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[gentle music]

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- Katie Gletty-Syoen:
Hello, and welcome to the

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Village of McFarland
Municipal Center.

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My name is Katie Gletty-Syoen.

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I'm the director of McFarland
Senior Outreach Services.

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And I'm so pleased
to see you all here today.

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Today, we're welcoming
doctor Carol Van Hulle,

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associate scientist

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at the University
of Wisconsin-Madison

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School of Medicine
and Public Health,

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who is here through
the Badger Talks,

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the speaker bureau
for the UW-Madison campus.

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For more information
on this great free resource

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for the state of Wisconsin,
please visit

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badgertalks.wisc.edu.

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Now, I'm pleased to introduce
Dr. Carol Van Hulle,

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who will be presenting today

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on vascular contributions
to dementia.

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Dr. Van Hulle received
her PhD in psychology

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with an emphasis
in quantitative genetics

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from the University of Colorado.

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She is now an academic
staff scientist

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with the Alzheimer's
Disease Research Center

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at the University
of Wisconsin-Madison.

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Her research focuses
on subject memory complaints

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and cerebrospinal
fluid-based biomarkers

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for early detection
of Alzheimer's disease.

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Please join me
in welcoming Dr. Van Hulle.

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[audience applauds]

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[laughs]
Hello, welcome.

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- Dr. Carol Van Hulle:
Hi, everybody.

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I wanna thank you
so much for coming out today,

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and I'm really grateful for
the opportunity to speak to you.

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I am Dr. Carol Van Hulle,
sorry. [laughs]

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And I titled my talk,

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"Vascular Contributions
to Dementia,"

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but I really should have
called it

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"Vascular Contributions
to Dementia Risk."

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So, we're gonna be
talking today about things

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that might raise your risk
of developing dementia,

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and hopefully things
that will lower your risk

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for developing dementia.

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So, I am a staff scientist

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with the Alzheimer's
Disease Research Center.

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I joined them in 2017.

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Prior to that, I was
studying child development.

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So, I went from one end
of the age span

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to the other end
of the age span.

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And my research does
broadly focus

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on identifying early signs
of Alzheimer's disease.

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But the research at our center

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runs the gamut
from basic science

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all the way through
to dementia care and caregivers.

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I like to start my talks
with this slide

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because I'm very proud
of the work

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that we do at the Alzheimer's
Disease Research Center,

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but also
because I wanna be very clear

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that I am speaking from the
perspective of a researcher

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and a statistician.

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I am not someone who
has had experience caregiving

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for someone with dementia,
and to my knowledge,

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I'm not living with dementia.

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[knocks on podium]
[audience laughs]

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As a stats person,

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also, I really love graphs, and
I do have quite a few graphs

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throughout this presentation.

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I will try to orient you to the
graph so they make sense to you,

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but I want you to focus
on the bars or the lines.

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'Cause I'm not trying
to fill your head

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with a lot of numbers.

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I just wanna give
you a quick snapshot.

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That said, we are gonna start
with a few numbers.

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I always also like
to start by acknowledging

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that dementia touches all of us.

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Whether you are living
with dementia

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or a caregiver
of someone demential,

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or not,
dementia is in our communities.

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It affects our neighbors,
our families, our friends.

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It is a difficult disease

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that requires a lot
of unpaid caregiving.

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It is a very costly disease,

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and it is the seventh
leading cause of death

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for people over the age of 65
in Wisconsin.

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However, the number one leading
cause of death for men and women

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over the age of 65 in Wisconsin
continues to be heart disease.

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So, for people who might be
unfamiliar with the lingo,

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when I'm talking about vascular
anything, vascular problems,

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vascular disease,
I'm referring to blood vessels.

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When I use a word
that starts with cardio,

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I'm referring to the heart.

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And when I use a word that
starts with cerebral or cerebro,

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that pertains to the brain.

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So, my immediate supervisor,
Dr. Cindy Carlsson,

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is a geriatrician,

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and I've heard her say
off the cuff, you know,

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in casual conversation
a few times,

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that people are
much more motivated to take care

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of their brains than they are
to take care of their hearts.

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So, the good news is that you
can do both at the same time.

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So, for those of you who have to
leave early or who fall asleep,

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the main message for today

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is that having
healthy blood vessels

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contributes to having a healthy
heart and a healthy brain.

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And regardless of what else--
health issues you may be facing,

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having healthy blood vessels,
especially in the brain,

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improves overall
quality of life.

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This is the outline
for the rest of my talk,

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so I wanna start
by defining dementia.

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I wanna talk about some of the
risk factors for dementia.

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And then, I'll talk about
vascular health

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and how it relates
to Alzheimer's disease.

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I'll talk a little bit about
what we know about therapies

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that target vascular
risk factors

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and cardiovascular health,

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and ways that we can
improve vascular health

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in the heart and the brain.

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So, what is dementia

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and how is dementia different
from Alzheimer's disease?

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This is a question we get a lot.

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You probably already know
the answer,

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but for those who don't,

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everyone likes
to use this umbrella metaphor

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'cause it is a
really good metaphor.

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Dementia is an umbrella term.

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It is a general term for
progressive loss of thinking,

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remembering, and
reasoning skills to the point

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that it interferes
with the person's ability

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to perform their daily tasks
and to care for themselves.

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There are many,
many causes of dementia,

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including reversible causes,

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including sleep disorders
and some vitamin deficiencies.

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If you are concerned
about your thinking skills

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or you are concerned about
someone else's thinking skills,

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it's very important
to go see a doctor

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and have a full physical
to rule out some

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of these reversible causes.

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However, the most common causes
of dementia are the progressive

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and irreversible
neurodegenerative disorders

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that are listed here
on this slide.

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The numbers at the bottom
indicate the number

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of dementia cases that are due

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to these different
neurodegenerative disorders,

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and you can see that

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Alzheimer's disease
is far and away

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the most common type or most
common cause of dementia,

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followed by vascular dementia.

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And each of these different
neurocognitive disorders

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has characteristic brain changes
that go along with them.

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But we've known since the 1920s
that people

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who are diagnosed with
Alzheimer's disease on autopsy

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also show signs
of vascular dementia.

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However, I think for a long time
it was under the pervasiveness

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of poor cerebrovascular health
and people

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with Alzheimer's disease
was underappreciated.

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So, I want to describe
the brain changes

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that characterize Alzheimer's
disease, in particular,

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because it is the
most common cause of dementia

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and because it's the one
that I study.

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So, here we have a depiction
of two brains.

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The one on the left is
a depiction of a healthy brain,

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and the one on the right
is an illustration

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of the brain of someone
with Alzheimer's disease.

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And if we could take
this little tiny red square.

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If you can see that, and zero in
on it, we would see the neurons.

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That's that purple,
those purple structures.

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And in this healthy brain,

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you can see the neurons
are kind of hanging out

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in what looks like
clean tissue.

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On the other side,

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when we look at that same area
in a person

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with Alzheimer's disease,
we see that around the neurons,

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we have these brown clumps that
represent amyloid plaques.

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And if you look closely,
and it might be hard to see

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from where you are,

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there's purple squiggles
inside the neurons.

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And that represents tau tangles.

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And these are the two hallmarks
that define Alzheimer's disease.

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Amyloid and tau exist
in our brains naturally.

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When amyloid becomes misfolded,
it gets very, very sticky.

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And that's why it forms
into those plaques.

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Tau exists in our neurons.

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It helps our neurons
communicate with each other.

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When it becomes misfolded,
it forms those tangles

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and it interferes
with the communication

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between our thinking cells
or our neurons in the brain.

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And these two processes
can be toxic,

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and that can lead
to the death of neurons

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and other cells in the brain.

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So, here we're looking
at an MRI image.

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And we use MRI
to look at the structures

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of the brains of individuals.

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And again, on the left,
you see a healthy brain.

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It's very full.

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It's filling
the whole skull cavity there.

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Whereas the brain of the person
with Alzheimer's disease,

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you can see there's a lot of
space in and around the brain.

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The arrows are pointing to
an area called the hippocampus.

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And the hippocampus is
heavily involved in memory.

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And it's one of the first areas

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where we see shrinkage or
atrophy in Alzheimer's disease.

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A lot of information

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that we have on brain changes
related to all

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of these different, all the
different neurocognitive

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or neurodegenerative disorders
that I showed you earlier,

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come from studies
of postmortem brain tissue.

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And that's true
for Alzheimer's disease as well.

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We're still learning a lot
from postmortem brain tissue.

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But we have come an
incredibly long way

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in being able to detect
amyloid plaques and tau tangles

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in people while they are alive.

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So, one of the primary ways we
do that is through PET imaging.

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So, the top here is a example
of a PET scan for amyloid.

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And you can see where
it's labeled positive scan.

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There's a lot of yellow and red.

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That's an indication that this
person has a lot of amyloid.

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The other scan, you see mostly
green and blue.

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On the bottom
is an example of a tau PET scan

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or a PET scan for tau tangles,

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and where it says positive scan,

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you see a lot of red
right here in this area,

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kind of above their ears.

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That's the medial temporal lobe.

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And tau has kind of
a very characteristic way

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of progressing as Alzheimer's
disease progresses.

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So, we start to see it here in
this area above your ears first.

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And then,
as the disease progresses,

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the tau tangles spread

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throughout the rest
of the brain.

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We can detect tau tangles,
or misfolded tau proteins

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and misfolded amyloid proteins

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in cerebrospinal fluid
and in blood.

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And so, this has really led
to a lot of advancement

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in understanding
Alzheimer's disease.

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So, this is a kind of
complicated slide.

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I wanna walk you through it.

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The top line there
is just depicting normal aging.

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Right, so we have thinking
skills doing the side here,

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where high is good
and low is worse.

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And with typical aging,
we all lose

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some of our thinking
and skills and our memory.

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I have terrible word-finding
difficulties myself.

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We forget names.

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We might forget to pay a bill
or something like that.

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All of that is very normal.

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The red line is depicting
a decline in thinking skills

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due to Alzheimer's disease
in this particular case.

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So, what I want you
to take away from this slide

248
00:12:46,166 --> 00:12:49,269
is that we start
to see brain changes.

249
00:12:49,336 --> 00:12:50,871
So, you can see the
accumulating brain changes

250
00:12:50,938 --> 00:12:53,640
on the bottom kind of correspond
to the decline

251
00:12:53,707 --> 00:12:56,577
in cognition
and thinking skills on the top.

252
00:12:56,643 --> 00:12:58,378
We see these brain changes start

253
00:12:58,445 --> 00:13:02,783
before we actually see
any change in cognition

254
00:13:03,317 --> 00:13:06,053
or any deviation
from typical aging.

255
00:13:06,119 --> 00:13:07,788
And that typically star--
what that does,

256
00:13:07,855 --> 00:13:09,957
I should say, start with
the accumulation

257
00:13:10,023 --> 00:13:12,259
of amyloid in the brain.

258
00:13:12,926 --> 00:13:17,731
And then we start to detect
tau tangles in the brain.

259
00:13:17,998 --> 00:13:19,833
And then we start
to see shrinkage

260
00:13:19,900 --> 00:13:23,003
in different areas of the brain,

261
00:13:23,070 --> 00:13:27,641
like I said before, typically
in the areas related to memory.

262
00:13:27,708 --> 00:13:30,978
And as those brain changes
become more severe,

263
00:13:31,044 --> 00:13:34,047
then we start to see
more severe symptoms

264
00:13:34,114 --> 00:13:38,252
of mild cognitive impairment
and dementia.

265
00:13:41,121 --> 00:13:42,956
So, the National Institute
on Aging

266
00:13:43,023 --> 00:13:44,525
and Alzheimer's Association

267
00:13:44,591 --> 00:13:48,395
has guidelines
for staging the brain changes

268
00:13:48,462 --> 00:13:50,531
that characterize
Alzheimer's disease,

269
00:13:50,597 --> 00:13:54,668
starting with nothing,
and then again we see amyloid,

270
00:13:54,735 --> 00:13:56,036
and then we have detectable tau.

271
00:13:56,103 --> 00:13:58,172
And then we see tau begin
to spread and spread

272
00:13:58,238 --> 00:14:01,375
and spread throughout the brain.

273
00:14:01,642 --> 00:14:03,644
We also have in these columns

274
00:14:03,710 --> 00:14:07,481
guidelines for staging
the symptoms of dementia

275
00:14:07,548 --> 00:14:10,117
that go along
with Alzheimer's disease,

276
00:14:10,184 --> 00:14:14,121
from no impairment
to subtle changes of impairment,

277
00:14:14,188 --> 00:14:16,423
where we think
we're detecting subtle changes

278
00:14:16,490 --> 00:14:18,759
in people's cognitive ability
or thinking skills,

279
00:14:18,825 --> 00:14:21,128
but they're not, like,
diagnosable symptoms,

280
00:14:21,195 --> 00:14:24,264
to mild cognitive impairment,
to dementia.

281
00:14:24,331 --> 00:14:28,235
And we can try to map
these things onto each other.

282
00:14:28,302 --> 00:14:30,971
So, these gray boxes
represent people

283
00:14:31,038 --> 00:14:33,874
whose symptoms match
what we would expect

284
00:14:33,941 --> 00:14:37,511
based on their brain changes,
and vice versa.

285
00:14:37,578 --> 00:14:38,679
A study called

286
00:14:38,745 --> 00:14:42,182
the Alzheimer's Disease
Neuroimaging Initiative,

287
00:14:42,249 --> 00:14:45,519
ADNI, it's a very famous study,
decided to try to place

288
00:14:45,586 --> 00:14:50,257
all of their participants
somewhere on this grid.

289
00:14:51,191 --> 00:14:55,229
So, how many or what
percentage of participants

290
00:14:55,295 --> 00:14:59,399
do you think fell neatly
in these gray boxes,

291
00:14:59,466 --> 00:15:02,202
where their symptoms match
their brain changes?

292
00:15:02,269 --> 00:15:05,739
And your options
are 40%, 60%, or 80%.

293
00:15:07,441 --> 00:15:09,776
And you can just shout it out.

294
00:15:09,843 --> 00:15:11,512
What do you think?

295
00:15:11,578 --> 00:15:13,247
- Attendee 1: 80%.
- 80%.

296
00:15:13,313 --> 00:15:15,549
- Attendee 2: 40%?
- 40%?

297
00:15:16,149 --> 00:15:18,385
Yes, it's closer to 40%.

298
00:15:18,785 --> 00:15:22,589
Less than half
of individuals' symptoms

299
00:15:23,357 --> 00:15:25,726
match their brain changes.

300
00:15:27,094 --> 00:15:30,898
Some people end up better,
doing better than expected

301
00:15:30,964 --> 00:15:32,900
based on the brain changes
that we see.

302
00:15:32,966 --> 00:15:35,702
And we call that brain reserve
or cognitive reserve.

303
00:15:35,769 --> 00:15:39,206
And that's the ability
to maintain function

304
00:15:39,273 --> 00:15:42,509
in the face
of these brain changes.

305
00:15:42,876 --> 00:15:46,246
Unfortunately,
it's about, like, 10% to 15%,

306
00:15:46,313 --> 00:15:49,950
which means that another
45% or so individuals

307
00:15:50,017 --> 00:15:52,352
end up in this pink range,

308
00:15:52,419 --> 00:15:55,055
where they're doing worse
than expected,

309
00:15:55,122 --> 00:16:00,227
based on just the Alzheimer's
disease-related brain changes,

310
00:16:00,294 --> 00:16:01,662
and that's often due

311
00:16:01,728 --> 00:16:05,232
to co-occurring
vascular dementia,

312
00:16:05,299 --> 00:16:07,334
or damage to blood vessels

313
00:16:07,401 --> 00:16:12,573
that is characteristic of
some types of vascular dementia.

314
00:16:12,639 --> 00:16:15,943
So, let's take a look at
the blood vessels in the brain.

315
00:16:16,009 --> 00:16:17,811
I really like this image.

316
00:16:17,878 --> 00:16:19,613
These are an image
of blood vessels

317
00:16:19,680 --> 00:16:21,181
in the brain of a living person.

318
00:16:21,248 --> 00:16:24,885
This is a very difficult type
of scan to do.

319
00:16:24,952 --> 00:16:27,554
I like that it really shows
the outline of the brain.

320
00:16:27,621 --> 00:16:30,891
You can see how enriched
the brain is with blood vessels,

321
00:16:30,958 --> 00:16:35,495
although, to be honest, it
doesn't even do it full justice.

322
00:16:35,562 --> 00:16:38,799
Our brains have used
so much blood.

323
00:16:38,866 --> 00:16:40,601
Our brains are a small part
of our body,

324
00:16:40,667 --> 00:16:42,936
2% of our body weight
on average,

325
00:16:43,003 --> 00:16:45,806
but it receives
an enormous amount of our energy

326
00:16:45,873 --> 00:16:47,774
and cardiac output.

327
00:16:48,308 --> 00:16:53,413
We need healthy blood vessels,
flexible blood vessels,

328
00:16:53,480 --> 00:16:55,816
to deliver oxygen and nutrients

329
00:16:55,883 --> 00:16:58,552
to the areas of our brain
that need it.

330
00:16:58,619 --> 00:17:02,890
We also need flexible and
healthy and strong blood vessels

331
00:17:02,956 --> 00:17:06,093
to clear out waste
from our brains

332
00:17:06,793 --> 00:17:10,264
so that misfolded proteins
don't build up.

333
00:17:10,330 --> 00:17:12,699
Sorry, I meant to mention
the blood-brain barrier.

334
00:17:12,766 --> 00:17:16,870
So, the larger vessels are
on the outside of the brain,

335
00:17:16,937 --> 00:17:19,406
and then as they go into
the substance of the brain,

336
00:17:19,473 --> 00:17:21,542
they get tinier
and tinier and tinier

337
00:17:21,608 --> 00:17:24,545
until we get to the
blood-brain barrier.

338
00:17:24,611 --> 00:17:26,480
And this is the tiniest part.

339
00:17:26,547 --> 00:17:30,050
And the blood-brain barrier
protects the brain

340
00:17:30,117 --> 00:17:33,053
from toxins or bacteria
or viruses

341
00:17:33,120 --> 00:17:35,923
that are in the bloodstream.

342
00:17:35,989 --> 00:17:39,760
And it also aids in removing
misfolded proteins,

343
00:17:39,826 --> 00:17:41,628
like amyloid plaques.

344
00:17:41,695 --> 00:17:43,530
So, it's very important
in maintaining

345
00:17:43,597 --> 00:17:44,798
the health of our brains.

346
00:17:44,865 --> 00:17:46,400
The integrity
of that blood-brain barrier

347
00:17:46,466 --> 00:17:50,771
is important to maintaining
the health of our brains.

348
00:17:50,838 --> 00:17:52,372
So, let's talk about some
of the things

349
00:17:52,439 --> 00:17:55,475
that can go wrong
with our blood vessels

350
00:17:55,542 --> 00:17:59,279
and contribute to risk
for dementia,

351
00:17:59,346 --> 00:18:02,115
either solely due
to vascular dementia

352
00:18:02,182 --> 00:18:05,118
or as a contributor
to Alzheimer's disease.

353
00:18:05,185 --> 00:18:06,987
So, I'm gonna go
counterclockwise,

354
00:18:07,054 --> 00:18:09,623
starting with B here on top.

355
00:18:09,957 --> 00:18:13,861
This arrow is pointing to an
area where there was a stroke.

356
00:18:13,927 --> 00:18:17,197
Strokes are a common cause
of vascular dementia,

357
00:18:17,264 --> 00:18:18,932
although the symptoms
of dementia

358
00:18:18,999 --> 00:18:21,869
don't necessarily show up
right away after a stroke.

359
00:18:21,935 --> 00:18:24,338
It can actually take
up to a year after a stroke

360
00:18:24,404 --> 00:18:27,741
for symptoms of dementia
to appear.

361
00:18:28,675 --> 00:18:31,645
In A, those arrows
are pointing to what we call

362
00:18:31,712 --> 00:18:33,981
white matter hyperintensities.

363
00:18:34,047 --> 00:18:35,582
We call them
that because they show up

364
00:18:35,649 --> 00:18:37,317
as bright white on these images.

365
00:18:37,384 --> 00:18:38,952
These are MRI images, again,

366
00:18:39,019 --> 00:18:42,623
so we're looking at the
structure of the brain.

367
00:18:42,689 --> 00:18:46,593
White matter hyperintensities
are thought to be indicators

368
00:18:46,660 --> 00:18:49,830
of damage to the white matter
tracts in our brain.

369
00:18:49,897 --> 00:18:51,832
So, the white matter tracts
in our brain

370
00:18:51,899 --> 00:18:55,836
help the thinking cells
communicate with each other.

371
00:18:55,903 --> 00:18:59,540
And we think of the white matter
as like the coating on a wire.

372
00:18:59,606 --> 00:19:01,742
So, you need that coating
on the wire

373
00:19:01,808 --> 00:19:03,844
for the electricity
to get through properly.

374
00:19:03,911 --> 00:19:07,114
We need good,
healthy white matter tracts

375
00:19:07,181 --> 00:19:08,448
in order for our cells

376
00:19:08,515 --> 00:19:11,451
to communicate
with each other well.

377
00:19:11,518 --> 00:19:13,320
The bottom, C here,

378
00:19:13,587 --> 00:19:16,256
these arrows are pointing
to areas of microbleeds.

379
00:19:16,323 --> 00:19:20,027
They show up as little
black dots on these scans.

380
00:19:20,093 --> 00:19:22,963
Microbleeds can occur
because of something called

381
00:19:23,030 --> 00:19:28,168
cerebral amyloid angiop--
angiopathy-- angiopathy?

382
00:19:29,736 --> 00:19:31,538
That is the buildup of amyloid

383
00:19:31,605 --> 00:19:34,508
in the walls
of the blood vessels.

384
00:19:34,575 --> 00:19:36,310
And that can weaken
those blood vessels

385
00:19:36,376 --> 00:19:39,246
and then lead to that bleeding.

386
00:19:39,313 --> 00:19:43,617
And then finally, in D here,
we have arrows pointing to--

387
00:19:43,684 --> 00:19:45,652
these are called
lacunar infarcts.

388
00:19:45,719 --> 00:19:49,022
So, infarcts is another word
for stroke or blockage.

389
00:19:49,089 --> 00:19:52,626
Lacunar just is a reference
to the smaller vessels.

390
00:19:52,693 --> 00:19:55,762
So, this is blockage
in smaller vessels in the brain.

391
00:19:55,829 --> 00:19:58,565
There's also microinfarcts,
which is blockages

392
00:19:58,632 --> 00:20:01,201
in even tinier little vessels
in the brain.

393
00:20:01,268 --> 00:20:03,770
And microinfarcts
tend to be more diffuse

394
00:20:03,837 --> 00:20:05,973
throughout the brain.

395
00:20:06,540 --> 00:20:08,342
These last three,
A, C, and D,

396
00:20:08,408 --> 00:20:12,079
often fall under the umbrella
term small vessel disease

397
00:20:12,145 --> 00:20:16,383
because they occur
in those smaller vessels.

398
00:20:17,150 --> 00:20:19,219
So, just like we can have
thickening and stiffening

399
00:20:19,286 --> 00:20:20,521
of blood vessels to the heart,

400
00:20:20,587 --> 00:20:22,022
we can have thickening
and stiffening

401
00:20:22,089 --> 00:20:26,693
of blood vessels in our brains
due to the same plaques

402
00:20:26,760 --> 00:20:29,263
that build up in the vessels
to our heart.

403
00:20:29,329 --> 00:20:30,564
We can have hypert--

404
00:20:30,631 --> 00:20:32,533
We can have high blood pressure
in our brains,

405
00:20:32,599 --> 00:20:33,934
just like we do in our bodies.

406
00:20:34,001 --> 00:20:38,138
That's called
hypertensive arteriopathy.

407
00:20:39,139 --> 00:20:42,442
And a really important
but very hard to detect

408
00:20:42,509 --> 00:20:43,677
vascular risk factor

409
00:20:43,744 --> 00:20:47,581
is the breakdown
of that blood-brain barrier.

410
00:20:47,648 --> 00:20:49,950
And that can lead
to harmful substances

411
00:20:50,017 --> 00:20:51,685
from the arteries
getting into the brain.

412
00:20:51,752 --> 00:20:54,521
And it can lead to buildup
of misfolded proteins

413
00:20:54,588 --> 00:20:57,391
that interfere
with the function of our brains.

414
00:20:57,457 --> 00:20:58,926
All of these changes,
by the way,

415
00:20:58,992 --> 00:21:00,194
that I'm talking about,

416
00:21:00,260 --> 00:21:02,796
happen quite naturally
with aging.

417
00:21:02,863 --> 00:21:07,768
They're very common in people
over the age of, like, 85 or 90.

418
00:21:07,835 --> 00:21:10,637
They usually aren't enough--

419
00:21:11,672 --> 00:21:15,576
aren't severe enough
to lead to dementia.

420
00:21:16,109 --> 00:21:19,880
Currently, we do not have ways
to develop these--

421
00:21:19,947 --> 00:21:21,815
to measure
these vascular problems

422
00:21:21,882 --> 00:21:24,451
in cerebral spinal fluid
or in blood.

423
00:21:24,518 --> 00:21:26,854
And that's a big barrier.

424
00:21:27,221 --> 00:21:29,790
These MRI images are great,

425
00:21:30,958 --> 00:21:33,727
but they are time-consuming
and they are costly.

426
00:21:33,794 --> 00:21:36,463
And if you have metal
in your head

427
00:21:36,530 --> 00:21:40,767
or certain types of implants,
you can't have an MRI.

428
00:21:40,834 --> 00:21:43,437
So, we're working very hard
on finding alternate ways

429
00:21:43,504 --> 00:21:47,274
to detect these vascular
brain changes.

430
00:21:50,010 --> 00:21:51,545
So, I'm gonna pivot now
and talk about

431
00:21:51,612 --> 00:21:55,482
some of the main risk factors
for Alzheimer's disease.

432
00:21:55,549 --> 00:21:57,951
And the absolute number one
biggest risk factor

433
00:21:58,018 --> 00:22:01,555
for Alzheimer's disease
and vascular dementia is age.

434
00:22:01,622 --> 00:22:03,156
So, what you're seeing
here on the bottom

435
00:22:03,223 --> 00:22:05,392
are age group
divided up into decades,

436
00:22:05,459 --> 00:22:07,361
starting with ages 60 to 69

437
00:22:07,427 --> 00:22:10,063
and ending with people
over the age of 90.

438
00:22:10,130 --> 00:22:13,200
The side is the proportion
of the population

439
00:22:13,267 --> 00:22:15,936
that is living with dementia,

440
00:22:16,003 --> 00:22:17,738
either vascular dementia
in green,

441
00:22:17,804 --> 00:22:22,743
Alzheimer's disease in teal,
or any type of dementia in red.

442
00:22:22,809 --> 00:22:26,180
And you can see when you start
out in that 60 to 69 range,

443
00:22:26,246 --> 00:22:30,584
like, maybe 2% of the population
is living with dementia.

444
00:22:30,651 --> 00:22:32,886
By the time you get to 90,

445
00:22:32,953 --> 00:22:34,555
the percentage of people
living with dementia

446
00:22:34,621 --> 00:22:36,557
has gone up quite a lot.

447
00:22:36,623 --> 00:22:41,428
I do wanna point out, though,
that top dot at 90-plus

448
00:22:44,131 --> 00:22:46,800
tops out at around 37% or 38%.

449
00:22:47,935 --> 00:22:49,403
That's a lot.

450
00:22:49,469 --> 00:22:53,407
But that means more than half
of individuals in that age range

451
00:22:53,473 --> 00:22:55,576
don't have dementia.

452
00:22:57,644 --> 00:23:00,147
So, age alone--
There's a sense, I think still,

453
00:23:00,214 --> 00:23:01,548
that if you just live
long enough,

454
00:23:01,615 --> 00:23:02,716
you're gonna get dementia.

455
00:23:02,783 --> 00:23:04,251
It's really not true.

456
00:23:04,318 --> 00:23:06,386
Aging is definitely
a risk factor,

457
00:23:06,453 --> 00:23:10,791
but aging alone
is not going to cause dementia.

458
00:23:13,327 --> 00:23:15,729
We are seeing a lot more
people living with dementia,

459
00:23:15,796 --> 00:23:17,631
and that's simply
because we are, in fact,

460
00:23:17,698 --> 00:23:20,033
living longer as people.

461
00:23:22,703 --> 00:23:24,605
The oldest segment
of the population,

462
00:23:24,671 --> 00:23:25,906
the segment
that's most at risk

463
00:23:25,973 --> 00:23:27,975
for developing dementia
due to age,

464
00:23:28,041 --> 00:23:31,144
is the fastest-growing segment
of the population

465
00:23:31,211 --> 00:23:32,813
in many places around the world

466
00:23:32,880 --> 00:23:35,549
and in some surprising places
around the world.

467
00:23:35,616 --> 00:23:37,451
This is a good thing,
in general.

468
00:23:37,518 --> 00:23:41,688
We want people to live longer,
but we want people to have--

469
00:23:41,755 --> 00:23:43,657
to be healthy well into old age.

470
00:23:43,724 --> 00:23:46,293
And you'll hear
people now talk about healthspan

471
00:23:46,360 --> 00:23:48,695
in addition to lifespan.

472
00:23:49,863 --> 00:23:54,268
To some extent, we're succeeding
in living healthier as we age.

473
00:23:54,334 --> 00:23:55,435
So, this is a graph.

474
00:23:55,502 --> 00:23:57,938
It's bars instead of lines.

475
00:23:58,005 --> 00:24:00,040
But it's similar to that graph
I showed you before.

476
00:24:00,107 --> 00:24:03,477
So, these are different
age groups across the bottom.

477
00:24:03,544 --> 00:24:05,045
And then the prevalence of--

478
00:24:05,112 --> 00:24:07,681
or the percent of people
living with dementia

479
00:24:07,748 --> 00:24:11,852
in each of those age groups
is shown kind of on the side.

480
00:24:11,919 --> 00:24:14,121
Yellow represents
the number of people

481
00:24:14,188 --> 00:24:17,424
who were living with dementia
in 2002,

482
00:24:17,491 --> 00:24:19,426
and blue represents
the percent of people

483
00:24:19,493 --> 00:24:21,228
living with dementia in 2012.

484
00:24:21,295 --> 00:24:24,097
So, this data was taken from
the Health and Retirement Study.

485
00:24:24,164 --> 00:24:25,832
This is a huge study.

486
00:24:25,899 --> 00:24:27,701
And you can see that,
in every age group,

487
00:24:27,768 --> 00:24:29,570
including the oldest age group,

488
00:24:29,636 --> 00:24:31,138
the number of people
living with dementia

489
00:24:31,205 --> 00:24:35,475
actually declined over time
as a percent of the population.

490
00:24:35,542 --> 00:24:38,312
And this has been shown
in different studies

491
00:24:38,378 --> 00:24:40,514
spanning different time periods.

492
00:24:40,581 --> 00:24:42,916
So, that does give us some hope.

493
00:24:42,983 --> 00:24:45,853
I apologize
for how tiny the font is

494
00:24:45,919 --> 00:24:48,288
on this particular figure.
[chuckles]

495
00:24:48,355 --> 00:24:50,991
In 2020,
the medical journal <i>Lancet</i>

496
00:24:51,058 --> 00:24:52,159
commissioned a review--

497
00:24:52,226 --> 00:24:53,961
it's kind of
a famous review now--

498
00:24:54,027 --> 00:24:56,363
of the most important
risk factors for dementia,

499
00:24:56,430 --> 00:24:58,799
and they assigned
a percent value

500
00:24:58,866 --> 00:25:00,100
to each of those risk factors.

501
00:25:00,167 --> 00:25:01,502
So, they said,
"How much of dementia

502
00:25:01,568 --> 00:25:04,204
is due to this
or that risk factor?"

503
00:25:04,271 --> 00:25:08,041
The big gray path represents
60% of dementias

504
00:25:08,108 --> 00:25:11,278
that are due to factors
that we can't change.

505
00:25:11,345 --> 00:25:13,280
And those are things
like our age,

506
00:25:13,347 --> 00:25:18,085
our genetics or family history,
our sex, and our race.

507
00:25:18,151 --> 00:25:21,021
So, women get--
develop dementia

508
00:25:21,088 --> 00:25:22,856
and Alzheimer's disease
in particular

509
00:25:22,923 --> 00:25:24,825
more often than men.

510
00:25:25,125 --> 00:25:29,162
And people who identify
as African American or Latino

511
00:25:29,229 --> 00:25:30,664
develop Alzheimer's disease

512
00:25:30,731 --> 00:25:34,401
more often than people
who identify as white.

513
00:25:34,468 --> 00:25:37,171
These colored paths, though,
represent what we call

514
00:25:37,237 --> 00:25:40,340
modifiable or potentially
modifiable risk factors,

515
00:25:40,407 --> 00:25:43,677
and they include several
cardiovascular risk factors.

516
00:25:43,744 --> 00:25:47,648
Things like high blood pressure,
obesity,

517
00:25:47,714 --> 00:25:50,851
high cholesterol, and diabetes.

518
00:25:52,019 --> 00:25:53,820
Why is that?

519
00:25:53,887 --> 00:25:58,825
Well, we have this idea now
of the heart-brain axis,

520
00:25:58,892 --> 00:26:00,794
where cardiovascular diseases

521
00:26:00,861 --> 00:26:03,931
result in damage to
or decline in blood flow

522
00:26:03,997 --> 00:26:05,399
to the brain.

523
00:26:05,465 --> 00:26:08,702
This leads to damage to the
blood vessels in the brain,

524
00:26:08,769 --> 00:26:11,471
which leads
to cognitive impairment.

525
00:26:11,538 --> 00:26:13,006
People
who are cognitively impaired

526
00:26:13,073 --> 00:26:14,474
may not engage in typic--

527
00:26:14,541 --> 00:26:17,244
in, you know,
heart-healthy behaviors,

528
00:26:17,311 --> 00:26:20,047
which leads to greater
cardiovascular dysfunction.

529
00:26:20,113 --> 00:26:21,782
And we go around.

530
00:26:22,916 --> 00:26:24,985
So, I wanna give
a couple of examples--

531
00:26:25,052 --> 00:26:27,054
an example from two studies

532
00:26:27,120 --> 00:26:29,489
showing the importance
of blood flow

533
00:26:29,556 --> 00:26:32,659
and how that's related
to Alzheimer's disease.

534
00:26:32,726 --> 00:26:35,495
This is a study
that was conducted at our center

535
00:26:35,562 --> 00:26:38,398
by my colleague,
Dr. Rivera-Rivera.

536
00:26:38,465 --> 00:26:41,835
And he used an imaging
technique called 4D-Flow.

537
00:26:41,902 --> 00:26:44,838
And that measures
the amount of blood flow

538
00:26:44,905 --> 00:26:46,640
through the larger vessels
in the brain.

539
00:26:46,707 --> 00:26:50,077
These are vessels that are found
kind of at the base of the skull

540
00:26:50,143 --> 00:26:52,713
and the sides of the brain.

541
00:26:52,779 --> 00:26:55,682
And he compared blood flow
in these different vessels

542
00:26:55,749 --> 00:26:58,318
in people
who had Alzheimer's disease,

543
00:26:58,385 --> 00:27:01,188
people who had mild
cognitive impairment,

544
00:27:01,255 --> 00:27:03,290
older people
who were cognitively unimpaired,

545
00:27:03,357 --> 00:27:07,261
and middle-aged people
who were cognitively unimpaired.

546
00:27:07,327 --> 00:27:09,563
And what he found
was that the people

547
00:27:09,630 --> 00:27:13,233
with the lowest blood flow
in those vessels in the brain

548
00:27:13,300 --> 00:27:15,369
were people
who had Alzheimer's disease.

549
00:27:15,435 --> 00:27:18,739
And, actually, we see
a very consistent pattern,

550
00:27:18,805 --> 00:27:20,407
so that people
with Alzheimer's disease

551
00:27:20,474 --> 00:27:22,309
have the least amount
of blood flow

552
00:27:22,376 --> 00:27:24,511
in these blood vessels,

553
00:27:24,578 --> 00:27:27,014
followed by people
with mild cognitive impairment,

554
00:27:27,080 --> 00:27:29,983
followed by older individuals
who are cognitively unimpaired,

555
00:27:30,050 --> 00:27:35,088
followed by those middle-aged,
unimpaired individuals.

556
00:27:35,155 --> 00:27:39,893
He followed this study up with
another study of pulsatility.

557
00:27:39,960 --> 00:27:44,264
And this is kind of a measure
of stiffness of the arteries.

558
00:27:44,331 --> 00:27:46,834
And again, the people
who have Alzheimer's disease--

559
00:27:46,900 --> 00:27:49,102
this time, those are people
who are shown in blue--

560
00:27:49,169 --> 00:27:51,505
have the stiffest vessels.

561
00:27:51,572 --> 00:27:54,208
Actually, the people
with Alzheimer's disease in blue

562
00:27:54,274 --> 00:27:56,009
and mild
cognitive impairment in red

563
00:27:56,076 --> 00:27:58,078
have kind of stiffer arteries

564
00:27:58,145 --> 00:28:00,180
than the older
or the middle-aged

565
00:28:00,247 --> 00:28:02,216
cognitively unimpaired
individuals.

566
00:28:02,282 --> 00:28:05,118
But across all these vessels,
people who are older

567
00:28:05,185 --> 00:28:07,688
have stiffer vessels
than people who are younger.

568
00:28:07,754 --> 00:28:11,525
So, again, these are things
that happen with typical aging.

569
00:28:11,592 --> 00:28:15,062
They don't always result
in dementia

570
00:28:15,596 --> 00:28:18,465
or Alzheimer's disease, though.

571
00:28:18,532 --> 00:28:20,801
So, how is it
that these vascular factors

572
00:28:20,868 --> 00:28:22,870
change our risk
for cognitive impairment

573
00:28:22,936 --> 00:28:24,771
due to Alzheimer's disease?

574
00:28:24,838 --> 00:28:26,473
I want to talk about
two different ways

575
00:28:26,540 --> 00:28:27,975
that this might happen.

576
00:28:28,041 --> 00:28:29,510
One is simply that,

577
00:28:29,576 --> 00:28:31,945
if you have
a lot of health problems,

578
00:28:32,012 --> 00:28:33,480
they just kind of add up.

579
00:28:33,547 --> 00:28:35,949
It's like knocking
the same glass off a table

580
00:28:36,016 --> 00:28:37,384
over and over again.

581
00:28:37,451 --> 00:28:39,586
The multiple hits eventually
overwhelms

582
00:28:39,653 --> 00:28:42,890
the brain's ability
to repair itself.

583
00:28:42,956 --> 00:28:45,459
And there's some evidence
for this.

584
00:28:45,526 --> 00:28:49,429
So, this graph comes from
a study conducted in 2005

585
00:28:49,496 --> 00:28:52,599
with a cohort
of 8,800 individuals.

586
00:28:52,666 --> 00:28:54,668
The study authors looked at

587
00:28:54,735 --> 00:28:56,904
four cardiovascular
risk factors.

588
00:28:56,970 --> 00:28:59,273
These were high blood pressure,
diabetes,

589
00:28:59,339 --> 00:29:02,109
high cholesterol, and smoking.

590
00:29:02,176 --> 00:29:05,012
And they found
that it didn't really matter

591
00:29:05,078 --> 00:29:08,549
which of these different
risk factors you had.

592
00:29:08,615 --> 00:29:10,884
If you had
more than one of them,

593
00:29:10,951 --> 00:29:15,289
your risk for
developing dementia increased.

594
00:29:16,323 --> 00:29:17,925
A more recent study came out

595
00:29:17,991 --> 00:29:21,962
of the Atherosclerosis Risk
in Communities, or ARIC, study.

596
00:29:22,029 --> 00:29:24,164
I don't know if people are
familiar with the ARIC study.

597
00:29:24,231 --> 00:29:26,266
It's another very famous one.

598
00:29:26,333 --> 00:29:29,770
And they showed
that midlife hypertension

599
00:29:29,837 --> 00:29:33,974
and the signs of amyloid plaques
in later life

600
00:29:34,041 --> 00:29:37,778
and diabetes in later life all
separately increase the risk

601
00:29:37,845 --> 00:29:41,315
of developing Alzheimer's
disease.

602
00:29:42,950 --> 00:29:45,219
On the other hand,
good vascular health

603
00:29:45,285 --> 00:29:47,287
could be protective.

604
00:29:47,654 --> 00:29:50,224
So, there was a study
back in 2005

605
00:29:50,290 --> 00:29:52,593
that showed that
cognitively unimpaired people

606
00:29:52,659 --> 00:29:54,761
with better blood flow
in their brains

607
00:29:54,828 --> 00:30:00,234
had larger hippocampal volume,
that region related to memory

608
00:30:00,300 --> 00:30:02,903
where we see the first signs
of shrinkage

609
00:30:02,970 --> 00:30:04,671
with Alzheimer's disease.

610
00:30:04,738 --> 00:30:07,107
It stands to reason
that if you're starting out

611
00:30:07,174 --> 00:30:10,344
with a healthier,
larger hippocampal volume,

612
00:30:10,410 --> 00:30:12,412
then as it starts to shrink,

613
00:30:12,479 --> 00:30:15,482
you're still going to be able
to maintain function

614
00:30:15,549 --> 00:30:19,119
'cause you just started out
with more.

615
00:30:20,420 --> 00:30:23,757
Another possibility
is that poor vascular health

616
00:30:23,824 --> 00:30:25,726
and plaques and tangles

617
00:30:25,792 --> 00:30:28,829
that are the hallmarks
of Alzheimer's disease

618
00:30:28,896 --> 00:30:32,266
interact with each other so
that they exacerbate each other.

619
00:30:32,332 --> 00:30:33,767
And so, that the whole
is greater

620
00:30:33,834 --> 00:30:36,069
than the sum of the parts.

621
00:30:36,136 --> 00:30:39,706
And there's evidence
for that as well.

622
00:30:40,307 --> 00:30:41,909
So, this study
was performed using

623
00:30:41,975 --> 00:30:44,778
the Wisconsin Registry
for Alzheimer's Prevention.

624
00:30:44,845 --> 00:30:46,480
And this is a large--

625
00:30:46,547 --> 00:30:49,082
the other large longitudinal
study, I should say,

626
00:30:49,149 --> 00:30:50,350
of Alzheimer's disease

627
00:30:50,417 --> 00:30:53,120
at the University of Wisconsin
in Madison.

628
00:30:53,187 --> 00:30:55,155
In this case,
participants were divided

629
00:30:55,222 --> 00:30:57,724
into four groups
based on whether or not

630
00:30:57,791 --> 00:30:59,193
they were amyloid positive,

631
00:30:59,259 --> 00:31:00,661
meaning they had
a concerning amount

632
00:31:00,727 --> 00:31:02,329
of amyloid in their brains.

633
00:31:02,396 --> 00:31:07,401
And that's indicated by being
AB- or AB+ on this graph.

634
00:31:07,734 --> 00:31:10,304
And then, whether or not they
had the presence or absence

635
00:31:10,370 --> 00:31:11,572
of one other risk factor,

636
00:31:11,638 --> 00:31:15,976
in this case,
either hypertension or obesity.

637
00:31:16,243 --> 00:31:19,847
Here, the people in green
are people who have--

638
00:31:19,913 --> 00:31:21,648
are amyloid positive.

639
00:31:21,715 --> 00:31:23,317
They have that concerning amount
of amyloid,

640
00:31:23,383 --> 00:31:25,552
and they have
one of these risk factors,

641
00:31:25,619 --> 00:31:27,221
hypertension or obesity.

642
00:31:27,287 --> 00:31:29,022
And you can see
that those people in green

643
00:31:29,089 --> 00:31:32,526
are declining the fastest on
this measure of thinking skills.

644
00:31:32,593 --> 00:31:36,363
This was a measure
of verbal learning and memory.

645
00:31:36,430 --> 00:31:38,065
And they're declining faster

646
00:31:38,131 --> 00:31:40,434
than if we just took
the orange line,

647
00:31:40,501 --> 00:31:43,737
which is somebody who has,
you know, just hypertension,

648
00:31:43,804 --> 00:31:45,973
and added it to the line,
the blue line,

649
00:31:46,039 --> 00:31:48,475
which is somebody
who had just amyloid.

650
00:31:48,542 --> 00:31:50,511
So, there's some interaction
going on there

651
00:31:50,577 --> 00:31:53,447
that's causing a greater decline
than we would expect

652
00:31:53,514 --> 00:31:58,986
if we just kind of added those
health problems up together.

653
00:32:00,120 --> 00:32:04,057
So, to summarize,
when we have reduced blood flow,

654
00:32:04,124 --> 00:32:06,894
either due to stiff vessels
or clogged vessels,

655
00:32:06,960 --> 00:32:09,796
there's a decrease in delivery
of oxygen and nutrients

656
00:32:09,863 --> 00:32:11,932
to the brain regions
that need them.

657
00:32:11,999 --> 00:32:13,400
We have impaired clearance

658
00:32:13,467 --> 00:32:16,336
of beta amyloid
and other toxic proteins.

659
00:32:16,403 --> 00:32:19,540
And there's an increased risk
of blockages.

660
00:32:19,606 --> 00:32:21,208
With weakening artery walls

661
00:32:21,275 --> 00:32:22,776
and weakening
of the blood-brain barrier,

662
00:32:22,843 --> 00:32:24,745
there's an increased risk
of bleeding

663
00:32:24,811 --> 00:32:26,547
and a reduction
in the brain's ability

664
00:32:26,613 --> 00:32:30,617
to protect itself
against outside toxins.

665
00:32:32,853 --> 00:32:34,421
So, that was a lot,

666
00:32:34,488 --> 00:32:36,723
so I thought I'd throw in
a little stretch break

667
00:32:36,790 --> 00:32:38,492
for everybody.
[audience chuckles]

668
00:32:38,559 --> 00:32:40,494
So, if you feel like it--
You don't have to,

669
00:32:40,561 --> 00:32:42,896
but if you feel like it,
you can just raise your arms

670
00:32:42,963 --> 00:32:44,631
up over your head.

671
00:32:44,932 --> 00:32:48,168
I always, like, do this
with my fingers when I do this.

672
00:32:48,235 --> 00:32:52,406
And then just twist
real gently to one side

673
00:32:52,472 --> 00:32:56,043
and then real gently
to the other side.

674
00:32:56,710 --> 00:32:58,045
Ooh, I get a nice crack there.

675
00:32:58,111 --> 00:33:00,314
And then just kind of
float your hands down,

676
00:33:00,380 --> 00:33:03,317
just kind of shake it out.
[blergh]

677
00:33:03,383 --> 00:33:04,484
Okay.

678
00:33:04,551 --> 00:33:06,887
Thank you for joining me.

679
00:33:08,589 --> 00:33:10,490
All right, so, what happens
when we treat

680
00:33:10,557 --> 00:33:14,094
cardiovascular-related
chronic conditions?

681
00:33:14,161 --> 00:33:16,763
Can we lower the risk
for dementia?

682
00:33:16,830 --> 00:33:21,168
There is a lot of interest
in drug repurposing.

683
00:33:22,169 --> 00:33:25,372
There's many advantages
to drug repurposing.

684
00:33:25,439 --> 00:33:27,841
It's very expensive
and time-consuming

685
00:33:27,908 --> 00:33:29,877
to develop new drugs.

686
00:33:29,943 --> 00:33:31,745
If we can capitalize

687
00:33:31,812 --> 00:33:34,281
on some investment
that we made in the past,

688
00:33:34,348 --> 00:33:37,918
that saves us that time
and that money.

689
00:33:37,985 --> 00:33:39,987
But also, drugs
that have been on the market

690
00:33:40,053 --> 00:33:43,357
for a long time already have
a known risk profile

691
00:33:43,423 --> 00:33:47,794
that can help doctors decide
whether their patient is--

692
00:33:47,861 --> 00:33:51,098
should be getting that drug
or not.

693
00:33:52,566 --> 00:33:56,870
We have treatments for
cardiovascular-related diseases.

694
00:33:56,937 --> 00:33:59,373
We don't have treatments
for any of these

695
00:33:59,439 --> 00:34:03,977
cerebrovascular health problems
that I mentioned earlier.

696
00:34:04,044 --> 00:34:07,781
We have a lot of observational
or correlational data

697
00:34:07,848 --> 00:34:10,784
showing that poor cardiovascular
health is related

698
00:34:10,851 --> 00:34:14,454
to these cerebrovascular
problems in the brain

699
00:34:14,521 --> 00:34:16,123
and to higher risk for dementia.

700
00:34:16,190 --> 00:34:19,092
So, it seems
like a no-brainer, right,

701
00:34:19,159 --> 00:34:22,896
that if we treat
cardiovascular health problems,

702
00:34:22,963 --> 00:34:27,234
we can reduce or prevent
cerebrovascular health problems,

703
00:34:27,301 --> 00:34:29,303
which will in turn
reduce or prevent

704
00:34:29,369 --> 00:34:31,505
the development
of vascular dementia

705
00:34:31,572 --> 00:34:33,707
or Alzheimer's disease.

706
00:34:33,774 --> 00:34:36,443
But efforts to show
that cardiovascular--

707
00:34:36,510 --> 00:34:39,780
treating cardiovascular-related
diseases

708
00:34:39,847 --> 00:34:41,715
lowers the risk of dementia

709
00:34:41,782 --> 00:34:45,352
haven't been completely
successful.

710
00:34:46,253 --> 00:34:49,523
So, we'll start
with the unsuccessful attempts.

711
00:34:49,590 --> 00:34:51,425
And this involves statins.

712
00:34:51,491 --> 00:34:53,760
Back in the early 2000s,

713
00:34:53,827 --> 00:34:56,430
researchers looked at people
with and without statin

714
00:34:56,496 --> 00:34:59,366
and whether or not
they had dementia or not.

715
00:34:59,433 --> 00:35:02,536
And it looked,
across several studies,

716
00:35:02,603 --> 00:35:07,574
as if statins had a protective
effect against dementia.

717
00:35:07,641 --> 00:35:10,878
People got really excited
about that.

718
00:35:10,944 --> 00:35:14,181
But the problem
with those studies

719
00:35:16,183 --> 00:35:19,987
is that they looked at people
at the same time, right?

720
00:35:20,053 --> 00:35:23,056
So, they looked at, "Are you on
a statin, yes or no, right now?

721
00:35:23,123 --> 00:35:26,793
Do you have dementia,
yes or no, right now?"

722
00:35:26,860 --> 00:35:29,763
Later studies took a
more prospective approach.

723
00:35:29,830 --> 00:35:31,565
So, they took a bunch of people
and said,

724
00:35:31,632 --> 00:35:33,734
"Are you on a statin,
yes or no, right now?

725
00:35:33,800 --> 00:35:36,370
"And then, let's follow you
over time

726
00:35:36,436 --> 00:35:38,138
"and see if you develop
dementia,

727
00:35:38,205 --> 00:35:41,975
or Alzheimer's disease
specifically, later on."

728
00:35:42,042 --> 00:35:45,312
So, there's a review that was
published a few years ago

729
00:35:45,379 --> 00:35:49,950
of 17 studies that followed
this prospective design.

730
00:35:50,017 --> 00:35:52,119
Ten of those studies did show

731
00:35:52,186 --> 00:35:56,390
that there was a reduction
in dementia among statin users.

732
00:35:56,456 --> 00:36:00,160
Seven of those studies
showed no relationship

733
00:36:00,227 --> 00:36:04,932
between statin use and risk for
dementia or Alzheimer's disease.

734
00:36:04,998 --> 00:36:07,901
So, it was almost evenly split.

735
00:36:08,468 --> 00:36:13,407
Clinical trials of statins
have been unable, to date,

736
00:36:13,473 --> 00:36:15,442
to show a reduction in dementia.

737
00:36:15,509 --> 00:36:17,211
However,
those same clinical trials

738
00:36:17,277 --> 00:36:19,746
also show no loss
in cognitive ability,

739
00:36:19,813 --> 00:36:23,917
and that was a concern
at one point in time.

740
00:36:23,984 --> 00:36:25,085
People were concerned

741
00:36:25,152 --> 00:36:26,787
that putting someone
on long-term statin use

742
00:36:26,854 --> 00:36:28,989
would actually increase
their risk for dementia,

743
00:36:29,056 --> 00:36:32,626
and that does not appear
to be the case.

744
00:36:33,727 --> 00:36:36,363
So, one drawback--
Oh, I forgot to say.

745
00:36:36,430 --> 00:36:38,232
A drawback
of these clinical trials

746
00:36:38,298 --> 00:36:39,833
is that they tend to be short.

747
00:36:39,900 --> 00:36:42,269
They're designed to show
a cardiovascular benefit,

748
00:36:42,336 --> 00:36:44,605
not a cognitive benefit.

749
00:36:44,671 --> 00:36:48,575
So, we have a new trial
that UW is a site for.

750
00:36:50,010 --> 00:36:51,111
This is a multi-site trial.

751
00:36:51,178 --> 00:36:52,880
We are one of the sites.

752
00:36:52,946 --> 00:36:57,084
The goal of this study
is to enroll 10,000 adults

753
00:36:57,150 --> 00:36:59,520
who are over the age of 75

754
00:36:59,586 --> 00:37:03,924
and randomly assign them
to receive a statin or not.

755
00:37:03,991 --> 00:37:07,995
And then, the outcome will be
years free of dementia

756
00:37:08,061 --> 00:37:10,864
or years free
from persistent disability.

757
00:37:10,931 --> 00:37:14,134
So, we're still enrolling people
in this study.

758
00:37:14,201 --> 00:37:16,837
We plan to follow them
for at least five years

759
00:37:16,904 --> 00:37:18,272
and hopefully longer,

760
00:37:18,338 --> 00:37:21,842
and hopefully show that being
on a statin in older age

761
00:37:21,909 --> 00:37:24,144
will actually result in

762
00:37:25,646 --> 00:37:29,883
more years free
from dementia or disability.

763
00:37:30,617 --> 00:37:32,953
Now, we go to the success.

764
00:37:33,787 --> 00:37:35,355
What has been successful
is showing

765
00:37:35,422 --> 00:37:39,593
that reducing blood pressure
reduces the risk

766
00:37:39,660 --> 00:37:43,030
for mild cognitive impairment
or dementia.

767
00:37:43,096 --> 00:37:44,631
And some of the best evidence
for that

768
00:37:44,698 --> 00:37:47,134
comes from
the SPRINT-MIND trial.

769
00:37:47,201 --> 00:37:50,137
This was a very large
clinical trial of 9,000 people

770
00:37:50,204 --> 00:37:52,139
who had high blood pressure.

771
00:37:52,206 --> 00:37:54,908
And they were assigned
care as usual

772
00:37:54,975 --> 00:37:57,477
or a more aggressive treatment.

773
00:37:57,544 --> 00:38:00,948
Care as usual,
meant keeping that top number,

774
00:38:01,014 --> 00:38:03,116
in the blood pressure numbers
that they give you,

775
00:38:03,183 --> 00:38:05,819
keeping the top one
to around 140.

776
00:38:05,886 --> 00:38:07,154
The more aggressive treatment

777
00:38:07,221 --> 00:38:11,091
was dropping that down even more
to 120.

778
00:38:11,158 --> 00:38:14,394
The main outcomes
were cardiovascular.

779
00:38:14,461 --> 00:38:16,830
So, it was reduction
in myocardial infarction,

780
00:38:16,897 --> 00:38:19,399
stroke, heart failure,
and death.

781
00:38:19,466 --> 00:38:22,769
And then, a secondary goal
was to show a reduction

782
00:38:22,836 --> 00:38:24,438
in the incidence
of mild cognitive impairment

783
00:38:24,505 --> 00:38:25,873
and dementia.

784
00:38:25,939 --> 00:38:29,810
This trial was so successful
at reducing the risk

785
00:38:29,877 --> 00:38:34,848
of stroke and heart failure
and death that it ended early.

786
00:38:34,915 --> 00:38:38,051
But they were still able to show
that there was, in fact,

787
00:38:38,118 --> 00:38:40,354
also a reduction in the risk

788
00:38:40,420 --> 00:38:45,759
for developing mild cognitive
impairment and dementia.

789
00:38:46,393 --> 00:38:48,629
There's also interest
in repurposing drugs

790
00:38:48,695 --> 00:38:50,030
for cardiovascular health

791
00:38:50,097 --> 00:38:55,002
in people who don't have
cardiovascular health issues.

792
00:38:55,068 --> 00:38:57,204
Can these drugs
still improve brain health

793
00:38:57,271 --> 00:39:00,207
independent
of any cardiovascular benefit

794
00:39:00,274 --> 00:39:01,942
they may provide?

795
00:39:02,276 --> 00:39:05,012
So, there's been a couple
of trials now,

796
00:39:05,078 --> 00:39:06,980
for example, metformin.

797
00:39:07,047 --> 00:39:09,650
If we give metformin to people
who don't have diabetes,

798
00:39:09,716 --> 00:39:11,185
Type 2 diabetes,

799
00:39:11,251 --> 00:39:13,687
do they nevertheless
see a benefit

800
00:39:13,754 --> 00:39:17,891
when it comes to slowing
cognitive decline?

801
00:39:21,061 --> 00:39:24,164
Another example of this
is a study of semaglutide,

802
00:39:24,231 --> 00:39:27,835
that you may know better
as Ozempic or Wegovy.

803
00:39:27,901 --> 00:39:29,570
Semaglutide is a medication

804
00:39:29,636 --> 00:39:33,006
that was developed
for Type 2 diabetes.

805
00:39:33,073 --> 00:39:38,111
And two studies were conducted.
EVOKE and EVOKE+.

806
00:39:38,178 --> 00:39:40,247
So, these were clinical trials.

807
00:39:40,314 --> 00:39:44,451
They each enrolled 1,800
participants ages 55 to 85.

808
00:39:44,518 --> 00:39:47,387
They were ongoing in parallel.

809
00:39:47,454 --> 00:39:49,289
And all of the people
who were enrolled

810
00:39:49,356 --> 00:39:54,728
had mild to moderate dementia
due to Alzheimer's disease.

811
00:39:54,795 --> 00:39:57,164
In the EVOKE study,
people were excluded

812
00:39:57,231 --> 00:39:59,499
if they had any signs
of small vessel disease.

813
00:39:59,566 --> 00:40:02,970
So, if they had any of those
microinfarcts or microbleeds

814
00:40:03,036 --> 00:40:05,539
or white matter
hyperintensities,

815
00:40:05,606 --> 00:40:07,941
they couldn't be
in that part of the trial.

816
00:40:08,008 --> 00:40:10,744
But they could be in the other
part of the trial, EVOKE+.

817
00:40:10,811 --> 00:40:13,080
So, basically, they had people

818
00:40:13,146 --> 00:40:14,781
with mild to moderate
Alzheimer's,

819
00:40:14,848 --> 00:40:16,250
dementia
due to Alzheimer's disease,

820
00:40:16,316 --> 00:40:17,818
with healthy brains,

821
00:40:17,885 --> 00:40:19,987
and people with mild
to moderate Alzheimer's,

822
00:40:20,053 --> 00:40:23,423
dementia due to Alzheimer's
disease, with unhealthy brains,

823
00:40:23,490 --> 00:40:27,794
at least in terms of the
blood vessels in their brain.

824
00:40:27,861 --> 00:40:31,732
Their goal was to slow
the progression of dementia

825
00:40:31,798 --> 00:40:33,367
in people on semaglutide,

826
00:40:33,433 --> 00:40:36,036
or to show that
that could happen.

827
00:40:36,103 --> 00:40:38,972
The results from this study
just very recently

828
00:40:39,039 --> 00:40:42,042
were presented at a conference
a couple months ago,

829
00:40:42,109 --> 00:40:45,345
and there was no difference
in progression

830
00:40:45,412 --> 00:40:47,047
between the two groups.

831
00:40:47,114 --> 00:40:49,249
This was a
very disappointing outcome,

832
00:40:49,316 --> 00:40:52,853
but it has not dampened
interest in semaglutide

833
00:40:52,920 --> 00:40:57,724
as a potential treatment
for Alzheimer's disease.

834
00:40:59,026 --> 00:41:02,729
As in other drugs that have
failed to have an effect

835
00:41:02,796 --> 00:41:05,332
in the mild-to-moderate
dementia phase,

836
00:41:05,399 --> 00:41:10,237
we are looking at earlier phases
of disease progression.

837
00:41:12,372 --> 00:41:14,608
It's not just medication

838
00:41:14,675 --> 00:41:17,411
that people are taking
an interest in repurposing.

839
00:41:17,477 --> 00:41:19,546
There are also studies
on supplements,

840
00:41:19,613 --> 00:41:23,584
particularly omega-3
and omega-6 fatty acids.

841
00:41:23,650 --> 00:41:25,252
Now, you may remember
there's been a lot

842
00:41:25,319 --> 00:41:27,654
of study
of cardiovascular benefits

843
00:41:27,721 --> 00:41:30,958
for omega-3s in particular
and fish oil.

844
00:41:31,024 --> 00:41:32,759
And it kind of goes
back and forth, right?

845
00:41:32,826 --> 00:41:36,597
It was like, "Yay, fish oil,"
and then, "Boo, fish oil."

846
00:41:36,663 --> 00:41:38,832
And now,
I think it's "yay" again.

847
00:41:38,899 --> 00:41:40,968
So, this is a study
that my supervisor,

848
00:41:41,034 --> 00:41:43,437
Dr. Cindy Carlsson, conducted.

849
00:41:43,504 --> 00:41:47,007
And we had
this eicosapentaenoic acid,

850
00:41:47,074 --> 00:41:48,675
which is an omega-3 fatty acid.

851
00:41:48,742 --> 00:41:51,545
And you can think of it
as a really concentrated dose

852
00:41:51,612 --> 00:41:52,813
of fish oil,

853
00:41:52,880 --> 00:41:55,182
even though it doesn't
technically come from fish.

854
00:41:55,249 --> 00:41:57,951
But we were hoping to show
that being on this supplement

855
00:41:58,018 --> 00:42:01,989
for 18 months would improve
blood flow in the brain.

856
00:42:02,055 --> 00:42:05,392
Unfortunately,
we were not able to show that.

857
00:42:05,459 --> 00:42:09,162
Our group that was on
the concentrated fish oil

858
00:42:09,229 --> 00:42:14,735
didn't improve-- or didn't have
a difference in their blood flow

859
00:42:14,801 --> 00:42:16,904
in their brains, on average,
than people who were taking

860
00:42:16,970 --> 00:42:19,439
this mineral gel placebo.

861
00:42:20,707 --> 00:42:22,943
That has not dampened
people's interest

862
00:42:23,010 --> 00:42:26,079
in omega 3-s and omega-6
fatty acids.

863
00:42:26,146 --> 00:42:28,949
There are still a lot of trials
of those supplements,

864
00:42:29,016 --> 00:42:32,553
and there are several trials
of Ginkgo biloba, as well,

865
00:42:32,619 --> 00:42:35,289
and a few other supplements.

866
00:42:37,157 --> 00:42:40,294
So, clinical trials have
been done looking at the impact

867
00:42:40,360 --> 00:42:42,462
of treating
cardiovascular risk factors.

868
00:42:42,529 --> 00:42:45,065
However, often dementia
is a secondary goal,

869
00:42:45,132 --> 00:42:48,168
which means it might be added
after the start of the trial.

870
00:42:48,235 --> 00:42:50,304
That happened several times.

871
00:42:50,370 --> 00:42:55,008
Often the ways that dementia
is measured is not the best way

872
00:42:55,075 --> 00:42:56,810
to measure dementia
in these clinical trials,

873
00:42:56,877 --> 00:42:58,345
and they tend to be too short.

874
00:42:58,412 --> 00:43:02,783
It takes a long time
for dementia to develop,

875
00:43:02,850 --> 00:43:04,284
especially Alzheimer's disease.

876
00:43:04,351 --> 00:43:06,820
We see those symptoms
of amyloid burden

877
00:43:06,887 --> 00:43:09,923
10, 15 years
before we actually see

878
00:43:09,990 --> 00:43:12,993
clinical symptoms of dementia.

879
00:43:13,627 --> 00:43:15,329
The best evidence
we have right now

880
00:43:15,395 --> 00:43:18,365
is for controlling
high blood pressure.

881
00:43:18,432 --> 00:43:21,435
And additional studies
are needed.

882
00:43:21,502 --> 00:43:24,404
And I can feel your eyes rolling

883
00:43:25,005 --> 00:43:26,406
because we always conclude that,
right?

884
00:43:26,473 --> 00:43:28,141
Additional studies are needed.

885
00:43:28,208 --> 00:43:30,410
We need additional studies,
first of all,

886
00:43:30,477 --> 00:43:32,346
for those drawbacks
that I just mentioned.

887
00:43:32,412 --> 00:43:33,680
We need longer studies.

888
00:43:33,747 --> 00:43:37,117
We need studies
that are designed specifically

889
00:43:37,184 --> 00:43:40,521
for detecting
a cognitive benefit.

890
00:43:41,455 --> 00:43:45,592
But we also need studies
that enroll people,

891
00:43:46,093 --> 00:43:49,429
a broader spectrum
of individuals.

892
00:43:50,097 --> 00:43:52,232
So, the typical study
participant,

893
00:43:52,299 --> 00:43:54,935
especially in studies
of Alzheimer's disease,

894
00:43:55,002 --> 00:43:56,904
looks like you guys.

895
00:43:57,504 --> 00:43:59,173
[chuckles]

896
00:43:59,873 --> 00:44:02,843
It is-- Or an older version
of me, right?

897
00:44:02,910 --> 00:44:04,411
It is a--

898
00:44:04,478 --> 00:44:07,714
Two-thirds of the people
in both our longitudinal studies

899
00:44:07,781 --> 00:44:09,783
of Alzheimer's disease
are women.

900
00:44:09,850 --> 00:44:12,152
Most of our participants
are white.

901
00:44:12,219 --> 00:44:14,621
They have a college degree,
they're middle-class,

902
00:44:14,688 --> 00:44:17,491
they live in an urban
or suburban area.

903
00:44:17,558 --> 00:44:21,195
And our participants
actually tend to be healthier

904
00:44:21,261 --> 00:44:23,096
than the general population.

905
00:44:23,163 --> 00:44:25,399
So, we need studies
that are able to reach out

906
00:44:25,465 --> 00:44:28,235
to communities
that are underrepresented.

907
00:44:28,302 --> 00:44:31,104
Sicker people, older people,

908
00:44:32,306 --> 00:44:37,177
people from rural areas
or lower socioeconomic areas.

909
00:44:37,244 --> 00:44:40,080
In order to really understand
Alzheimer's disease

910
00:44:40,147 --> 00:44:42,616
and vascular contributions
to Alzheimer's disease,

911
00:44:42,683 --> 00:44:44,551
we need more people.

912
00:44:47,154 --> 00:44:48,989
So, there are things
that we can do

913
00:44:49,056 --> 00:44:51,992
to manage chronic conditions--

914
00:44:52,059 --> 00:44:54,728
Besides managing chronic
conditions, I should say,

915
00:44:54,795 --> 00:44:57,598
to improve brain
and heart health.

916
00:44:57,664 --> 00:44:59,533
This is called
Life's Essential 8,

917
00:44:59,600 --> 00:45:03,203
and this was put together by
the American Heart Association.

918
00:45:03,270 --> 00:45:06,573
But these recommendations
overlap entirely

919
00:45:06,640 --> 00:45:10,744
with recommendations
for improving your brain health.

920
00:45:10,811 --> 00:45:12,946
So, I'm not gonna spend
a lot of time on this

921
00:45:13,013 --> 00:45:15,549
because these infographics
are everywhere.

922
00:45:15,616 --> 00:45:18,085
And you've probably heard
a lot of this from your doctor.

923
00:45:18,151 --> 00:45:20,220
And if you aren't hearing
this from your doctor,

924
00:45:20,287 --> 00:45:21,822
get a new doctor.

925
00:45:21,889 --> 00:45:23,423
[audience laughs]

926
00:45:23,490 --> 00:45:25,826
I do wanna point out
a couple of things.

927
00:45:25,893 --> 00:45:27,961
First of all,
the American Heart Association

928
00:45:28,028 --> 00:45:31,832
has adopted
that more aggressive approach

929
00:45:31,899 --> 00:45:34,501
to managing
high blood pressure,

930
00:45:34,568 --> 00:45:37,471
so, keeping it down around 120.

931
00:45:38,272 --> 00:45:43,143
I want to be very clear
about what I'm about to say.

932
00:45:43,210 --> 00:45:48,015
It is never too late
to adopt a healthier lifestyle,

933
00:45:48,615 --> 00:45:53,287
but it's always better
to start earlier if you can.

934
00:45:54,988 --> 00:45:57,324
And that's especially true
for high blood pressure.

935
00:45:57,391 --> 00:46:01,628
We find that treating
high blood pressure in midlife--

936
00:46:01,695 --> 00:46:07,167
and midlife is defined as 55
to 65 years of age, typically--

937
00:46:08,302 --> 00:46:11,672
treating high blood pressure
in that age range

938
00:46:11,738 --> 00:46:13,006
or starting in that age range

939
00:46:13,073 --> 00:46:14,741
gives you the most bang
for your buck.

940
00:46:14,808 --> 00:46:17,311
So, if you know people
in that age range,

941
00:46:17,377 --> 00:46:19,246
tell them to go see
their doctor,

942
00:46:19,313 --> 00:46:20,848
get their blood pressure
checked out,

943
00:46:20,914 --> 00:46:24,351
and if they need medication,
start taking it.

944
00:46:24,418 --> 00:46:25,986
The other thing is,

945
00:46:26,053 --> 00:46:30,123
when I hear "physical activity,"
I think exercise.

946
00:46:30,190 --> 00:46:34,795
And I just can't find the joy
in exercise personally.

947
00:46:34,862 --> 00:46:36,763
But actually, physical activity

948
00:46:36,830 --> 00:46:38,966
doesn't just have to be
exercise.

949
00:46:39,032 --> 00:46:42,202
It can be gardening,
it can be cleaning the house,

950
00:46:42,269 --> 00:46:44,738
it can be running around
doing errands.

951
00:46:44,805 --> 00:46:48,542
And there's been a few studies
now on sedentary behavior,

952
00:46:48,609 --> 00:46:50,310
just sitting, that have shown

953
00:46:50,377 --> 00:46:53,380
that sitting
for 10 hours or more

954
00:46:54,915 --> 00:46:58,819
really substantially
raises the risk of dementia.

955
00:46:58,886 --> 00:47:02,122
So, any amount of activity
is better than no activity.

956
00:47:02,189 --> 00:47:04,992
And sprinkling your activity
throughout the day,

957
00:47:05,058 --> 00:47:09,096
even if it's a, you know,
pretty moderate, low activity

958
00:47:09,162 --> 00:47:11,398
is gonna be beneficial.

959
00:47:11,798 --> 00:47:14,568
There are a couple things
I want to bring up

960
00:47:14,635 --> 00:47:15,736
just because that you're here

961
00:47:15,802 --> 00:47:18,272
and I feel like I need
to spread the word,

962
00:47:18,338 --> 00:47:20,541
as somebody said earlier.

963
00:47:20,607 --> 00:47:23,544
There are some specific risks--

964
00:47:23,610 --> 00:47:25,846
or risks that are specific
to dementia.

965
00:47:25,913 --> 00:47:27,881
So, I get a lot of questions
about drinking

966
00:47:27,948 --> 00:47:29,683
when I go out
and give these talks.

967
00:47:29,750 --> 00:47:33,353
Heavy drinking is really bad
for your brain

968
00:47:33,420 --> 00:47:35,355
and for the blood vessels
in your brain.

969
00:47:35,422 --> 00:47:36,523
And I can't imagine

970
00:47:36,590 --> 00:47:40,260
it's particularly good
for your heart.

971
00:47:40,894 --> 00:47:42,863
But it's okay
to drink moderately.

972
00:47:42,930 --> 00:47:46,333
I recommend that people treat
drinking as a treat,

973
00:47:46,400 --> 00:47:50,137
or, like we say in my household,
as a sometimes food.

974
00:47:50,204 --> 00:47:52,039
There's not really--

975
00:47:52,105 --> 00:47:55,342
There's some studies
that show a mild benefit

976
00:47:55,409 --> 00:47:57,611
to drinking red wine
or something like that.

977
00:47:57,678 --> 00:48:00,480
There's other studies
that show no benefit.

978
00:48:00,547 --> 00:48:02,082
So, again, if you like

979
00:48:02,149 --> 00:48:04,418
having a drink once in a while,
that's great.

980
00:48:04,484 --> 00:48:06,620
You don't have to give it up,
but it's not like

981
00:48:06,687 --> 00:48:09,957
you need to start
for the health benefits.

982
00:48:10,023 --> 00:48:11,291
Hearing loss.

983
00:48:11,358 --> 00:48:14,895
We are learning more and more
about how hearing loss,

984
00:48:14,962 --> 00:48:17,397
especially hearing loss
in midlife,

985
00:48:17,464 --> 00:48:20,968
is a risk factor
for developing dementia.

986
00:48:21,034 --> 00:48:25,772
So, treating hearing loss,
we think, is really key.

987
00:48:25,839 --> 00:48:28,041
Again, if you--
This is another area

988
00:48:28,108 --> 00:48:31,078
where you get the most bang for
your buck if you start early.

989
00:48:31,144 --> 00:48:33,680
So, if you are starting
to have--

990
00:48:33,747 --> 00:48:37,251
notice hearing problems,
get checked out.

991
00:48:37,317 --> 00:48:40,687
If you know somebody
who's in that midlife range

992
00:48:40,754 --> 00:48:42,823
or you're
in that midlife range yourself,

993
00:48:42,890 --> 00:48:44,291
go get your hearing checked.

994
00:48:44,358 --> 00:48:47,961
If you need a hearing aid,
try to get one and <i>wear it.</i>

995
00:48:48,028 --> 00:48:49,696
[chuckles]

996
00:48:50,097 --> 00:48:51,398
There's a couple reasons

997
00:48:51,465 --> 00:48:54,234
why we think hearing loss
is leading to dementia,

998
00:48:54,301 --> 00:48:56,270
but the main one is most likely

999
00:48:56,336 --> 00:48:59,640
that people with hearing loss
become socially isolated.

1000
00:48:59,706 --> 00:49:01,975
And that's the last thing
I wanted to mention.

1001
00:49:02,042 --> 00:49:06,713
We are seeing more and more
that throughout disease--

1002
00:49:06,780 --> 00:49:09,449
Alzheimer's disease progression,

1003
00:49:09,516 --> 00:49:12,186
being socially active,
staying socially active

1004
00:49:12,252 --> 00:49:15,923
improves quality of life
across the board.

1005
00:49:15,989 --> 00:49:20,661
So, it's really important
for us to stay socially active.

1006
00:49:20,727 --> 00:49:24,831
But it's also important for us
to incorporate our friends,

1007
00:49:24,898 --> 00:49:27,100
our family, our neighbors
who may be experiencing

1008
00:49:27,167 --> 00:49:29,469
some mild cognitive impairment
or dementia,

1009
00:49:29,536 --> 00:49:31,738
to stay engaged with them

1010
00:49:31,805 --> 00:49:34,141
so that they are able to be
socially active as well.

1011
00:49:34,208 --> 00:49:36,877
That is a real gift to people.

1012
00:49:38,278 --> 00:49:39,980
So, the last thing
I'm gonna talk about

1013
00:49:40,047 --> 00:49:42,683
is the multidomain approach.

1014
00:49:42,749 --> 00:49:47,054
Typically, when we study
modifiable risk factors

1015
00:49:47,120 --> 00:49:50,924
or these modifiable
lifestyle factors,

1016
00:49:52,192 --> 00:49:53,527
we study them one at a time.

1017
00:49:53,594 --> 00:49:54,695
So, we look at exercise.

1018
00:49:54,761 --> 00:49:57,998
Does exercise improve something?

1019
00:49:58,565 --> 00:50:02,035
Diet, does diet help anything,
right?

1020
00:50:02,102 --> 00:50:03,237
We look at them, you know,

1021
00:50:03,303 --> 00:50:06,006
like we're looking
for a magic bullet.

1022
00:50:06,073 --> 00:50:08,375
The multidomain approach
says,

1023
00:50:08,442 --> 00:50:09,576
"We don't need to do that.

1024
00:50:09,643 --> 00:50:12,646
"Let's just make people
as healthy as possible,

1025
00:50:12,713 --> 00:50:14,882
"however we need to do that,
all at once.

1026
00:50:14,948 --> 00:50:18,719
We will do all the things
all at once."

1027
00:50:18,785 --> 00:50:22,022
So, this is
the U.S. POINTER study.

1028
00:50:22,623 --> 00:50:25,125
This was a multidomain study
that was patterned

1029
00:50:25,192 --> 00:50:29,930
after a similar study out of
Finland called the FINGER study.

1030
00:50:29,997 --> 00:50:31,265
And in this study,

1031
00:50:31,331 --> 00:50:34,401
2,000 cognitively unimpaired
individuals were enrolled,

1032
00:50:34,468 --> 00:50:38,705
and all of these individuals
were at high risk for dementia

1033
00:50:38,772 --> 00:50:42,009
due to poor diet,
lack of exercise,

1034
00:50:42,576 --> 00:50:44,444
and one other risk factor,

1035
00:50:44,511 --> 00:50:46,446
which includes
elevated blood pressure,

1036
00:50:46,513 --> 00:50:50,117
elevated LDL,
the bad cholesterol,

1037
00:50:50,184 --> 00:50:51,985
or a high A1C value.

1038
00:50:53,420 --> 00:50:57,658
Individuals were then randomized
to a self-guided intervention

1039
00:50:57,724 --> 00:51:02,062
or to a structured intervention
for two years.

1040
00:51:02,763 --> 00:51:04,831
So, again,
this is a little hard to read

1041
00:51:04,898 --> 00:51:06,466
probably from
where you're sitting.

1042
00:51:06,533 --> 00:51:11,004
The bottom part here
is the self-guided intervention.

1043
00:51:11,071 --> 00:51:13,106
The self-guided
intervention group

1044
00:51:13,173 --> 00:51:15,475
got to identify their own goals.

1045
00:51:15,542 --> 00:51:18,245
They had six
facilitated group meetings

1046
00:51:18,312 --> 00:51:20,480
to talk about
those health goals.

1047
00:51:20,547 --> 00:51:22,683
And they really didn't get
a whole lot more than that.

1048
00:51:22,749 --> 00:51:26,119
They got some education,
they got some online tools,

1049
00:51:26,186 --> 00:51:29,223
and they got
some health monitoring.

1050
00:51:29,289 --> 00:51:31,391
The people in the
structured intervention group

1051
00:51:31,458 --> 00:51:35,562
were given goals to meet in
the areas of physical exercise,

1052
00:51:35,629 --> 00:51:38,332
nutrition, cognitive
and social activities,

1053
00:51:38,398 --> 00:51:40,868
and they were provided
with health coaching.

1054
00:51:40,934 --> 00:51:44,438
They went to 38
facilitated meetings

1055
00:51:44,505 --> 00:51:48,208
to talk about their health goals
and how they were doing.

1056
00:51:48,275 --> 00:51:52,012
The people who were
in the self-guided group

1057
00:51:52,079 --> 00:51:56,316
got a $75 gift card
at each of those meetings

1058
00:51:56,383 --> 00:51:58,785
to put towards their
health goal.

1059
00:51:58,852 --> 00:52:02,656
The people in the
structured intervention group--

1060
00:52:02,723 --> 00:52:07,294
I really like this detail--
got a monthly rebate.

1061
00:52:08,495 --> 00:52:13,834
Not the money, a rebate,
up to $10 towards blueberries.

1062
00:52:13,901 --> 00:52:18,472
So, their reward for all
of that was blueberries.

1063
00:52:19,239 --> 00:52:21,341
But it must have worked.

1064
00:52:21,408 --> 00:52:23,143
Cognitive ability
or thinking skills

1065
00:52:23,210 --> 00:52:25,379
was measured every six months.

1066
00:52:25,445 --> 00:52:27,814
And both groups improved
over the two years.

1067
00:52:27,881 --> 00:52:30,617
So, the top line,
those dark purple dots,

1068
00:52:30,684 --> 00:52:33,554
represent the group that was
on the structured intervention,

1069
00:52:33,620 --> 00:52:37,057
and the lavender
triangles represent the people

1070
00:52:37,124 --> 00:52:39,693
who were on the self-guided
intervention.

1071
00:52:39,760 --> 00:52:42,696
So, we expect people
to do better on a test

1072
00:52:42,763 --> 00:52:45,365
if they've been exposed to it
repeatedly, right?

1073
00:52:45,432 --> 00:52:47,334
If you're taking
the same test every six months,

1074
00:52:47,401 --> 00:52:50,737
we hope that you learn
how to do the test.

1075
00:52:50,804 --> 00:52:52,806
And we call this
practice effects.

1076
00:52:52,873 --> 00:52:54,541
But even so,

1077
00:52:56,777 --> 00:52:59,279
the structured intervention
group actually improved

1078
00:52:59,346 --> 00:53:02,382
more than the self-guided group.

1079
00:53:02,449 --> 00:53:05,853
This was a statistically
significant difference.

1080
00:53:05,919 --> 00:53:08,722
Everybody was very excited
about that.

1081
00:53:08,789 --> 00:53:11,525
But you can kind of
eyeball it, right?

1082
00:53:11,592 --> 00:53:15,963
You can see that
the difference isn't real big.

1083
00:53:16,029 --> 00:53:17,898
My takeaway--
and not just my takeaway,

1084
00:53:17,965 --> 00:53:20,701
some other clinicians
have weighed in on this--

1085
00:53:20,767 --> 00:53:24,338
is that even minimal
intervention,

1086
00:53:24,404 --> 00:53:28,141
a little bit of infrastructure,
a little bit of incentive,

1087
00:53:28,208 --> 00:53:31,645
has the potential to improve
people's cognitive function.

1088
00:53:31,712 --> 00:53:34,214
And this is cognitive function
in people who are, remember,

1089
00:53:34,281 --> 00:53:36,884
at high risk
for developing dementia.

1090
00:53:36,950 --> 00:53:39,753
So, if we can help improve
people's health,

1091
00:53:39,820 --> 00:53:42,122
if we can improve
their cognitive function,

1092
00:53:42,189 --> 00:53:44,091
we can contribute
to that brain reserve

1093
00:53:44,157 --> 00:53:45,893
or that cognitive reserve

1094
00:53:45,959 --> 00:53:48,161
that helps people
maintain function

1095
00:53:48,228 --> 00:53:53,734
in the face of any other brain
changes that may be going on.

1096
00:53:53,800 --> 00:53:56,603
So, here's my final takeaways.

1097
00:53:56,670 --> 00:53:58,739
First of all,
it's never too early or too late

1098
00:53:58,805 --> 00:54:02,509
to take care of your heart
and your brain at the same time.

1099
00:54:02,576 --> 00:54:05,012
It's all the same stuff.

1100
00:54:05,078 --> 00:54:06,480
Definitely talk to your doctor

1101
00:54:06,547 --> 00:54:09,082
if you haven't in a while
about your blood pressure

1102
00:54:09,149 --> 00:54:11,218
and whether it makes sense
for you

1103
00:54:11,285 --> 00:54:14,087
to be on that
more aggressive approach

1104
00:54:14,154 --> 00:54:16,757
to lowering high blood pressure.

1105
00:54:16,823 --> 00:54:19,092
And in general,
do what makes sense for you.

1106
00:54:19,159 --> 00:54:21,428
There's a lot of infographics
like this.

1107
00:54:21,495 --> 00:54:23,664
It's, like, ten steps
to good brain health,

1108
00:54:23,730 --> 00:54:25,165
Twelve steps
to good brain health.

1109
00:54:25,232 --> 00:54:26,867
We're not all gonna do
all those things.

1110
00:54:26,934 --> 00:54:29,069
That's not realistic.

1111
00:54:29,937 --> 00:54:31,471
So, it's important
to kind of sit down

1112
00:54:31,538 --> 00:54:34,541
and think, "What makes sense
for me to do?

1113
00:54:34,608 --> 00:54:36,143
"What can I do
to improve my health?

1114
00:54:36,210 --> 00:54:37,344
What am I gonna stick with?"

1115
00:54:37,411 --> 00:54:38,512
That's really important.

1116
00:54:38,579 --> 00:54:40,314
"What can I be consistent with?"

1117
00:54:40,380 --> 00:54:42,349
It's also important--
What I've learned

1118
00:54:42,416 --> 00:54:44,918
from the U.S. POINTER study
and from the FINGER study

1119
00:54:44,985 --> 00:54:47,287
and a couple
other multidomain studies

1120
00:54:47,354 --> 00:54:50,224
is that I think
it really helps to have a team.

1121
00:54:50,290 --> 00:54:52,259
Have your doctor involved.

1122
00:54:52,326 --> 00:54:54,962
Maybe meet with a nutritionist
if that's available to you.

1123
00:54:55,028 --> 00:54:57,231
Involve your family
and your friends.

1124
00:54:57,297 --> 00:55:01,768
Have a support group
to help you with your goals.

1125
00:55:02,769 --> 00:55:04,905
So, I have a couple of
final slides that have nothing

1126
00:55:04,972 --> 00:55:08,542
to do with vascular risk
for dementia.

1127
00:55:09,710 --> 00:55:11,612
None of this information
would be possible

1128
00:55:11,678 --> 00:55:13,547
without study volunteers.

1129
00:55:13,614 --> 00:55:16,383
So, even though a lot
of our study volunteers

1130
00:55:16,450 --> 00:55:18,018
are kind of people
like yourselves,

1131
00:55:18,085 --> 00:55:20,521
we still need more of you.
[chuckles]

1132
00:55:20,587 --> 00:55:22,523
We need so many
more participants,

1133
00:55:22,589 --> 00:55:25,259
especially for clinical trials.

1134
00:55:25,325 --> 00:55:27,461
If you've tried
to be a part of a study before

1135
00:55:27,528 --> 00:55:29,997
and you've been turned down,
please check back.

1136
00:55:30,063 --> 00:55:31,832
We always have new studies
starting

1137
00:55:31,899 --> 00:55:34,434
at the University of Wisconsin
in Madison.

1138
00:55:34,501 --> 00:55:35,936
And right now, a lot of effort

1139
00:55:36,003 --> 00:55:38,906
is being put towards
home assessments

1140
00:55:38,972 --> 00:55:41,808
so that people can cut down
on their travel

1141
00:55:41,875 --> 00:55:47,214
or maybe not even travel at all
for some of these studies.

1142
00:55:47,281 --> 00:55:49,783
A good place
to just see what's out there

1143
00:55:49,850 --> 00:55:54,421
is TrialMatch at the
Alzheimer's Association website.

1144
00:55:54,488 --> 00:55:56,823
You can kind of--
You can use search terms

1145
00:55:56,890 --> 00:55:59,259
to look for different things
that you're interested in

1146
00:55:59,326 --> 00:56:01,195
and see what trials
are going on.

1147
00:56:01,261 --> 00:56:03,797
And endalznow.org
is another place

1148
00:56:03,864 --> 00:56:07,301
where you can kind of see
what studies are available.

1149
00:56:07,367 --> 00:56:09,269
We have a ton of information

1150
00:56:09,336 --> 00:56:13,774
at our Alzheimer's Disease
Research Center website.

1151
00:56:13,841 --> 00:56:17,110
We have a fall community event
every year, and that's recorded.

1152
00:56:17,177 --> 00:56:19,313
So, you can go to our website
and you can listen

1153
00:56:19,379 --> 00:56:21,315
to a wonderful talk
from Kim Mueller,

1154
00:56:21,381 --> 00:56:24,051
who is a language specialist.

1155
00:56:24,117 --> 00:56:27,221
Dr. Nate Chin, who's
a geriatrician with our center,

1156
00:56:27,287 --> 00:56:29,690
hosts the
<i>Dementia Matters</i> podcast.

1157
00:56:29,756 --> 00:56:32,793
I can't believe there are
over 200 episodes already.

1158
00:56:32,860 --> 00:56:33,961
It's amazing.

1159
00:56:34,027 --> 00:56:36,163
They're really wonderful
discussions.

1160
00:56:36,230 --> 00:56:37,631
We have an exercise class

1161
00:56:37,698 --> 00:56:40,667
and a healthy living with
mild cognitive impairment class.

1162
00:56:40,734 --> 00:56:43,637
And in April, we have our annual

1163
00:56:44,037 --> 00:56:48,175
Solomon Carter Fuller
Brain Health Brunch.

1164
00:56:49,109 --> 00:56:50,811
This is hosted by

1165
00:56:50,878 --> 00:56:53,914
the African Americans Fighting
Alzheimer's in Midlife study,

1166
00:56:53,981 --> 00:56:57,317
but it is free
and open to the public.

1167
00:56:58,118 --> 00:57:00,988
The University of Wisconsin
has a new initiative

1168
00:57:01,054 --> 00:57:03,056
called RISE-THRIVE.

1169
00:57:03,690 --> 00:57:05,592
And the goal of RISE-THRIVE

1170
00:57:05,659 --> 00:57:08,328
is to invest broadly
in healthy aging.

1171
00:57:08,395 --> 00:57:11,131
So, again,
focusing on that healthspan

1172
00:57:11,198 --> 00:57:13,233
rather than a lifespan.

1173
00:57:13,300 --> 00:57:15,469
And they are just
getting up and running,

1174
00:57:15,536 --> 00:57:18,038
but hopefully
in the next year or two,

1175
00:57:18,105 --> 00:57:21,642
they'll have a lot
of exciting things going on

1176
00:57:21,708 --> 00:57:24,378
and exciting public events.

1177
00:57:25,712 --> 00:57:30,551
So, I wanna leave you
with this one last thought,

1178
00:57:30,617 --> 00:57:32,553
'cause I know we've
talked about a lot of things

1179
00:57:32,619 --> 00:57:35,322
that are kind of,
you know, hard to hear

1180
00:57:35,389 --> 00:57:38,725
and, "Oh, aging,
blah, blah, blah."

1181
00:57:40,627 --> 00:57:42,629
So, this was a cartoon

1182
00:57:43,163 --> 00:57:46,200
that somebody made
in response to an article

1183
00:57:46,266 --> 00:57:48,702
that purported
to find the best age.

1184
00:57:48,769 --> 00:57:49,870
And in this cartoon,

1185
00:57:49,937 --> 00:57:52,639
this person has brains in jars
through the ages.

1186
00:57:52,706 --> 00:57:55,943
So, the first age is 18 to 24,
and you probably can't read it,

1187
00:57:56,009 --> 00:57:58,779
but that brain is labeled
"Green."

1188
00:57:58,846 --> 00:58:00,781
And then there's ages 25 to 36,

1189
00:58:00,848 --> 00:58:04,284
and that brain is labeled
"Overrated."

1190
00:58:04,351 --> 00:58:06,587
And then there's ages 37 to 50,

1191
00:58:06,653 --> 00:58:09,823
and that brain is labeled
"Distracted."

1192
00:58:09,890 --> 00:58:13,493
And then there's 51 and up,
and that brain is "Just right."

1193
00:58:13,560 --> 00:58:15,596
So, everybody in this room
can rest easy.

1194
00:58:15,662 --> 00:58:18,632
Your brains are just right.
[audience chuckles]

1195
00:58:18,699 --> 00:58:20,767
Thank you, everyone, for coming.

1196
00:58:20,834 --> 00:58:22,836
[audience applauds]