– English Lyrics

Lyrics & Translation

[English]

[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]

Key Vocabulary

Vocabulary	Meanings
practice /ˈpræktɪs/ B1	noun - the work or business of a doctor, lawyer, etc.
salvage /ˈsælvɪdʒ/ C1	noun - a place where discarded items or wrecked cars are gathered for parts
fender /ˈfɛndər/ B2	noun - the mudguard or area around the wheel of a vehicle
vision /ˈvɪʒən/ B2	noun - an idea or mental image of what something could be in the future
appointment /əˈpɔɪntmənt/ A2	noun - an arrangement to meet someone at a particular time and place
dementia /dɪˈmɛnʃə/ C1	noun - a chronic or persistent disorder of the mental processes caused by brain disease
prognosis /prɒɡˈnəʊsɪs/ C1	noun - the likely course of a disease or ailment
helpless /ˈhɛlpləs/ B1	adjective - unable to defend oneself or to act without help
neuron /ˈnjʊərɒn/ C1	noun - a specialized cell transmitting nerve impulses; a nerve cell
maintain /meɪnˈteɪn/ B1	verb - to keep something in good condition by checking or repairing it regularly
debris /ˈdɛbriː/ B2	noun - scattered pieces of rubbish or remains
prevent /prɪˈvɛnt/ B1	verb - to keep something from happening
obesity /əʊˈbiːsɪti/ B2	noun - the state of being grossly fat or overweight
eradicate /ɪˈrædɪkeɪt/ C1	verb - to destroy completely; put an end to
genetic /dʒɪˈnɛtɪk/ B2	adjective - relating to genes or heredity
antibody /ˈæntibɒdi/ C1	noun - a blood protein produced in response to and counteracting a specific antigen
diagnose /ˈdaɪəɡnəʊz/ B2	verb - to identify the nature of an illness or other problem by examination
biopsy /ˈbaɪɒpsi/ C1	noun - an examination of tissue removed from a living body to discover the presence, cause, or extent of a disease