus a lower target
of one twenties or below. And I actually stopped the
trial early. The results were so good. After three and
(24:04):
a half years of just lowering the blood pressure from
one forties to one twenties, not a big drop, people
were able to reduce their chances of developing the earliest
symptomatic phase of dementia called mild cognitive impairment by nineteen percent,
well nineteen percent, just by optimizing blood person. So again
the concept here is normal versus optimal. Same thing with cholesterol.
(24:26):
I see so many people out there with ldl's that's
you know, the bad cholesterol LDL cholesterols one thirties, one forties,
one fifties, on sixties, one seventies, And doctors will say, eh,
I don't know, let's.
Speaker 4 (24:38):
See it back in the year.
Speaker 3 (24:38):
Go eat less fast food and the person's like going
on any fast food. The take on point with cholesterol
is you can eat everything right and still a high cholesterol.
So what we try to do fundamentally is if a
person is doing everything right from a nutrition perspective and
their cholesterol is still high, then we may need to
use a pharmacologic agent, a drug, a prescription drug. And
(24:59):
when we don't know what to do, we may look
at the heart because the calcium score in the heart
basically predicts what your heart risk is for the following
ten years. And if person has elevated calcium in their
heart vessels, they are at a much higher risk of
vascular cognitive impairment or vascular dementia twenty years later. And
(25:19):
what we can look at in the heart potentially as
a proxy for brain is if a younger woman is
at risk and their calcium score is zero, but they
have soft plaque building up in their heart that hasn't
turned hard yet, and they're in their forties or fifties
or sixties, then that's someone If they have borderline cholesterol,
I'd rather treat them, and as a clue that we
(25:41):
should treat earlier rather than later. Now, there are some
women and some men that just their vessels are clean,
their brain looks clean, there's no soft plaque, there's no
hard plaque, and they have borderline or elevated cholesterol. And
maybe those cases are okay not to treat, but there's
so much nuance here, and you know it's an evolving story.
Speaker 1 (25:57):
Yeah, that's tough one. So talk to me about statins
a little bit, because you know, I have a few
patients that will come to me saying I'm not going
to take that statin because it actually causes dementia because
it impacts my mitochondria, the powerhouses of the cells.
Speaker 3 (26:09):
Yeah yeah, okay, my favorite topic, I'm so go advertised
is being recorded. Hop Yeah, it's the same, right, I'd
love to do this again. Don't get me wrong if
there's a glitch. But okay, let me start by saying
the totality of evidence is extremely strong, that the net
positive effects of statins are absolutely net positive and protective
(26:30):
on brain health, and the lion's share of studies, the
vast majority of studies where people have been on statins,
and these are epidemiological studies and they follow them over time.
People that take statins are at a lower risk of
dementia and Alzheimer's disease. That's what I would say. There
are certain cases. This goes back to the whole personalized
care and precision medicine there are certain cases, and I
(26:51):
would say this is a small number of cases, but
there's a lot of internet chatter about this where people
who take statins feel that they have brain fog. People
that have statins can also have muscle soreness, and there's
all sorts of things that can happen from statins. But
I would say, on the whole, the vast majority of
people that take statins will be most likely to benefit
from statins on the overall net effects. So I guess
(27:14):
what I would say is, I don't have all the answers.
I don't have the perfect answers, but the totality of
evidence suggests that statins are protective. You know, I don't
have the perfect answer for precision based cholesterol treatment, but
this is something we're studying in our research.
Speaker 1 (27:26):
Let's talk about sugar. Most people will go the doctor
and hemoglobin a one ce by point six, it's okay,
you don't have diabetes. By point eight it's okay, you
don't have diabetes. But it's insulin resistance absolutely, And so
talk to us about that. What should be our target
for our measurements of our glucose metabolism?
Speaker 5 (27:45):
Yes?
Speaker 1 (27:45):
Why?
Speaker 4 (27:46):
Yeah?
Speaker 3 (27:46):
So I think I mentioned earlier that people with diabetes,
and it's a frank diagnosis of diabetes where hemoglobin a
one cee as much higher, is two times the risk
of Alzheimer's. But insulin resistance just really fast forwards amyloid
accumulation and amyloid isn't that bad protein the pathological protein
that builds up in the brain of a person with
Alzheimer's disease and insulin resistance, I think fast forwards brain aging.
(28:10):
As the belly size gets larger, the memory center in
the brain gets smaller. Fat around the mid section, around
the visceral organs, especially for women, Women that have increased
belly fat are at an increased risk of dementia.
Speaker 1 (28:23):
That's huge because it's such a problem for perimen apostle women.
Speaker 4 (28:28):
Stubborn area to get rid of it.
Speaker 3 (28:29):
And women could do everything right and still have trouble
getting rid of that fat. And you know, there's some
you know stuff which I'm sure we're going to talk
about GLP ones, which is.
Speaker 4 (28:37):
A very interesting topic, hot button.
Speaker 3 (28:39):
That's our big hot button topic which you and I
have both talked about and implemented in our clinical practices.
But women and men need to gain muscle mass, and
the more muscle you have, the better your metabolism. Women
and men need to lose belly fat and that can
be hard, and that's you know, through a targeted exercise,
lower intensity zone to training that some people talk about.
(29:00):
Through nutrition changes obviously sometimes these new drugs that can help,
but yeah, insulin resistance, just fast forwards brain aging and
fast forwards amyloid and you know, as one of the
most critical things that we need to optimize in the
fight against Alzheimer's disease.
Speaker 1 (29:15):
Give us your exercise prescription. Is it zone two cardio?
Is it strength training? Three times a week? Like? What
is the exercise prescription to prevent dementia?
Speaker 3 (29:26):
Everyone that I see gets an individualized exercise prescription based
on what I would say are three factors. We call
it the ABC's of Alzheimer's Protection. My next question, so A,
is anthropometrics. Anthropometrics is a big fancy word for body composition.
Body composition is percent body fat and muscle mass, and
(29:50):
to me, the percent of lean mass is the most important.
And it's not just about what the percent body fat is,
but where it is in a woman that has stubborn
belly fat, especially perry or postmenopausal. We recommend really a
multi prong attack. So number one, zone two training, which
is about steady state cardio where a person is exercising
(30:11):
walking fast, for example, but the person can still carry
on a conversation. This is not, you know, high intensity
interval training, This is not sprinting. This is lower intensity
steady state or zone two means zone two of your
cardiovascular rate where you can take your maximum heart rate
and you multiply that by point six or point sixty five,
so at sixty to sixty five percent of what your
(30:34):
maximum heart rate is and try to stay in that
heart rate zone for forty five to sixty minutes to
burn the carbs that are in your blood and basically
lose body fat. And I think most people are unaware that.
Like high intensity interval training, for example, where someone's either
on a peloton bike at a hit class or an
orange theory or berries, that's a great way to get
(30:55):
a great workout and sweat a lot and make your
heart stronger. But a lot of the times you're just
not being efficient at burning body fat. You actually burn
body fat more efficiently when you're at a lower steady state.
The zone two cardio, where again this could be walking
fast with a weighted for forty five to sixty minutes
and you do that three times a week and if
your doctor says, okay, you know, I can't give anyone
(31:17):
individual medical advice here, but the doctor says, okay, even
doing it fasted in the morning, and that's another way
to jump start body fat loss. So if a woman
is trying to lose fat around the midsection, we recommend
at least a few times a week, two to three
times a week of Zone two training. We absolutely, absolutely,
absolutely recommend strength training. Strength training is tricky in women
(31:38):
during the peri and postmenopause because many women have trouble
gaining muscle mass after the perimenopause.
Speaker 1 (31:43):
You gotta lift heavy, yep.
Speaker 3 (31:44):
But like there are certain women that just cannot gain muscle,
And then what do you do? Is it protein? Is
it creatine? Is it testosterone?
Speaker 4 (31:52):
Hormones? Hormones and hormones exactly, And that's what I thought
you were going.
Speaker 1 (31:55):
To say, persistence, lift heavy yep, safely yep, and hormones
and hormones.
Speaker 3 (32:00):
And I agree with that, and I had to put
nutrition and protein and all that kind of stuff. But
you can't just do zone two, and you can't just
do strength training, and you can't just do high intense
interval training. If a woman is muscled, then you want
to do more strength training.
Speaker 1 (32:14):
For brain health, what should we aim for in terms
of percent body fat, percently muscle mass.
Speaker 3 (32:19):
These are tricky things, so we recommend dex's scans. So
DEXes are a little bit of radiation, but it's like
less than a chest X ray minimal, and you look
at body fat, muscle mass, and you look at bone density.
So to me, when I'm giving a woman recommendations for
brain health, I'm also very interested in their bone health.
And if a woman has osteoporosis or low bone mass,
(32:41):
I'm going to prioritize strength training, maybe more so than
would otherwise. You know, obviously I'm trying to prevent someone
from getting dementia, but when it comes to women, I
also want to prevent them from having like a fracture.
You know, my mom, when she was eighty two, fractured
her femur, her hip.
Speaker 4 (32:57):
She broke her hip.
Speaker 3 (32:58):
And like you learn in medical school that once a
woman breaks their hip, they usually die within six months.
And six months later, my mom passed away, So you
really taken the whole picture.
Speaker 1 (33:10):
Talk to me about other prevention maneuvers that you can do.
Social engagement, neuroplasticity, cognitive reserve, keeping your mind nimble, and
learning new things.
Speaker 3 (33:19):
Yeah, so if you don't use it, you lose it.
I mean, the list goes on and on. You know,
forty five percent of cases of dementia maybe preventable. There
are so many modifiable risk factors, you know. For example,
hearing loss is something that people just they hear and
they're like, wait, what what do you mean treating hearing loss?
At like eight percent of cases of dementia may be
attributable to hearing loss, And that's confusing, like why would
(33:42):
that be well, less socialization, less interaction, less verbal whatever.
So hearing loss is key. Vision screening is key. Socialization
is absolutely critical. Learning something new, a new language, musical instrument.
Stay engaged. It's not just you can do all the
sodoka you want and you're just going to get better
at sodoku, but learning something new, socializing with friends, staying engaged.
(34:06):
Stress reduction is key. Stress mitigation something called mindfulness based
stress reduction NBSR. It's tied to better brain health outcomes.
Speaker 1 (34:14):
So you do a lot of work in biomarkers. Oh yeah, right,
So tell us the utility of biomarkers, what they are
and when does Alzheimer's start? Does it start in our
forties and we just don't know that it's starting and
biomarkers can help us with that.
Speaker 4 (34:30):
Or talk to us. Yeah.
Speaker 3 (34:31):
So, you know, I've been talking about trying to develop
and create and prove a cholesterol test of the brain
to fruition. And what I mean by that is just
like everyone goes to their doctors and hopefully starting in
their thirties and forties, they get a cholesterol test where
you look at your total cholesterol, your HDL, your LDL
which is the bad cholesterol, and triglycerides, and then doctors
(34:52):
know how to treat it. There's going to be what
I colloquially call the cholesterol tests for the brain, and
instead of those markers, you're going to have the amyloid
and the TAO and this and the that. And currently
in our lab we have over one hundred and fifty
markers that we're looking at and that we're tracking over time.
So what I would say is, you know, it's still
early days. There are blood tests that are available today
(35:13):
that if a person has symptoms and the person's doctor
thinks that the symptoms could be related or due to
Alzheimer's disease, then there are blood tests out there today.
They can be used to basically say, aha, this is
a good screening test, these symptoms are probably due to Alzheimer's.
I think when it comes to prevention and risk reduction
and doing a risk assessment, our work has shown that
(35:34):
you can't just order one test. You can't just order
a handful of tests. You have to order a panel
of tests and really interpret them within the context of
each other. So I hope and I believe that people
in the coming years will go to their doctors in
their thirties, forties, fifties, sixties, seventies, eighties and beyond before
they have symptoms and get this cholesterol test for the brain,
(35:54):
this risk assessment panel to figure out are they at risk?
And then not just are they at risk, but based
on the markers, what you can do about it. If
a person has high tau before symptoms, what do you do.
If a person has high amyloid before symptoms, what do
you do? It's the same thing like what do you
do if you have an LDL cholesterol that's high, Well,
you take this medicine or that medicine, or you do
(36:15):
a scan. We kind of understand that for preventive cardiology.
We're just starting to understand that now for preventive neurology,
and you know, I hope that very soon we'll be
able to offer these tests to people. I think the
challenge with blood tests for Alzheimer's disease one, sometimes you
can have elevated levels and they're not really elevated. They
(36:37):
could be a false positive. What we've seen in our
in our work is that people with active viral illnesses.
I've seen people with you know, for example, herpes lesions
or herpes herpie simplex one. I've seen someone who just
had COVID and their markers were off the charts, and
then a few weeks later we retest and the markers
came down. I've seen people that looked like they had
elevated brain biomarkers worrisome for Alzheimer's disease triggered by things
(37:02):
that were transient. I had someone going through a divorce,
sleep deprived, terrible like situation, really rough, and one of
these brain markers was through the roof, came back six
months later. I was pretty worried about the person. Divorce
was over the person that slept. We repeated the markers
and everything was normal.
Speaker 1 (37:24):
It's time for a quick break. But when we return,
doctor Isaacson and I will get into some of the
biggest hot button issues around long term cognitive health, and
we get into what the future of diagnostics and treatment
will look like for Alzheimer's and dementia. Decoding women's health
will be right back. Let's do some hot button topic. Sure,
(37:56):
of course, talk to me about testosterone in women's brain health.
Speaker 3 (37:59):
So I was for both women and men a decade ago,
like I would say anti testosterone, I would say, what
are these people doing or reving up the system? Like
why are we using testosterone? That's my performance enhancing drugs?
Like I would say, that's the way I was a
decade ago. I was wrong what I've seen clinically, and
this is a shotal shift for me. I mean, there's
(38:21):
probably ten men and women that have started on testosterone
that I mean one more muscle mass or sustained muscle mass.
Two felt better clinically, you know, was tired yet.
Speaker 4 (38:35):
Yeah, exactly.
Speaker 3 (38:36):
People don't even realize how bad they feel until they
start taking testosterone, and like that was really surprising to me.
I didn't really understand that. And what I would say
is when I say estrogen replacement plus progesterone like slam dunk,
better brain outcomes on the whole. With testosterone, I would
say a lot of people on testosterone, I don't see
(38:59):
much of a brain health brain biomarker change, but some
people I do, it's just less robust of a change.
So please don't take this as fact. Then we haven't
studied this, but I've never seen brain biome marker worsening
in the ten or so people that have started on.
Speaker 1 (39:15):
Testosterroen important because yeah, some some women with lower testosterone
levels have fatigue. And it's interesting because we always asked
this question like how do you feel? And it really
speak could you feel better?
Speaker 4 (39:24):
Right?
Speaker 1 (39:25):
You know, let's get really controversial. Okay, I'm ready microdosing
GLP ones for brain help. Yeah, my favorite topic.
Speaker 4 (39:32):
Yeah, this is the whole.
Speaker 1 (39:32):
Thing lands me in hot water all the time.
Speaker 4 (39:35):
Oh you're telling me forget it? Okay.
Speaker 3 (39:38):
So I did not wake up one day and say
I'm gonna try to advance the narrative on microdosing. What
happened was I had a patient that needed a GLP
one for insulin resistance that did not seem to benefit
from lower carb diets, exercising out to wazoo, you know,
(40:00):
doing the zone two, doing the strength training, was still
insulin resistant eight POE four. Just too many risk factors
and I just did not feel comfortable. Was the person
diet No is this off label by the FDA? Yes,
but their doctor put them on tr zeppetide, which is,
you know, one of the GLP ones two point five milligrams,
(40:22):
and that person felt really sick, lost some body fat,
which is good, also lost a little muscle mass which
wasn't as good. And basically the recommendation was try half
of the dose. And in that one case, that's what
kind of like changed it for me. The person did better,
felt better, their insulin resistance went away, and their brain
biomarkers improved. And this was using less than the FDA
(40:44):
approved regular dose of the drug. So the drug companies
will say, oh, that's never been studied, you can't use it.
I mean people use drugs off label all the time,
like blood pressure medicine, can't tolerate it, get lightheaded. Use
less pain medications. Oh boy, getting lightheaded, but you're still
in pain. Use less some people it works for right.
So I think, you know, using drugs off label is controversial,
and I think you know, obviously the doctor has to
(41:06):
talk to their patient about this and make informed decisions.
But in our data set, you know, we have a
subset of people that have taken less than the lowest
dose recommended or FTA approved of glp ones, the injectables.
And also I want to say that there is twenty
years of data on glp ones, the oral ones that
(41:28):
show that people that are on these glp ones for
long periods of time have a lower likelihood of developing dementia.
It's not like we're trying these things willy nilly. I mean,
there's like many studies that have shown this. There's also
a study that's going to be published sometime later this
year to look at is the oral dose of semaglutide
and commercial name is Rabelsis, but semiglutide is the generic name,
(41:49):
and a fourteen milligram pill is being studied in two
studies called Evoke and Evoke plus and people with mild
cognitive impairment, which is the earliest symptomatic phase of Alzheimer's
to see. You know, does it improve symptoms? Does it
delay progression? Like?
Speaker 4 (42:02):
How do these people do?
Speaker 1 (42:03):
These are people without diabetes or without insulin resistance crack.
These are just like all comme. So how much of
the effect do you think is a direct effect of
the gl maybe as an anti implammatory And how much
of the effect of this microdose sing do you think?
Is it just change in body comp and decrease of
visceral fat.
Speaker 3 (42:19):
Yeah, I don't know. I think there's more to it
than just the body fat loss. I think there's some
sort of direct effect. I think something happens with inflammation.
I also am very you know, I'm an advocate that
if people are on glp ones and they're losing muscle
mass or losing a majority of their weight is due
(42:39):
to muscle mass, I tell their doctors or or I advocate,
because I'm not usually prescribing these, please stop, or please
go on a lower dose, like we don't want to
lose muscle mass. And you know, I guess what I
would say is in the right person, at the right
dose and for the right duration of time, as long
as the person's doing strength training, eating enough protein and
carbs around their workouts so they don't lose muscle mass,
(43:02):
and eating brain healthy and otherwise, I really think GLP
one's at lower doses if possible, when possible, maybe one
one of our most like helpful things for dementia.
Speaker 1 (43:14):
Prevention keytnes keto.
Speaker 4 (43:17):
Yeah.
Speaker 3 (43:19):
I spent a lot of my time earlier in my career,
like probably fifteen years ago on keytnes and ketosis, and
I really do think that there's something to this and
lower carbs and ketogenic diet, time restricted eating, intermittent fasting.
There's what I would say, is this The answer here
is personalized medicine and precision nutrition. And I haven't figured
out like the exact algorithm I think, but I'm not
(43:40):
certain that people without an apoe four variant may benefit
more from keytnes and ketosis.
Speaker 1 (43:47):
And that's because you can use them as an alternate
energy source for the brain. Right. This is like tapping
into the brain's energy production exactly.
Speaker 3 (43:53):
So the brain can only use two things as fuel. Sugar,
which is, you know, the stuff that we don't want
to overload the brain with because it causes inflammation, insulin
resistance and key tones. KEYTNES is like, you know, a
cleaner burning fuel. It's like the hybrid car model, Like
you have the hybrid battery, which is the KEYTNES, and
then you have the gasoline, which is the sugar. And
of course what do you want to do? You want
to use the keytones right if you can. I think
(44:14):
there is probably a role for ketogenic diet maybe and
if someone can handle it, but I don't fully have
it all worked out.
Speaker 1 (44:21):
Yet looking forward to that answer. And some of these interventions,
like lifestyle interventions impact women more than men. Actually, is
that correct or yeah?
Speaker 3 (44:30):
So you know, we actually published a paper on this.
We took our Alzheimer's Prevention Clinic cohort and we actually
showed that the interventions, the lifestyle interventions in our Alzheimer's
Prevention Clinic actually on the whole worked better in women
than in men.
Speaker 1 (44:44):
So like some good news for women.
Speaker 4 (44:46):
It's really good news. And you know, we're not powerless.
Speaker 3 (44:51):
And our data shows that while yes, on the whole
for everyone, it work, meaning lifestyle interventions and managing risk factors.
On average, the people in our study got twenty one
different interventions, so This wasn't like, you know, eat a
magic blueberry and think you can prevent Alzheimer's disease. But
between the synergies you have the exercise, the brain healthy nutrition,
the olive oil, omega three fatty a acids, the stress reduction,
(45:12):
the staying engaged and modifying your blood pressure, cholesterol, diabetes.
Like you do all of these things together, socialization making
sure someone gets adequate sleep. Doing all these things together works,
and it works better in women. And it worked regardless
if a woman had either one, zero or two copies
of the Apoi four variant.
Speaker 1 (45:33):
What have I not asked you about today? Do you
think is important for especially for midlife women, in their
brain health.
Speaker 3 (45:39):
I've seen so many women over the last fifteen years
that are concerned about their brain health, and women are
more likely to be affected. The Apoi four gene affects women,
you know, more in a negative way. There's so many
individual risk factors for women that are really confusing, complicated,
and I would say, in some way scary, and the
best thing that I could do is just tell women
(46:00):
to just just pause, take a deep breath, and it's
going to be okay. Genes are not our destiny. The
field of Alzheimer's disease is changing so rapidly. The things
that I can talk about now, like I couldn't even
dream about ten years ago. I went from like seeing
patients and you know, doing all these like cognitive tests
and some blood draws to now like running a comprehensive
(46:24):
blood biomarker lab where we have multiple pieces of equipment
and we like finger prick techt Like I have a
fingerprint card and my backpack over there, Like we're going
to be doing finger print card testing soon. It's not there,
it's not one drop of blood, but it's like with
nine drops of blood, we can detect one hundred and
twenty brain proteins. Like things are getting better. And what
I would say to women out there, regardless if you're premenopausal, perimenopausal,
(46:47):
or postmenopausal, there are things that you can do today
to improve your brain helth tomorrow. You know, we have agency.
We can take control of our brain health. Talk to
your doctor, get online, learn there are resources out there
we can win the fight against Alzheimer's disease.
Speaker 1 (47:02):
Where can we find information, Like because a lot of
doctors don't talk about this and it's not well recognized
but where can we get the real information?
Speaker 3 (47:09):
Yeah, so back in twenty fourteen, you know, we created
the first I believe kind of evidence based curriculum about
Alzheimer's prevention. We studied it in a randomized controlled trial,
and we published on it and we put coursework out there.
We've then updated that and now we have two different resources.
So one people can go to id dot org. I
in D stands for the Institute for Neurodegenerative Diseases i
(47:33):
ND dot org and if you go to the learn
page i ind dot org backslash learn, you can watch
video after video after video. There's over fifty videos interviews
about brain healthy nutrition and the latest on blood testing
and exercise and all sorts of information. It's all available
for free. The other website is also a randomized controlled
study that we've done. It was funded by the NIH
and National Students of Health, where people can go to
(47:55):
Retain your Brain dot com and basically using a software
platform that gets to know you from the comfort of
your own cell phone. You can do a risk assessment,
you can do cognitive activities and then the software will
learn about you. You can actually type in your APO
if you know it, if you checked it on twenty
three and meters and basically the SOFTWARELD then put you
(48:16):
on a kind of a risk education plan to try
to get you to adopt brain healthier habits. So what
we've tried to do is take everything we've learned in
our research studies, take everything that we've learned from other
people's research studies, and we've tried to put it out there.
Speaker 4 (48:31):
And I think that's going to be the way to
It's pretty cool.
Speaker 1 (48:34):
That's kind of a model for like a lot of
issues that we can prevent, right, not just brain health.
But it's like a great paradigm.
Speaker 3 (48:41):
Yeah, I mean, access to care is so difficult, and
you've said this before. We're a sick care system. Were
not a healthcare system. There's no diagnostic code that a
doctor can bill an insurance company for the term Alzheimer's prevention.
We lost so much money at the Alzheimer's Prevention Clinic.
It was like impossible. We were collecting twenty eight cents
on the dollar, and we had to get grant funding
and donations and all this kind of thing. Preventive care
(49:03):
is like it doesn't pay, doctors can't build for it.
So we've decided to just put it out there online
for free.
Speaker 1 (49:09):
Yeah, that's great. I mean to really focus on preventative care.
Thank you so much for joining us today. So appreciate it. It's,
like I said, such an honor to have you.
Speaker 4 (49:17):
I appreciate it. Thank you.
Speaker 1 (49:22):
The landscape of Alzheimer's prevention is changing. Leading neurologists like
doctor Isaacson are proving through robust research that evidence based
strategies can delay and even in some cases, prevent the
disease from ever taking hold. And there are meaningful steps
that you can start today. First, know your genetic risk.
(49:44):
A simple test can tell you which APOE variant that
you carry. Even if you have one or two copies
of the APOE for variant, it does not mean that
you're destined to develop Alzheimer's. Understanding your risk helps you
take action early. Talk to your doctor about hormone support.
Estrogen is a brain protective hormone. Beginning therapy around menopause
(50:08):
is ideal, but even later into your sixties and beyond
may still offer cognitive benefits, and I look forward to
that research in the future. Monitor your numbers, keep an
eye on blood pressure, cholesterol, and hemoglomina ONEC borderline isn't optimal,
and there is a big difference between optimal and borderline,
(50:31):
so it's not something to shrug off. Even small improvements
in metabolic and vascular health can positively affect brain function.
Understand your body composition. A DEXA scan can help you
track visceral fat, which is linked to cognitive decline, as
well as bone density and muscle mass. Zone two. Cardio
(50:51):
and strength training are really powerful tools for shifting body composition.
And if insulin resistance is severe, talk with your doctor
about whether a golp one medication might help protect your
mental well being. Chronic stress is neurotoxic. Find practices that
help you slow down, breathe, and enjoy your life, and finally,
(51:15):
stay hopeful. We are living in a moment of unprecedented progress.
Do what you can today, knowing that even more effective
tools are coming tomorrow. Coming up on the next episode
of Decoding Women's Health, I speak with a pioneer and
weight loss surgery about his own experiences not only as
a clinician, but also as a patient.
Speaker 5 (51:37):
Society, including a lot of doctors, think people are taking
the easy way out because there's this absolute myth and
it's a myth that you can do this sort of
weight loss on your own and keep it off.
Speaker 1 (51:55):
Decoding Women's Health is a production of Pushkin Industries and
the Adrea Health and Research Institute. This episode was produced
by Rebecca Lee Douglas. It was edited by Amy Gaines McQuaid,
mastering by Sarah Burguier. Our associate producer is Sonia Gerwitt.
Our executive producer is Alexandra Garreton. Our theme song was
(52:15):
composed by Hannes Brown. Concept creative development and fact checking
by Shavon O'Connor. A special thanks to Alan Tish, David Saltzman,
Sarah Nix, Eric Sandler, Morgan Rattner, Amy Hagdorn, Owen Miller,
Jordan McMillan, and Greta Cohne. If you have a question
(52:37):
about women's health in midlife, leave us a voicemail at
four f five two oh one three three eight five,
or send us a message at Decoding Women's Health at
Pushkin dot Fm. I'm doctor Elizabeth Pointer, and thanks for listening.
Until next time.
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