The Alzheimer's Project (2009–…): Season 1, Episode 3 - Momentum in Science - full transcript

I THINK FORGETTING SO MANY THINGS...

I HAVE PROBLEMS EVERY DAY WITH SOMETHING.

I CAN STILL COOK,

BUT I SOMETIMES FORGET
TO PUT AN INGREDIENT IN.

I MADE A...

A PUMPKIN PIE FOR
HIM THE OTHER DAY.

AND JUST BEFORE I
PUT IT IN THE OVEN...

I LICKED MY FINGER,

AND I COULD TELL THAT
THERE WAS NO SUGAR IN IT.

THERE... THERE ARE DAYS

WHEN I WAKE UP
AND I DON'T KNOW IF I...



OR WHEN MORNING COMES,

I'M NOT SURE WHETHER
I'VE BEEN ASLEEP AT ALL.

I DON'T KNOW WHAT IT IS.

I DON'T KNOW WHAT TO CALL IT.

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.

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.

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.

WE DO HAVE
THE RESEARCH SCIENTISTS.

WE DO HAVE THE KNOWLEDGE.

AND I THINK WE CAN BEAT
ALZHEIMER'S DISEASE.

ALZHEIMER'S DISEASE
DESTROYS NERVE CELLS,

AND IT DESTROYS NERVE CELLS

IN THE BRAIN REGIONS

THAT CONTROL THE FEATURES

THAT GIVE US OUR
HUMAN QUALITIES.

OKAY, SOME
OF THE QUESTIONS

THAT I ASK TODAY MAY
BE TOUGHER THAN OTHERS.

AND THE REASON THAT WE ASK
QUESTIONS THAT ARE TOUGH IS

WE WANT TO STRAIN YOUR MEMORY.

WE WANT TO FIND OUT

WHERE ANY MEMORY AND
THINKING PROBLEMS MIGHT BE.

AND IF THE QUESTIONS
WERE ALL VERY EASY,

YOU'D BE ABLE TO ANSWER THEM
AND WOULDN'T BE ABLE TO PICK UP

IF THERE WAS ANY KIND
OF A MEMORY CHANGE.

I'M GONNA READ YOU A SHORT STORY

OF ABOUT FOUR OR FIVE LINES.

"THE AMERICAN LINER, NEW YORK,

STRUCK A MINE NEAR
LIVERPOOL MONDAY EVENING.

IN SPITE OF A BLINDING
SNOWSTORM AND DARKNESS,

THE 60 PASSENGERS,
INCLUDING 18 WOMEN,

WERE ALL RESCUED,

THOUGH THE BOATS
WERE TOSSED ABOUT

LIKE CORKS IN THE HEAVY SEA.

THEY WERE BROUGHT
INTO PORT THE NEXT DAY

BY A BRITISH STEAMER."

TELL ME WHAT YOU CAN RECALL.

THEY'RE NOT THINGS
I CAN REMEMBER.

I CAN REMEMBER
LIVERPOOL.

OKAY.

ANYTHING ELSE, MISS VASSE?

OKAY.

NOW I'M GONNA GIVE YOU
THE NAMES OF THREE OBJECTS.

THE THREE OBJECTS
ARE APPLE, TABLE, PENNY.

APPLE, TABLE, PENNY.

PLEASE WRITE A SENTENCE FOR ME.

IT CAN BE ANY
SENTENCE THAT YOU WISH.

THANK YOU.

WHAT WERE THOSE THREE WORDS

THAT I ASKED YOU TO
REMEMBER FROM EARLIER?

ONE OF THEM WAS APPLE.

YES.

WAS PEAR ONE OF THEM?

OKAY.

THE THIRD ONE... NO IDEA.

NOW YOU SIT RIGHT HERE.

SO WHO DOES THE SHOPPING...
GROCERY SHOPPING?

- JUNE DOES.
- AND HOW DOES SHE DO?

SOMETIMES SHE EITHER FORGETS
TO BRING THE LIST WITH HER,

OR SHE COMES HOME AND SHE FINDS

THAT SHE HAS NOT BOUGHT
EVERYTHING THAT IS ON HER LIST.

- MISSED SOME ITEMS ON THE LIST?
- YEAH.

WHERE WAS THANKSGIVING
DINNER THIS YEAR?

AT BASIL'S HOUSE.

BASIL IS THE MIDDLE BROTHER.

- OKAY.
- IN SPRINGFIELD, OHIO.

MRS. VASSE, PLEASURE TO
MEET YOU. HOW ARE YOU?

WELL, NOT AS WELL AS I'VE
BEEN OTHER TIMES.

PLEASE HAVE A SEAT FOR ME.

YOUR HUSBAND TOLD
ME YOU GO BACK TO OHIO,

AND YOU WERE THERE
FOR THANKSGIVING MAYBE.

I DON'T THINK SO. BUT
I COULD HAVE BEEN.

WHERE DID YOU
SPEND THANKSGIVING?

JUST AT HOME.

JUST YOU AND YOUR HUSBAND?

YES, IF I...

IT'S POSSIBLE I WENT
BACK THERE AND...

DO YOU REMEMBER?

NOT FOR SURE.

THE AREA THAT YOU
ARE CONCERNED ABOUT...

THE MEMORY... IS DOWN,

SHORT-TERM MEMORY
IN PARTICULAR, OKAY?

MANY PEOPLE SAY, "WELL,
GEE, I'M GETTING OLDER.

CAN'T AGE HAVE SOMETHING TO
DO WITH IT... JUST NORMAL AGING?"

BUT WHAT YOU HAVE, I
THINK, IS MORE THAN THAT.

SO I DON'T THINK WE CAN SAY

THAT THIS IS SIMPLY A
MATTER OF GETTING OLDER.

WHAT WE WORRY ABOUT MOST,

BECAUSE IT'S THE MOST
FREQUENT, IS ALZHEIMER'S.

BUT IT'S BY FAR
NOT THE ONLY ONE.

THERE ARE OTHER KINDS
OF CONSIDERATIONS.

BUT WHAT I REALLY THINK
WE NEED TO DO AS WELL

IS TO GET A SENSITIVE
IMAGE OF THE BRAIN...

M.R.I. SCAN.

I JUST WANT TO LET YOU KNOW

WE'RE NOT GONNA
SIT BY PASSIVELY.

THERE ARE THINGS THAT
WE CAN DO TO BE PROACTIVE.

OKAY?

IT'S TOUGH TO IMAGINE HER NOT...

NOT ENJOYING

THE REST OF HER LIFE

LIKE I WOULD LIKE
TO SEE HER ENJOY,

AND LIKE I BELIEVE
SHE WOULD LIKE TO.

THE HUMAN BRAIN PRESENTS
VERY SPECIAL CHALLENGES.

AND SOLVING A DISEASE

OF OUR MOST HUMAN QUALITIES...

THE ABILITY TO REASON
AND THINK AND CONTEMPLATE,

AND USE ABSTRACT THOUGHT...

IT'S A CHALLENGE TO FIGURE OUT

HOW THAT GOES WRONG
IN CERTAIN REGIONS,

IN CERTAIN SYNAPSES
WITHIN THE BRAIN.

HERE IS A SYNAPSE THAT IS
TRANSMITTING INFORMATION...

THIS FLASH OF
LIGHT THAT YOU SEE.

THE SYNAPSES ARE SO IMPORTANT.

THEY'RE THE INFORMATION
SWITCHES IN OUR BRAIN.

AND WHEN THEY'RE
NOT WORKING PROPERLY,

WE SIMPLY CAN'T REMEMBER.

IN ALZHEIMER'S DISEASE,
THE SYNAPSE GOES COLD.

IT NO LONGER CAN
TRANSMIT INFORMATION,

AND THE ACTUAL SYNAPSE DIES OUT.

AND THAT'S WHAT HAPPENS IN
THE ALZHEIMER'S PATIENT'S BRAIN.

IN THE CLINIC, WE
SEE SYNAPTIC FAILURE.

SO THESE CLOCKS ARE EXAMPLES

OF WHAT I ASK MY
PATIENTS TO DO...

"CAN YOU DRAW A CLOCK...
THE FACE OF A CLOCK,

AND PUT THE HANDS
IN SO IT READS 4:45?"

AND MY PATIENTS
DO DIFFERENT THINGS.

HERE THIS PATIENT PUTS IN THE
HANDS INCORRECTLY FOR 4:45.

THIS MORE ADVANCED
ALZHEIMER'S PATIENT

CAN ONLY PUT A SIMPLE BOX

AROUND THE NUMBERS
FOUR AND FIVE.

THIS PATIENT IS VERY ADVANCED,

AND SHE REALLY HAS SUCH
SEVERE ALZHEIMER'S DISEASE

THAT SHE CAN'T REALLY
PUT A CLOCK TOGETHER.

IN THE PATIENT'S BRAIN

WE SEE THESE
CLASSICAL ABNORMALITIES

THAT ALZHEIMER HIMSELF
DESCRIBED WAY BACK IN 1906.

SO THIS IS A HIGH-POWER VIEW

OF A LITTLE PART OF
THE BRAIN OF A PATIENT

WHOM I FOLLOWED DURING LIFE.

THIS WAS A 69-YEAR-OLD GENTLEMAN

WHO HAD A FAMILY
HISTORY OF ALZHEIMER'S

AND DIED AFTER ABOUT
10 YEARS OF DISEASE.

AND WHEN I TOOK THE BRAIN
OUT AND MADE THIS PICTURE,

WE SAW TWO SPHERICAL
DEPOSITS OF PROTEIN

CALLED "AMYLOID PLAQUES."

AND THEY'RE
COMPOSED OF A PROTEIN

THAT WE CALL
"AMYLOID BETA PROTEIN,"

SOMETIMES CALLED
"BETA-AMYLOID" OR A "BETA."

AND SURROUNDING THESE PLAQUES

ARE DEGENERATING SYNAPSES

AND NERVE ENDINGS.

ADJACENT TO THE PLAQUES

ARE "TAU TANGLES."

THESE ARE BIG
CONGLOMERATIONS OF PROTEIN

THAT SHOULDN'T BE THERE.

SO ALZHEIMER BROUGHT
THIS TO LIGHT IN 1906

AND SAID THAT IN THE PATIENT

WHO DIES OF A PROGRESSIVE
MEMORY FAILURE OF A CERTAIN TYPE,

YOU WILL SEE PLAQUES
AND TANGLES IN THE BRAIN.

AND EVER SINCE HIS DAY,

WE'VE BEEN STRUGGLING
TO FIGURE OUT

HOW THESE TWO RELATE TO EACH
OTHER AND WHAT IT ALL MEANS.

WHAT WE'VE KNOWN FOR A LONG
TIME IS THAT THIS AMYLOID PLAQUE

IS A STICKY SUBSTANCE.
IT'S VERY HARD TO DIGEST.

WHEN ALL THE OTHER PROTEINS
AND ALL THE OTHER CELLS IN THE BRAIN

ARE BROKEN DOWN, WHAT
REMAINS IS THESE AMYLOID PLAQUES.

GO AHEAD AND LEAN FORWARD
FOR ME AS FAR AS YOU CAN GO.

- GOOD.
- DOES IT HELP IF I HOLD ON TO YOU?

- THAT'S FINE.
- YEAH, THAT WOULD BE GOOD.

ALL RIGHT, JUST LIKE LAST TIME,

THERE'S GONNA BE A LITTLE BIT
OF A PINCH AND A BURN HERE, OKAY?

THAT'S THE NUMBING MEDICINE.

WHEN YOU FEEL THE
PINCH, DON'T MOVE.

HOW MANY YEARS HAVE YOU
BEEN AN ELECTRICIAN FOR?

40 SOMETHING.

IN THIS KIND OF STUDY
WHAT WE'RE DOING IS

WE'RE HAVING PEOPLE WHO
HAVE ALZHEIMER'S DISEASE,

THEY COME INTO THE STUDY

AND THEY HAVE THIS
SPINAL CATHETER PLACED

SO THAT WE CAN SAMPLE
CEREBRAL SPINAL FLUID

ONCE AN HOUR FOR 36 HOURS.

AND THE PURPOSE OF MEASURING ALL
THESE SAMPLES OVER ALL THOSE HOURS

IS TO GET A MEASUREMENT
OF THE SPEED

AT WHICH AMYLOID BETA'S
PRODUCED BY THE BRAIN,

AND HOW QUICKLY THAT
AMYLOID BETA'S CLEARED AWAY.

CEREBRAL SPINAL FLUID...

THIS IS THE STUFF THAT
SURROUNDS YOUR BRAIN

AND YOUR SPINAL
CORD, FLOWS THROUGH.

YOU KNOW, YOU MAKE 20 MILS OF THIS
AN HOUR, EVERY HOUR OF YOUR LIFE?

- PRETTY NEAT.
- YEAH.

IT'S VERY DIFFICULT TO GET
ACCESS TO A HUMAN BRAIN.

AND SO ONE KEY
ACCESS WE HAVE TO IT

IS THE CEREBRAL SPINAL FLUID.

THIS FLUID REFLECTS
WHAT'S GOING ON IN THE BRAIN.

AND THAT'S WHERE THE
AMYLOID BETA ENDS UP.

SO WE'RE GONNA BE ANALYZING
THAT VERY CAREFULLY.

WHY IS THIS AMYLOID
BETA DEPOSITING

IN THESE STICKY AMYLOID PLAQUES

AND DOING DAMAGE TO THE NEURONS?

WHY IS IT KILLING
THE NEURONS OFF

AND DESTROYING THE SYNAPSES?

NOW WHAT'S RECENTLY
BEEN DISCOVERED

IS THAT THE PROTEIN WHERE
AMYLOID BETA COMES FROM

EXISTS IN NEURONS MOSTLY AT
THE SYNAPSES, WHERE IT'S CUT.

IT'S POSSIBLE THAT WHEN THE
NEURON FIRES AT THE SYNAPSE

TO COMMUNICATE WITH
ITS NEIGHBORING NEURON,

IT'S PRODUCING
MORE BETA-AMYLOID.

AND SO NEURONS FIRE

ANYWHERE FROM ONE
UP TO 100 TIMES A SECOND.

AND SO EVERY SECOND
THAT NEURON'S ALIVE,

IT'S PRODUCING PACKETS,
AMOUNTS OF THIS BETA-AMYLOID

INTO THE OUTSIDE
SPACE OF THAT NEURON.

YOUNG, HEALTHY PEOPLE PRODUCE
AND CLEAR THEIR AMYLOID BETA.

IN ALZHEIMER'S DISEASE, WE
THINK SOMETHING GOES AWRY.

WE THINK EITHER THEY'RE PRODUCING
TOO MUCH OF THIS BETA-AMYLOID,

OR THEY'RE CLEARING
IT AWAY TOO SLOWLY,

SO THAT THOSE PROCESSES
ARE NOW OUT OF BALANCE.

IF IT'S NOT CLEARED AWAY,
THIS BETA-AMYLOID BUILDS UP

INTO THE LARGER STRUCTURES

THAT WE CALL THE
"AMYLOID BETA PLAQUES"

THAT APPEAR TO BE TOXIC
TO NEURONS AND SYNAPSES.

YOU CAN SEE HERE

THESE NEURONS GET
SICKER AND SICKER.

THEY LOSE CONNECTIONS
TO EACH OTHER,

SO THAT THEY CAN'T
COMMUNICATE ANYMORE.

AND EVENTUALLY
THESE NEURONS WILL DIE.

AND WHEN ENOUGH NEURONS DIE

AND ENOUGH SYNAPSES
ARE LOST IN THE BRAIN,

THAT LEADS TO THE
CLINICAL SYMPTOMS

OF DEMENTIA AND
ALZHEIMER'S DISEASE.

ANYTHING WE CAN DO TO LOWER
DOWN THE LEVELS OF AMYLOID BETA

WE THINK IS LIKELY TO
HELP ALZHEIMER'S DISEASE.

AND THAT'S WHY TARGETING
THIS BETA-AMYLOID

AND LOWERING DOWN ITS PRODUCTION

IS A KEY STEP TOWARDS THE
TREATMENT OF ALZHEIMER'S DISEASE.

FROM THE DAYS OF
SHAKESPEARE AND BEFORE,

SENILITY'S BEEN WELL-DESCRIBED.
IT'S THROUGHOUT HISTORY.

AND FOR THE FIRST
TIME WE ACTUALLY...

MOST OF US THINK THAT
WE HAVE A GOOD CHANCE

OF CHANGING THAT COURSE.

OKAY, I HAVE THE BRAIN OUT.

THIS WAS A MAN IN HIS 80s.

HE HAD A CLINICAL DIAGNOSIS
OF ALZHEIMER'S DISEASE,

SO HE HAD DEMENTIA

THOUGHT TO BE DUE
TO ALZHEIMER'S DISEASE.

WE WANT TO GET THAT
BRAIN OUT AS SOON AS WE CAN,

IN ORDER TO FREEZE
THAT BRAIN CHEMISTRY

JUST THE WAY IT WAS DURING LIFE.

JUST A QUICK, GROSS EXAM.

THE BRAIN WEIGHT WAS 1100g,

AND THAT IS A LITTLE
LOW FOR A MALE.

ALSO, HERE, THE HIPPOCAMPUS
HAS A MILD DEGREE OF SHRINKAGE.

AND THAT IS CHARACTERISTIC
OF ALZHEIMER'S DISEASE...

THAT SHRINKAGE OF
THE HIPPOCAMPUS.

THE PREEXISTING DOMINANT
THEORY OF ALZHEIMER'S CAUSATION,

WHICH IS THAT ALZHEIMER'S IS
CAUSED BY THE ACCUMULATION

OF A SINGLE PROTEIN
CALLED "A BETA" IN THE BRAIN...

TOO MUCH OF THIS
PROTEIN IS MADE...

A CHEMICAL REACTION GONE BAD.

TOO MUCH OF THIS
PRODUCT IS MADE.

TOO MUCH A BETA IS MADE.
IT DEPOSITS IN THE BRAIN,

AS THOSE AMYLOID PLAQUES

THAT WE SEE UNDER
THE MICROSCOPE.

THIS IS THE DOMINANT THEORY OF
ALZHEIMER'S DISEASE CAUSATION.

AFTER SOMEONE DIES,
BRAIN CHEMISTRY CHANGES.

MOLECULES DECAY.

THAT'S WHY WE WANT
TO GET THE BRAINS

OUT OF THE PERSON VERY QUICKLY

AND INTO THIS -80°
CELSIUS FREEZER,

WHERE WE FREEZE THE
CHEMISTRY FOR DECADES.

DISEASES ARE, IN ESSENCE,
CHEMICAL REACTIONS GONE BAD.

THAT'S WHAT THE RESEARCHERS
ARE DOING WITH THE TISSUE...

THEY TAKE A PIECE OF
TISSUE, TRY AND ANALYZE

ALL THE CHEMICAL
REACTIONS IN THE TISSUE...

A TOUGH JOB.

BUT IF THEY CAN DO IT,

THEY CAN IDENTIFY THE
BEGINNING OF THE DISEASE,

THE CHEMICAL
REACTION THAT WENT BAD.

THEN THEY CAN DEVISE A
DRUG, WHICH IS A CHEMICAL TOO.

A DRUG IS A CHEMICAL THAT CAN
GO INTO A CHEMICAL REACTION

AND EITHER SPEED IT
UP OR SLOW IT DOWN...

JUST WHAT'S NEEDED.

I'M GONNA GO IN HERE AND LOOK

- AND SEE WHAT I CAN FIND.
- FOR DINNER?

MM-HMM, SEE WHAT I
CAN FIND FOR DINNER.

MIGHT BE LOOKING A LONG TIME.

ALZHEIMER'S IS

LIKE BEING IN AN
EXTREMELY BRIGHT LIGHT,

AND THE LIGHT JUST
SLOWLY FADES TO DARK.

AND THEN THERE'S NOTHING.

SHE SAYS I HAVE ALZHEIMER'S.

THIS IS A FAMILY
PORTRAIT OF MY MOTHER

AND ALL OF HER
BROTHERS AND SISTERS,

HER FATHER, HER STEPMOTHER.

THIS IS WILLIE... MY MOTHER.

AND THIS IS WILLIE
BELLE... HER SISTER.

SHE HAD ALZHEIMER'S.

THIS IS HER TWIN.
HIS NAME IS WILLIAM.

AND FOR THE MOST PART HE'S OKAY,

BUT I HAVE MY SUSPICIONS.

WHAT I WANT TO KNOW
ABOUT ALZHEIMER'S IS,

IS IT HEREDITARY?

WHAT CAN WE DO TO STOP IT?

THIS IS S A TIME WHEN THE
SCIENTIFIC OPPORTUNITIES

ARE ENORMOUSLY
EXCITING, UNPRECEDENTED.

IN THE AREA OF ALZHEIMER'S
DISEASE RESEARCH,

FOR EXAMPLE, OVER
THE PAST FEW YEARS

WE'VE LEARNED ABOUT GENES

THAT CAN PREDISPOSE
TO ALZHEIMER'S DISEASE,

THE WAY IN WHICH THE
MOLECULES COATED BY THESE GENES

ARE LIKELY TO BE
DEVELOPING INTO THE PROCESS.

WE'VE LEARNED ABOUT
THE HUMAN GENOME

AND ARE NOW ABLE, AS WE COULD
NEVER HAVE IMAGINED BEFORE,

TO ACTUALLY SEARCH ALL
THE GENES IN THE GENOME

FOR ANY OF THOSE GENES

WHICH MIGHT INFLUENCE THE
PROCESS OF ALZHEIMER'S DISEASE,

PROVIDE NEW UNDERSTANDING
AND NEW CLUES,

IN AN EFFORT TO
IDENTIFY NEW GENES

WHICH AFFECT THE
LIKELIHOOD, THE RISK,

THE PROBABILITY OF
GETTING ALZHEIMER'S DISEASE.

ONE
OF THE THINGS THAT GENETICS

CAN BRING TO
ALZHEIMER'S RESEARCH

IS UNDERSTANDING THE VERY
FIRST EVENT THAT OCCURS...

WHAT HAPPENS IN A CELL
THAT'S FUNCTIONING NORMALLY,

AND THEN SOMETHING HAPPENS,

AND NOW IT STARTS TO FUNCTION
JUST A LITTLE BIT INCORRECTLY,

JUST A LITTLE BIT NOT OPTIMALLY,

AND THAT LEADS TO ALZHEIMER'S.

DOING GENETICS AT THE
BEGINNING, WE HAD THESE

EARLY-ONSET FAMILIES...
FAMILIES WHERE EACH INDIVIDUAL

WHO WAS A DESCENDENT OF
SOMEBODY WITH THE DISEASE

HAD A 50/50 CHANCE OF
GETTING THE DISEASE.

THE FIRST GENE
THAT WAS IMPLICATED

IN THE GENETICS OF ALZHEIMER'S
AND ALZHEIMER'S DISEASE

IS THE GENE THAT
MAKES THE PROTEIN

THAT ENDS UP IN THE PLAQUES.

AND IF YOU HAVE A
MUTATION IN THAT GENE,

YOU GET ALZHEIMER'S VERY EARLY...

IN THE MID-40s TO MID-50s...

A VERY SEVERE FORM
OF ALZHEIMER'S DISEASE.

WHAT THAT SHOWED IS IF YOU
HAVE A MUTATION IN THAT GENE,

YOU GET ALZHEIMER'S.

YOU HAVE A MUTATION
IN THAT GENE.

THAT GENE MAKES THE PROTEIN
THAT ENDS UP IN THE PLAQUE.

YOU'VE GOT THIS DIRECT
CAUSE-AND-EFFECT PROOF

THAT YOU HAVE TO PAY ATTENTION TO
THAT PROTEIN THAT'S IN THAT PLAQUE.

SO WE FOCUSED ON THOSE
EARLY-ONSET FAMILIES

BECAUSE WE REALLY KNEW
HOW TO HANDLE THOSE.

WE KNEW HOW TO DO THE
SCIENCE TO FIND THE GENES.

THE LATE-ONSET HAS
BEEN MUCH MORE DIFFICULT.

THE VAST MAJORITY OF
PEOPLE HAVE LATE-ONSET.

THAT'S MUCH MUCH MORE COMMON.

GETTING HARD TO DO, HUH?

MM-HMM.

SOMETIMES I FORGET THINGS.

ARE YOU BEING TREATED FOR IT?

I DON'T KNOW. AM I?

MM-HMM.

YOU TAKE TWO MEDICINES
FOR IT... ALZHEIMER'S.

HAVING A FAMILY
HISTORY OF ALZHEIMER'S,

YOU WONDER CONSTANTLY

IF YOU'RE GONNA HAVE IT,
WHEN YOU'RE GONNA HAVE IT.

AND YOU CERTAINLY
DON'T WANT TO HAVE IT.

THE WAY WE THINK OF LATE-ONSET
ALZHEIMER'S IN TERMS OF GENETICS

IS WE THINK THAT THERE ARE
A LOT OF DIFFERENT GENES

THAT MAKE VERY
SMALL CONTRIBUTIONS

TO WHETHER YOU'RE GONNA
GET THE DISEASE OR NOT.

WE CALL THESE
"SUSCEPTIBILITY FACTORS."

NO ONE SINGLE
SUSCEPTIBILITY GENE

MAKES THAT BIG OF A DIFFERENCE

WHETHER YOU'RE
GONNA GET IT OR NOT.

BUT IF YOU HAVE FIVE OR
10 SUSCEPTIBILITY GENES,

AND YOU'VE GOT THE BAD
FORM OF ALL FIVE OR 10,

THAT'S GONNA INCREASE YOUR RISK.

WE DO HAVE ONE WELL-DEFINED
SUSCEPTIBILITY GENE

CALLED ApoE, OR
APOLIPOPROTEIN E.

SO RIGHT AWAY WE HAVE A
PATHWAY... A CHOLESTEROL PATHWAY

THAT WE IMPLICATE IN
ALZHEIMER'S DISEASE.

THAT'S SOMETHING WE CAN USE.

THAT'S ONE SUSCEPTIBILITY GENE.

THIS TECHNOLOGY THAT WE'RE
USING IS JUST PHENOMENAL.

AND IT'S REALLY CAUSED
GENETICS OF LATE-ONSET

TO REALLY EXPLODE
IN THE LAST FEW YEARS.

THE D.N.A. IS PUT ON
THESE VERY TINY CHIPS

THAT HAVE 500,000
TO A MILLION SPOTS

THAT LOOKS AT 500,000
TO A MILLION SITES

IN THAT PERSON'S D.N.A.

GENOME-WIDE ASSOCIATION
STUDIES ARE DESIGNED

TO GIVE US MANY MORE
SUSCEPTIBILITY GENES.

AND EACH ONE OF THOSE
WE HAVE TO LOOK AT AND SAY,

"IS THIS A GOOD DRUG
TARGET? IS THIS THE ONE

WE WANT TO REALLY FOCUS A
LOT OF MONEY AND ATTENTION ON?"

YOU KNOW, I THINK WE'RE A YEAR
OR TWO AWAY FROM AT LEAST HAVING

OUR FIRST CROP OF THESE
GENES COME THROUGH.

THE MORE SUSCEPTIBILITY
GENES YOU HAVE,

THE MORE CANDIDATES FOR
DRUG TARGETS YOU HAVE,

AND THE BETTER CHANCE
YOU'LL FIND ONE THAT...

"THIS IS A GOOD ONE.
WE'RE GONNA AIM AT IT.

WE'RE GONNA PUT A
LOT OF MONEY INTO IT

AND SEE IF WE CAN
PREVENT THE DISEASE."

AS PEOPLE GET OLD,

EVERYBODY'S RISK
GETS PRETTY HIGH.

SO ONE THING IS IF YOUR PARENT

HAD ALZHEIMER'S
IN THE EARLY 80s,

LIKE MY DAD DID, THAT'S
PROBABLY NOT THAT ATYPICAL.

SO SOMEBODY GETTING
ALZHEIMER'S THAT LATE,

AS A GENETICIST, I THINK
MAYBE HE DIDN'T HAVE

THAT MANY SUSCEPTIBILITY GENES;

THEREFORE, I PROBABLY
MIGHT NOT HAVE

THAT MANY SUSCEPTIBILITY GENES.

SO I'M NOT REALLY THAT
WORRIED ABOUT MY RISK.

BECAUSE IT IS... YOU KNOW,
THE ONSET IS SO LATE.

AND REALLY, MOST
ALZHEIMER'S ONSET

TYPICALLY IS LATE
70s, EARLY 80s.

THAT'S WHEN THE MOST
PEOPLE START TO GET IT.

IT SCARES
ME. IT REALLY SCARES ME

WHEN YOU HAVE SOMEONE
THAT HAS ALZHEIMER'S.

BUT...

THAT'S THE HARDEST
PART RIGHT THERE,

BECAUSE IN A LOT OF WAYS

I FEEL LIKE I'VE ALREADY
LOST MY MOTHER.

SHE'S HERE PHYSICALLY,

BUT THAT'S NOT THE MOTHER

THAT I'VE KNOWN THE
MAJORITY OF MY LIFE.

IT'S OUR BELIEF THAT THERE
ARE SEVERAL PATHWAYS

TO DEVELOPING
ALZHEIMER'S DISEASE.

AND ONE OF THE MOST
PROMINENT PATHWAYS,

PARTICULARLY FOR THE
LATE-ONSET FORM OF THE DISEASE,

IS THROUGH FACTORS
RELATING TO INSULIN RESISTANCE.

INSULIN HAS A VERY
IMPORTANT ROLE TO PLAY

IN AGING OF THE BODY

AS WELL AS AGING OF THE BRAIN.

IN FACT, ONE OF THE MOST
IMPORTANT PREDICTORS

OF HOW SUCCESSFULLY YOU'LL AGE

IS HOW INTACT YOUR INSULIN
SYSTEM REMAINS AS YOU AGE.

SO INSULIN IS PRODUCED
EVERY TIME YOU EAT.

IT'S THE PEPTIDE, WHICH
IS A SMALL PROTEIN.

AND IT'S PRODUCED
IN THE PANCREAS

IN RESPONSE TO GLUCOSE.

GLUCOSE IS THE PRIMARY FUEL

FOR ALL CELLS IN THE BODY,

AS WELL AS IN THE BRAIN.

BUT IT NEEDS INSULIN
IN ORDER TO BE ABLE

TO BE TRANSPORTED INTO
THE CELLS TO DO ITS WORK.

IF INSULIN CANNOT ALLOW GLUCOSE

TO GET INTO NEURONS,

THEN THEY'RE NOT ABLE TO
CARRY OUT THEIR FUNCTIONS

RELATING TO THINKING

AND MEMORY AND
ATTENTION EFFECTIVELY.

WHEN INSULIN IS NOT
WORKING CORRECTLY

AND GLUCOSE BUILDS
UP OUTSIDE THE CELL,

THAT PROCESS INITIATES
INSULIN RESISTANCE.

INSULIN RESISTANCE

LEADS DIRECTLY TO
CARDIOVASCULAR DISEASE.

IT LEADS TO HYPERTENSION.

IT LEADS TO SMALL
VESSEL STROKES.

AND IT LEADS TO DIABETES.

SO IT IS THE UNIFYING
UNDERLYING PATHOLOGY

FOR ALL OF THOSE RISK FACTORS,

EACH OF WHICH, AS WE KNOW,

CONTRIBUTES TO THE RISK
OF ALZHEIMER'S DISEASE.

WITH LACK OF ACTIVITY

AND CHANGES IN OUR DIET,

INSULIN RESISTANCE IS BEGINNING

EARLIER IN LIFE THAN
WE MIGHT APPRECIATE.

WE BELIEVE IT STARTS IN MIDLIFE.

AND THIS IS A PERIOD
IN WHICH MANY PEOPLE

BEGIN TO EXPERIENCE
OBESITY AND BODY-WEIGHT GAIN

AND OTHER METABOLIC CHANGES.

AND IT'S THE TIME AT
WHICH INSULIN RESISTANCE

AND HIGH LEVELS OF INSULIN
ALSO BECOME APPARENT.

SIMULTANEOUSLY, WE BELIEVE,

BETA-AMYLOID IS INCREASING,

IN LARGE PART BECAUSE
OF THESE CHANGES

IN INSULIN RESISTANCE
AND INSULIN.

AND AS A RESULT WE SEE
SYMPTOMS BEGIN TO OCCUR,

PROBLEMS WITH MEMORY,

WHICH WORSEN OVER TIME

UNTIL A PERSON
MIGHT BE ON THEIR WAY

TO DEVELOPING
ALZHEIMER'S DISEASE.

INSULIN RESISTANCE IS

IN MOST CASES
EMINENTLY TREATABLE.

AND THERE ARE A NUMBER
OF WAYS TO TREAT IT.

BY FAR THE MOST POTENT TREATMENT

OF INSULIN
RESISTANCE IS EXERCISE.

AEROBIC EXERCISE

IMPROVES INSULIN FUNCTION

DRAMATICALLY AND IMMEDIATELY.

SO ONE BOUT OF
AEROBIC EXERCISE...

A 30-MINUTE AEROBIC
EXERCISE PERIOD...

WILL IMPROVE YOUR INSULIN
FUNCTION FOR 24 HOURS.

AND THEN DIET
CERTAINLY PLAYS A ROLE.

SO A DIET THAT IS RICH

IN GOOD FATS AND
COMPLEX CARBOHYDRATES,

AND LOW IN BAD FATS
AND SIMPLE SUGARS

OFFERS SOME BENEFIT.

AND INTERESTINGLY, DOING
BOTH OF THOSE THINGS TOGETHER

SEEMS TO OFFER A
SYNERGISTIC BENEFIT.

IN THIS STUDY WE
ASK PARTICIPANTS

TO CONSUME A HIGH-FAT,
HIGH-SUGAR DIET

FOR A FOUR-WEEK PERIOD,

OR A LOW-FAT, LOW-SUGAR DIET

FOR THE SAME AMOUNT OF TIME.

WHEN YOU CONSUME A MEAL

THAT'S VERY HIGH
IN SATURATED FAT

AND HIGH IN SUGAR,

YOUR INSULIN LEVELS SKYROCKET.

AND THEY REMAIN ELEVATED

FOR A VERY LONG PERIOD OF TIME.

AND THIS IS A VERY
ABNORMAL STATE OF AFFAIRS.

INSULIN IS DESIGNED

TO RISE QUICKLY AFTER A MEAL

AND THEN BE CLEARED
VERY QUICKLY AS WELL.

AND THAT'S HOW IT WORKS BEST.

BUT THE SATURATED FAT

IMPAIRS THE
CLEARANCE OF INSULIN,

AND THE HIGH SUGAR CAUSES

THE INSULIN LEVELS TO SPIKE.

THE PARTICIPANTS
IN THE HIGH-FAT DIET

SHOWED INCREASED BETA-AMYLOID

IN THEIR SPINAL FLUID.

AND THE PARTICIPANTS
IN THE LOW-FAT DIET

IMPROVED THEIR PROFILE.

THEY HAD LOWER INSULIN LEVELS

AND LOWER LEVELS
OF BETA-AMYLOID.

SO EVEN FOUR
WEEKS OF EATING WELL

PRODUCED A BENEFIT
FOR THESE INDIVIDUALS.

SO I THINK WE'RE
AT THE BEGINNING

OF A VERY EXCITING ERA,

WHERE WE ARE GOING TO BE ABLE

TO START PUTTING
TOGETHER THESE SYSTEMS

AND UNDERSTAND A DISEASE
LIKE ALZHEIMER'S DISEASE,

WHICH IS CLEARLY, YOU KNOW,

A DISEASE OF THE
ENTIRE ORGANISM,

NOT JUST OF THE BRAIN.

IF YOU LOOK AT THE PATHOLOGY
OF ALZHEIMER'S DISEASE,

THAT SAME PATHOLOGY

THAT ALOIS ALZHEIMER
SAW 102 YEARS AGO...

YOU SEE MILLIONS OF MICROSCOPIC,

HIGHLY INERT,

ABNORMAL DEPOSITIONS
OF A MOLECULE CALLED

AMYLOID BETA
PEPTIDE, BETA-AMYLOID.

YOU KNOW, WHEN I LOOKED
AT THAT FIRST, I SAID,

"GOSH, THAT'S JUST GOTTA BE...

THAT'S GOTTA
STIMULATE INFLAMMATION."

I MEAN, IT'S LIKE HAVING SOMEONE

JUST THROWING
DIRT IN YOUR BRAIN.

SURELY, THAT WOULD
STIMULATE INFLAMMATION.

WHAT IS INFLAMMATION ABOUT?

WHAT IS... WHY DOES
YOUR BODY HAVE IT?

WELL, YOUR BODY USES
INFLAMMATION TO RID ITSELF

OF FOREIGN INVADERS AND
ABNORMAL MOLECULES AND TOXINS,

THINGS LIKE
BACTERIA AND VIRUSES.

THOSE STIMULATE INFLAMMATION

WHEN THEY'RE
PRESENT IN THE BRAIN,

OR ANYWHERE IN YOUR BODY
WHERE THEY SHOULDN'T BE.

AND INFLAMMATORY
MOLECULES AND CELLS

MOVE INTO THAT AREA AND ATTACK

AND CLEANSE THE BODY

OF THOSE FOREIGN INVADERS
OR FOREIGN MATERIAL.

AMYLOID BETA PEPTIDE
IS CLEARLY ABNORMAL.

IT'S ALMOST LIKE A
SPLINTER IN YOUR BRAIN.

AND YOU'VE GOT
THOUSANDS OF THEM.

AND SO YOU'RE GONNA HAVE
AN INFLAMMATORY ATTACK,

AS THE INFLAMMATORY
CELLS MOVE IN

AND TRY TO GET THAT
OUT OF THE BRAIN.

WE'VE STAINED THE AMYLOID
HERE WITH A BROWN STAIN.

AND LOOK IN THE
BELLIES OF THE MICROGLIA.

THEY'RE FULL OF THE AMYLOID.

THEY ACTIVELY EAT THIS STUFF UP.

AND THAT'S WHAT YOU WOULD EXPECT

IN AN EFFICIENT
INFLAMMATORY RESPONSE...

YOU ATTACK THINGS
AND YOU CLEAR THEM

AND REMOVE THEM FROM THE BODY.

OBVIOUSLY, IN THE
ALZHEIMER'S PATIENT

THIS MAY BE WORKING,

BUT IT'S NOT WORKING WELL ENOUGH

BECAUSE THE PATIENTS HAVE
THOUSANDS AND THOUSANDS

OF MICROSCOPIC AMYLOID DEPOSITS.

BUT WE SUSPECTED THAT
THIS PROCESS WAS ONGOING.

IT WAS JUST A TOUGH TOUGH
ASSIGNMENT FOR THE MICROGLIA,

BECAUSE, FOR ONE THING,
AMYLOID IS SO VERY INSOLUBLE.

INFLAMMATION IS ALWAYS
A TWO-HEADED SWORD.

IT DESTROYS, AND
THAT'S BENEFICIAL.

WHEN YOU HAVE FOREIGN INVADERS,

INFLAMMATION DESTROYS
THOSE FOREIGN INVADERS.

THE PROBLEM IS, IT
CAN ALSO DESTROY

HEALTHY TISSUE IN THE PROCESS.

SO YOU'VE GOT TO BE
VERY CAREFUL ABOUT THAT.

LET ME GIVE YOU AN EXAMPLE.
WHEN YOU CUT YOUR FINGER,

YOU MAY GET SOME DIRT
AND BACTERIUM IN THE CUT.

AND THE CUT THEN
BECOMES INFLAMED.

YOU HAVE INFLAMMATION AS
INFLAMMATORY MOLECULES AND CELLS

MOVE IN TO CLEANSE THE WOUND.

AND THAT'S HOW
INFLAMMATION DOES IT.

IT'S NOT MAGIC.

INFLAMMATION JUST
DESTROYS EVERYTHING IN SIGHT.

OVER TIME THIS IS
GOING TO, WE BELIEVE,

KILL A LOT OF BRAIN CELLS

AND, PARTICULARLY, A
LOT OF THE PROCESSES,

THE NERVE FIBERS THAT
CONNECT NERVE CELLS...

OVER TIME. IT WILL
TAKE SOME TIME

BECAUSE IT'S A
LOW-GRADE INFLAMMATION.

BUT WE THINK THAT IT IS
ONE OF THE MAJOR CAUSES

OF DAMAGE IN
ALZHEIMER'S DISEASE.

SO WHAT HAVE WE GOT HERE?

HERE WE GOT HAPPY NERVE
CELLS, A LOT OF CONNECTIONS.

AND THEY LOOK HAPPY
AS CLAMS. YOU'RE RIGHT.

I MEAN, YOU CAN SEE JUST
PROFUSE CONNECTIONS

BETWEEN THE NERVE CELLS.
THAT'S ONE OF THE THINGS

THAT WE KNOW THAT
NERVE CELLS LIKE TO DO,

IS MAKE CONNECTIONS
WITH EACH OTHER.

AND THEY DO THAT WHEN
THEY'RE HEALTHY AND HAPPY.

OKAY, SO WHAT IF WE PUT
THESE SAME NERVE CELLS

TOGETHER WITH MICROGLIA?

AND WHAT IF WE ADD
AMYLOID TO THIS MIX?

WHAT DO WE SEE?

AH, WOW.

THE MOST IMPORTANT
THING HERE IS,

THE CONNECTIONS
BETWEEN THE NERVE CELLS

THAT WERE SO
VIVID... THEY'RE GONE.

THIS PARALLELS VERY
CLOSELY, ACTUALLY,

WHAT IS SEEN IN THE
ALZHEIMER'S BRAIN.

IT HAS NOW BEEN CONFIRMED

BY THOUSANDS OF
LABORATORIES AROUND THE WORLD

THAT THIS INFLAMMATORY RESPONSE

IS ONGOING IN THE
ALZHEIMER'S BRAIN,

AND IT'S ONGOING FOR
YEARS AND YEARS AND YEARS.

THERE ARE A NUMBER

OF EMERGING ANIMAL
STUDIES, FOR EXAMPLE,

WHERE YOU GIVE TRANSGENIC
MICE, WHO ARE MADE TO HAVE...

GENETICALLY ENGINEERED
TO HAVE ALZHEIMER'S DISEASE

OR SOMETHING LIKE IT...

YOU GIVE THEM COMMON
ANTI-INFLAMMATORY DRUGS...

THEIR MEMORY
PROBLEMS ARE DECREASED

AND THEIR AMYLOID BURDEN,

THESE BETA-AMYLOID
DEPOSITS ARE DECREASED.

THERE ARE A NUMBER OF
STUDIES WHICH PROVIDE EVIDENCE

FOR THE IMPORTANCE OF INTERACTION
BETWEEN WHAT WE CALL ALZHEIMER'S DISEASE...

A DISEASE CHARACTERIZED BY
SPECIFIC LESIONS IN THE BRAIN,

SUCH AS PLAQUES AND TANGLES,

AND OTHER CONTRIBUTANTS
TO BRAIN FUNCTION...

FOR EXAMPLE, ABNORMALITIES IN
THE CEREBRAL VASCULAR SYSTEM,

THE BLOOD VESSELS OF THE BRAIN.

AND SOME OF OUR
IMPORTANT ONGOING STUDIES

ARE LOOKING PARTICULARLY
AT IMPACTS OF INTERVENING

TO MORE CLOSELY
REGULATE GLUCOSE LEVELS

IN INDIVIDUALS WITH DIABETES,

OR TO CONTROL LIPID LEVELS

IN PEOPLE AT RISK FOR
CARDIOVASCULAR DISEASE,

TO UNDERSTAND WHETHER
THIS SET OF INTERVENTIONS

MAY ALSO BE FUNCTIONALLY USEFUL

IN PREVENTING DEMENTIA
OR ITS PROGRESSION.

THERE'S ALREADY A GOOD DEAL
OF EVIDENCE THAT SUGGESTS

THAT THE CORONARY ARTERIES
IN ALZHEIMER'S DISEASE

HAVE MORE SEVERE ATHEROSCLEROSIS
THAN THE CORONARY ARTERIES

IN PEOPLE WHO DO NOT
HAVE ALZHEIMER'S DISEASE.

BUT WE WANT TO LOOK AT OTHER
ASPECTS OF THE HEART AS WELL.

FOR INSTANCE, WE WANT TO LOOK
AT THE EFFECTS OF HYPERTENSION.

HIGH BLOOD PRESSURE
CHANGES THE HEART.

BECAUSE OF HIGH BLOOD PRESSURE,

THE HEART HAS TO WORK HARDER.

AND AS THE HEART IS
ESSENTIALLY A MUSCLE,

WHEN ANY MUSCLE WORKS HARDER,

IT GETS BIGGER, IT ENLARGES.

AND THAT WORKS FOR A
WHILE, PUMPING THE BLOOD OUT

AGAINST THAT HIGH BLOOD
PRESSURE, UP TO THE BRAIN.

BUT EVENTUALLY THE HEART FAILS.

AND WHEN THE HEART FAILS,

BLOOD CANNOT BE
PUSHED OUT OF THE HEART.

SOME OF THE BLOOD
REMAINS IN THE HEART

AND DOES NOT GET OUT TO
THE BODY AND UP TO THE BRAIN.

AND CLEARLY, AGAIN,

THAT CANNOT BE GOOD
FOR BRAIN FUNCTION.

YOU KNOW, IN THE
COURSE OF OUR STUDIES

WE'VE CUT UP A LOT
OF BRAIN ARTERIES.

HUNDREDS AND HUNDREDS,

IF NOT THOUSANDS OF
SECTIONS HAVE BEEN MADE.

AND IT'S CONTINUALLY
AMAZING, OR EVEN SHOCKING...

THE EXTENT TO WHICH SOME OF
THESE BRAIN ARTERIES ARE PLUGGED.

YOU CAN SEE HERE, THIS
IS A MORE NORMAL ARTERY...

THESE ONES HERE, WHERE
THEY HAVE A BIG CENTER

WHERE THE BLOOD FLOWS THROUGH.

THERE'S A LARGE-CALIBER OPENING

THAT THE BLOOD CAN FLOW THROUGH,

WHEREAS OVER IN
SOME OF THESE ARTERIES

THAT HAVE BEEN COMPLETELY...
MORE OR LESS COMPLETELY PLUGGED UP

BY THESE YELLOWISH
CHOLESTEROL DEPOSITS...

AND IN SOME OF THEM,
THE REMAINING AREA

FOR THE BLOOD TO FLOW THROUGH

IS EXTREMELY SMALL, AS
YOU CAN SEE IN THAT ONE.

WHAT WE FOUND GENERALLY
IS THAT ALZHEIMER'S PATIENTS

ARE ABOUT TWICE AS LIKELY

TO HAVE VESSELS LIKE
THIS THAN NORMAL PEOPLE.

ATHEROSCLEROSIS IS
AN INFLAMMATORY LESION.

THE CHOLESTEROL DEPOSITS
ON THE ARTERY WALL...

THAT IS LIKE A LITTLE SORE,

AN OPEN WOUND THAT THE BODY'S

INFLAMMATORY CELLS HOME
IN ON, TO TRY TO REPAIR.

ONCE THE BRAIN
CAPILLARIES ARE INFLAMED,

THEY BECOME INVOLVED

WITH THE REACTIONS
OF INFLAMMATION

AND THEY'RE LESS ABLE
TO DO THEIR NORMAL JOB.

ONE OF THEIR NORMAL JOBS,

IT IS BECOMING
INCREASINGLY APPARENT,

IS TO DELIVER EXCESS "A" BETA

OUT OF THE BRAIN,
INTO THE BLOOD,

AND TO THE LIVER AND
KIDNEYS FOR DISPOSAL.

CLEARLY, IF THE MICROVESSELS,

THE CAPILLARIES,

AREN'T DOING THEIR JOB
BECAUSE OF INFLAMMATION,

THEY MAY NOT BE

GETTING RID OF THAT "A"
BETA THE WAY THEY SHOULD.

AND THE "A" BETA CAN ACCUMULATE
IN THE BRAIN AS PLAQUES.

THE GREAT POTENTIAL

OF THE VASCULAR HYPOTHESIS
IN ALZHEIMER'S DISEASE

IS THAT WE CAN
REPLICATE THE SUCCESS

THAT SCIENTISTS IN
CARDIOVASCULAR DISEASE HAVE HAD,

WHICH IS TO GIVE DRUGS

ON THE BASIS OF RISK FACTORS...

HIGH BLOOD CHOLESTEROL,
HIGH BLOOD PRESSURE...

TO PREVENT DISEASE,

RATHER THAN TO TRY TO
CURE IT ONCE IT'S HAPPENED.

TURN THE PALMS UP
AND CLOSE YOUR EYES.

NOW DON'T WORRY.
I HAVE YOU, OKAY?

- NOW I SEE SOME SWELLING ON YOUR FEET.
- YES.

HOW LONG'S THAT BEEN GOING ON?

- QUITE A WHILE.
- UH-HUH.

IT MAKES A DIFFERENCE
IF HE KEEPS HIS FEET UP.

HE TRIES TO KEEP HIS FEET UP
WHEN HE'S WATCHING TELEVISION.

ESPECIALLY AT NIGHT. YEAH YEAH.

'CAUSE, YOU KNOW, THE DIABETES
AFFECTS THE BLOOD VESSELS.

AND SOMETIMES, ESPECIALLY IN
THE LEGS, YOU CAN GET INTO TROUBLE.

- THAT'S POINTY.
- OKAY.

- NOT SO POINTY?
- NOT SO POINTY.

OKAY, SAME THING DOWN HERE?

- CAN YOU FEEL THAT EVEN?
- NO.

- DO YOU FEEL A LITTLE NUMBNESS THERE?
- YES, NUMBNESS.

SPREAD YOUR FINGERS.

DON'T LET ME PUSH THEM
TOGETHER. EXCELLENT.

SO THERE'S NO SIGN OF
WEAKNESS. EVEN THOUGH

HE'S HAD THAT STROKE, THERE'S JUST
ABSOLUTELY NO SIGN OF WEAKNESS.

OKAY, RELAX RELAX RELAX.

AND HOW ABOUT HIS
BLOOD PRESSURE?

IT'S BEEN GOOD TOO,
BECAUSE HE TAKES

- MEDICATION FOR THAT.
- OKAY.

SO HOW DOES VASCULAR DISEASE
LEAD TO COGNITIVE IMPAIRMENT?

AND THE BIGGER QUESTION IS,

WHAT ABOUT THE OTHER BIG CAUSE

OF COGNITIVE IMPAIRMENT...
ALZHEIMER'S DISEASE?

HOW DOES VASCULAR DISEASE
WORK WITH ALZHEIMER'S DISEASE?

SO LET ME START BY SAYING

THAT VASCULAR DISEASE
CAN INJURE THE BRAIN

AND CAUSE COGNITIVE PROBLEMS,

OR PROBLEMS WITH THINKING
AND MEMORY ALL BY ITSELF,

JUST LIKE ALZHEIMER'S
DISEASE CAN CAUSE

PROBLEMS WITH MEMORY
AND THINKING ALL BY ITSELF.

BUT WHAT WE KNOW FOR
SURE IS THAT AS WE GET OLDER,

THE TWO MOST COMMON

ABNORMALITIES OF THE BRAIN...

WHEN PEOPLE DIE AND YOU
LOOK AT THE BRAIN AFTER DEATH,

THE TWO MOST COMMON
ABNORMALITIES THAT WE SEE

ARE ALZHEIMER'S AND
VASCULAR DISEASE.

YEAH, SO HE'S LOST HIS REFLEXES.

AND AGAIN, THAT'S
PROBABLY FROM THE DIABETES.

ONE FIFTH OF ALL OF OUR BLOOD
GOES STRAIGHT TO OUR BRAIN.

WHY? BECAUSE OUR
BRAIN NEEDS THAT.

AND THINGS THAT INJURE
THOSE BLOOD VESSELS

END UP INJURING OUR BRAIN.

AND AS WE GET OLDER,
THESE INJURIES ACCUMULATE.

THEY ADD UP AND
MAKE US VULNERABLE

TO LATE-LIFE DISEASES
SUCH AS ALZHEIMER'S DISEASE.

HOW OLD ARE YOU?

I'M 76.

OKAY, I'M GONNA
SAY SOME NUMBERS.

I WANT YOU TO LISTEN CAREFULLY.

AND WHEN I'M THROUGH,

I WANT YOU TO SAY
THEM RIGHT AFTER ME.

NINE, ONE, EIGHT,

FOUR, TWO, SEVEN.

NINE, FOUR,

- EIGHT, ONE, FOUR, SEVEN.
- OKAY.

HAVE YOU NOTICED ANY
DIFFERENCES OR ANY CHANGES?

IF SO, THEY'RE VERY GRADUAL.

I HAVEN'T NOTICED
ANYTHING MAJOR.

OKAY, HIS BIGGEST ISSUE,

OR THE COMPLAINT
HE WAS HAVING WAS

THAT HE WAS HAVING TROUBLE
COMPLETING A SENTENCE,

- FINDING THE RIGHT WORDS.
- CORRECT, YEAH.

TELLS THE SAME
STORY OVER AND OVER.

OKAY, AND IS THAT MORE FREQUENT
NOW THAN IT HAS BEEN IN THE PAST?

I THINK SO, YEAH.

OKAY, ON THIS PAGE
THERE ARE SOME NUMBERS.

AND WHAT I WANT YOU TO DO
IS TO CONNECT THEM IN ORDER.

YOU'RE GONNA ALTERNATE
BETWEEN NUMBER AND LETTER.

SO YOU'RE GONNA
GO FROM ONE TO A,

A TO TWO, TWO TO B, AND SO ON.

WHAT COMES AFTER THREE?

- SO, FROM C...
- FOUR.

YEAH.

GOOD.

OKAY, ALL RIGHT.

- YOU'RE DOING JUST FINE.
- NO, I'M NOT.

- GO AHEAD.
- OKAY.

MR. HEPPE...

HIS STROKE IS BIGGER
THAN I THOUGHT IT WOULD BE.

THE OTHER THING IS, HE'S GOT
ATROPHY OF BOTH HIPPOCAMPI.

IT'S NOT HUGE, RIGHT?

SO IT'S HARD TO KNOW.

BUT THAT MAKES ME
A LITTLE SUSPICIOUS.

SO I THINK HE PROBABLY HAS
LARGE-VESSEL ATHEROSCLEROSIS.

WE KNOW HE HAS
MICROVASCULAR DISEASE.

HE SHOULD BE SEVERELY DEMENTED,

YET HE'S DOING
REALLY REALLY WELL.

AND WE'RE DEBATING... I
DON'T THINK WE'RE DEBATING.

I THINK HE STILL HAS MILD
COGNITIVE IMPAIRMENT.

HIS WIFE IS REALLY WORRIED ABOUT
THE BIG A... ALZHEIMER'S DISEASE.

RIGHT NOW WE'LL JUST
KEEP AN EYE ON HIM.

WE HAVE EVIDENCE
THAT IF YOU HAVE

THIS ATHEROSCLEROSIS
IN THE ARTERIES

AND YOU TAKE A
CHOLESTEROL-LOWERING DRUG

COMMONLY KNOWN AS A STATIN...

THAT THAT WILL ACTUALLY
BEGIN TO GO AWAY.

IN ADDITION, THERE'S SOME
EVIDENCE, EPIDEMIOLOGICAL EVIDENCE...

AGAIN, LOOKING AT
POPULATION STUDIES,

THAT PEOPLE WHO
TAKE THESE STATINS

FOR HIGH CHOLESTEROL
OR ABNORMAL CHOLESTEROL

ACTUALLY HAVE A MUCH LOWER
FREQUENTLY OF ALZHEIMER'S DISEASE,

AGAIN SUGGESTING THAT IF WE
NORMALIZE THE CHOLESTEROL,

EITHER LOWER IT
FROM TOO HIGH A LEVEL,

OR CHANGE THE TYPES OF
CHOLESTEROL IN THE BLOOD,

THAT IT WILL NOT ONLY ACT
TO HELP THE VASCULAR SYSTEM,

BUT PROBABLY CHANGE
THE WAY THIS AMYLOID,

THIS ABNORMAL PROTEIN,
IS PROCESSED IN THE BRAIN,

AND LOWER YOUR RISK
FOR ALZHEIMER'S DISEASE.

YOU, SIR, SIT NEXT TO YOUR WIFE.

HE GETS EXCITED
SITTING NEXT TO ME.

ISN'T THAT SWEET?

GEE.

WE KNOW THAT YOU HAVE

THESE RISK FACTORS FOR A STROKE.

SO WE KNOW THAT
YOU HAVE DIABETES.

YOU HAVE THE
IRREGULAR HEART RATE.

YOU HAVE THE HYPERTENSION.

YOU DIDN'T KNOW THAT
YOU HAD HAD A STROKE.

WE DID A BRAIN SCAN,

WHICH I'LL SHARE
WITH YOU IN A LITTLE BIT.

AND IT DOESN'T LOOK LIKE
YOU'VE HAD ANY NEW STROKES.

- OH.
- OKAY?

AND YOU CERTAINLY HADN'T HAD
ANY SYMPTOMS OF NEW STROKES.

AND AS I UNDERSTAND IT,

AND I THINK YOU GUYS ALL AGREE

THAT WHILE YOU'RE HAVING
A LITTLE BIT OF TROUBLE,

IT'S NOT INTERFERING IN YOUR
LIFE SUCH THAT YOU NEED HELP.

DO I THINK ALZHEIMER'S
DISEASE IS ACTING RIGHT NOW?

- ABSOLUTELY NOT, OKAY?
- OKAY.

I AGREE WITH DR. FARIAS.
THERE'S NO EVIDENCE

THAT ALZHEIMER'S
DISEASE IS ACTING.

AND I WILL SAY BECAUSE YOU'RE
CONTROLLING YOUR DIABETES,

BECAUSE YOU'RE CONTROLLING
YOUR CHOLESTEROL,

BECAUSE YOU'RE CONTROLLING
YOUR BLOOD PRESSURE,

THAT YOU'RE DOING WELL, OKAY?

HAD THESE NOT BEEN CONTROLLED
AND THERE WERE MORE STROKES,

I WOULD REALLY BE WORRIED
ABOUT YOUR THINKING.

AND I WOULD SAY YOUR
THINKING WOULD DECLINE.

- THAT'S MY BIGGEST CONCERN.
- THANK YOU.

IT WAS INTERESTING TO
HAVE IT ALL EXPLAINED.

- THIS FEELS VERY SPECIAL.
- YOU ARE VERY SPECIAL.

BYE.

LET'S SEE.

I THINK THE MOST
INTERESTING PART WAS

TO SEE THOSE MRI
IMAGES OF YOUR BRAIN,

- THOSE LITTLE...
- LITTLE HOLES.

THOSE LITTLE HOLES IN YOUR HEAD.

YOU'VE GOT HOLES IN YOUR HEAD.

- THEY'RE NOT VISIBLE.
- SEE, I KNEW SHE'D PULL THIS OUT.

WE'VE GOT TO
KEEP IT LIGHT, DEAR.

WE COULD BROOD ABOUT
IT. NO FUN DOING THAT.

- NO.
- NO.

WE HAVE TREATMENTS
FOR VASCULAR DISEASE.

WE'RE WORKING ON THE
TREATMENTS FOR ALZHEIMER'S DISEASE.

BUT THE TREATMENTS FOR VASCULAR
DISEASE ARE ALREADY THERE.

IF PEOPLE PURSUED
HEALTHY LIFESTYLES...

EXERCISED,
CONTROLLED THEIR DIET,

AND USED THE MEDICATIONS
THAT ARE AVAILABLE,

THAT NO MATTER WHAT HAPPENS
WITH THE ALZHEIMER'S DISEASE,

AT LEAST SOME PEOPLE

ARE GOING TO DO
BETTER AT LATER LIFE

BECAUSE THEY'VE MANAGED
THIS ONE DISORDER.

WE'RE ALL INTERESTED IN REDUCING
OUR RISK FOR ALZHEIMER'S DISEASE.

THERE ARE SOME FACTORS WE CAN
CONTROL, AND SOME WE CANNOT...

FOR EXAMPLE, OUR GENETIC MAKEUP.

WE INHERIT THAT
FROM OUR PARENTS.

WE CANNOT AFFECT THAT.

IT'S NOT MODIFIABLE.

BUT THERE ARE OTHER
THINGS THAT WE CAN DO

IN TERMS OF OUR HEALTH,
OUR DIET AND OUR LIFESTYLE,

THAT MAY HELP US REDUCE OUR
RISK FOR ALZHEIMER'S DISEASE.

HOW DO
YOU DEVELOP A BRAIN THAT,

AS THE PATHOLOGY ACCUMULATES,

YOU DON'T LOSE YOUR MEMORY?

EXERCISE CAN
INDUCE GROWTH FACTORS IN THE BRAIN.

IT CAN HELP BUILD NEW
NEURONS INTO THE CIRCUITS.

IT CAN BUILD SYNAPSES.

OH MY GOSH, WHAT DRUG
WILL DO THAT? NOTHING.

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.

WE'RE TRYING TO USE
TECHNOLOGIES THAT CAPTURE CELL SICKNESS

TO ASK THE QUESTION... WHEN
DOES ALZHEIMER'S BEGIN?

THERE'S A SENSE OF EXCITEMENT

IN THE FIELD OF DRUG DEVELOPMENT

FOR ALZHEIMER'S DISEASE

THAT I THINK IS BEYOND

ANYTHING ELSE IN HEALTH CARE NOW.