00:02
Let’s talk about Alzheimer’s disease.
00:03
The most common cause
of dementia in elderly:
slow,
relentless,
and it’s progressive.
00:10
Oh man, you know when this
kicks in, that poor patient.
00:14
And actually, beyond that, what about the
surrounding family and friends, huh?
Really frustrating.
00:24
Introduce yourself every
single day and there’s no
guarantee that he or she might
remember you the next day.
00:29
Initial symptoms of forgetfulness
and memory disturbances.
00:32
Initial.
00:34
Progressive issues with language,
and of course, loss of higher
function referring to the memory,
language skills and such.
00:42
And the total duration from
initial symptoms to death,
well, it varies but in
general, about a decade,
and this is something that
you want to keep in mind.
00:52
At some point in time, we’ll get
into more of your rapid onset,
but a decade, in general,
from initial onset until death.
01:01
Varies from patient to patient.
01:05
Risk factors: older age, female sex,
head trauma, family history, genetics.
01:12
And if you were doing imaging,
and this’s a beautiful
little schematic.
01:17
Let me show you as to what
we’re looking at here.
01:19
On your left is a
control or the normal.
01:21
I want you to hone in
on the hippocampus.
01:24
And the hippocampus, of course, is
responsible for storing your memories.
01:29
And if you compare this control to our
patient who has Alzheimer’s disease,
well, would you please first take a look at
the size of the brain compared to control
and the disease on your right?
You’ll notice that the size of the brain is
extremely,
well, much
significantly smaller.
01:45
That’s because of your
cerebral cortical atrophy.
01:48
In addition, what about the sulci?
What does sulci mean?
It’s the actual crevice, huh?
It’s the crevice between the gyri,
and you should know that with anything
that is causing cerebral atrophy,
that the sulci is going to deepen,
deepen, deepen, deepen, deepen.
02:06
So now, it would become a huge gorge
because of all that loss
of your cortical brain.
02:13
This is not good.
02:14
And if that brain keeps getting smaller,
what kind of veins are going to pull on?
We had this discussion earlier.
02:21
The veins that it could pull on
would be your bridging veins.
02:24
It may result possibly
in subdural hematoma.
02:27
You keep going here, please.
02:29
As the brain, the cortex gets
smaller and smaller and smaller,
then the lateral ventricles
look like they’re enlarged.
02:34
Take a look at the disease on the right,
and I want you to compare
that to the left.
02:39
The lateral ventricles
look enlarged.
02:42
That’s interesting.
02:43
That should happen
in hydrocephalus.
02:45
Sure.
02:46
Why is the lateral
ventricle enlarged here?
Well, you’ve lost the brain,
the parenchyma, the cortex.
02:52
So therefore, we call this
hydrocephalus ex-vacuo.
02:55
And what about the pressure?
What pressure?
Intracranial pressure.
02:59
Perfectly normal.
03:01
And what about that hippocampus?
Look at the control in your left,
and you find that hippocampus.
03:07
And on the right, the
diseased, Alzheimer’s.
03:10
It’s almost gone.
03:11
It’s almost a cavity now.
03:13
Imagine there being no hippocampus
over, let’s say, 8-10 years.
03:18
The memory in this
patient, non-existent.
03:21
Beautiful images here of normal on
your left and diseased on the right.
03:27
We’re going to start depositing things
into the hippocampus and the cortex.
03:32
That is extremely characteristic
of Alzheimer’s, aren’t we?
So we’ll get into our plaques, and we’ll
get into our neurofibrillary tangles.
03:39
Are you ready?
Let’s talk about
genetic factors.
03:43
This is a huge, huge high yield table.
03:48
So, asterisk this.
03:49
Paste this on your forehead.
03:51
I don’t care what you do.
03:52
Sleep with it.
03:54
This is your table.
03:55
Know everything in it
like most of your tables.
03:58
High association with
Down’s syndrome.
04:00
I want you to group that
and group this together.
04:03
Why?
You associate Down’s syndrome.
04:06
APP stands for amyloid precursor protein.
04:09
The topic for this slide is AD,
which is Alzheimer’s disease.
04:13
You want to know amyloid precursor
protein, you will see why upcoming.
04:17
Look at your
chromosome here, 21.
04:19
In other words, you’ve
heard of trisomy 21.
04:22
I want you to take a look
at the onset of the age.
04:24
In Down’s syndrome,
young patient, huh?
Less than 35.
04:28
If there is amyloid
precursor protein mutation,
and I’ll show you why,
your patient is a little bit older,
but actually, not that old, huh?
45, not that old.
04:38
And early onset with Down’s
syndrome, you’re already 35.
04:44
Early onset, it’s already happening.
04:47
With amyloid precursor
protein, yes, less than 1%.
04:52
And in terms of percentage of all cases,
well, with APP or amyloid precursor
protein mutation, less than 0.1.
05:02
But nonetheless, you
need to know it.
05:05
Why?
Let’s take a look.
05:07
A beautiful picture here that
I’m going to walk you through.
05:10
Number one on your left is the
amyloid precursor protein.
05:14
And in it, do you see
that little green rod?
That green rod represents
the beta amyloid.
05:21
Look what happens when
there is a mutation.
05:24
Holy Moly!
Now, the amyloid precursor protein
is basically disintegrating.
05:30
And what’s happening is that the
beta amyloid is now being detached.
05:34
And look what all of the beta
amyloid, those green rods do
in illustration number
three to your right.
05:40
They’re going to get together, huh?
And they’re going to have a grand
old time and they form a plaque.
05:45
You see that plaque?
In other words, think
of it as being a plate.
05:49
This is a plate that is being served in
Alzheimer’s disease with beta amyloid.
05:55
That is a huge point.
05:57
These are beta amyloid plaques.
05:59
You could find these mutations.
06:01
This is not a good thing.
06:04
Continue with the table.
06:06
There is something
called PS1 mutation.
06:09
This is a chromosome 14
if you can remember it.
06:11
These are early onset.
06:12
Look at this, 28.
06:15
Horrible, horrible.
06:16
By the time your patient is 40, even
35 to 40, I mean, it is severe.
06:22
So, what you can expect in
maybe a 70-year-old patient
is what you would see in a maybe
35 or 40-year-old patient
or even 55, which is still
young for Alzheimer’s.
06:30
Keep that in mind.
06:32
Look at this, percentage
of early onset, 50%.
06:35
This is a PS1 mutation.
06:37
Percentage of all
cases, 1% to 2%.
06:40
That's still very high.
06:41
In my opinion, that’s
pretty high, pretty young.
06:44
PS2.
06:46
PS2, here it is.
06:47
I’m not going to talk
about this much.
06:49
I’d focus on PS1 if I were you.
06:51
APP, and obviously,
Down’s syndrome.
06:53
And you definitely want to
know about APOE e4, please.
06:56
Now, APOE e4, you definitely
want to know chromosome,
everything in this row, 19.
07:02
Age of onset, greater than 60.
07:04
This is the one in which 40% of
all cases of Alzheimer’s disease,
which you’re going
to find issues with.
07:08
It’s called APOE e4.
07:10
In terms of early onset,
not applicable here, okay?
Not applicable.
07:15
This is the one in which greater than 60,
and so therefore, the one that is
your classic or traditional type.
07:21
You know the table well.
07:23
Make sure that you pause and make sure
you understand amyloid precursor protein
and the development of
this beta amyloid plaques,
and I’ll come right back
to it in a few minutes.