the heart brain connection because in a
sense we all are really dealing with
some of the same kind of problems the
vessels just happen to be in one organ
system versus another so I'm going to
mention first of all some of my
investigator involvement with various
companies some lectureships a bit of
consulting some of our grant funding and
salary support for which I'm very
grateful
I don't have any stock or equity
interests and I never created a patent
that someone then stole from me so I
thought what I would first do is a
little cross-cultural education and talk
about small vessel disease in the brain
because that's something that's become
very fascinating to me in the last
decade or two and it's very important in
association with cognitive impairment
through direct you know injury to brain
regions but also because it affects the
clearance of a substance called amyloid
which some of you will know can happen
in the heart it's called amyloidosis and
when it happens in the brain it's called
Alzheimer's disease so clearance
problems and aging of the vessels
contributes to the development of
Alzheimer's disease may be one of the
reasons that aging is one of the most
potent risk factors for Alzheimer's
disease of the typical kind so what I
wanted to do is illustrate the
importance of cardiovascular diseases
including obvious things like
hypertension heart attack hyper
perfusion syndromes couldn't just a part
failure for example particularly atrial
fib fibrillation and how they're kind of
increasingly being recognized is very
important with respect to brain health
and Cardon impairment and I needn't tell
this audience that the rigorous
management of vascular risk factors is
hugely important not just for the heart
but for the brain and everything is
exercise exercise exercise and it'll
give you your brain and your body a
better chance so I want to start with
this little picture which is of the
brains vascular Network
looking up I've heard these different
claims about how many miles are
represented by the vasculature and I
thought the the comment that there four
hundred miles of capillary if you did
them end to end of capillary network in
the brain seemed like it couldn't be
possible four hundred miles
so when searching and you can't find
much on this but there's there's the
Franklin Institute has some statistics
on this and I'm not sure it's a sort of
Education and Research Institute and the
number that they came up with was so
unbelievable that it can't be right it
said that there's a hundred thousand
miles of vasculature in the human body
in the adult human body so I guess the
brain is maybe forty percent of that
that includes capillaries veins
arterioles the whole works but there's a
lot at a vessel and in the last several
years we've begun to try to define what
we mean by the different diseases that
affect the small vessels of the brain
are there have been some consensus
get-togethers so that we're all talking
about the same thing and it has multiple
faces and I thought they would just take
you through a whirlwind tour of what
some of these are and what they look
like because you're going to see them at
a lot of your patients with heart
disease congestive heart failure with
various you know valve diseases etc and
just that you don't usually do an mr of
your patients brains but maybe you
should maybe shouldn't so here's one
example if I can get the how do I get
this laser to work where's the laser
there's a relator well that's the late I
mean just really is this is a serious
laser this looks like a surgical laser
okay I will try not to poke anybody okay
so I guess we'll have to do it on this
so this is what we mean by white matter
disease but this would be what a recent
lacunae inferred infarct looks like and
it may or may not turn into a hole
that's something that it doesn't always
happen it may be a partial infarct but
that would be around the ventricle here
this is part of the brain that would be
a recent infarct this would be what's
called the white matter hyper intensity
means it doesn't have a hole this is if
that cavitate s' you actually have a
hole in the brain there are some there's
some new understanding because we can
see them better of what we call the peri
vascular spaces shown here along the
actually that there venules in the brain
this is again looking at the ventricles
and you see these radiating out these
may be important because that's also
part of the pathway for exiting amyloid
from the brain in a in a kind of garbage
removal system what happens which
happens particularly during deep sleep
which is why sleep is so important
because during deep sleep your brain is
on garbage patrol and it's getting rid
of various proteins including amyloid so
if you don't sleep or if your vessels
are not healthy enough to do that job
then you will accumulate amyloid as you
get older then there are microbeads
where you get leakage of red blood cells
out of the arteries that are getting
weakened by usually amyloid but also you
can have it from hypertension and then
this is the most interesting recent
development with the use of 3t scanning
high resolution 3t scanning this is a
close-up of a sulcus in the brain and
you see this little dit cyl here which
would be about a millimeter it's a micro
infarct we can now see these at 3t if
you have to be a little on the OCD in
order to look for them because they
could be everywhere but it's one of the
ways that atrial fibrillation may be
affecting cognition our group has tried
to take seriously all these different
types of small vessel disease as well as
actual focal infox and at the same time
measure the thickness of the cortex and
the different brain volumes and this
just kind of shows you a pipeline which
tries to be comprehend
many of the pipelines that are used in
the field of Alzheimer's disease only
look at atrophy and there's this
inconvenient truth that there's a lot of
white matter disease and people with
Alzheimer's with Parkinson's with
whatever you want to call it as they age
and it's kind of you try to ignore it
because it messes up your pipeline we've
taken the approach that you have to
embrace and measure all these things
because that's telling you what really
is going on in the brain and some of the
what's left after you remove all that is
what we call the brain foreign coma
I'll show you more about what some of
these things mean which have to do with
thickening of the veins so what you are
mostly aware of is that there's our
Tyrael small vessel disease where you
get collagen OSIS and hila gnosis
eventually in any organ but in the brain
it sort of looks like this it
illiterates you get increased vascular
resistance decreased Auto regulation
which is very important in the brain
because in the brain we automatically
attune our pleasure to whatever is
coming in in order to maximize brain
flow but if you have hypertension you
start to set that to high and you can
cause damage to the brain because of
decreased in Auto regulation there's
also endothelial changes by bringing
barrier leakage and these peri vascular
changes which are actually very
important because that's where the
amyloid and the are the arbiter garbage
is getting out along the very vascular
spaces here so small when you have
blockage of those arterioles you get
what are called lacunae little Kuhn
silent lagoon so-called but you also can
show that these lagoons are associated
with increased arterial stiffness
carotid femoral pulse wave velocity
central pulse pressure pulse until
eighty index are all sort of associated
with these lesions so it has to do with
putting putting extra stress on the
brain and therefore may be affecting the
vessels diabetes will also do this so
you end up with these highly nosed
arteries arterioles and little
holls that's not the whole thing though
because you may not have to actually
occlude a vessel you can also just get
old and keep remodeling the vessel just
like you may get remodeling and the
carotid artery or the vertebral artery
or whatever and this shows you what an
arterial in your brain should look like
when it's penetrating in from the
surface into the toy the ventricle and
that's hopefully what everybody in this
room looks like terms their artery but
as you get older they start to twist
sometimes they twist so much and turn
that you actually do not have any
circulation you may as well have it
occluded so that is why you can have
elderly people who have no vascular risk
factors that you would recognize other
than age can end up with holes in their
brain and perfusion problems this is an
example of what a good artery would look
like again penetrating from the surface
down this is what an artery looks like
when you have a MoIT along it so the
other important bit of information I'd
like to share with you is that amyloid
in the brain gets out a long it gets
escapes from the brain along the
arteries primarily or the other vessels
as well and in so doing it can actually
damage those arteries and it can also be
associated with ischemic change as well
as bleeding so that is what an artery
looks like that has a lot of amyloid
around it if you look at the peel
surface of the brain this is showing the
peel all the peel arterial supply
heavily interconnected network of
vessels and these like blotches here and
there are where you've got amyloid
deposits and you see this rather ugly
it's supposed to be nice clean looking
surface showing the effects of amyloid
so amyloid is actually a vascular toxin
as well as a cellular toxin in other
respects may be there as an acute phase
reactants against infections as one of
its duties and why it's there
but it can end up
imaging the brain and when you have
amyloid angiopathy this is how you may
present to the emergency department this
is a businessman he started bumping into
things and his co-workers thought that
maybe he was drunk they eventually got
him to the hospital they did that they
do now which if they take a scan and
here's his big occipital hemorrhage on
the left side he was talking a little
funny he was like phasic he couldn't
calculate they had a field effect and he
eventually after a number of years he
partly recovered from this he eventually
developed what often happens with Emma
Lloyd angiopathy he developed the
parenchymal form of amyloid which is
Alzheimer's disease so Alzheimers
pathology can deposit in fibrillar
plaques but it can also be along the
vessels so these are the peri vascular
spaces that I mentioned and when you
look at scans
here's mr scans and you see these holes
a lot of people say those are strokes
well they're not necessarily especially
around the deep part of the brain
they're just in large spaces around the
arterioles and they some of it can be
sort of naturally there but they all
also may reflect some changes in the
vessels that are going on over time this
shows you some other examples you can
see them in longitudinal perspective so
what's interesting is that when you see
the peri vascular spaces in these areas
that's where you're going to start to
see the amyloidosis in amyloid
angiopathy and that's what this
gentleman had when he had that bleed but
deep in the basal ganglia area deep in
the brain with the thalamus and the
basal ganglia is that's associated with
hypertension so that's where you get a
lot of pounding going on whereas in the
white matter there's a kind of a
reduction in the pulse pulsatilla t but
that's where you can get these peri
vascular spaces they're thought that
they may actually through the pulsations
it might be helping to get mo8 out of
the brain now what everybody almost
everyone has
you're age 65 is a little bit of what we
call white matter disease this shows you
different amounts of white matter change
and what it looks like on a brain be not
uncommon to see this and a 65 or 70 year
old you know who's had a heart attack
and certainly stroke patients we see it
a lot this just shows you increasing
amounts when you get to have this amount
and you will have a bit of a syndrome
where you'll be slowed in your thinking
you have some gating balance problems
you may have a little bit of
irritability and stubbornness and you're
kind of under-motivated
so it's got a bit of a clinical syndrome
this is called periventricular white
matter hyper intensity now it turns out
that these hyper intensities actually
co-localize with the deep penetrating
venules of the brain which have been
totally under the radar and I'm sure in
the heart to you talk about congestive
heart failure and arterial supply but
there's also a venous system in the
heart and diseases of the veins can be
part of the story that develops and
certain types of congestive heart
failure but certainly in the brain
there's a kind of venous insufficiency
syndrome that this periventricular white
matter disease represents the pathology
associated with this if you take a white
matter hypertensive post-mortem is
actually thickening of the deep
penetrating venules so it's actually a
vino occlusive disease which again may
vascular resistance to the incoming
blood that leads to leakage and in fact
that white matter hyper intensity is
probably leakage vasogenic edema so
these are again mention of the micro
infarct this is showing it in the
studying of a couple of brain slices you
practically need a magnifying glass but
there's a little bit cyl there this is
on t1 these are micro infarcts and you
can see them scattered around the cortex
mostly are most often associated with
some sort of embolic source particularly
afib but you can also see in amyloid
angiopathy
small infarcts as well in the cortex and
the likelihood of people being demented
with micro infarct at autopsy as shown
here it is yes you're more likely
to be demented in fact these little bit
souls are relevant and the more you have
the worse it is now with respect to
vascular risk factors this audience
knows all of these you might not know
that homocysteine perhaps you do it it's
it has its injurious - vast vasculature
so it is associated with more of the
white matter disease and vascular brain
disease but the you know age is still I
think super-important hypertension
really bad for the brain and physical
activity is really inactivity is really
bad for the brain because it's
interfering with that cyclic removal in
deep sleep of the garbage collected
during the previous day including
amyloid as well as it's causing volts of
adrenaline when your apneic that
contributes to hypertension stroke
Alzheimer's disease and heart attack so
this is to show you that midlife blood
pressure is increased it increases the
risk that you're going to have dementia
in later age and it's not always just
vascular dementia it can be Alzheimer's
disease these are the sorts of numbers
three times or or five times the risk
when with your head when you have
untreated hypertension in midlife I
think we're seeing less of that now but
it's still a worry and I just wanted to
show you when the brain has Alzheimer's
disease
there's amyloidosis and telepathy in the
brain those are the plaques and the
tangles it's not the whole brain that
shrinks there's actually a pattern
there's a topographical pattern that's
why doing brain studies there's a little
more interesting perhaps than doing
heart studies because we've got these
functional networks we've got regions
that mean different things and so you
can spend a whole lifetime just kind of
trying to understand what these
different centers and their injury may
do to a person's ability to speak or to
understand or to think into reason so
this shows you the signature pattern of
thinning in Alzheimer's disease and
right side on the
lateral surface medial surface these are
like the key signature areas that thin
because the brain is being injured and
destroyed by the Alzheimer process so
now look at blood pressure cholesterol
and glucose which were studied in a in
an elderly population where they were
looking at blood pressure that wasn't
too high because they treated some of
those were people who had blood pressure
when they first came in and they looked
at the cortical thinning using these
modern methods that we have and it's
actually almost the same areas that are
prime areas for attack in Alzheimer's
disease cholesterol it was a little bit
different but some are the same and
glucose seemed to involve the anterior
cingulate and the hippocampal area is
slightly different a minute so I have
only a couple more minutes oh my god
she's I'm just getting there okay all
right so coronary artery disease how
many of you know that people show
cognitive decline in significant amounts
verbal memory is often poor in people
heart disease and verbal memory
performance if you follow people decline
and this is showing something called
mild cognitive impairment with cardiac
disease this is where you've got memory
problems but you're still functioning it
increases in people who have cardiac
disease and this is just saying the same
thing that there's there's some people
who develop cognitive problems and
they're more likely to do so if they
have that white matter disease or if
they have a small hippocampal volume
it's the hippocampus is another area
that's attracted that's attractive to
Alzheimer's disease and that's that's
what we can now do can isolate the
hippocampus and measure it hemodynamics
I don't have time to go into this but
basically the lower your cardiac output
the more stress the brain is under in
terms of its day-to-day functioning and
you can show that you get lower brain
volumes in association with cardiac
output it's also shown here with cardiac
index in the Framingham study that your
ear you're showing greater chance of
becoming demented
also know they've got brain volumes to
show that your brain volumes are
affected not many of you may know that
the anti colander the cholinesterase
inhibitors may actually be
cardioprotective and in some rap models
of congestive heart failure Dan a
pizzelle which is the typical drug
that's used in Elsa MERS disease is
actually protective because of its and
although the the cholinesterase
inhibitors have this reputation of being
bad for your heart because people come
in with with if they have branded kardea
they shouldn't be on them you know with
syncope etc there was a study done in
Sweden showing that the commissaries
inhibitors were associated with a
reduced likelihood of heart attack and
death probably because of some vagal
protection so afib is a whole topic on
its own we are getting more and more
interested in this because it's
associated with cognitive impairment
this is just kind of showing that a fib
always favors being impaired I don't
have time to go into the very
interesting work recently that's coming
along with respect to treatment of
embolic strokes of uncertain source
looking now at left atrial enlargement
which is a big risk factor for cardiac
first stroke for embolic stroke and it's
reduced by the use of anticoagulants as
opposed to aspirin through a mechanism
that's not fully understood but it looks
like an abnormal atrium is a bad thing
to have especially with atrial
fibrillation and increases your chances
of stroke there's now a study that's
going to be looking at that to really
nail it down and to see whether it's
beneficial to have a pack as opposed to
aspirin and people who may have atrial
they call it each film Aiyappa the--
cardiomyopathy with or without atrial
fibrillation finally patent foramen
ovale I needn't tell you that that's
become very interesting just in the last
few years we used to advise against
closure because of the complications
whereas now it looks like the new
techniques are improving your chances of
not having a stroke if you have modern
closure in the last few years so now
it's becoming a little more complex in
terms of when you say yes or no to
having your patent foramen ovale closed
so there this is sort of summarizing
some of the data to date with who should
or should not have this because it's now
much more of an option than it was even
a couple of years ago finally fitness
and brain health I needn't tell you that
this is important this was just a
nursing study that looked at physical
activity over the decades in elderly
ladies in their 80s and they found that
their performance on cognitive tests was
associated with how much physical
activity they had throughout their
lifespan but particularly in the teenage
years it was protective so we have a
problem in our society right now because
they're all at home
sitting in front of their computers or
texting as we speak
finally there are there's marks well
actually just recently maybe the most
interesting thing is that the Framingham
study just published some data on
walking even light physical activity
saying that in a population they started
over a number of years
if you walk 75 if you have 75 7,500
steps a day your brain is bigger than if
you don't
so in conclusions I think we all both
the neurologists and the cardiologists
the heart ologists really need to be
trying to understand these relationships
a lot more we are all part of a vascular
system whether we like it or not and
it's aging you have to understand people
small vessels these understand that what
is most commonly seen is actually a
venous disease where they have this in
at least in people who are well treated
for hypertension over the years it's the
venous disease now that we're seeing
more and more and 95% of people over the
age of 65 have some degree of
small vessel disease showing up as hyper
intensities these covert lesions the
attention we now have to be much more
aware of the micro in forex which may be
an indication that a person has a fifth
we now have ways of monitoring and to
find that and to treat that and vascular
risk factors are turning out to be of
great interest but particularly now
physical inactivity of the need to make
sure that everybody is moving so fine I
think that's it let me just see this is
just some acknowledgments and my staff
and Sunnybrook it's up north there in
case you didn't know