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[applause]
[music]
>> I started practicing medicine 15 years
ago. Jim was one of my first patients.
When he came into my practice, he had a
huge smile on his face. As we leaned in
to shake hands, I said, "Jim, what's
been going on?"
He said, "Oh, well, I had a great day at
the junkyard."
It wasn't really what I was expecting.
So,
we got to talking and it turns out Jim,
when he retired, had bought a 1964
Mustang.
This car was in need of a lot of love,
and he was always looking for parts for
it. And he'd taken to going to salvage
yards to try and find things that had
been overlooked by others. That morning,
he had found a fender, and he was really
excited about it.
You see, Jim had a vision.
He was going to complete his 1964
Mustang. He was going to ship it out to
the Pacific Coast Highway, and he was
going to blast down that road with the
top down, the sun in his face, and the
wind in his hair.
Jim and I got to know each other pretty
well over the years, and whenever he
came in for an appointment, he would
always give me an update on the car.
One day, though, he came in and he had
an issue.
Doc, he said, "I had something really
weird happen the other day.
I went to the salvage yard, and I found
the steering wheel I'd been looking for.
I was really excited about it. And
I got it home, I was cleaning it up, and
I looked over, I already had a steering
wheel. This was the second one I had
bought. I didn't remember getting the
first one at all.
Not only that, my wife's been teasing
me. She says I've been having more
senior moments. And the thing that's
most concerning to me is that my father
had dementia and Alzheimer's. He ended
up having to live in a memory care unit
in his last years of life.
Doc, is there anything you can do for
me?"
Well, I was worried about Jim because I
knew that one in three people over the
age of 85 will develop signs and
symptoms of Alzheimer's.
Doc, he said, "Is there anything you can
give me to let me know if I have
Alzheimer's or if this is just normal
aging? Is this the early onset of this
disease?" And I said, "Well,
there's nothing we can really do. We had
It's a wait and see sort of situation.
We'll see if things progress. We can do
a test functionally see how your memory
is doing, but it doesn't tell us if this
is Alzheimer's and it doesn't tell us
your likely prognosis.
Okay, he said, "Well, I really don't
want to end up like my dad. Are there
any effective treatments that you can
give me? Something that can help push
this off into the future or maybe even
stop it?" Again, I'm sorry. We're just
going to have to wait and see. There's
some medications we give later in the
course of the disease, but they don't
really meaningfully bend the curve.
Jim got he said, "Thanks for the help."
And that word help sort of hung in the
air because of course I hadn't helped
him at all. In fact, he and I both felt
pretty helpless in the face of this
disease that he might be facing.
Time went on
and unfortunately Jim's scores on his
test were getting worse.
One day he missed an appointment with me
and his wife called. "Doc, no one seen
Jim since this morning." "Oh, no." I
said, "Well, he missed his appointment
today."
She couldn't get a hold of him on the
phone. She ended up calling friends and
family and going to all of Jim's
favorite places to visit. They ended up
finding him in another salvage yard
with a couple of parts in his hands, but
he'd been there for several hours. He
was lost and confused.
After that, his wife made sure she took
really good care of him. She stayed by
his side.
She made sure he was never alone.
She called me, "Doctor, is there
anything we can do? Anything you can do
to help me?"
Sorry, it's wait and see. That same
feeling of helplessness again.
Things progressed. Jim ended up going
into a memory care facility.
His kids called me. Same conversation.
Same feeling of helplessness.
The way it went with Jim is the way we
all understand the story of Alzheimer's.
It's the way that it's always gone.
But what I want to share with you
tonight is that there have been changes
in the last few years that are
completely changing this story
for patients like Jim.
First of all, what is Alzheimer's?
Alzheimer's is the build-up of abnormal
proteins in the brain. They're called
amyloid and tau. They build up in
tangles, and they strangle the neurons.
They prevent them from working
correctly. They even kill them. And when
enough of this has happened, your memory
starts to slip. I like to think of it
like one of the engines that Jim used to
work on.
If you don't maintain it, rust and
debris builds up over time, and
eventually the engine struggles. It may
even break down.
An important parallel between these two
is that they're both processes that go
on for years and years. By the time you
become symptomatic with Alzheimer's, the
disease may have been affecting you for
10 or 20 years.
This may make you think,
"What can I do to prevent this?"
Well, we've learned a lot about that
since I first saw Jim. We now know 14
risk factors, lifestyle factors, that
you can try and change to reduce your
risk of the disease.
These are things like avoiding obesity,
avoiding diabetes,
treating conditions like high blood
pressure and high cholesterol,
having a healthy diet, specifically a
DASH or a Mediterranean diet,
exercise, in particular aerobic
exercise, is good at reducing your risk.
Things that engage your mind like social
engagement, being married, volunteering,
working, these things all keep your mind
active and help reduce your risk of
disease.
Finally, things that affect the input
into your brain like treating loss of
eyesight or treating difficulties with
hearing can reduce your risk. That
having been said, this is not going to
be enough to eradicate the disease, and
that's not really surprising to us. We
know there's a genetic component to this
disease. There's some rare cases of
Alzheimer's where
people are virtually guaranteed to get
the disease because of a genetic defect
in their 30s and 40s.
The more common variant of Alzheimer's
is associated with a gene called APOE.
You get a copy from your mother and a
copy from your father. And if you get
one bad copy of this gene, your odds of
getting Alzheimer's go up threefold.
If you get two bad copies of this gene,
your odds of getting Alzheimer's go up
by a factor of eight.
So, it shouldn't be surprising that
lifestyle factors will not eradicate
this disease entirely.
But, this is where changes in the last 2
years are completely upending how we
think about this disease.
Making us hopeful that people like Jim
will have a different story in the
future.
The first of these findings
is the development of a new class of
medications called monoclonal
antibodies.
Monoclonal antibodies are medications
that trigger your immune system to fight
diseases in ways that they wouldn't
normally.
They've been used to treat diseases like
cancer. They've been used to treat
autoimmune diseases. And as of 2023, for
the first time, one of these medications
was approved to treat Alzheimer's
disease.
And not just treat it, but attack the
underlying cause of Alzheimer's disease.
These medications help tag the abnormal
proteins that are building up for your
own immune system to clear them.
And the initial study on these
medications,
>> [snorts]
>> they took patients who already had
memory deficits, and they gave down the
progress of the Alzheimer's by 30%.
While that may not seem like a huge
number, it's the first time that we've
changed the course of the disease by
directly treating it. Everything before
this was a band-aid. This is changing
the underlying physiology.
So, if we go back to the
analogy of the engine, you may ask
yourself, why do we wait for the engine
to break down before we start trying to
fix it? Jim had the oil changed in his
Mustang every 3,000 mi.
Well, that's always been an issue. You
see, when we saw Jim, the story was
there's no way to diagnose Alzheimer's.
We had no no way of identifying the
patients who were at risk.
In fact, when Jim saw me, the only way
to diagnose Alzheimer's was with a
biopsy of the brain.
Inconvenient, expensive, and as doctors
like to put it, uncomfortable.
A little later, if you were fortunate
enough to live near an academic center,
they could have put a needle into your
spine and drawn the fluid off of it and
sent it to a specialized lab and been
able to help you know your risk of
Alzheimer's that way.
Again, inconvenient and inexpens- and
expensive.
A little bit later, now what they do is
they have a CAT scan of the brain
that they can take after giving you a
radioactive injection.
Still not something that everybody wants
to do.
But, as of last year, just in 2025 for
the first time, a new test was developed
that can detect these abnormal proteins
in your peripheral blood. What this
means is you can go to the doctor's
office and get a blood draw and know
your risk of Alzheimer's.
Now, between these two findings, you may
say, "Great, let's identify the people
and start treating them."
Well, these medications are not without
risk. They trigger an immune response in
your brain, which can cause swelling and
cause side effects.
But, the good news is that they're
already studying
this mechanism of action. They're
already studying this.
They've taken these monoclonal
antibodies, identified patients with the
blood test that I talked about, and
they're giving different types of
patients different types of doses of
these medications and trying to see
which one's most effective. If there's a
way that we can slow down Alzheimer's
even more than we can now and maybe even
push it off indefinitely into the
future.
What this means is that now, not in the
future, the story has already changed.
When a patient like Jim comes into my
office and they're worried, "Might I
have really early Alzheimer's? Is this
normal or not?" There's a blood test I
can give him that's as accurate as what
used to take invasive testing.
When Jim says, "Is there anything you
can do for me that's going to change the
underlying course of this disease?" The
answer is, "Yes, there is.
It's already available."
Not only that, but in the future,
in the next 3 years, 2027, 2028, these
medications may be approved to be given
even earlier and make even more of an
impact than what we have now.
And my hope is that the end of the story
will ultimately change now that the
first two parts have changed.
That instead of Jim ending up sick and
requiring care and his car rusted out in
a garage somewhere,
the story can end with Jim living out
his life with increased vitality and
functionality.
He gets that car out to the Pacific
Coast Highway. He blasts down the road
with the top down, the sun in the face,
the wind in his hair, and miles and
miles of road ahead of him.
Thank you.
>> [music]
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