The Alzheimer's Project (2009–…): Season 1, Episode 4 - Caregivers - full transcript

I KNEW ABOUT ALZHEIMER'S,

BUT I NEVER THOUGHT I'D GET IT.

AND WHEN IT HAPPENED,

I JUST...

THE FIRST THING I SAID TO CATHEE...

"ARE YOU GONNA LEAVE ME?"

THAT'S ABSOLUTELY RIGHT.

THAT'S THE EXACT RIGHT MEMORY.

UH-HUH, I THOUGHT MY...

I WAS DOOMED.

IS THAT IT?



'CAUSE I THOUGHT

IT WAS THE END OF ME.

IF WE FAIL TO CURE OR
PREVENT ALZHEIMER'S DISEASE

IN THE YEARS AND
DECADES TO COME,

WE'RE FACING

AN ENORMOUS INCREASE
IN THE HUMAN SUFFERING,

AS WELL AS THE FINANCIAL AND
SOCIETAL IMPACT THAT WILL OCCUR.

THERE'S BEEN AN
EXPONENTIAL INCREASE

IN OUR UNDERSTANDING OF WHAT
CAUSES ALZHEIMER'S DISEASE,

HOW WE CAN TARGET IT
AND HOW WE CAN TREAT IT.

Dr. Virginia Lee: IT
REALLY IS MIRACULOUS

THAT IN A SHORT PERIOD OF TIME...

WHICH IS REALLY 25 YEARS...

WE KNOW A LOT ABOUT THE DISEASE.



WE ARE AT THE BRINK
OF CONTROLLING

ONE OF THE MAJOR DISEASES
AFFECTING WORLD HEALTH.

Dr. Lennart Mucke: THERE'S A TRUE
EXPLOSION IN EXCITING NEW DISCOVERIES,

MANY OF WHICH AIMED AT THE
ROOT CAUSES OF THE DISEASE,

AND THEREFORE IMPLYING
ENORMOUS THERAPEUTIC POTENTIAL.

Dr. John C. Morris: WE DO HAVE
THE RESEARCH SCIENTISTS.

WE DO HAVE THE KNOWLEDGE.

AND I THINK WE CAN BEAT
ALZHEIMER'S DISEASE.

THE HISTORY OF MODERN
MEDICINE IS REALLY TRACKED BACK

TO AROUND 500 YEARS
AGO WHEN PEOPLE DECIDED

THAT IT MIGHT BE A GOOD
IDEA TO CRACK OPEN THE BODY

AND ACTUALLY SEE
WHERE THE DISEASE IS.

IF SOMEONE IS BILIOUS,

IS HIS LIVER REALLY AFFECTED?

IF SOMEONE IS DEMENTED,
IS HIS BRAIN AFFECTED?

AND IT'S NOT THAT LONG AGO,

BUT THAT REALLY
GAVE RISE TO THIS IDEA

THAT WE ACTUALLY HAVE TO SEE
THE DISEASE TO UNDERSTAND IT.

ALOIS ALZHEIMER

WAS A GERMAN NEUROPATHOLOGIST.

HIS USE OF NOVEL
STAINING TECHNIQUES

IN DEAD BRAIN UNDER
THE MICROSCOPE

ALLOWED HIM FOR
THE FIRST TIME TO SEE

THIS CONSTELLATION
OF AMYLOID PLAQUES,

NEUROFIBRILLARY TANGLES.

AND IT ULTIMATELY JUSTIFIED
CALLING THIS DISEASE

ALZHEIMER'S DISEASE.

NOW IT'S INTERESTING
TO POINT OUT THAT,

IF YOU LOOK AT TEXTBOOKS OF
NEUROLOGY, PSYCHIATRY, MEDICINE...

FOR DECADES THEREAFTER,
INTO THE '30s, '40s, '50s,

THERE'S NARY A MENTION
OF ALZHEIMER'S DISEASE.

Dr. Steven DeKosky: SERIOUS AND FOCUSED
RESEARCH ON ALZHEIMER'S DISEASE

REALLY BEGAN A LITTLE
OVER 20 YEARS AGO

WHEN THE NATIONAL
INSTITUTE OF AGING

AND A VARIETY OF OTHER
RESEARCHERS, BRAIN RESEARCHERS,

REALIZED THAT WHAT WE
HAD BEEN CALLING DEMENTIA,

OR SENILE DEMENTIA,

OR HARDENING OF THE ARTERIES,

OR ARTERIOSCLEROSIS IN LATE LIFE

THAT EVERYONE JUST
CALLED "DEMENTIA,"

ACTUALLY IN THE VAST MAJORITY
OF CASES WAS ALZHEIMER'S DISEASE.

WHEN WE STARTED, NO
ONE KNEW ANYTHING ABOUT

WHAT PLAQUES OR TANGLES...

THE THINGS WE SEE IN
THE BRAIN... WERE MADE OF.

WE BELIEVE THAT
THE BETA-AMYLOID,

THE BAD ACTOR IN PLAQUES,

LEADS TO THE DISRUPTION
OF TAU PROTEIN,

AND RESULTS IN
NEUROFIBRILLARY TANGLES.

BOTH THE PLAQUE AND
THE TANGLE DO OCCUR

IN THE BRAINS OF
ALZHEIMER'S DISEASE PATIENTS.

AND A GREAT ENIGMA
IS HOW THEY ARE LINKED.

DO THEY JUST EVOLVE
INDEPENDENTLY

OR IS THERE SOME SHARED PROCESS,

SOME SHARED
PATHOLOGICAL PROCESS?

WE KNOW THAT IN PATIENTS
WITH ALZHEIMER'S DISEASE,

THAT PROBABLY

PLAQUES OCCUR FIRST AND
THEN TANGLES OCCUR LATER.

BUT SINCE PATIENTS
AT AUTOPSY HAVE BOTH,

THEN IT'S VERY DIFFICULT

TO REALLY TEASE OUT
HOW THIS HAPPENS.

JOHN AND I BELIEVE THAT
NEUROFIBRILLARY TANGLES

PLAY A VERY IMPORTANT ROLE
IN THE DEMISE OF NEURONS.

AND AS IT TURNS OUT,
TAU IS A KNOWN PROTEIN.

AND IN FACT,

IT IS A VERY ABUNDANT
PROTEIN IN NERVE CELLS.

TAU ACTUALLY STABILIZES

THE TRANSPORT
SYSTEM IN NERVE CELLS.

HOWEVER, IN ALZHEIMER'S DISEASE,

TAU FALLS OFF THIS
TRANSPORT SYSTEM

AND BEGINS TO CLUMP TOGETHER

AND FORM
NEUROFIBRILLARY TANGLES.

AND WHEN THE
TANGLES BEGIN TO FORM,

THESE EXTENSIONS
BEGIN TO SHRINK.

AND YOU CAN SEE THAT
THEY'RE SHRINKING.

AND EVENTUALLY
THEY'RE TOTALLY GONE.

AND THEN THESE THESE
NERVE CELLS EVENTUALLY DIE.

THE CONUNDRUM RIGHT NOW IS

THAT PEOPLE ARE DIAGNOSED
WITH ALZHEIMER'S DISEASE

WHEN THEY HAVE
SIGNIFICANT MEMORY FAILURE.

WE HAVE GOOD REASON TO BELIEVE

THAT ALREADY THEIR BRAINS
HAVE BEEN ACCUMULATING

PLAQUES AND TANGLES FOR
FIVE, 10, POSSIBLY 15 YEARS.

SO THE PATHOLOGY BEGINS

MANY MANY MORE YEARS
BEFORE SYMPTOMS APPEAR.

PITTSBURGH COMPOUND
B, OR PiB, AS IT'S KNOWN,

IS A RADIOACTIVE TRACER
THAT YOU GIVE IN A VEIN

THAT, WHEN YOU DO AN IMAGE,

SHOWS YOU THE AMYLOID
PLAQUES THAT ARE IN THE BRAIN

OF PEOPLE WITH
ALZHEIMER'S DISEASE.

Man: START.

Dr. William Klunk: THE BASIC
GOAL WAS TO BE ABLE TO SEE

THE AMYLOID PLAQUES
THAT ARE CHARACTERISTIC

OF ALZHEIMER'S DISEASE
IN A LIVING PERSON,

AND TO BE ABLE TO TELL
HOW MUCH OF IT WAS THERE.

IT WAS A GOAL OF OURS
TO DO THIS FOR MANY YEARS.

AND WE WANTED TO BE THE FIRST,

OR AMONG THE FIRST,
TO BE SUCCESSFUL AT IT.

WHAT'S THE VALUE OF SUCCEEDING?

THE MOST OBVIOUS IS,
WELL, IMPROVED DIAGNOSIS.

YOU KNOW, WE CAN DO NOW...
WE COULD DO IN A LIVING PERSON

WHAT YOU NOW HAVE TO WAIT
UNTIL AUTOPSY AFTER DEATH TO DO.

THANK YOU VERY MUCH.

Dr. DeKosky: WE BEGAN
STUDYING FAMILIES

WHO HAVE EARLY-ONSET DISEASE.

WE KNEW THAT THEY WERE
DEVELOPING AMYLOID IN THEIR BRAINS,

AND CERTAINLY AT AN EARLIER
AGE THAN OTHERS... 30s AND 40s.

THERE ARE ONLY 200 TO
300 FAMILIES IN THE WORLD

WHO HAVE THESE
KINDS OF MUTATIONS

THAT LEAD TO FAMILIAL
EARLY-ONSET DISEASE.

AND THEREFORE WE
THOUGHT IT WOULD BE

A VERY GOOD TEST
OF PiB TO SEE AMYLOID

AND SHOW US WHAT HAPPENED
AS THE DISEASE PROGRESSED.

THE FIRST IMAGES
THAT I SAW OF PiB WERE

IN THE CLASSIC THREE DIMENSIONS.

AND IT WAS AN ABSOLUTELY
MOUTH-DROPPING MOMENT.

AND I KNEW INSTANTLY,

AS DID EVERY OTHER ONE
OF OUR RESEARCH TEAM,

THAT THIS WAS GOING TO CHANGE

THE WAY ALZHEIMER'S
DISEASE WAS STUDIED FOREVER.

Dr. Klunk: ONE OF THE VALUES
OF STUDYING THIS FAMILY...

ALL SIX INDIVIDUALS
THAT PARTICIPATED,

THEY'VE COME BACK
FOR REPEATED SCANS.

AND WE HAVE A RANGE OF 14 YEARS

FROM THE YOUNGEST TO THE OLDEST.

THESE FAMILIES HAVE
THE OPPORTUNITY

TO LEAD US TO
EFFECTIVE TREATMENTS.

OKAY, THIS IS MY SIX
CHILDREN, TAKEN IN ABOUT 1977.

THIS IS BRIAN AND
KARLA... LITTLE KARLA...

SKINNY LORI THERE,

JAMIE, DEAN AND DOUG.

DOUG LOOKS JUST THE SAME.

MY HUSBAND HAD ALZHEIMER'S.

AND HIS MOTHER DID BEFORE HIM.

AND SHE DIED AT 53.

WE DIDN'T KNOW
WHAT IT WAS, DID WE?

YOU JUST THOUGHT YOU
WERE MAKING YOUR DAD MAD?

THERE WAS A LOT OF
COMMOTION AT HOME.

AND HIS MOOD CHANGED.

HE WAS VERY ANGRY A LOT.

AND YOU HAVE SIX
KIDS COMING AND GOING.

- A LOT OF ACTIVITY.
- THE ACTIVITY IS HARD.

- AND THAT'S HARD FOR THEM.
- THAT'S VERY HARD.

WHEN I GOT THE NEWS THAT I
DIDN'T CARRY THE MUTATED GENE,

I KNEW OF COURSE THEN,

THAT I WAS GOING TO BE,

YOU KNOW, WITHOUT
THEM ALL SOMEDAY.

AND I, YOU KNOW, MADE UP MY MIND

THAT I WAS GONNA DO
EVERYTHING IN MY POWER

TO MAKE SURE THAT MY SIBLINGS

GET THE RESPECT AND HELP

THAT THEY DESERVE THROUGH THIS.

WE STARTED WORKING
WITH THE FAMILIES

WHO HAVE EARLY-ONSET FAMILIAL
ALZHEIMER'S DISEASE FOR TWO REASONS:

FIRST, WE KNOW THAT THEY
GET AMYLOID IN THEIR BRAINS.

AND THEY GET IT AT A MUCH
EARLIER TIME, OBVIOUSLY,

THAN PEOPLE WHO HAVE
LATE-ONSET DISEASE.

WE WANTED TO KNOW,

TO SEE, IF PiB REALLY WAS
WORKING, WHAT WOULD IT SHOW US?

THE ONLY WAY TO
BE ABLE TO DO THAT

WOULD BE WITH AN
IMAGING TRACER LIKE PiB

THAT WOULD LET US LOOK AT
THEM REPEATEDLY OVER TIME

AND BE ABLE TO
CORRELATE IT WITH THEIR

PAPER-AND-PENCIL
TESTING AT THE SAME TIME.

DRAW A CLOCK. PUT
ALL THE NUMBERS ON IT.

AND SET THE TIME
AT 10 AFTER 11:00.

OKAY. ALL DONE.

SINCE LAST YEAR WHEN WE
SAW HIM, HOW IS HE OVERALL?

IS HE BETTER, WORSE OR
THE SAME, DO YOU THINK?

I THINK HE HAS GOTTEN
A LITTLE BIT WORSE.

AND THEN HE'S SLOWED DOWN A LOT.

LET'S TALK ABOUT
LORI FOR A MINUTE.

HOW DO YOU THINK
SHE'S DIFFERENT?

- IS IT HER MEMORY? IS IT HER MOOD?
- YEAH.

- EVERYTHING?
- YEAH.

WE SAW HER LAST YEAR. SHE
REALLY HADN'T CHANGED VERY MUCH,

AT LEAST AS FAR AS HER
FORMAL TESTING WAS CONCERNED.

HER SHORT-TERM MEMORY IS...

IT SEEMS TO BE
REALLY HARD FOR HER.

THE THING IS, SHE KNOWS,

SHE RECOGNIZES IT.

I'M GOING TO NAME THREE OBJECTS.

AND I WANT YOU TO SAY
THEM BACK AFTER I STOP.

APPLE, PENNY, TABLE.

I KNOW THAT I'M PROGRESSING.

SO YOU JUST LIKE...

KINDA FEEL LIKE, "WELL, WHEN...

YOU KNOW, WHEN I AM GONNA
NOT BE ABLE TO DO THAT?"

IF WE WERE TO ASK YOUR HUSBAND

IF HE THOUGHT YOU
WERE BETTER, WORSE

OR THE SAME AS LAST YEAR,
WHAT DO YOU THINK HE'D SAY?

HE'D PROBABLY SAY
A LITTLE BIT WORSE.

- MAYBE A LITTLE BIT?
- YEAH.

KNOWING HOW EARLY

MY FATHER DIED,

SO, YOU KNOW, HE DIDN'T
GET TO ENJOY HIS GRANDKIDS.

IF MY DAUGHTERS GET MARRIED,

I ALWAYS KNEW I WOULD BE

A REALLY REALLY GOOD GRANDMA.

AND I PROBABLY WON'T GET TO.

WE'RE GONNA TALK ABOUT THE
RESULTS OF YOUR PiB SCANS.

SO THIS IS

A TYPICAL LATE-ONSET
ALZHEIMER'S DISEASE.

AND THESE FIVE ARE

YOUR FAMILY MEMBERS
FROM YOUNGEST TO OLDEST.

THIS IS DOUG'S SCAN.

AND THIS IS LORI'S SCAN.

IN LATE-ONSET ALZHEIMER'S

WE HAVE ALL THESE
AMYLOID DEPOSITS,

WHEREAS IN YOUR FAMILY

THERE'S THIS INTENSE
FOCAL DEPOSIT,

BUT THEN THERE'S LITTLE
BITS IN OTHER PLACES.

YOU'RE ALL SITTING HERE,
YOU'RE BEING VERY STRONG.

BUT WE'RE TALKING ABOUT THINGS

THAT ARE, YOU KNOW,
INTIMATELY INVOLVED

WITH YOUR LIFE AND YOUR
PRESENT AND YOUR FUTURES.

AND, YOU KNOW, YOU'RE LOOKING

AT ONE REPRESENTATION
OF THE DISEASE

ON THE SCREEN
HERE... THE AMYLOID.

IT MAKES IT VERY
REAL AND VERY TOUGH.

- Lori: DOES IT MAKE YOU WONDER?
- YEAH.

Dr. Klunk: THIS ISN'T
AN EASY THING.

Gail: YEAH, PICTURE HER, THE ONLY
ONE THAT DOESN'T CARRY THE GENE,

TRYING TO DO SO MUCH
FOR THE REST OF US.

THERE'S A LOT OF
PAIN IN THAT TOO.

I DON'T KNOW, I THINK I'LL BE

SO ALONE WITHOUT THEM.

THERE'S TOO MANY...
TOO MANY OF THEM.

AND SOMETIMES YOU JUST NEED
YOUR BROTHERS AND SISTERS.

Lori: I UNDERSTAND THAT.

WHAT I HOPE... AND
I THINK ONE THING

THAT WE'RE LEARNING
FROM THIS RESEARCH

IS THAT WE CAN SEE AMYLOID

MUCH SOONER THAN
THE SYMPTOMS START.

SO THAT'S A GOLDEN OPPORTUNITY.

THAT'S A TIME WHEN
YOU MAY BE ABLE

TO GET TO THE DISEASE WHEN
YOU CAN HAVE THE MOST SUCCESS.

Gail: I'M SO PROUD OF MY FAMILY

TO HAVE PARTICIPATED,
EACH ONE OF THEM,

AND DID IT SO WILLINGLY.

- YOU GUYS GO THROUGH A LOT.
- I'M REALLY PROUD OF THEM.

Dr. DeKosky: I THINK ONE OF
THE THINGS THE DeMOES SHOW

IS THE INCREDIBLE
DEDICATION OF THESE FAMILIES

WHO HAVE A VERY SERIOUS
DISEASE IN THEIR GENES

TO RESEARCH.

THEY COME TO US FROM FAR AWAY.

THEY COME BACK EVERY YEAR.

THEY UNDERSTAND THAT WE'RE
LEARNING ABOUT THE DISEASE,

AND THAT IT MAY HELP
THEIR NEXT GENERATION,

OR THE GENERATION AFTER THAT,

BUT IT ISN'T GOING TO HELP THEM.

AND YET THEY STILL COME.

THEY DO WHATEVER
WE ASK THEM TO DO.

THEY ARE REALLY
PARTNERS IN THIS FIGHT.

WELL, WE REALLY
APPRECIATE YOU COMING IN.

- WE APPRECIATE EVERYTHING.
- THANK YOU VERY MUCH.

Dr. Hodes: THE IMAGING OF THE BRAIN
THAT WE'RE CURRENTLY ABLE TO DO

COULD NOT HAVE BEEN
IMAGINED 20 OR 30 YEARS AGO.

ALL OF THIS GIVES
US AN OPPORTUNITY

TO CARRY OUT RESEARCH OF A SORT

THAT COULD NOT HAVE BEEN
IMAGINED A DECADE OR TWO AGO,

AND ARE THE REASON
FOR THE EXCITEMENT

THAT I THINK PERVADES THE FIELD

AND GIVES APPROPRIATE AND
JUSTIFIED REASON FOR HOPE

TO SCIENTISTS AND
TO THE PUBLIC AS WELL.

AGE-RELATED MEMORY DECLINE

IS CHARACTERIZED BY AFFECTING

TWO GENERAL AREAS OF THE BRAIN:

THE FRONTAL LOBES,
THE PREFRONTAL CORTEX;

AND AN AREA CALLED
THE HIPPOCAMPUS,

WHICH IS DEEP WITHIN
THE TEMPORAL LOBES.

IF YOU MISPLACE YOUR KEYS,

IF YOU CAN'T REMEMBER
WHERE YOU PARKED YOUR CAR,

IF YOU CAN'T QUITE
REMEMBER THE NAME

OF A CLIENT YOU
JUST MET A WEEK AGO,

BUT YOU CAN REMEMBER CLIENTS
THAT YOU MET, YOU KNOW, YEARS AGO,

THAT'S A PROBLEM WITH
SAVING NEW INFORMATION.

AND THAT'S AN EXAMPLE OF
HIPPOCAMPAL DYSFUNCTION.

I'M WORRIED ABOUT THE
BEGINNING OF ALZHEIMER'S...

EARLY ALZHEIMER'S.

I JUST HAVE... I FEEL MY...

I KNOW EVERYBODY SAYS THEY
HAVE PROBLEMS WITH THEIR MEMORY,

BUT I'VE LIVED WITH SOMEONE
WHO HAD ALZHEIMER'S.

AND I SEE MYSELF IN HIM.

AND I'M VERY
APPREHENSIVE ABOUT IT.

THE EARLIEST STAGE
OF ALZHEIMER'S

IS ONE WHERE THE
CELLS ARE STILL THERE.

YOU MIGHT NOT HAVE
FULLY-FORMED PLAQUES AND TANGLES,

BUT THE CELLS ARE
JUST MALFUNCTIONING.

SO NOW WE'RE TRYING
TO USE TECHNOLOGIES

THAT CAPTURE CELL SICKNESS

TO ASK THE QUESTION, "WHEN
DOES ALZHEIMER'S BEGIN?"

- HELLO.
- Woman: HELLO, ANITA.

- HOW ARE YOU?
- IS DR. SMALL HERE?

AND THIS IS SOMETHING THAT
WE'RE CURRENTLY TESTING.

BUT IT'S NOT THAT SIMPLE,

BECAUSE THE HIPPOCAMPUS
COULD BE AFFECTED

BOTH BY NORMAL AGING AND
BY EARLY ALZHEIMER'S DISEASE.

AND THAT'S ONE OF THE
REASONS WHY WE FOCUS SO MUCH

ON THE SYMPTOMS THAT
RELATE TO THE HIPPOCAMPUS.

BECAUSE AS CLINICIANS WE WORRY...

MIGHT THAT BE AN INDICATOR
OF EARLY ALZHEIMER'S DISEASE?

VERY NICE OF YOU
TO INVITE ME IN.

- HAVE A SEAT.
- THANK YOU.

- HOW HAVE YOU BEEN?
- PRETTY GOOD, CONSIDERING.

SO GIVE ME SOME EXAMPLES
OF FORGETFULNESS.

I DON'T LIKE THIS FEELING OF...

WHEN I'M SPEAKING TO PEOPLE,

IN THE MIDDLE OF WHATEVER
WE'RE SPEAKING ABOUT,

I GO COMPLETELY BLANK,
AND I CAN'T PULL UP...

- AND IT COMES BACK LATER.
- MAYBE.

YOU KNOW, I MEAN,
WHEN IT'S NOT IMPORTANT.

- RIGHT.
- BUT NOT ONLY THAT,

I DO THE SAME THING WITH WORDS.

I CAN'T FIND... MY VOCABULARY
HAS ABSOLUTELY DISINTEGRATED.

AS YOU KNOW, WE DO
OCCASIONALLY A MEMORY TEST.

I'M GONNA GIVE YOU
THREE OBJECTS...

APPLE, TABLE, PENNY.

APPLE, TABLE, PENNY.

KEEP THEM IN YOUR MEMORY.

I'M GONNA ASK YOU TO
REPEAT THEM IN A FEW MINUTES.

BUT FOR NOW

I'M GONNA ASK YOU TO
REPEAT SOME NUMBERS,

BUT YOU DON'T NEED TO
REMEMBER THE NUMBERS, OKAY?

SIX, TWO, NINE.

SIX, TWO, NINE.

FOUR, TWO, SEVEN, THREE, ONE.

- FOUR, TWO, SEVEN, THREE, ONE.
- GOOD.

WHAT WERE THOSE THREE
OBJECTS I ASKED YOU TO REMEMBER?

VERY EASY. I HAVE
A WAY OF DOING IT.

- THAT'S OKAY. TRICKS ARE ACCEPTED.
- OKAY?

I PUT THE APPLE ON TOP
OF THE PENNY ON THE TABLE.

EXCELLENT. SO WHO WAS
THE PRESIDENT BEFORE BUSH?

- IT WASN'T CLINTON?
- YES.

- OH, IT WAS?
- SEE? TRUST YOURSELF.

WHO WAS BEFORE CLINTON?

- OH, BUSH.
- GOOD.

AND WHO WAS BEFORE BUSH?

OH...

JOHNSON? NO.

- YES?
- NO.

WE'RE CURRENTLY
FUNDED BY THE N.I.H.

TO IMAGE HUNDREDS
OF HEALTHY ELDERS,

GENERATE THESE PATTERNS
IN THE HIPPOCAMPAL FORMATION

AND FOLLOW THESE
SUBJECTS PROSPECTIVELY.

AND THE QUESTION TO US WILL BE...

"CAN WE DETECT THE EARLIEST
STAGES OF ALZHEIMER'S DISEASE

VERSUS NORMAL AGING ITSELF?"

SO WE NOW HAVE OPTIMIZED

AN M.R.I.-BASED TECHNOLOGY

THAT ALLOWS US
TO REALLY VISUALIZE

THE HIPPOCAMPAL SUBREGIONS
IN MICE AND HUMANS.

AND WE'VE BEEN APPLYING
THAT TECHNOLOGY

ACROSS NUMEROUS STUDIES

TO REALLY TRY TO
TEST THIS QUESTION,

OR TEST THIS HYPOTHESIS...

DOES ALZHEIMER'S
AND NORMAL AGING

TARGET DIFFERENT SUBREGIONS
OF THE HIPPOCAMPUS?

SO REMEMBER THAT THIS IS

A RESEARCH PROJECT
THAT YOU'VE PARTICIPATED IN.

THERE'S A BASIC
ASSUMPTION WE'RE MAKING

THAT ALZHEIMER'S STARTS

IN ONE PART OF THE
HIPPOCAMPAL FORMATION.

THE ENTORHINAL CORTEX

WILL BE TARGETED BY ALZHEIMER'S,

WHEREAS THIS NEIGHBORING
AREA SHOWN IN WHITE...

THE DENTATE GYRUS...

SHOULD BE TARGETED
BY NORMAL AGING.

THESE TWO AREAS SEEM
TO GIVE US THE MOST...

- INFORMATION? -... INFORMATION

IN TRYING TO DISSOCIATE
ALZHEIMER'S FROM AGING.

IT'S THIS AREA OF THE
HIPPOCAMPUS... THE DENTATE GYRUS...

THAT WE FIND, IN YOUR
BRAIN IS RELATIVELY DOWN.

CAN WE IDENTIFY

AT THE MOLECULAR LEVEL

WHAT'S WRONG IN THE
ENTORHINAL CORTEX

IN ALZHEIMER'S DISEASE,

WHAT'S WRONG WITH THE
DENTATE GYRUS IN NORMAL AGING,

AS A WAY TO BEGIN
TO GET AT CLUES

AT AN UNDERLYING
MOLECULAR MECHANISM?

IN THE ENTORHINAL CORTEX

WE'VE BEEN ABLE TO
UNCOVER A NEW MECHANISM

THAT PLAYS A ROLE IN
THE PRODUCTION OF A BETA.

AND THIS IN TURN
SUGGESTS NEW WAYS

IN WHICH WE COULD
BEGIN TO EXPLORE

DIFFERENT THERAPIES
BASED ON THIS FINDING.

YOU KNOW, YOUR CHIEF COMPLAINT
IS FORGETFULNESS, RIGHT?

- REMIND ME, HOW OLD ARE YOU?
- 81.

I THINK THAT YOU
HAVE NORMAL AGING.

I DON'T THINK THAT YOU HAVE
EARLY ALZHEIMER'S DISEASE.

GOOD. GOOD.

WE KNOW THAT NORMAL AGING ITSELF

ALSO CAUSES CELL SICKNESS,

BUT NEVER PROGRESSES OUTSIDE
OF THE CELL-SICKNESS STAGE.

BECAUSE IF YOU THINK
ABOUT ALL THE SUCCESSES

THAT WE'VE MADE IN
MEDICINE, THEY'VE REALLY COME

ON THE HEELS OF BEING ABLE
TO VISUALIZE THE PROBLEM,

WHETHER IT'S CANCER,
HEART DISEASE,

AND, IN FACT, BRAIN DISORDERS...

STROKE, M.S... MULTIPLE
SCLEROSIS... TUMORS.

ONE OF THE GREAT CHALLENGES
OF ALZHEIMER'S DISEASE

IS THE FACT THAT UNTIL RECENTLY

IT'S BEEN RELATIVELY
INVISIBLE TO OUR TECHNOLOGIES.

AND I THINK THAT'S WHY IT'S
BEEN SUCH A GREAT CHALLENGE.

BUT THAT, I THINK,
IS SHIFTING NOW.

ALL RIGHT, COME ON
IN TO THE MAGNET.

JUST WHAT I NEED.

SO THE FIRST PART...
YOU'RE GONNA CLIMB

ALL THE WAY UP THESE STAIRS.

AND WE WANT YOU TO
BE VERY STEADY HERE.

WE GOT INTERESTED IN THIS IDEA
OF LOOKING AT MEMORY FORMATION

BECAUSE I THINK IN
ALZHEIMER'S DISEASE

THE MEMORY TROUBLE
ALZHEIMER'S PATIENTS EXPERIENCE

ACTUALLY BEGINS AT THE
FIRST MOMENT THEY ENCODE,

OR TRY TO LEARN,
NEW INFORMATION.

SO WE KNOW THAT
ALZHEIMER'S PATIENTS

LOSE INFORMATION
MORE QUICKLY OVER TIME.

BUT WE ALSO THINK THAT

EVEN THE WAY THEIR BRAIN
LEARNS THAT INFORMATION

IS UNFORTUNATELY ABNORMAL.

SO REMEMBER, THESE ARE
GONNA GO IN YOUR EARS.

ALL RIGHT. THAT'S GOOD.

MAKE SURE IT'S NOT
PUSHING ON YOUR...

WE'RE FOLLOWING
OLDER INDIVIDUALS

BECAUSE WE ARE ABLE
NOW TO LOOK AT INDIVIDUALS

WHO ARE STILL NORMAL,

OR JUST HAVE A LITTLE
BIT OF MEMORY TROUBLE,

AND SEE IF THEY HAVE ONE OF THE HALLMARK
PATHOLOGIES OF ALZHEIMER'S DISEASE.

BECAUSE IN THE SETTING
OF ALZHEIMER'S PATHOLOGY,

THE BRAIN WILL WORK DIFFERENTLY.

AND WE SEE EVIDENCE
THAT THE BRAIN HAS TO USE

COMPENSATORY AREAS
OF NETWORKS TO ACTIVATE

IN THE SETTING OF
THIS EARLY PATHOLOGY.

AND WE MAY BE ABLE
TO SEE THAT THREE, FIVE,

MAYBE EVEN 10 YEARS BEFORE
SOMEONE'S GONNA DEVELOP DEMENTIA.

- DO YOU FEEL OKAY?
- MM-HMM.

COME ON RIGHT OVER
HERE, MRS. HAMILTON.

SO HE'S IN THERE, AND YOU CAN
SEE IF YOU LOOK IN THE BACK...

YOU CAN ACTUALLY SEE THE
SCREEN FLASHING ON AND OFF.

AND THIS IS ACTUALLY
WHAT HE'S SEEING...

- THESE PICTURES OF NAMES AND FACES.
- OH, NAMES AND FACES.

RIGHT, AND THERE'S A FEW OF THEM

- THAT REPEAT AGAIN AND AGAIN.
- VERY INTERESTING.

FOR EACH FACE NAME YOU SEE,

TRY TO REMEMBER

WHICH NAME GOES WITH WHICH FACE.

AND THE HIPPOCAMPUS
IS REALLY IN THE CENTER,

DEEP IN THE BRAIN, AND
INTEGRATES ALL OF THE INFORMATION

FROM VISUAL CENTERS COMING IN,

AUDITORY CENTERS AND
ALSO THOUGHT CENTERS

THAT ARE IMPORTANT FOR KNOWING

WHETHER OR NOT
SOMETHING IS NEW AND OLD.

AND WE THINK THAT THE
HIPPOCAMPUS BINDS TOGETHER

THIS INFORMATION IN A NEW,
COHESIVE MEMORY TRACE.

OKAY, I KNOW HE NEEDS
EVERY SECOND. AND GO. GO NOW.

OKAY, WE'RE ALL DONE. WE'RE
COMING IN TO GET YOU NOW.

ALL RIGHT, LET'S GET HIM OUT
AND MAKE SURE HE'S COMFORTABLE.

WE'RE GONNA HAVE YOU
DO THE FUN PART NOW...

THE TESTING OF HOW YOUR
MEMORY IS FOR THE NAMES AND FACES.

Mr. Hamilton: I DON'T
REMEMBER LOUIS OR ISAAC.

"GAIL." I DON'T
REMEMBER HER AT ALL.

THEY'RE MIXING TOGETHER
IN MY MIND SO QUICKLY.

YOU CAN SEE EVIDENCE
THAT HE'S GOT A LOT OF LOSS

OF CORTICAL TISSUE, AS WELL
AS HIPPOCAMPAL ATROPHY.

SO HERE YOU SEE MORE BLACK.

THERE'S LOSS OF TISSUE
IN THE HIPPOCAMPUS

AND LOSS OF TISSUE
ALL AROUND THE CORTEX,

PARTICULARLY IN THE
PARIETAL LOBE HERE.

HERE'S A PERSON WHO WAS ONE
OF THE MOST PROLIFIC WRITERS

IN THE WHOLE LAW
SCHOOL... 70-80 PEOPLE.

BUT HIS EVALUATIONS
BEGAN TO FALL OFF.

AND FOR BOB HAVING
HIS EVALUATIONS

DROP TO 80th PERCENTILE
OR 75th PERCENTILE

WAS UNTHINKABLE,
WAS HUMILIATING.

IT WAS A BIT PAINFUL.

I WOULD DESCRIBE IT THAT WAY.

IT WASN'T, YOU KNOW, "OH
MY GOD, MY LIFE HAS ENDED."

BUT IT WAS A BIT OF A SHOCK.

ONE OF THE MOST
SURPRISING THINGS WE FOUND

WHEN WE STARTED TO STUDY

OLDER INDIVIDUALS
WITH FUNCTIONAL IMAGING

IS THAT SOME PARTS OF THE BRAIN

ACTUALLY HYPER TURN
ON, OR HYPERACTIVATE.

THAT WAS REALLY SURPRISING,

BECAUSE THE
ORIGINAL IDEA WAS THAT

AS A PROGRESSION OF
ALZHEIMER'S DISEASE,

THAT YOU JUST LOSE EVERYTHING

AND EVERYTHING GOES
DOWN IN A NICE LINEAR FASHION.

BUT IT ACTUALLY TURNS OUT

THAT SOME PARTS OF THE BRAIN,

PARTICULARLY
EARLY IN THE DISEASE

WHEN PEOPLE ARE AT A PHASE OF
WHAT WE CALL MILD COGNITIVE IMPAIRMENT

WHERE THEY'VE GOT A LITTLE
BIT OF MEMORY TROUBLE

BUT ARE STILL ABLE TO FUNCTION,

WHAT WE'VE SEEN
USING FUNCTIONAL M.R.I.

IS THAT THESE
PARTS OF THE BRAIN,

IN PARTICULAR THE HIPPOCAMPUS
THAT'S SO IMPORTANT FOR MEMORY,

GOES INTO HYPERDRIVE.

AND IN ORDER TO
FORM A NEW MEMORY

IT ACTUALLY WORKS HARDER.

AND WE THOUGHT THAT PERHAPS
THIS IS EVIDENCE OF COMPENSATION,

OR TRYING TO COMPENSATE FOR
EARLY ALZHEIMER'S PATHOLOGY.

SO IT'S REVVING AND
DRIVING AS FAST AS IT CAN,

AND DURING THAT
PHASE OF HYPERACTIVITY

YOU'RE ABLE TO MAINTAIN MEMORY.

AND UNFORTUNATELY,
WHAT WE'VE SEEN IS THAT,

AS PEOPLE PROGRESS,
THEY LOSE ACTIVATION

IN EXACTLY THE AREA
THAT WAS HYPERACTIVATING.

SO ALTHOUGH THIS MAY BE
COMPENSATORY EARLY ON,

IT'S ALSO A SIGN OF IMPENDING
FAILURE OF THE HIPPOCAMPUS.

AND MORE AND MORE WE'VE
SEEN THAT THIS HYPERACTIVATION

IS ACTUALLY A VERY
GOOD PREDICTOR

OF WHO'S GONNA DECLINE
OVER THE NEXT TWO YEARS.

UNFORTUNATELY... YOU CAN SEE
HIS HIPPOCAMPUS OVER HERE...

VERY VERY LITTLE
HIPPOCAMPAL ACTIVATION.

NO HIPPOCAMPAL ACTIVATION,
NO PRECUNEUS DEACTIVATION.

OKAY.

HERE, EVEN IN A SINGLE
ALZHEIMER'S PATIENT,

IT'S JUST A VERY GOOD EXAMPLE
OF HOW THIS MEMORY NETWORK

IS REALLY NOT
FUNCTIONING AT ALL.

YOU CAN SEE THAT
ALTHOUGH PARTS OF HIS BRAIN...

THE PARTS THAT ARE IMPORTANT
FOR VISION AND BASIC ATTENTION...

ARE WORKING, HIS HIPPOCAMPUS,

THIS MEMORY CENTER'S REALLY
NOT ABLE TO TURN ON AT ALL.

YOU GUYS HAVE BEEN REAL TROUPERS
ALL THE WAY THROUGH THIS TRIAL.

WELL, WE JUST FEEL
LUCKY TO BE PART OF IT.

I THINK BOB FEELS THAT WAY TOO.

EVEN THOUGH I CLEARLY HAVE

ALZHEIMER'S PROBLEMS,

THEY REALLY HAVE NOT

SLOWED ME DOWN SIGNIFICANTLY.

SEE, I KEEP SEEING YOUR WIFE
HAVE A SLIGHTLY DIFFERENT OPINION.

- I KNOW SHE DOES.
- I HAVE A SLIGHTLY DIFFERENT PERSPECTIVE.

- AND I CAN TELL YOU THAT... - BECAUSE
SHE CORRECTS ALL MY MISTAKES.

BUT, YOU KNOW, THAT'S
SO COMMON THAT OFTEN

IT DOESN'T BOTHER THE
PATIENT NEARLY AS MUCH

AS IT BOTHERS THE FAMILY
MEMBERS AND OTHERS.

I THINK THAT'S PROBABLY TRUE.

SHE FEELS THAT, I'M QUITE SURE.

ULTIMATELY, USING SINGLE
SUBJECT DATA LIKE THIS,

WE MIGHT BE ABLE TO
ASSESS TREATMENT.

SO IF WE CAN LOOK
IN A GIVEN PERSON

WHO'S NOT ABLE TO
ACTIVATE THEIR HIPPOCAMPUS,

AND THEY'RE FAILING
AT THIS MEMORY TASK,

IF WE COULD GIVE
THEM A TREATMENT,

AN ANTI-AMYLOID TREATMENT
SUCH AS AN ANTIBODY

OR ANOTHER WAY OF
REDUCING AMYLOID IN THE BRAIN,

AND SEE IF WE CAN
ACTUALLY RESTORE FUNCTION

TO THAT PART OF THE BRAIN,

THAT'S THE HOLY GRAIL.

AND SO IT'S THE COMBINATION

BETWEEN THE BRAINWAVES
AND THE MAGNETIC FIELDS

THAT THIS INSTRUMENT RECORDS.

THIS IS A VERY
EXCITING DAY FOR US

BECAUSE THIS IS
THE FIRST PATIENT

WE'RE ENROLLING IN OUR
CLINICAL INVESTIGATION

TO LOOK FOR SUBCLINICAL
EPILEPTIC FORM ACTIVITY,

OR ABNORMAL BRAINWAVE
ACTIVITY IN PEOPLE

WITH EARLY-STAGE ALZHEIMER'S
DISEASE OR RELATED DEMENTIAS.

HOW'S THAT? ARE YOUR EARS OKAY?

THE STUDY INCLUDES

THE ADMISSION OF
PATIENTS TO THE HOSPITAL

FOR A 36-HOUR PERIOD.

AND DURING THAT PERIOD

THEIR BRAINWAVES ARE
CONTINUALLY RECORDED

AND THEN ANALYZED FOR
ANY ABNORMAL FREQUENCIES

OR EVEN PERHAPS BURSTS
THAT MIGHT REFLECT

SUBCLINICAL SEIZURE ACTIVITY.

WE WERE IMPRESSED CLINICALLY

BY THE VERY SIGNIFICANT
FLUCTUATIONS

THAT PEOPLE WITH
ALZHEIMER'S DISEASE

AND OTHER DEMENTIAS
SHOW IN THEIR FUNCTIONING.

SO SOMETIMES ONE
COMES IN THE ROOM

AND THE PATIENT HAS
REASONABLY GOOD ORIENTATION

AND EVEN RECOGNIZES
THEIR RELATIVES JUST FINE.

AND YOU CAN COME BACK
SOMETIMES IN THE AFTERNOON

AND THE PATIENT IS
UTTERLY CONFUSED

AND DOESN'T RECOGNIZE HIS
OR HER DAUGHTER ANYMORE.

AND WE THINK THAT THE
LIKELIEST EXPLANATION

FOR THESE FLUCTUATIONS

ARE INSTABILITIES IN
NEURAL NETWORK FUNCTION.

NOW I'D LIKE YOU TO COUNT
BACKWARDS FROM 100.

96, 95,

94, 93,

92, 91...

UH... ( chuckles )

- 90.
- 90.

LET'S SEE...

WE SUSPECT THAT
AN IMPORTANT PART

OF THE CELL DEATH PROCESS

IS ENERGY DEPLETION,

WHICH CAN COME ABOUT

EITHER BECAUSE NEURONS
ARE OVERSTIMULATED

AND CAN'T KEEP UP

WITH ALL THE DISCHARGING
THAT THEY HAVE TO DO.

SO THIS WOULD BE CONSISTENT WITH

WHAT HAS BEEN REFERRED
TO AS "EXCITOTOXICITY"...

TOO MUCH EXCITATION

RUNNING THE CELL INTO THE GROUND

BECAUSE IT JUST CAN'T KEEP
UP WITH ITS OWN ACTIVITY.

AND I THINK A KEY
PLAYER VERY LIKELY IS

THE AMYLOID BETA PEPTIDE...

A SMALL FRAGMENT
OF A LARGER PROTEIN

THAT WE ALL MAKE.

AND WE KNOW THAT IT IS
GENERATED AND CLEARED

VERY RAPIDLY THROUGHOUT THE DAY

MULTIPLE TIMES UNDER
NORMAL CIRCUMSTANCES.

AND IT LOOKS LIKE
EXCESS AMYLOID BETA

CAN GET THE CELL INTO OVERDRIVE.

- DEBORAH.
- YES?

HI, I'M DR. MUCKE.

- HOW ARE YOU DOING?
- FINE, THANK YOU.

I WANTED TO HEAR FROM
YOU A LITTLE BIT ABOUT

HOW YOU SEE THINGS
ARE DIFFERENT NOW

COMPARED TO, SAY, HOW THEY WERE

10-15 YEARS AGO.

I DON'T KNOW.

IT WAS VERY GRADUAL.

I WOULD LIKE TO SEE IF
YOU CAN COPY THAT FOR ME.

YOU CAN START
ANYWHERE ON THE PAGE.

BUT IF YOU CAN TRY TO
COPY THAT CUBE FOR ME...

- NO.
- IT'S TOUGH, RIGHT?

- THAT'S A REAL TOUGH ONE FOR YOU, I KNOW.
- ( laughs )

AND HER MINI MENTAL-STATE EXAM...

OVERALL SCORE
WAS A 20 OUT OF 30.

SHE GOT A 27 ABOUT A YEAR AGO.

SO THAT'S QUITE
A DROP, ACTUALLY.

THAT'S QUITE A DROP
OVER THAT TIME FRAME.

- YEAH.
- YEAH.

BASICALLY THE BOTTOM LINE IS

THAT THERE WERE ONLY
SOME SHARP TRANSIENTS,

BUT NOT ANY REAL CLEAR-CUT
EPILEPTIC FORM ACTIVITY.

NOT WHAT WE WOULD
CALL A JUICY SPIKE.

I THINK WHAT WE WOULD BE KIND OF

INTERESTED IN MOSTLY
IS THE SHARP ACTIVITY.

I BELIEVE THAT THE
DISEASE REALLY REQUIRES

A VERY OPEN-MINDED
APPROACH, IF YOU WILL,

WHERE ONE HAS TO UNDERSTAND

THAT IT COMES ABOUT
VIA DIFFERENT PROCESSES,

AND THAT ONE MAY
HAVE TO BLOCK IT ALSO

FROM MANY DIFFERENT ANGLES.

SO DIFFERENT
PATIENTS MAY REQUIRE

A SLIGHTLY DIFFERENT
THERAPEUTIC APPROACH

FROM THE NEXT PERSON.

AND WE'RE BEGINNING NOW
IN OUR ANIMAL MODELS TO TEST

ALL THE DIFFERENT
ANTI-EPILEPTIC DRUGS THAT EXIST

TO FIND OUT

IF ANY OF THEM
ACTUALLY CAN INHIBIT

THE EPILEPTIC FORM,
EPILEPSYLIKE ACTIVITY

THAT THE AMYLOID
PROTEINS SEEM TO INDUCE.

- WE HAVE ENOUGH MATERIAL.
- WE DO.

AND WE ALSO NEED TO MAKE SURE

THAT OUR
DRUG-DEVELOPMENT PORTFOLIO

THAT THE COMMUNITY IS
BUILDING OVER THE YEARS

IS NOT TOO SINGLE-MINDED,

BECAUSE WE MAY BE BETTING
ON THE WRONG HORSE.

SO IT'S VERY IMPORTANT FOR US

TO DIVERSIFY

THE DRUG-DEVELOPMENT PORTFOLIO.

A CATEGORY OF
STUDY WHICH HAS BEEN

ENORMOUSLY IMPORTANT
TO ALZHEIMER'S RESEARCH

HAS BEEN THE LONGITUDINAL
STUDY OF HUMANS,

IN WHICH A GROUP OF PEOPLE

ARE EXTENSIVELY
WELL-CHARACTERIZED

AND THEN FOLLOWED THROUGH
MANY YEARS AND DECADES OF LIFE

IN AN EFFORT TO
BETTER UNDERSTAND

THE VARIABLES WHICH AFFECT THEM,

THE RISK FACTORS

IN THEIR BIOLOGICAL
OR LIFESTYLE BEHAVIORS,

AND HOW THESE TRANSLATE
INTO THE LIKELIHOOD OF RISK

OR PROTECTION AGAINST
A VARIETY OF DISEASES.

( tower bell chiming )

( organ playing )

♪ HALLELUJAH ♪

♪ HALLELUJAH ♪

♪ HALLELUJAH ♪

♪ HALLELUJAH ♪

Dr. David Benne IN THE
RELIGIOUS ORDER STUDY,

WE HAD ONE OF THE
FIRST PUBLICATIONS

SHOWING THAT ENGAGING

IN MENTALLY STIMULATING ACTIVITY

MAY DELAY THE TIME

UNTIL YOU REACH GETTING
ALZHEIMER'S DISEASE.

Sister Caulfield: GOOD MORNING.

I'M APOLOGIZING
FOR INTERRUPTING.

SISTER CATHERINE,

WHO DIED IN IOWA
CITY TWO DAYS AGO,

GAVE HER BODY TO SCIENCE.

THE FAMILY WILL COME TOGETHER

FOR A MEMORIAL MASS AUGUST 23rd.

I WANT YOU TO KNOW
THAT I'M IN THE STUDY.

- Woman: ARE YOU?
- OH YEAH.

AND IT HELPS THE RESEARCH.

OH, IT HELPS RESEARCH. OH, SURE.

THAT'S RIGHT. THAT'S
THE IMPORTANT PART.

- THAT'S THE REASON WE DO IT.
- THAT'S TRUE.

- QUITE LARGE, ISN'T IT?
- SO THESE ARE TWO NUNS

FROM DUBUQUE, RIGHT?

RIGHT, THEY'RE TWO
NUNS FROM DUBUQUE.

OKAY.

THEY BOTH HAVE
SIGNIFICANT ATROPHY.

YOU CAN SEE THE ATROPHY HERE.

THIS ONE DOES LOOK
MORE SEVERE TO ME.

THE RELIGIOUS
ORDER STUDY INVOLVES

OLDER NUNS, PRIESTS AND
BROTHERS WITHOUT DEMENTIA

WHO AGREE TO BE
TESTED EVERY YEAR

TO TELL US ALL KINDS OF
THINGS ABOUT THEMSELVES.

AND A CONDITION OF ENTRY
IS THAT THEY HAVE TO AGREE

TO ORGAN DONATION
AT THE TIME OF DEATH.

WE'RE INTERESTED IN:

WHAT ARE THE COMMON
CHANGES IN THE BRAIN

THAT CAUSE PEOPLE

TO LOSE MEMORY
AS THEY GET OLDER?

HOW ARE DIFFERENT
RISK FACTORS THAT ARE

CAUSING MEMORY LOSS...
WHAT'S THE PATHWAY?

HOW ARE THEY DOING THAT?

WHAT ARE THEY DOING TO THE BRAIN

TO ACTUALLY CAUSE
THE MEMORY LOSS?

AND WE'RE OFTEN VERY SURPRISED,

WITH A LOT OF PATHOLOGY

WITH A PERSON WITH NO
COGNITIVE IMPAIRMENT,

OR VERY LITTLE PATHOLOGY

IF THE PERSON DID HAVE
ALZHEIMER'S DISEASE.

SO THIS IS A NUN FROM DUBUQUE.

SHE DIED. SHE WAS
ABOUT 80 YEARS OLD.

SHE HAD 18 YEARS OF EDUCATION.

AND SHE CLEARLY
HAD A MILD DEMENTIA

AT THE TIME THAT
WE LAST SAW HER...

PROBABLY ALZHEIMER'S DISEASE.

AND LET'S SEE WHAT
IT DID SHOW HERE.

AND YOU CAN ALREADY SEE

THE ABNORMALITY OF THE PLAQUES.

ALL OF THESE BLACK
STRUCTURES HERE

ARE PLAQUES WITHIN HER BRAIN.

OKAY, SO THE FIRST CASE...

PRETTY TYPICAL
ALZHEIMER'S DISEASE.

AND THE SECOND CASE...

SHE WAS OVER 90 OVER YEARS OLD.

SHE HAD 20 YEARS OF EDUCATION,

NO DECLINE OVER THE YEARS

OVER THREE YEARS OF FOLLOW-UP.

WHAT DO YOU THINK
WE'RE GONNA SEE HERE?

IT LOOKS LIKE SHE SHOULD HAVE

A SOMEWHAT NORMAL BRAIN.

SHE HAS A SIGNIFICANT
NUMBER OF PLAQUES,

AND ENOUGH PLAQUES TO CONFIRM

A DIAGNOSIS OF
ALZHEIMER'S DISEASE.

SO HER BRAIN LOOKS VERY SIMILAR

TO THE NUN THAT WE SAW
THAT DID HAVE DEMENTIA.

AND YET THIS WAS
SOMEBODY WHO WAS OLDER,

FUNCTIONING PRETTY WELL,

AND HAD REALLY NO
REASON FOR US TO SUSPECT

THAT SHE HAD
ALZHEIMER'S DISEASE.

WE'RE DEVELOPING THIS IDEA

THAT CERTAIN TYPES
OF THINKING ABILITIES

CAN ACTUALLY HELP YOU TOLERATE

THE PATHOLOGY OF
ALZHEIMER'S DISEASE

SO IT'S NOT EXPRESSED
AS MEMORY LOSS.

AND WE TALK ABOUT MEMORY
LOSS 'CAUSE THAT IS REALLY

THE HALLMARK OF CLINICAL
ALZHEIMER'S DISEASE.

THE BASIC IDEA BEHIND
COGNITIVE RESERVE

IS THAT TWO PEOPLE WITH THE SAME
AMOUNT OF ALZHEIMER'S CHANGES...

ONE WILL HAVE MEMORY
LOSS AND DEMENTIA,

AND THE OTHER ONE COULD
BE COMPLETELY NORMAL.

SO WHAT UNDERLIES THAT?

WHY IS IT THAT PATHOLOGY

OF, YOU KNOW, SO
MUCH IN ONE PERSON

IS HAVING SUCH A
DEVASTATING EFFECT,

AND THE SAME AMOUNT IS
NOT HAVING THAT EFFECT

IN ANOTHER PERSON?

AND SO THE IDEA OF A RESERVE

IS THAT PATHOLOGY IS DEVELOPING

IN THE CONTEXT OF AN INDIVIDUAL

THAT CAN SOMEHOW PROTECT IT.

AND THE QUESTION THEN BECOMES...

WHAT'S THE NATURE
OF THE PROTECTION?

ONE THING WE'VE
LOOKED AT, FOR EXAMPLE,

IS THE EXTENT OF
YOUR SOCIAL NETWORK,

SO HOW MANY PEOPLE YOU
FEEL COMFORTABLE WITH

TALKING TO AND CONFIDING IN.

AND THE LARGER THAT NETWORK,

THE LESS LIKELY
YOU ARE TO DECLINE,

AND THE LESS LIKELY
YOU ARE TO EXPERIENCE

CLINICAL ALZHEIMER'S DISEASE.

SO I ACTUALLY HAVE SOME DATA.

THE ONE THAT DID NOT
SHOW ANY MEMORY LOSS

HAD A SOCIAL NETWORK
THAT WAS 10 TIMES LARGER

THAN THE OTHER SISTER.

ALL RIGHT.

AND THE ONE THAT DID NOT
SHOW ANY COGNITIVE LOSS

ALSO WAS LESS LIKELY
TO BE DISTRESSED.

THERE'S SOMETHING
ABOUT THOSE FACTORS

IN THESE TWO WOMEN
WHERE THEY DIFFERED.

AND SOMEHOW THEY CHANGED

THE WAY THE BRAINS TOLERATED

AND RESPONDED TO THE
PATHOLOGY OF ALZHEIMER'S DISEASE.

IF YOU THINK ABOUT PEOPLE
THAT HAVE LARGER NETWORKS

VERSUS PEOPLE WITH
SMALLER NETWORKS...

I MEAN, WHAT'S DIFFERENT
ABOUT THOSE INDIVIDUALS?

IT'S HARD TO DEVELOP
A LARGE NETWORK.

IT TAKES WORK
AND IT TAKES SKILL.

ENGAGEMENT IN COGNITIVELY
STIMULATING ACTIVITIES...

TURNS OUT THAT PEOPLE
THAT SPEND MORE TIME

IN MORE VARIETIES OF
PROCESSING INFORMATION

ACTUALLY MAINTAIN
THEIR COGNITIVE ABILITIES.

AND, IN PARTICULAR,
THEY MAINTAIN

THEIR BRAIN EFFICIENCY.

THEY'RE QUEEN
ANNE'S LACE, WE CALL IT.

- QUEEN...?
- QUEEN ANNE'S LACE.

Together: QUEEN ANNE'S LACE.

ALL RIGHT.

EVERYTHING IN THIS
LESSON IS PERFECT.

"THE LITTLE GIRL
HAS PINK CHEEKS."

- PINK CHEEKS.
- SO THE DOUBLE VOWEL MAKES IT LONG.

WHAT IS CHEEKS? ( laughs )

- AH, HERE.
- MM-HMM.

- PINK CHEEKS, OKAY.
- ALL RIGHT, GOT IT.

Dr. Benne IN THE EVENT THAT
SOME CATASTROPHE COMES...

NOT AN ACCIDENT, BUT
ALZHEIMER'S CHANGES,

IF YOU TAKE YOUR BRAIN WITH YOU

INTO YOUR 10TH DECADE, AS
YOU ENTER THAT 10TH DECADE,

YOU WANT THE MOST
ROBUST, EFFICIENT,

RAPID-DECISION-MAKING,

MULTITASKING BRAIN THAT
YOU POSSIBLY CAN HAVE.

BECAUSE THAT'S WHAT'S
GONNA ALLOW YOU

TO MAINTAIN YOUR COGNITION,

DESPITE ALL THE OTHER THINGS
THAT'S GONNA HAPPEN TO IT.

( birds chirping )

Mrs. Galvani: I KNOW
FROM LIVING WITH HIM

HOW HE JUST LOVED BEING
OUT AND DOING ALL THE WORK

HE WAS DOING ON
COMMITTEES AND LOCAL CLUBS,

AND PLAYING CARDS...
A LITTLE DIVERSION...

BUT ALSO BEING TOASTMASTER
AT MANY MANY FUNCTIONS.

HE HAD A LOT OF ENERGY TO
KEEP DOING ALL THESE THINGS.

AND I HAD B.C. FOOTBALL TICKETS

UNTIL THREE YEARS AGO

WHEN I COULDN'T SEE OR
CLIMB THE STAIRS ANYMORE.

SO I GAVE UP MY SEASON TICKETS

THREE YEARS AGO. I WAS 91.

( both laugh )

WITH THE INCREASE IN LONGEVITY

THAT WE ARE OBSERVING
IN THE PAST DECADES

COMES A GREAT DEAL OF CONCERN

WHETHER INCREASED LIFESPAN
IS GOING TO BE ACCOMPANIED

BY A GREATER PERIOD
OF TIME WITH DISABILITY,

WITH LOSS OF DEPENDENCE,
WITH POOR QUALITY OF LIFE,

OR WHETHER INCREASED
LIFE EXPECTANCY

CAN BE ACCOMPANIED BY A
LONGER PERIOD IN GOOD HEALTH.

IN THAT REGARD, THERE'VE
BEEN SOME VERY GRATIFYING

RESULTS OF STUDIES
OVER THE PAST YEARS,

WHICH HAVE INDICATED
THAT IN THE YEARS

FROM 1982 THROUGH PRESENT...
THE LAST COUPLE OF DECADES...

THERE IN FACT HAVE BEEN
SUBSTANTIAL DECREASES

IN THE RATES OF DISABILITY
IN OLDER MEN AND WOMEN.

THIS IS VERY IMPORTANT

BECAUSE IT
INDICATES THAT IN FACT

DISABILITY WITH OLD AGE
IS BY NO MEANS INEVITABLE.

AND THERE IS REAL PROMISE
FOR BEING ABLE TO INCREASE

THE QUALITY OF INDEPENDENCE

AND DISABILITY-FREE
LIFE WITH AGE.

( people chattering )

MARY, WHAT ARE YOU DOING?

HI, VIC. HOW ARE YOU
DOING? WHAT'S GOING ON?

- GOOD TO SEE YOU.
- GOOD TO SEE YOU.

- VIC LOOKS FANTASTIC.
- OF COURSE HE DOES.

ONE OF THE STUDIES WHICH
HAS BEEN PARTICULARLY VALUABLE

HAS BEEN THE
FRAMINGHAM HEART STUDY...

A STUDY WHICH WAS INITIATED TO
FOCUS ON CARDIOVASCULAR DISEASES...

DISEASES OF THE HEART... BUT
HAS PROVEN TO BE AN ASSET

TO THE GATHERING OF INFORMATION
IN THE FUNCTION OF THE BRAIN

AND BRING IT TO BEAR IN
A BETTER UNDERSTANDING

OF DEMENTIA AND
ALZHEIMER'S DISEASE.

USING THE FRAMINGHAM
DATA, WE'RE ABLE TO ESTIMATE

WHAT IS THE PROBABILITY

THAT A MAN OR WOMAN AT AGE 65

WILL DEVELOP A
STROKE OR DEMENTIA

DURING THE REMAINDER
OF THEIR LIFE.

AND THE PROBABILITY
COMES OUT TO BE

ONE CHANCE IN THREE

THAT A MAN WILL DEVELOP
STROKE OR DEMENTIA

AND ONE CHANCE IN TWO

THAT A WOMAN WILL
DEVELOP STROKE OR DEMENTIA

DURING THE REMAINDER
OF THEIR LIFE,

WHICH IS A REALLY
TERRIFYING STATISTIC.

OKAY, THIS FIRST ONE GOES
FOR A MINUTE AND A HALF.

JUST HOLD VERY STILL, OKAY?

Man: IT'S REALLY WONDERFUL TO
SEE WHAT OUR BRAIN LOOKS LIKE,

AND WHAT HAPPENS
TO IT OVER THE YEARS.

- HAVE YOU EVER SEEN AN M.R.I. LIKE THIS BEFORE?
- NO, NEVER.

WE OFTEN EXPECT...

WHEN YOU HAVE PEOPLE
WHO ARE ABOUT 70 YEARS OLD,

YOU FIND THAT OVER HALF OF THEM

WOULD HAVE A LOT OF CHANGES,

MORE CHANGES IN
THEIR WHITE MATTER

- THAN WHAT YOU DO.
- I SEE.

SO THAT'S GOOD.

THAT EXPLAINS TO SOME EXTENT

WHY YOU'RE DOING SO WELL

IN TERMS OF BEING
QUICK IN YOUR THINKING,

BEING ABLE TO
REMEMBER THINGS WELL.

THIS IS A PART OF THE BRAIN
CALLED THE HIPPOCAMPUS,

- WHERE WE FORM MEMORIES.
- RIGHT.

AND THIS IS SOMETHING
THAT SHRINKS

- WHEN YOU HAVE ALZHEIMER'S.
- I SEE.

NOW THIS IS FROM A
MORE RECENT SCAN.

IF IT HAD SHRUNK, YOU WOULD SEE

- MORE OF THIS WHITE FLUID
AROUND IT... - OF THE WHITE, YES.

AND MUCH LESS
OF THE GREY MATTER.

WE LIKE THE FACT THAT
WE ARE ABLE TO SEE

HOW BIG YOUR HIPPOCAMPI ARE,

HOW THEY CHANGED OVER
TIME, AND THAT HASN'T CHANGED.

Dr. Hodes: THERE'S GREAT HOPE

THAT THESE EXAMPLES
OF SUCCESSFUL AGING,

EVEN IF IT'S IN THE
EXCEPTIONAL FEW,

ARE REASON TO HOPE
THAT MANY MORE OF US,

IF NOT ALL OF US, CAN
ACHIEVE THAT SAME OUTCOME

ONCE WE ARE CAPABLE
OF BETTER UNDERSTANDING

WHAT DISTINGUISHES THIS
SUCCESSFUL BRAIN AGING

FROM LESS SUCCESSFUL
BRAIN AGING,

AND DETERMINE WHAT MANIPULATIONS

ARE CAPABLE OF TRANSFORMING

THE UNSUCCESSFUL
INTO THE SUCCESSFUL.

THERE'S ENORMOUS INTEREST NOW

IN WHAT THE EFFECTS OF
LIFESTYLE INTERVENTIONS

SUCH AS EXERCISE AND DIET

MAY HAVE ON THE RISK
FOR ALZHEIMER'S DISEASE

OR ON BRAIN HEALTH
AND FUNCTION IN GENERAL.

IN ANIMAL MODELS...

MOUSE MODELS OF ALZHEIMER'S
DISEASE, FOR EXAMPLE...

THERE IS RECENT
EVIDENCE SUGGESTING

THAT EXERCISE AND DIET

CAN MODIFY THE
PROGRESSION OF THE LESIONS

OF ALZHEIMER'S DISEASE
IN THESE ANIMAL MODELS.

ONE OF THE BREAKTHROUGHS
IN THE FIELD IS TO BE ABLE

TO HAVE A MOUSE MODEL
OF ALZHEIMER'S DISEASE

CALLED A TRANSGENIC MOUSE.

AND IT SIMULATES A
LOT OF THE PATHOLOGY

THAT DEVELOPS IN THE HUMAN
BRAIN WITH ALZHEIMER'S DISEASE.

I HAD THIS IDEA THAT
MAYBE A GROWTH FACTOR,

OR NEUROTROPHIC FACTOR,

WHICH IS KIND OF A NUTRIENT
OR A FERTILIZER TO NEURONS,

WHICH ALSO MAKES THEM SMARTER,

MIGHT BE NATURALLY
INCREASED WITH EXERCISE.

WE TAKE TWO GROUPS...

ONE IS JUST SORT
OF IN THEIR CAGE

AND DON'T HAVE ACCESS
TO A SORT OF A RUNNING GYM;

AND THE OTHERS GET IN THEIR
RUNNING WHEELS AT NIGHT

AND THEY EXERCISE.

IN ORDER TO TEST THEIR LEARNING,

WE BASICALLY TAKE THE TWO GROUPS

AND PUT THEM IN THIS
MORRIS WATER MAZE.

THEY ARE PUT IN THE TANK.

AND THEY DON'T LIKE THE WATER.

AND WHAT THEY HAVE TO DO IS

THEY HAVE TO FIND
A LITTLE PLATFORM

THAT'S SORT OF
BELOW THE SURFACE.

IT'S REALLY KIND OF
EQUIVALENT TO FINDING YOUR CAR

IN A PARKING LOT AT AN AIRPORT

WHEN YOU CAN'T REALLY SEE IT,

BUT YOU SORT OF HAVE TO LEARN

FROM THE CUES AROUND THE AIRPORT

OF WHERE YOU PARKED.

Man: THE SEDENTARY ANIMAL
STILL HAS NOT LOCATED

THE PLATFORM AT THIS POINT.

ALL RIGHT.

WE FIND CONSISTENTLY

THAT THE ANIMALS
THAT HAVE EXERCISED

ARE ABLE TO LEARN
FASTER AND BETTER

THAN THE ANIMALS
THAT HAVEN'T EXERCISED.

- Woman: ALL RIGHT!
- Dr. Cotman: YAY!

Man: HE DID IT.

WE LOOKED AT THEIR
BRAIN, AND LO AND BEHOLD,

BDNF WAS INCREASED
IN THE PART OF THE BRAIN

THAT IS CONTROLLING
THINKING AND LEARNING

AND IS VULNERABLE TO
ALZHEIMER'S DISEASE.

AND ALL I CAN SAY TO MYSELF,

AND MY STUDENTS WOULD SAY,

"HOLY KAMOLEY, THAT IS SO SMART.

THE BRAIN KNEW SOMETHING

IN HOW TO LOOK OUT FOR ITSELF

THAT WE HAD NO IDEA ABOUT."

SO IT KINDA HAS A
SELF-PRESERVATION MECHANISM

THAT ALSO MAKES IT
SMARTER AND TO LEARN BETTER.

CERTAINLY IN ANIMAL MODELS
THERE'S NO QUESTION ABOUT IT...

EXERCISE CAN INDUCE
GROWTH FACTORS IN THE BRAIN.

IT CAN HELP BUILD

NEW NEURONS INTO THE CIRCUITS.

IT CAN BUILD SYNAPSES,
IMPROVE LEARNING.

AND IT CAN BASICALLY
IMPROVE VASCULAR FUNCTION.

OH MY GOSH, YOU KNOW,
WHAT DRUG WILL DO THAT?

NOTHING.

AND, YOU KNOW,
IT'S SIMPLE EXERCISE.

YOU CAN IDENTIFY NEW NEURONS

BY STAINS, YOU
KNOW, THAT HIGHLIGHT

THE NEW CELLS
THAT ARE JUST BORN.

AND WHEN YOU LOOK,
THERE'S FEWER OF THEM

IN THE ANIMALS THAT
ARE JUST SEDENTARY

THAN IN THE EXERCISED ANIMALS.

AND IT'S REALLY QUITE DRAMATIC.

SO EXERCISE ACTUALLY INCREASES
THE NUMBER OF NEW NEURONS

THAT COULD BE ADDED
TO THE HIPPOCAMPUS.

THE EXCITING CONCLUSION IS

THAT WHEN WE TESTED THE ANIMALS

THAT DEVELOP ALZHEIMER'S
DISEASE IN THE BRAIN,

THEY BENEFIT AS
WELL FROM EXERCISE,

JUST LIKE THE WILD TYPE.

SO THEY LEARN FASTER AND BETTER,

WHICH IS VERY ENCOURAGING
BECAUSE IT MEANS

THAT MAY HELP DELAY THE
ONSET OF ALZHEIMER'S DISEASE

FROM THE EXPERIENCE OF EXERCISE.

IF YOU ASKED
SOMEBODY 10 YEARS AGO,

"HOW ARE YOU GOING
TO FIX BRAIN AGING?"

OR "WHAT ARE YOU GONNA DO?"

THEY WOULD HAVE TOLD
YOU IT'S A MEDICATION.

NOW WE KNOW
THERE'S GREAT PROMISE

IN TERMS OF BEHAVIORAL
INTERVENTIONS

THAT CAN BE ADJUNCTS
TO MEDICATIONS

AND GOOD HEALTH POLICY.

NICE YOU SEE YOU.
HOW ARE YOU DOING?

OH, IT'S SO GOOD TO SEE YOU.

I'M GONNA CHECK A FEW THINGS,
LISTEN TO YOUR HEART AND LUNGS.

NO SPINNING
SENSATION, NO NAUSEA,

- VOMITING, NOTHING LIKE THAT?
- NO NO.

IF THINGS GO WELL, YOU'LL BE
ABLE TO STAY ON THE MEDICINE,

AND THEN HOPEFULLY
THIS WILL BE APPROVED

FOR THE GENERAL
PUBLIC DOWN THE ROAD

FOR TREATING THIS DISEASE, OKAY?

WELL, THAT'S WHAT WE'RE
HOPING AND PRAYING FOR.

ONE OF THE BEST
PIECES OF NEWS IS

THAT THERE ARE MANY
CLINICAL TRIALS NOW

WITH VERY PROMISING AGENTS

FOR ALZHEIMER'S
DISEASE... DOZENS.

THEY'RE BEING CONDUCTED BY

THE ALZHEIMER'S DISEASE
COOPERATIVE STUDY... THE ADCS.

THEY'RE BEING CONDUCTED BY
THE PHARMACEUTICAL INDUSTRY.

THEY'RE BEING CONDUCTED IN THIS
COUNTRY AND IN OTHER COUNTRIES.

YOU'LL START WITH
THE EVENING DOSE.

THE EVENING. OKAY.

- THANKS FOR COMING. SEE YOU IN THREE MONTHS.
- SEE YOU IN THREE MONTHS.

- HOW'RE YOU FEELING TODAY?
- GOOD.

BEEN AN OKAY EXPERIENCE FOR YOU?

VERY VERY MUCH SO.

TWO IN THE MORNING,
TWO AT NIGHT.

THE PIVOTAL TRIALS
OF ALZHEIMER'S DISEASE

THAT ARE OCCURRING NOW... TRIALS
OF DISEASE-MODIFYING TREATMENTS,

OF ANTI-AMYLOID TREATMENTS,

BECAUSE THEY ARE TRYING
TO SLOW THE PROGRESSION

OF THIS DISEASE
OVER THE LONG TERM,

AND BECAUSE THE PROGRESSION

VARIES FROM ONE
PERSON TO ANOTHER,

IN FACT THEY REQUIRE

MANY MANY PARTICIPANTS
IN THESE TRIALS.

YOU CAN DIRECTLY PLUG
THIS MACHINE INTO THE WALL.

OKAY, PUT IT UP TO YOUR NOSE.

Man: NO MATTER WHERE I HAVE
TO TAKE THIS WOMAN IN THE WORLD

TO FIND SOMETHING

THAT CAN HELP HER
MAINTAIN A LIFESTYLE,

AND A GOOD
LIFESTYLE, I WILL DO IT.

WITHOUT THE COOPERATION

OF INDIVIDUALS
AND THEIR FAMILIES

WE HAVE A ROADBLOCK,

WE WILL NOT PROGRESS
TO TREATMENTS.

- CAN YOU PICK UP YOUR FOOT?
- UH-HUH.

AND BRING IT OVER. THERE YOU GO.

OKAY.

WE GOT INVOLVED
IN THE ELAN TRIALS,

THE 2001 ELAN TRIALS,
BECAUSE OUR SON-IN-LAW

SAW IT ADVERTISED IN THE PAPER

AND HE CALLED US AND SAID,

"I THINK THIS MAY BE SOMETHING
YOU'D BE INTERESTED IN."

- YEAH.
- AND WE WERE INTERESTED IN IT.

SO EARL AND I RAN OUT THERE

TO GET INVOLVED IN IT,
AND EXCITED ABOUT IT.

I WAS JUST HOPING

THAT SOMETHING

WOULD SURFACE

THAT WOULD HELP ME.

THERE'S A VARIETY OF APPROACHES

TO TRY AND BLOCK

THE PROGRESSION OF
ALZHEIMER'S DISEASE.

ONCE YOU HAVE IT, HOW CAN YOU...

HOW CAN YOU GO AFTER
THE PLAQUES OR THE TANGLES,

TRY AND REDUCE
THEM, REMOVE THEM,

SO THAT YOU CAN CHANGE
THE COURSE OF THE DISEASE?

ONE OF THE LOGICAL WAYS TO DO IT

IS TO REDUCE THE PRODUCTION
OF BETA-AMYLOID FROM THE GET-GO.

THE MORE SURPRISING WAY TO DO IT

THAT WE DISCOVERED
IN THE LATE '90s

IS THAT, IF YOU ACTUALLY
IMMUNIZE OR VACCINATE

WITH THE BETA-AMYLOID
PEPTIDE ITSELF,

AND STIMULATE THE IMMUNE SYSTEM,

THAT THE IMMUNE SYSTEM

CAN THEN ACTUALLY EITHER
PREVENT... TOTALLY PREVENT...

OR REVERSE THE PLAQUES
IN THE BRAIN TISSUE.

THE IDEA WAS TO VACCINATE

JUST LIKE YOU GET
VACCINATED FOR POLIO...

VACCINATE WITH
A SYNTHETIC PIECE,

A LITTLE PEPTIDE
PROTEIN FRAGMENT

OF THE BETA-AMYLOID
INTO THE MICE.

AND WHEN YOU GET
VACCINATED, WHAT DO YOU DO?

YOU RAISE ANTIBODIES
IN YOUR BLOOD.

AND THAT'S WHAT PROTECTS YOU

IF YOU'RE BEING VACCINATED
AGAINST SOME INFECTION.

HERE IT'S A LITTLE
DIFFERENT. WHAT WE HOPED IS

THAT THOSE ANTIBODIES WOULD
CIRCULATE THROUGH THE BODY.

AND WHAT ANTIBODIES DO IS THEY BIND
TO WHATEVER THEY'VE BEEN MADE TO.

AND WE HOPED THESE ANTIBODIES
WOULD BIND TO THE BETA-AMYLOID

AND HELP CLEAR IT,
HELP GET RID OF IT...

A VERY SIMPLE IDEA, AN
EXTREMELY SIMPLE IDEA.

AND THIS IS WHAT YOU SEE

IN UNTREATED
MICE. THIS IS A BRAIN.

THE BROWN MATERIAL
IS THE PLAQUES.

THEN AFTER THEY'VE
BEEN VACCINATED,

THIS IS WHAT YOU
SEE INSTEAD OF THAT

IN THE TREATED ANIMALS.

AND IT WAS SO
BLACK-AND-WHITE AND SO OBVIOUS

THAT I REMEMBER...
DORA SAW THIS FIRST.

YOU COULD WITH
100% ACCURACY SAY,

"THIS ANIMAL WAS TREATED
AND THIS ONE WASN'T."

ONCE WE REALIZED THAT
WE COULD ACTUALLY TREAT

OUR MOUSE MODEL OF
ALZHEIMER'S DISEASE

WITH THE BETA-AMYLOID PEPTIDE...

IN OTHER WORDS BY
VACCINATING THEM,

OR IMMUNIZING THEM WITH
THE BETA-AMYLOID PEPTIDE...

WE IMMEDIATELY REALIZED
THAT THAT HAD POTENTIAL

FOR TREATMENT OF
ALZHEIMER'S PATIENTS.

WE BEGAN WHAT WE
CALL CLINICAL TRIALS.

AND THAT'S A VERY
LONG PROCESS, ACTUALLY.

AND THE WAY IT'S DONE IS,

MOST OF WHAT YOU DO IS MAKE SURE

THAT WHAT YOU'RE DOING IS SAFE.

SO YOU DO A FEW
NUMBER OF PATIENTS,

A VERY CONTROLLED ENVIRONMENT,

VERY CAREFUL AMOUNTS, ET CETERA,

AND SHOW THAT IT'S SAFE.

AND WE CALL THAT PHASE
I TRIALS. SO WE DID THAT

AND EVERYTHING LOOKED FINE.

AND THEN WE WENT
ONTO LARGE STUDIES.

AND NOW WE'RE TALKING
SEVERAL HUNDRED PATIENTS,

370 PATIENTS,

WHERE WE DID WHAT'S
CALLED A PHASE II STUDY

WHERE AGAIN A LOT
OF IT IS ABOUT SAFETY.

MOST OF IT'S ABOUT SAFETY.
BUT YOU'RE STARTING TO LOOK

AT THINGS LIKE, "GEE,
IS THIS WORKING?

ARE THE PATIENTS PERFORMING
FUNCTIONS BETTER? HOW ARE THEY DOING?"

HE HAD THREE INJECTIONS

PROBABLY OVER A
PERIOD OF THREE MONTHS

OR SOMETHING LIKE
THAT, MAYBE EVEN LONGER.

WHEN HE WAS GIVEN
THE FIRST INJECTION,

HE HAD A BIT OF A
REACTION TO A PROTEIN,

AN ALLERGEN TYPE REACTION.

AND I SAID, "I THINK
YOU GOT THE VACCINE."

AND SURE ENOUGH, HE DID.

AND SO IT WAS EXCITING

BECAUSE WE WERE ACTUALLY FEELING

LIKE IT WAS DOING SOME GOOD...

- YEAH YEAH.
- EVEN INITIALLY.

IT GAVE ME A LOT OF HOPE.

WE WERE JUST WELL UNDERWAY.
EVERYTHING WAS GOING FINE.

AND AFTER THE SECOND DOSE

WE RAN INTO A PROBLEM
WITH ENCEPHALITIS

IN A VERY SMALL
SUBSET OF PATIENTS...

ABOUT 5% OR 6% OF THEM.

AND ALTHOUGH IT WAS
TRANSIENT, IT WAS SEVERE ENOUGH

THAT WE FELT IT WAS
PRUDENT TO STOP DOSING.

- WHEN THEY ENDED THE TRIALS...
- UH-HUH.

WELL, WE WERE CUSSING.

WE ACTUALLY WERE ANGRY.

I KEPT SAYING, "OH, THAT
WAS A MOSQUITO IN FRANCE.

IT DOESN'T HAVE ANYTHING
TO DO WITH THIS VACCINE."

BUT I THINK BACK,
AND I KEPT SAYING

TO EVERYONE WHO ASKED,
"SO HOW'S EARL DOING?"

I WOULD SAY, "HE'S
MAINTAINING. HE'S MAINTAINING."

- AND THAT WAS REALLY IMPORTANT.
- YEAH.

BECAUSE YOU WERE
FUNCTIONING WELL AT THAT TIME.

- OH, YEAH.
- AND JUST TO STAY THERE WOULD HAVE BEEN A BLESSING.

BECAUSE IT WAS WORKING.

AND WE SAID THAT
FOR MANY MANY YEARS.

- YEAH.
- I'M THINKING BACK NOW...

WE PROBABLY FOR THREE
OR FOUR OR FIVE YEARS SAID,

"HE'S MAINTAINING.
EVERYTHING IS GOOD."

TO OUR AMAZEMENT,

IF YOU LOOK AT THE BOTTOM ROW
HERE AND COMPARE IT WITH THE TOP,

AT THE TOP IS THE TYPICAL
SORT OF PATHOLOGY

THAT ONE SEES IN PATIENTS
WHO HAVE ALZHEIMER'S DISEASE.

THE TOP THREE ARE BRAIN SECTIONS

WHERE THE BROWN
IS THE BETA-AMYLOID...

THE TYPICAL
PLAQUELIKE APPEARANCE.

ON THE BOTTOM IS THE
COMPARISON OF WHAT YOU SEE

AFTER THE PATIENT
HAS BEEN VACCINATED,

WHERE THERE'S BRAIN REGIONS

THAT ARE NEARLY COMPLETELY
VOID. THE PLAQUES ARE GONE.

WE ARE REALLY VERY
EXCITED THAT WE CAN REMOVE...

LITERALLY REMOVE AMYLOID
PLAQUES FROM PATIENTS

SUFFERING FROM
ALZHEIMER'S DISEASE.

AND AS WE MOVE FORWARD
NOW, WHAT THIS MEANS IS,

SINCE WE CAN DO IT, WE'RE
DELIVERING NEW TREATMENTS,

THINGS LIKE BAPINEUZUMAB,

WHICH IS A VERY LONG
WORD, A FANCY WORD

FOR A HUMAN ANTIBODY

THAT IS MOVING

THROUGH THE PROCESS
OF CLINICAL TRIAL.

INSTEAD OF THE PATIENT

HAVING TO MAKE THE
ANTIBODIES AND DO THE WORK,

WE'RE PROVIDING THE PATIENT
DIRECTLY WITH THE ANTIBODIES.

NOW THE GOOD PART ABOUT
DOING THIS IS THAT YOU CAN GIVE

EXACTLY THE AMOUNT AND THE
DOSE THAT YOU WANT TO GIVE.

IN OTHER WORDS, IT'S MUCH MORE
CONTROLLED WHEN YOU GIVE THE ANTIBODIES.

AND SO THAT'S WHAT
BAPINEUZUMAB IS.

ONCE IT'S IN THE BLOODSTREAM,

THE ANTIBODY WILL LAST
AS LONG AS THREE WEEKS.

Dr. Marwan Sabbagh: THIS IS
ONE OF THE LEADING DRUGS

THAT'S IN THE HORSE
RACE TO GET AN APPROVAL.

THIS IS THE END OF
THE PHASE II STUDY.

AND THE SPONSORS
ACTUALLY HAVE MOVED

THIS DRUG BAPINEUZUMAB
INTO PHASE III,

BECAUSE THEY ARE VERY
EXCITED ABOUT ITS PROGRESS.

Dr. Schenk: AND SO THAT
ANTIBODY CIRCULATES AROUND,

AND A LITTLE BIT OF
IT, THIS BAPINEUZUMAB,

GETS THROUGH INTO THE BRAIN.

AND IF THERE'S PLAQUES THERE,
IT WILL BIND TO THOSE PLAQUES

AND NEUTRALIZE THEM

OR STIMULATE THE
CLEARANCE OF THEM.

DR. GARGAS WAS A SURGEON IN
WISCONSIN FOR MANY MANY YEARS.

WELL, YEAH.

I THINK I'M VERY...

I WALKED INTO

SOMETHING THAT WAS VERY GOOD.

OUR DECISION TO
PARTICIPATE IN THE TRIAL

SEEMED LIKE A NO-BRAINER.

IF WE COULD DO ANYTHING
TO HELP OUR FAMILIES,

AND ALL THE OTHER
FIVE MILLION FAMILIES

OF THE PEOPLE
AFFECTED BY ALZHEIMER'S,

IT'S THE LEAST WE CAN DO.

AND WE HOPE FOR GOOD RESULTS.

I THINK ONE OF THE FEW THINGS
THAT EXPERIENCE CAN TEACH YOU

IS YOU ACTUALLY GET A SENSE

FOR WHEN THE
SCIENCE IS VERY RICH.

AND IT'S A MAGICAL TIME.

AND IT DOESN'T
HAPPEN VERY OFTEN.

AND I THINK THE FIELD
IS AT THAT POINT...

THE DIAGNOSTIC TOOLS,

THE UNDERSTANDING OF THE
DISEASE AT SO MANY LEVELS.

ACTUALLY, PERHAPS THE
MOST IMPORTANT THING IS

THAT THE BIOLOGY AND THE
CLINICAL UNDERSTANDING

ARE, AS WE SPEAK, GETTING
PUT TOGETHER AT LAST.

IT'S FINALLY GETTING
PUT TOGETHER.

AND WE'RE GONNA SEE REAL
TREATMENTS HAPPEN AS A RESULT OF THAT.

IT'S A MAGIC TIME. IT'S
A MAGICAL TIME FOR US.

AND WE REALLY HOPE

THE PATIENTS ARE
GONNA BENEFIT FROM THIS.

Dr. Bateman: WE THINK
THAT THESE DRUGS

THAT ARE COMING
THROUGH THE CLINICAL TRIALS

HAVE A VERY GOOD CHANCE

OF REALLY CHANGING THE
COURSE OF ALZHEIMER'S DISEASE.

Dr. Morris: THERE IS HOPE.

AND WE WANT TO MAKE A COMMITMENT

TO SEEING IF WE CAN'T
PREVENT THE ILLNESS.

INTERNATIONAL CONFERENCE
ON ALZHEIMER'S DISEASE.

Dr. DeKosky: IF WE COULD
ACTUALLY DELAY IT 10 YEARS,

WE COULD WIPE OUT
MOST OF THE DISEASE

IN THE COUNTRY, IN THE WORLD.

BUT I THINK FOR ALL OF THIS,
WE WILL NEED MORE ENERGY,

MORE PEOPLE, MORE PROGRAMS,

MORE FUNDING TO
SUPPORT THESE EFFORTS.

IT REALLY MATTERS
TO ME THAT SOMEDAY

I'M GONNA TAKE A PRESCRIPTION
PAD OUT OF MY DRAWER

AND WRITE A PRESCRIPTION

THAT'S GONNA PREVENT YOU
FROM GETTING ALZHEIMER'S DISEASE.

Dr. Hodes: OUR COMMITMENT
IS TO PURSUE AND ANSWER

AS RAPIDLY, AS
EXPEDITIOUSLY AS WE CAN,

SO THAT WE MINIMIZE
THE PROBABILITY

THAT A FEW YEARS FROM NOW
SOMEONE ELSE IS GONNA TURN

AND ASK US THE
VERY SAME QUESTION,

"WHY IS IT WE STILL
DON'T HAVE THE ANSWER?"

( instrumental music playing )