Well I'm Marilyn Albert and
I'm really pleased to talk to you this morning.
I think you can tell that the theme of the presentations that
we have today is about diagnosis, and
the title that I was asked to talk about is A Blood Test for
Alzheimer's Disease.
And I can tell right in the beginning that we don't
have a blood test for Alzheimer's disease, but
it certainly is the holy grail.
And so, what I thought I would do would be to
frame seven questions around why it really would be good
to have a blood test for Alzheimer's Disease.
And I'll list for you the questions and
then I'll try to answer them.
So first of all, what is Alzheimer's disease?
Obviously I know you know a lot about it.
But in fact, our concepts about it have changed a lot.
And I'm gonna try to tell you about that.
Why are we hearing so much about Alzheimer's disease?
We hear the words tsunami or epidemic.
Why is it so common?
Why is an accurate diagnosis important?
You probably know that we don't have effective treatments for
Alzheimer's disease, so why would we even wanna know?
And I'll try to address that.
And what makes accurate diagnosis so difficult?
It's extremely challenging.
And I'll try to give you some sense about that.
And then because it's so
difficult researchers are turning to something that we
call biomarkers, and the previous
speakers have been telling you also about biomarkers.
Things that we can measure that will give us some indirect
reflection of the disease that is present,
and I'll try to discuss that.
And then of course that leads to the title of my talk.
Why is finding a test for Alzheimer's disease in blood, so
particularly difficult.
It seems to be the holy grail.
And then what does the future hold with respect
to Alzheimer's disease.
So first of all, what is Alzheimer's disease.
So you all I'm sure know.
That Alzheimer's disease is a form of dementia.
It ultimately means that people have progressive cognitive
declines that start mild and get to the point where people are no
longer able to manage independently.
And it's that inability to manage independently
that we call dementia.
Now, the Alzheimer's disease is not the only form of dementia
but it's the most common form, and the cause of that is
something that also has to do with plaques, but not the kind
of plaques that our speaker was talking about before.
But these are plaques and
something called tangles in the brain and we now know that
the plaques contain something called amyloid and the tangles
contain something called tao and I'll talk about that later.
Now, the plaques cause this increase in accumulation of
proteins that ultimately kill cells, but
that takes a very very long time.
And we now know, when patients come to our clinic and
we are asking how they're doing, and when the symptoms began,
and how they progressed over time.
That for patient with Alzheimer's disease,
the most common answer is that the symptoms began many
many years ago and progressed very, very gradually over time.
If we were told that somebody was fine until six months ago
and then got dramatically worse, and
we're seeing somebody who we can see has dementia, we know
right away that it's probably not Alzheimer's disease.
So because it has this very very long phase of development,
ultimately what we came to realize is that there is this
interim phase.
Of course, it makes perfect sense.
If you're normal and it's gonna take years before you develop
dementia then there must be this in between phase which we
sometimes call prodromal disease or
a disease that's going to be developing into something bad.
And we now use the term mild cognitive impairment which you
may have heard about to refer to that interim phase of a disease.
But the most remarkable thing and
the thing that we've only just begun to really appreciate
recently is that there are people who are cognitively
normal who have these plaques and tangles in their brain.
They don't have nerve cell loss, so they don't have symptoms, but
they have these plaques and tangles in their brain.
And so what that means is we now have changed our concept
of the disease so we think of it as a continuum.
We don't just think of it as dementia, we think of it as
starting when people are normal, gradually progressing over time
ultimately resulting in people who have full blown dementia.
So why are we hearing so much about it?
Is this a new disease?
Did we just begin to be able to diagnose it?
If any of you ever read Aristotle or
ancient text you would read descriptions
who had what they called drying up of the mind.
We know that Alzheimer's disease has always been around.
But in fact,
we used to think that it was really uncommon, so it went.
Dr. Alzheimer first described the disease in 1906.
It was in a patient who was 56 years of age.
And my husband, when he was in medical school,
was told that Alzheimer's disease was so rare,
that he might never see a case of it.
But our concept now is that it's a disease that's related to age,
that it's the major cause of dementia in
people who are older, and of course,
what's happening to the aging population.
There are more and
more people who are living into the age of risk.
And what we know is that the risk for Alzheimer's disease
gets dramatically greater the older you get.
So there's a kind of geometric increase in risk.
Where at 60 to 65 it's maybe 5% of people,
it's twice that much in the next decade and
twice that much again in the following decade.
So, and the portion of the population that's growing
most rapidly, are the people over 85.
And among people over 85, we now know,
that at least one in four people have Alzheimer's disease.
So this is really an enormous problem.
I was involved many, many years ago in a study in Boston.
That was the first community study looking at the prevalence
of Alzheimer's disease.
And what we reported in that study that
made all the headlines was that among people 85 and over,
about 50% of people had Alzheimer's dementia.
Now that is a really high number and there are really, there
are a lot of reasons why we found that number, but everybody
agrees that the smallest number is 25% of people 85 and over.
And these are people who need full time care, for
somebody, at least one or two people in their family.
Enormous amounts of difficulty and distress in families.
And if you think about what we're facing it's really
quite remarkable.
So in the 1950s, the number of patients with Alzheimer's,
dementia was very low.
We didn't hear about it.
By 2000, the number had gotten to be dramatically high.
And that's why we began to hear so much about it.
But when we project to 2050, think about all the numbers of
people who are going to have this disease.
And do you have a sense of where they might be in the world?
What people might be most affected by it?
It's the people in under developed countries,
because those are the places that are gonna begin to have
individuals living into the age of risk.
And more and more cases are going to be occurring
in under developed parts of the world.
So it's really an enormous problem and
it's one that we're all working really very hard to attack.
But the problem is accurate diagnosis is hard.
But why would we want to have accurate diagnosis?
I said that we don't have a good treatment.
Well part of the reasons we would want to have an accurate
diagnosis is that there are causes of cognitive decline
that are treatable.
So if you go into a clinic and you get an evaluation for
progressive memory loss, what people will actually do is look
for treatable causes of cognitive decline.
They'll maybe do an MRI scan to see if there's a brain tumor or
a stroke.
They'll look at the medications that you're taking to see if
the medications are causing some sort of cognitive impairment.
They'll do tests to look to see how your kidney, your liver,
your lungs are functioning,
because problems like that can also cause cognitive decline.
So they're essentially looking to rule out
other causes of impairment.
And those are all treatable.
So that's the first really important reason
to get a diagnosis.
And when we do give the diagnosis, because we can't be
a hundred percent sure, we still say it's probably or possible.
But the first important reason for
a diagnosis is because some things are treatable.
Now, the other reason I think it's important to have a good
diagnosis, even if it turns out to be Alzheimer's disease or
some other form of dementia that's not treatable Is that
the symptoms in different types of disorders are different.
The kinds of medications that you might wanna use,
the things that you would have to expect that you might
reasonably anticipate in the future would be different.
So for example, if somebody turns out to have Ffontotemporal
dementia as opposed to Alzheimer's disease or
as opposed to lewy body disease.
They are all different, we don't have good treatments for
them, but at least we can have good expectations and
go to physicians who are really the best in those disorders.
But from my perspective, because I spend everyday trying to
figure out how to find better treatments,
one of the most important reasons we need an accurate
diagnosis is for clinical trial.
So right now, we know that there are many many clinical trials
looking for medications that have failed.
And we now look at the history from those failed trials and
we know that among the trials given to people with Alzheimer's
dementia Approximately 20% of the people in the trials
didn't actually have Alzheimer pathology in their brain.
[COUGH] There are trials set of been done and
people with mild cognitive impairment.
And up to 40% the people with mild cognitive
impairment diagnosed in really good places may not have
Alzheimer pathology in the brain.
And of course if we want to do a clinical trial
in people who are normal, who are just beginning to develop
these pathological markers in the brain, we would have to have
some other way of accurately diagnosing that that's present.
And so that's kind of the way that the whole field is going,
where Absolutely still focusing on treatments for
people with full blown dementia.
We wanna be able to find treatments that can delay
progression of the disease.
Some of the studies that are going on are using medications.
Some are using non-pharmacological
interventions.
There's an enormous amount of work still going on in that
area, but more and
more the pharmaceutical companies are going earlier.
And most of the clinical trials that are being
done now are being done in people with this mild,
cognitive impairment that I mentioned.
So we're going to the earlier phase of disease.
And right now, really all around the world, all the major
pharmaceutical companies are beginning to plan for studies.
And people who are normal but might have pathology.
There are a few studies like that going on which
we could talk about later.
But, that's kind of where the field is going.
But we're faced with this terrible challenge that we
are not so good at diagnosis.
So what should we do?
And why is there this challenge in diagnosis.
And there are really two primary reasons.
So the first is that many of the things that we look at,
that we want to use for diagnosis, not only are common
in Alzheimer's disease, but they change with age.
So when you're looking at cognitive decline and
you're trying to figure out how much is too much,
you have the problem that you and I as we get older are going
to likely have more trouble remembering the names of people.
Right, I'm sure none of you have that problem
>> [LAUGH]
>> And maybe
we get a little slower at things, right.
And a little bit more trouble rapidly switching from
one thing to another.
So those things are normal.
But when do they get bad enough that they're abnormal?
And these plaques and
tangles in the brain, also increase with age.
And actually, really cutting edge research at Johns Hopkins.
Is telling us now that the tau starts to get deposited when
people are in their 20's and the amyloid starts
to get deposited when people are in their 40's.
And so, here you have the increase that's normal for
age, but when is it too much?
Right And then,
of course, the other part that makes a diagnosis so challenging
is that the brain is really a very difficult thing to measure.
It's what we call a privileged organ.
It has a blood-brain barrier that is designed to protect it.
But it means that it's very,
very difficult to measure things inside the brain.
And in fact, the pathological hallmarks
of Alzheimer's disease we can only see under a microscope.
And the nerve cell loss that's key to the symptoms,
of course we can only see under a microscope.
So right now, the way that we think of the disease is that
the plaques and tangles are developing when the nerve cell
loss begins to happen is when we begin to see symptoms.
But we really need to have better ways of helping us
know when these things are happening.
And that brings me to biomarkers.
Blood is a biomarker.
What kinds of biomarkers are people looking at?
A biomarker is pretty simple.
It's essentially an indirect reflection of the pathology in
the brain and something we can measure that will tell us that
these changes are going on.
And of course you just heard the previous speakers essentially
talking about biomarkers and their own disorders.
In Alzheimer's disease the biomarkers that we're
interested in looking at and
have been looking at for many many years now are several.
So one is cerebral spinal fluid.
You probably know that the brain produces this fluid
that washes around it that we call cerebral spinal fluid.
And because it's floating around the brain.
It ends up containing substances that tell us a lot about what's
in the brain.
And in fact, we can measure in cerebral spinal fluid,
things that will tell us whether or not there's amyloid and
tau in the brain.
Now, we have PET scans, so we have PET scans
Some of which will tell us if amyloid is in the brain.
You may know that PET scans have now been approved for
medical use for amyloid measurement, and we now also
have Tau scans that are being developed, and MRI scans.
So you heard about MRI scans, we can also use MRI.
It's not going to tell us about the plaques and tangles.
But it's a sort of indirect reflection of the nerve cell
loss, and it actually turns out to be a really good measure
of the progression of the disease.
So the best of all of these is cerebral spinal fluid.
It's absolutely remarkable because it can tell us if
the amyloid or tau is present.
I do research in early diagnosis of Alzheimer's disease,
I have a very large study, and almost everybody in the study is
getting lumbar punctures and getting cerebral spinal fluid
and we know it's the very most valuable thing we can have.
Now as I said, there are pet scans that have been approved,
the first one was approved in 2012
It's hard to get Medicare to pay for it so
most of the time it has to be paid for out of pocket.
We're beginning to develop patau scans.
Our research group at Hopkins is going to be doing that.
And we believe that that's gonna give us a really important
window into the brain.
And then the MRI scans, which had been around for
a very long time, were able to measure them.
With great accuracy.
Look at the volume.
Look at the shape of different regions, and
track disease over time.
So all of those are really, really important and valuable.
So what about blood?
So that was the title of my talk.
So why is blood's so difficult a measure to use as a biomarker.
And it's because of what I said before,
that the brain is a privileged organ.
So it works both ways.
It hard for things to get in and it's hard for things to get out.
And if we measure blood, it's not gonna tell us very much
accurate information about What the proteins are in the brain or
the fats are in the brain or whatever.
So we're hoping to have a blood biomarker,
we certainly don't have one right now/.
It's absolutely the holy grail and
many of us are working on it.
So what is the future hold?
I am optimistic.
I've been working in what I guess we'd call the modern era
of Alzheimer's disease, so
I've been working since 1980 in this field.
When I started, there were, we never even thought about
accurate diagnosis, we never thought about treatment.
As you probably know, there are some very,
very modestly effective treatments on the market.
But right now, all around the world,
there are major clinical trials on their way.
And as I said, they're on their way in people with dementia,
they're on their way in people with MCI, and
they're beginning in people with this very early what
we call pre-clinical Alzheimer's disease.
There's lots of work going on to find better biomarkers.
We in our own research group are looking for
instance at the cerebral spinal fluid at blood to see if we can
find better measurements.
And the thing that I often say to people is that
while the terrible thing about Alzheimer's disease Is how
common it is.
The good thing is that because it's common,
pharmaceutical companies all around the world are trying
really hard to find better treatments.
So, even though we don't yet have better treatments,
I do feel that we're on the cusp of them and that's what
makes me come in every day with some sense of optimism.
Thanks very much.
>> [APPLAUSE]