[applause]
00:03
[music]
00:05
>> I started practicing medicine 15 years
00:06
ago. Jim was one of my first patients.
00:08
When he came into my practice, he had a
00:12
huge smile on his face. As we leaned in
00:13
to shake hands, I said, "Jim, what's
00:15
been going on?"
00:17
He said, "Oh, well, I had a great day at
00:18
the junkyard."
00:20
It wasn't really what I was expecting.
00:21
So,
00:23
we got to talking and it turns out Jim,
00:24
when he retired, had bought a 1964
00:25
Mustang.
00:27
This car was in need of a lot of love,
00:28
and he was always looking for parts for
00:30
it. And he'd taken to going to salvage
00:32
yards to try and find things that had
00:33
been overlooked by others. That morning,
00:35
he had found a fender, and he was really
00:36
excited about it.
00:38
You see, Jim had a vision.
00:40
He was going to complete his 1964
00:42
Mustang. He was going to ship it out to
00:44
the Pacific Coast Highway, and he was
00:46
going to blast down that road with the
00:48
top down, the sun in his face, and the
00:49
wind in his hair.
00:52
Jim and I got to know each other pretty
00:54
well over the years, and whenever he
00:55
came in for an appointment, he would
00:56
always give me an update on the car.
00:58
One day, though, he came in and he had
01:00
an issue.
01:02
Doc, he said, "I had something really
01:04
weird happen the other day.
01:05
I went to the salvage yard, and I found
01:07
the steering wheel I'd been looking for.
01:10
I was really excited about it. And
01:11
I got it home, I was cleaning it up, and
01:14
I looked over, I already had a steering
01:15
wheel. This was the second one I had
01:17
bought. I didn't remember getting the
01:18
first one at all.
01:20
Not only that, my wife's been teasing
01:22
me. She says I've been having more
01:23
senior moments. And the thing that's
01:24
most concerning to me is that my father
01:26
had dementia and Alzheimer's. He ended
01:28
up having to live in a memory care unit
01:31
in his last years of life.
01:33
Doc, is there anything you can do for
01:36
me?"
01:37
Well, I was worried about Jim because I
01:38
knew that one in three people over the
01:40
age of 85 will develop signs and
01:41
symptoms of Alzheimer's.
01:43
Doc, he said, "Is there anything you can
01:45
give me to let me know if I have
01:47
Alzheimer's or if this is just normal
01:48
aging? Is this the early onset of this
01:50
disease?" And I said, "Well,
01:52
there's nothing we can really do. We had
01:55
It's a wait and see sort of situation.
01:57
We'll see if things progress. We can do
01:58
a test functionally see how your memory
02:00
is doing, but it doesn't tell us if this
02:02
is Alzheimer's and it doesn't tell us
02:04
your likely prognosis.
02:06
Okay, he said, "Well, I really don't
02:08
want to end up like my dad. Are there
02:10
any effective treatments that you can
02:11
give me? Something that can help push
02:12
this off into the future or maybe even
02:14
stop it?" Again, I'm sorry. We're just
02:16
going to have to wait and see. There's
02:19
some medications we give later in the
02:20
course of the disease, but they don't
02:21
really meaningfully bend the curve.
02:23
Jim got he said, "Thanks for the help."
02:26
And that word help sort of hung in the
02:28
air because of course I hadn't helped
02:29
him at all. In fact, he and I both felt
02:31
pretty helpless in the face of this
02:33
disease that he might be facing.
02:35
Time went on
02:38
and unfortunately Jim's scores on his
02:39
test were getting worse.
02:41
One day he missed an appointment with me
02:43
and his wife called. "Doc, no one seen
02:45
Jim since this morning." "Oh, no." I
02:47
said, "Well, he missed his appointment
02:49
today."
02:50
She couldn't get a hold of him on the
02:51
phone. She ended up calling friends and
02:52
family and going to all of Jim's
02:54
favorite places to visit. They ended up
02:56
finding him in another salvage yard
02:58
with a couple of parts in his hands, but
03:01
he'd been there for several hours. He
03:02
was lost and confused.
03:04
After that, his wife made sure she took
03:07
really good care of him. She stayed by
03:09
his side.
03:10
She made sure he was never alone.
03:12
She called me, "Doctor, is there
03:15
anything we can do? Anything you can do
03:17
to help me?"
03:18
Sorry, it's wait and see. That same
03:19
feeling of helplessness again.
03:21
Things progressed. Jim ended up going
03:24
into a memory care facility.
03:26
His kids called me. Same conversation.
03:28
Same feeling of helplessness.
03:31
The way it went with Jim is the way we
03:34
all understand the story of Alzheimer's.
03:37
It's the way that it's always gone.
03:38
But what I want to share with you
03:40
tonight is that there have been changes
03:41
in the last few years that are
03:43
completely changing this story
03:44
for patients like Jim.
03:47
First of all, what is Alzheimer's?
03:50
Alzheimer's is the build-up of abnormal
03:52
proteins in the brain. They're called
03:54
amyloid and tau. They build up in
03:56
tangles, and they strangle the neurons.
03:57
They prevent them from working
04:00
correctly. They even kill them. And when
04:01
enough of this has happened, your memory
04:03
starts to slip. I like to think of it
04:05
like one of the engines that Jim used to
04:07
work on.
04:08
If you don't maintain it, rust and
04:09
debris builds up over time, and
04:11
eventually the engine struggles. It may
04:12
even break down.
04:13
An important parallel between these two
04:15
is that they're both processes that go
04:17
on for years and years. By the time you
04:19
become symptomatic with Alzheimer's, the
04:21
disease may have been affecting you for
04:23
10 or 20 years.
04:25
This may make you think,
04:28
"What can I do to prevent this?"
04:30
Well, we've learned a lot about that
04:32
since I first saw Jim. We now know 14
04:33
risk factors, lifestyle factors, that
04:35
you can try and change to reduce your
04:38
risk of the disease.
04:39
These are things like avoiding obesity,
04:41
avoiding diabetes,
04:43
treating conditions like high blood
04:45
pressure and high cholesterol,
04:47
having a healthy diet, specifically a
04:49
DASH or a Mediterranean diet,
04:51
exercise, in particular aerobic
04:53
exercise, is good at reducing your risk.
04:55
Things that engage your mind like social
04:58
engagement, being married, volunteering,
05:00
working, these things all keep your mind
05:02
active and help reduce your risk of
05:04
disease.
05:07
Finally, things that affect the input
05:09
into your brain like treating loss of
05:10
eyesight or treating difficulties with
05:13
hearing can reduce your risk. That
05:15
having been said, this is not going to
05:16
be enough to eradicate the disease, and
05:17
that's not really surprising to us. We
05:19
know there's a genetic component to this
05:20
disease. There's some rare cases of
05:22
Alzheimer's where
05:24
people are virtually guaranteed to get
05:26
the disease because of a genetic defect
05:28
in their 30s and 40s.
05:30
The more common variant of Alzheimer's
05:32
is associated with a gene called APOE.
05:35
You get a copy from your mother and a
05:37
copy from your father. And if you get
05:38
one bad copy of this gene, your odds of
05:39
getting Alzheimer's go up threefold.
05:41
If you get two bad copies of this gene,
05:44
your odds of getting Alzheimer's go up
05:45
by a factor of eight.
05:47
So, it shouldn't be surprising that
05:49
lifestyle factors will not eradicate
05:51
this disease entirely.
05:53
But, this is where changes in the last 2
05:55
years are completely upending how we
05:57
think about this disease.
05:59
Making us hopeful that people like Jim
06:01
will have a different story in the
06:03
future.
06:04
The first of these findings
06:06
is the development of a new class of
06:08
medications called monoclonal
06:09
antibodies.
06:10
Monoclonal antibodies are medications
06:11
that trigger your immune system to fight
06:14
diseases in ways that they wouldn't
06:15
normally.
06:17
They've been used to treat diseases like
06:19
cancer. They've been used to treat
06:21
autoimmune diseases. And as of 2023, for
06:22
the first time, one of these medications
06:24
was approved to treat Alzheimer's
06:26
disease.
06:27
And not just treat it, but attack the
06:28
underlying cause of Alzheimer's disease.
06:30
These medications help tag the abnormal
06:32
proteins that are building up for your
06:35
own immune system to clear them.
06:37
And the initial study on these
06:39
medications,
06:40
>> [snorts]
06:41
>> they took patients who already had
06:42
memory deficits, and they gave down the
06:43
progress of the Alzheimer's by 30%.
06:46
While that may not seem like a huge
06:52
number, it's the first time that we've
06:53
changed the course of the disease by
06:56
directly treating it. Everything before
06:58
this was a band-aid. This is changing
07:00
the underlying physiology.
07:02
So, if we go back to the
07:05
analogy of the engine, you may ask
07:08
yourself, why do we wait for the engine
07:09
to break down before we start trying to
07:11
fix it? Jim had the oil changed in his
07:12
Mustang every 3,000 mi.
07:15
Well, that's always been an issue. You
07:17
see, when we saw Jim, the story was
07:18
there's no way to diagnose Alzheimer's.
07:21
We had no no way of identifying the
07:25
patients who were at risk.
07:27
In fact, when Jim saw me, the only way
07:30
to diagnose Alzheimer's was with a
07:31
biopsy of the brain.
07:33
Inconvenient, expensive, and as doctors
07:35
like to put it, uncomfortable.
07:37
A little later, if you were fortunate
07:41
enough to live near an academic center,
07:43
they could have put a needle into your
07:46
spine and drawn the fluid off of it and
07:47
sent it to a specialized lab and been
07:49
able to help you know your risk of
07:50
Alzheimer's that way.
07:52
Again, inconvenient and inexpens- and
07:53
expensive.
07:55
A little bit later, now what they do is
07:57
they have a CAT scan of the brain
07:59
that they can take after giving you a
08:02
radioactive injection.
08:04
Still not something that everybody wants
08:07
to do.
08:10
But, as of last year, just in 2025 for
08:11
the first time, a new test was developed
08:15
that can detect these abnormal proteins
08:16
in your peripheral blood. What this
08:19
means is you can go to the doctor's
08:21
office and get a blood draw and know
08:22
your risk of Alzheimer's.
08:25
Now, between these two findings, you may
08:26
say, "Great, let's identify the people
08:29
and start treating them."
08:31
Well, these medications are not without
08:32
risk. They trigger an immune response in
08:34
your brain, which can cause swelling and
08:36
cause side effects.
08:37
But, the good news is that they're
08:39
already studying
08:40
this mechanism of action. They're
08:44
already studying this.
08:45
They've taken these monoclonal
08:48
antibodies, identified patients with the
08:49
blood test that I talked about, and
08:51
they're giving different types of
08:53
patients different types of doses of
08:54
these medications and trying to see
08:55
which one's most effective. If there's a
08:57
way that we can slow down Alzheimer's
08:59
even more than we can now and maybe even
09:01
push it off indefinitely into the
09:03
future.
09:05
What this means is that now, not in the
09:07
future, the story has already changed.
09:09
When a patient like Jim comes into my
09:12
office and they're worried, "Might I
09:13
have really early Alzheimer's? Is this
09:15
normal or not?" There's a blood test I
09:17
can give him that's as accurate as what
09:19
used to take invasive testing.
09:21
When Jim says, "Is there anything you
09:24
can do for me that's going to change the
09:25
underlying course of this disease?" The
09:27
answer is, "Yes, there is.
09:29
It's already available."
09:31
Not only that, but in the future,
09:34
in the next 3 years, 2027, 2028, these
09:37
medications may be approved to be given
09:41
even earlier and make even more of an
09:43
impact than what we have now.
09:45
And my hope is that the end of the story
09:47
will ultimately change now that the
09:50
first two parts have changed.
09:51
That instead of Jim ending up sick and
09:53
requiring care and his car rusted out in
09:56
a garage somewhere,
09:58
the story can end with Jim living out
10:00
his life with increased vitality and
10:02
functionality.
10:04
He gets that car out to the Pacific
10:05
Coast Highway. He blasts down the road
10:07
with the top down, the sun in the face,
10:09
the wind in his hair, and miles and
10:12
miles of road ahead of him.
10:13
Thank you.
10:16
>> [music]
10:20
歌词与翻译
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重点词汇
开始练习
| 词汇 | 含义 |
|---|---|
|
practice /ˈpræktɪs/ B1 |
|
|
salvage /ˈsælvɪdʒ/ C1 |
|
|
fender /ˈfɛndər/ B2 |
|
|
vision /ˈvɪʒən/ B2 |
|
|
appointment /əˈpɔɪntmənt/ A2 |
|
|
dementia /dɪˈmɛnʃə/ C1 |
|
|
prognosis /prɒɡˈnəʊsɪs/ C1 |
|
|
helpless /ˈhɛlpləs/ B1 |
|
|
neuron /ˈnjʊərɒn/ C1 |
|
|
maintain /meɪnˈteɪn/ B1 |
|
|
debris /ˈdɛbriː/ B2 |
|
|
prevent /prɪˈvɛnt/ B1 |
|
|
obesity /əʊˈbiːsɪti/ B2 |
|
|
eradicate /ɪˈrædɪkeɪt/ C1 |
|
|
genetic /dʒɪˈnɛtɪk/ B2 |
|
|
antibody /ˈæntibɒdi/ C1 |
|
|
diagnose /ˈdaɪəɡnəʊz/ B2 |
|
|
biopsy /ˈbaɪɒpsi/ C1 |
|
重点语法结构
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我们正在更新此部分，敬请期待！
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