>> GOOD EVENING. WELCOME, EVERYONE. MY NAME IS MONIQUE. I'M DIRECTOR OF COMMUNITY HEALTH AND WELLNESS HERE AT SUBURBAN HOSPITAL. IT GIVES ME GREAT PLEASURE AND EXCITEMENT TO SEE ALL OF YOU HERE THIS EVENING AND TO WELCOME YOU TO OUR THIRD ANNUAL MEDICINE FOR THE PUBLIC, HOSTED HERE AT SUBURBAN HOSPITAL BUT HISTORICALLY A LONG TIME TRADITION OF MEDICINE FOR THE PUBLIC, BEING OFFERED AT NIH, AND WE'RE SO EXCITED TO PARTNER AND BRING BOTH NIH, JOHNS HOPKINS MEDICINE AND SUBURBAN HOSPITAL ALL TOGETHER TO BRING YOU THE MOST LATEST, GREATEST UP TO DATE KNOWLEDGE RIGHT HERE AT HOME. A FEW THINGS THAT I WOULD LIKE TO REMIND YOU THIS EVENING. ONE, GOOD NEWS. PARKING IS FREE AFTER 5:00 P.M.. SO EVEN THOUGH YOU MIGHT HAVE A TICKET, THAT'S JUST TO REMINDS THE PARKING GARAGE THAT YOU ARE HERE AFTER 5:00. SO IF YOU ARRIVED AFTER 5:00 P.M., PARKING IS FREE AND THAT'S INCLUDING IF YOU EVER VISIT ON THE WEEKENDS. IT'S ALSO FREE. IT'S ALWAYS FREE AFTER 5:00. ALSO, IF YOU HAVE A CELL PHONE OR PAGER, IF YOU PLEASE WOULD KINDLY TURN THAT OFF OR ON VIBRATE TO GIVE OUR SPEAKERS YOUR FULL ATTENTION AND RESPECT THIS EVENING. WE ARE GRATEFUL FOR THAT. THANK YOU. ALSO, I HOPE YOU ARE ENJOYING THE HEALTHY TREATS. WE DO RECYCLE HERE AT SUBURBAN HOSPITAL, SO KINDLY, WE HAVE BLUE CONTAINERS IN THE BACK FOR YOU TO DEPOSIT YOUR WATER BOTTLES, AND IF YOU WILL TAKE ANY OF YOUR PAPER PLATES, NAPKINS WITH YOU AT THE END OF THE SESSION, SO WE CAN KEEP OUR AUDITORIUM IN GOOD CONDITION FOR TOMORROW MORNING. RESTROOMS ARE LOCATED JUST OUTSIDE THE DOOR TO THE LEFT. ONE OF US WILL BE THERE TO ASSIST YOU IF YOU NEED TO EXCUSE YOURSELF DURING THE PRESENTATION. AND ALSO, AS EACH -- AND EVERY ONE YOU ARRIVE THIS EVENING, HOPEFULLY IN YOUR HANDOUT AND PACKET OF ALL THE GREAT INFORMATION YOU HAVE IS ALSO AN EVALUATION, AND WE ARE VERY, VERY SENSITIVE TO THE AMAZING FEEDBACK THAT YOU GIVE US. WE WANT TO KNOW THE GOOD AND THE BAD, HOW TO MAKE THESE PRESENTATIONS EVEN BETTER FOR YOU EACH AND EVERY TIME. SO PLEASE LET US FOE YOUR COMMENTS, HOW OUR SPEAKERS, THE INFORMATION THAT YOU RECEIVED FROM OUR SPEAKERS. WE DO MAKE SURE THAT THAT FEEDBACK GETS BACK TO THEM AS WELL. AND ALSO, ANY ADDITIONAL TOPICS THAT YOU WOULD LIKE TO HEAR ABOUT IN THE FUTURE, THE INFORMATION THAT YOU PROVIDE REALLY HELPS US PUT TOGETHER THE NEXT PRESENTATIONS FOR THE FUTURE. SO PLEASE LET US KNOW YOUR THOUGHTS. SO WITHOUT FURTHER ADO, LET'S START OUR PROGRAM. I WOULD LIKE TO INTRODUCE MISS KELLY CARINGTON, FROM THE OFFICE OF COMMUNICATIONS AT THE NIH CLINICAL CENTER AND SHE WILL GIVE YOU A LITTLE BIT MORE INFORMATION ON OUR PROGRAM, SO PLEASE RELAX, TAKE GREAT NOTES, AND ENJOY THE EVENING. THANK YOU. [APPLAUSE] >> GOOD EVENING. I'M HERE ON BEHALF OF DR. JOHN GALLIN AND SO ON BEHALF OF THE CLINICAL CENTER, WE ALSO WOULD LIKE TO THANK YOU IN WELCOMING YOU TO THIS EVENING'S LECTURE. WE'RE REALLY EXCITED TO HAVE SO MANY OF YOU OUT HERE THIS EVENING. WE WANT TO MOERND EVERYONE THAT WE ARE VIDEO CASTING -- REMIND VIDEO CASTING THIS LECTURE AND WE WILL BE POSTING THE RECORDING ON OUR WEBSITE AT CLINICALCENTER.NIH CLINICALCENTER.NIH.GOV. IT WILL BE THERE IN ABOUT A WEEK AND PLEASE SHARE THE LECTURE WITH YOUR FAMILY AND FRIENDS. OUR LECTURE COMES IN THE MIDST OF A LOT OF ACTIVITIES SURROUNDING ALZHEIMER'S RESEARCH, AND WE'RE GLAD TO BE A RESOURCE FOR EDUCATION AND AWARENESS. SOME OF THE RECENT ACTIVITY INCLUDES PROMISING NEWS THAT NEW RESEARCH MAY BRING ABOUT BETTER TREATMENT, AND WE'LL HEAR A LITTLE BIT ABOUT THAT TODAY. NEW HOPE FOR PATIENTS AND THEIR CAREGIVERS THROUGH THE NATIONAL ALZHEIMER'S PLAN, WHICH WAS RECENTLY ANNOUNCED. THE PLAN FOCUSES ON INCREASING RESEARCH IN EDUCATION AND REDUCE THE BURDEN OF DISEASE ON PATIENTS AND THEIR FAMILIES. AND JUST LAST WEEK, THE NATIONAL ENSTITUTE ON AGING, PART OF THE NATIONAL INSTITUTES OF HEALTH, HELD A SUMMIT, COSPONSORED A SUMMIT THAT'S LOOKING AT RESEARCH OPPORTUNITIES TO HELP MEET THE GOALS OF PREVENTING AND EFTHIVELY TREATING ALZHEIMER'S DISEASE BY 2025. AS MANY OF YOU KNOW, ALZHEIMER'S DISEASE AFFECTS ABOUT FIVE MILLION AMERICANS, AND NEARLY 15 MILLION FAMILY MEMBERS AND FRIENDS WHO ARE THE NON-PAID CAREGIVERS. TODAY'S LECTURE WILL LOOK AT THE QUESTION, IS IT MEMORY LOSS OR ALZHEIMER'S DISEASE? OUR EXPERTS WILL EXPLORE PROCESS OF AGING, EMERGENCYING -- EMERGING RESEARCH IN EARLY ALZHEIMER'S DISEASE, PRACTICAL PERSPECTIVES FOR TREATMENT, AND CARE GIVING STRATEGIES SPECIFIC TO PEOPLE WITH ALZHEIMER'S. SO TO MAXIMIZE THE TIME OUR PRESENTERS HAVE WITH YOU THIS EVENING AND THE QUESTION-AND-ANSWER TIME, I'LL INVITE YOU TO GO OOUR WEBSITE TO READ THE FULL BIOGRAPHIES OF OUR SPEAKERS. TONIGHT'S SPEAKERS ARE DR. BISETI, STAFF CLINICIAN IN THE LABORATORY OF BEHAVIORAL NEUROSCIENCE AT THE NATIONAL INSTITUTE OF AGING. AN AJUNCT ASSISTANT PROFESSOR OF NEUROLOGY AT JOHN HOPKINS UNIVERSITY SCHOOL OF MEDICINE. AND DR. HARRY GILL, MEDICAL DIRECTOR FOR THE SUBURBAN HOSPITAL'S BEHAVIORAL HEALTH SERVICES, EXECUTIVE DIRECTOR FOR THE WASHINGTON SCHOOL OF PSYCHIATRY, AND CLINICAL ASSIST ASSISTANT PROFESSOR FOR GEORGE WASHINGTON UNIVERSITY. SO TO KEEP OUR PROGRAM RUNNING RATHER SMOOTHLY, WE'LL INVITE OUR SPEAKERS TO COME UP AND REPRESENT ONE BEHIND ANOTHER AND THEN AFTER THEIR PRESENTATIONS, WE'LL HAVE A PANEL QUESTION QUESTION-AND-ANSWER SESSION AND SO WITHOUT FURTHER ADO, I INVITE DR. BISETI TO JOIN US AT THE PODIUM. [APPLAUSE] >> GOOD EVENING, EVERYONE. THANK YOU, KELLY, FOR THAT INTRODUCTION. IT'S A GREAT PLEASURE TO BE HERE STHENG AND TO SEE SUCH A FULL HOUSE. THIS EVENING AND TO SEE SUCH A FULL HOUSE. [PAUSE BRTH [PAUSE] SO I AM A NEUROLOGIST. I'M ALSO A NEUROSCIENTIST. I SPEND A LOT OF MY TIME DOING RESEARCH. MY RESEARCH FOCUSES ON DEVELOPING NEWER AND MORE ACCURATE METHODS FOR EARLY DIAGNOSIS OF ALZHEIMER'S DISEASE, AND WHEN I'M INNOCENT LAB, I TAKE CARE OF PATIENTS THAT COME TO THE MEMORY CLINIC AT THE JOHNS HOPKINS BAY VIEW MEMORY AND ALZHEIMER'S TREATMENT CENTER. SO WHAT I'D LIKE TO DO TODAY OVER THE COURSE OF THE NEXT 15 OR 20 MEN'S IS TO TRY AND PUT YOU THROUGH A MEDICAL SCHOOL EXPERIENCE. WE'LL TRY AND GIVE YOU A WHIRLWIND TOUR, AS IT WERE, OF THE BASIC BIOLOGY UNDERLYING NORMAL AGING AND HOW IT DIFFERS SIGNIFICANTLY FROM ALZHEIMER'S DISEASE. THE ASSUMPTION IS, OF COURSE, THAT UNLESS WE TRY AND UNDERSTAND WHAT NORMAL AGING IS, WE REALLY WOULDN'T BE ABLE TO GET TO UNDERSTANDING WHAT ALZHEIMER'S DISEASE IS ALL ABOUT. AND I'LL TRY AND DO THAT AND THAT WILL SET US UP HOPEFULLY NICELY FOR DR. GILL'S PRESENTATION ABOUT THE CLINICAL IMPLICATIONS OF THE SOME OF THE CHANGES THAT WE'RE GOING TO TALK ABOUT. SO, I'M GOING TO CALL MY HALF OF THE PRESENTATION A TALE OF TWO BRAINS, OKAY? SO HERE IS THE BRAIN OF A PATIENT WHO DIED WITH ALZHEIMER'S DISEASE, AND HERE IS A NORMAL BRAIN. AND YOU DON'T HAVE TO BE A NEUROLOGIST TO SEE THAT THERE IS A STRIKING DIFFERENCE.B]¨ THE HUMAN BRAIN IS ARRANGED ON THE OUTER SURFACE IN THE FORM OF LITTLE RIDGES, AND LITTLE VALLEYS IN BETWEEN THE RIDGES, SO THE RIDGES OR THE HILLS ARE CALLED THE GYRI, AND THE GAPS OR THE VALLEYS IN BETWEEN THE GYRI ARE CALLED THEgbW SULF FY-AND YOU CAN SEE A NORMAL BRAIN WHERE A WELL-ROUNDED PROFILE OF GYRI AND MODERATELY DEEP VALLEYS IN BETWEEN THE GYRI. AND YOU CAN SEE IN AN ZIRMS MAIN -- ALZHEIMER'S BRAIN IT SLUNK IN SIZE. IT SEEMED TO HAVE FLATTENED OUT IN KMAERNS IT A BRAIN WITH -- WITHOUT ALZHEIMER'S DISEASE. AND AS FAR AS THE VALLEYS IN BETWEEN THE RIDGES, YOU CAN SEE THAT THEY'RE A WHOLE LOT DEEPER THAN A NORMAL BRAIN. SO THAT'S A STRIKING DIFFERENCE, AND YOU DON'T NEED A FANCY BRAIN SCAN. YOU DON'T NEED A MICROSCOPE TO SEE THAT THERE ARE VERY OBVIOUS DIFFERENCES BETWEEN NORMAL AGING AND ALZHEIMER'S DISEASE. SO THE FIRST QUESTION THAT I WANT TO ADDRESS IS WHAT HAPPENS TO THE NORMAL BRAIN DURING AGING? AND THIS IS A QUESTION THAT WE SPENT A LOT OF TIME AS RESEARCHERS, ESPECIALLY IN THE NATIONAL INSTITUTE OF AGING WHERE I'M BASED AND HERE IS AN KPAFLE PAPER THAT MY COLLEAGUES PUBLISHED ALMOST TEN YEARS AGO NOW. AND CRIF TO -- I'D LOVE I LOVE TO READ SCIENTIFIC PAPERS LIKE THESE THAT HAVE THE ANSWER RIGHT IN THE TITLE. YOU REALLY DON'T NEED TO GO THROUGH TONS OF READING TO GET AT WHAT THE AUTHORS FOUND. SO WHAT MY COLLEAGUES DID IN THE STUDY WAS THEY TOOK A GROUP OF RESEARCH PARTICIPANTS, VERY HEALTHY INDIVIDUALS BETWEEN 60 AND 85 YEARS OF AGE AND THEY ASKED THEM TO COME IN EVERY YEAR FOR BRAIN MI SCANS AND THEY DID THAT TO BE ABLE TO MEASURE THE BRAIN VOLUMES IN THESE INDIVIDUALS AS THEY AGED. AND IT'S VERY IMPORTANT TO REMEMBER THAT THESE INDIVIDUALS ARE COG NITIVELY NORMAL. THEY DIDN'T HAVE ANY SYMPTOMS. THERE WERE PARTICIPANTS IN THE BALTIMORE STUDY OF AGING. SOME OF YOU MIGHT BE PARTICIPANTS. IT'S AMONG THE LARGEST AND LONGEST RUNNING STUDIES OF NORMAL AGELING IN THE UNITED STATES. IT WAS STARTED IN 1958 AND WE'VE STUDIED ABOUT 3,000 RESEARCH PARTICIPANTS IN THIS STUDY AND SINCE 1998, WE ALSO HAVE A NEUROIMAGING STUDY AND THESE INDIVIDUALS IN THIS STUDY WERE PARTICIPANTS IN THE NEUROIMAGING PART OF THE BLSA. SO WHAT WE FOUND IN THE STUDY WAS THAT DURING NORMAL AGING, THE BRAIN SHRINKS. THE TECHNICAL TERM IS ATROPHY. SO THERE IS A DEGREE OF BRAIN ATROPHY EVEN IN NORMAL AGING IN INDIVIDUALS WITHOUT ANY SIGNS OF MEMORY COMPLAINTS. AND THAT'S A VERY IMPORTANT OBSERVATION. WE ALSO FOUND THAT NOT ALL PARTS OF THE BRAIN ATROPHY AT THE SAME RATE. THERE ARE REGIONS OF THE BRAIN THAT SEEM TO A-- ATROPHY MORE AND FASTER THAN OTHER REGIONS. HOW MUCH DOES THE BRAIN SHRINK DURING NORMAL AGING? IN IN TH STUDY MY COLLEAGUES CALCULATED THAT YOU LOSE ABOUT FIVE MILL LITERS OF BRAIN VOLUME YEAR IN YEAR DURING THE PROCESS OF NORMAL AGING. HOW MUCH IS FIVE MILL LITERS? WELL, IT'S ABOUT A TEASPOON FULL OF LIQUID IN TERMS OF VOLUME AND THAT'S ABOUT THE EXCEPT OF BRAIN VOLUME LOSS THAT IS SEEN ASSOCIATED WITH NORMAL AGING. AND HERE IS A COLOR-CODED PICTURE OF A BRAIN DURING NORMAL AGING SHORING THE -- SHOWING THE DIFFERENT AGES OF THE BRAIN AT ATROPHY COMPARES TO OTHER BRAINS. SO THE NEXT QUESTION OF COURSE IS WHAT HAPPENS TO THE BRAIN DURING ALZHEIMER'S DISEASE? WELL, THERE ARE SEVERAL STUDIES THAT HAVE USED VERY SIMILAR METHODS, SO MRIS, SCANS OF THE BRAIN AND HAVE CALCULATED THAT THE BRAIN IN ALZHEIMER'S DISEASE UNDERGOES MUCH GREATER RATES OF SHRINKAGE COMPARED TO NORMAL AGING. IN TERMS OF AN ESTIMATE, IT'S ABOUT THREE TO FIVE TIMES FASTER THAN WHAT YOU SEE DURING NORMAL AGING. SO THAT MEANS IT'S ABOUT THREE TO FIVE TEASPOONS OF VOLUME THAT ARE LOST YEAR IN YEAR IN A BRAIN WITH ALZHEIMER'S DISEASE. AND BECAUSE WE AS SCIENTISTS LIKE TO COMPLICATE THINGS QUITE A BIT, WE ARE USED TO LOOKING AT VOLUMES NOT AS TEASPOONS BUT IN THE FORM OF GRAPHS AND HERE IS AN EXAMPLE OF WHAT A GRAPH THAT SHOWS THE SAME RESULTS LOOKS LIKE. SO HERE A BRAIN VOLUMES OF INDIVIDUALS WITHOUT ALZHEIMER'S DISEASE, WITH NORMAL COG IN ADDITION, WITH NO MEMORY PROBLEMS, AND HERE YOU HAVE A BRAIN VOLUMES OF PATIENTS WITH ALZHEIMER'S DISEASE, WHO HAD MRI SCANS, AND WHEN YOU EXPRESS THE SAME RESULT AS A PERCENTAGE AND HERE YOU ARE SHOWING THE RESULTS AS WHAT PERCENTAGE OF BRAIN LOSS HAPPENS YEAR IN YEAR, IN SOMEBODY WITH ALZHEIMER'S DISEASE, COMPARED TO SOMEBODY WHO DOESN'T? AND YOU CAN SEE THAT PATIENTS WITH ALZHEIMER'S DISEASE HAVE SIGNIFICANTLY GREATER RATES OF ATROPHY THAN NORMAL ELDERLY INDIVIDUALS. COMING BACK TO OUR INITIAL FIGURE OF AN ALZHEIMER'S BRAIN AND THE NORMAL BRAIN, AND WE NOW KNOW FROM WHAT I'VE TOLD YOU THAT THERE IS A SIGNIFICANT AMOUNT OF ATROPHY IN THE ALZHEIMER'S BRAIN. ARE THERE REGIONS OF THE BRAIN THAT ARE ESPECIALLY VULNERABLE TO SUCH CHANGES? INDEED THERE ARE. SO IF YOU LOOK AT THE SAME BRAENS AND SECTION THEM AND TAKE A LOOK AT THE DEEP STRUCTURES THAT LIE BENEATH THE OUTER SURFACE OF THE BRAIN, YOU CAN SEE THAT THERE ARE CERTAIN REGIONS THAT SEEM TO BE ESPECIALLY VULNERABLE TO THE SHRINKAGE OR THE ATROPHY THAT WE SEE IN ALZHEIMER'S DISEASE. SO HERE IS AN EXAMPLE OF THAT. WE'VE NOW SECTIONED THESE BRAINS AND CUT THEM AND HERE IS A NORMAL BRAIN. ONE HALF OF A NORMAL BRAIN AND HERE IS A BRAIN WITH ALZHEIMER'S DISEASE. AND AGAIN, YOU CAN SEE THAT THE JAIRA, WHICH ARE THESE HILL-LIKE PATTERNS OF ARRANGEMENT OF NORMAL TISSUE SEEMS TO HAVE FLATTENED OUT IN ALZHEIMER'S DISEASE. THE VALLEYS IN BETWEEN THE RIDGES DEEP DEEPER BUT WHAT I'D LIKE YOU TO REALLY FOCUS ON IS THIS LITTLE STRUCTURE THAT'S SITUATED DEEP IN THE TEMPLE LOBE OF THE BRAIN. THE TEMPLE LOBE OF THE BRAIN IS THIS REGION. IT'S A PART OF THE BRAIN UNDERLYING THIS PART OF THE SKULL, AND IF YOU LOOK AT THAT REGION IN THE BRAIN WITH ALZHEIMER'S DISEASE, YOU CAN SEE STRAIGHT AWAY THAT IT'S MUCH SMALLER. LOOK AT THE SAME REGION IN THE NORMAL BRAIN. IT'S WELL ROUNDED. IT'S PROMINENT. AND IT SEEMS MUCH HEALTHIER THAN THIS LITTLE ATROPHYED STRUCTURE IN THE ALZHEIMER'S BRAIN. WELL, THIS STRUCTURE IS VERY IMPORTANT. IT'S VERY CRITICAL TO MEMORY PROCESSS AND CRITICAL TO LEARNING AND WE THINK IT'S AMONG THE REGION REGIONS THAT ARE MOST RESPONSIBLE FOR THE DEVASTATING LOSS OF MEMORY THAT WE SEE IN ALZHEIMER'S DISEASE. AND THIS STRUCTURE THAT'S SITUATED DEEP UNDERSTAND THE TEMPLE LOBE OF THE BRAIN IS CALLED A HIPOCAMPUS. WELL, WE CAN SEE THE SAME THING IN LIVING PATIENTS WHEN YOU SCAN THE BRAINS WITH AN MRI SCAN OR A CAT SCAN. SO YOU CAN SEE THE SAME PATTERNS OF ATROPHY THAT I'VE JUST SHOWED YOU. AND HERE, FOR INSTANCE, OUR MRI SCANS FROM A NORMAL HEALTHY INDIVIDUAL AND AN INDIVIDUAL WITH ALZHEIMER'S DISEASE. SO ON THE LEFT HAND PANEL YOU HAVE A NORMAL BRAIN. ON THE RIGHT HAND PANEL YOU HAVE A BRAIN WITH ALZHEIMER'S DISEASE AND YOU CAN SEE THE HIPOCAMPUS IN THE NORMAL BRAIN AND ONE HIP HIPOCAMPI SO THE HIPOCAMPI HERE SEEM WELL-ROUNDED, PROMINENT AND QUITE HEALTHY. CONTRAST TO TO THE HIPOCAMPUS IN HAL ZIRMS DISEASE. REALLY RAGGED, ATROPHIED AND SLUNKEN. AND SOMETIMES I THINK THESE CHANGES ARE SO OBVIOUS, EVEN A BOARD-CERTIFIED NEUROLOGIST CAN SEE THAT. OKAY? [LAUGHTER] INTERESTINGLY, THE WORD HIP HIPOCAMPUS COMES FROM ANCIENT GREEK. FROM HIPPOS, MEANING HORSE AND CAMPOS MEANING SEA MONSTER. IT'S EASY TO SEE WHY THE SEA HORSE GIVES ITS NAME TO THE HIPOCAMPUS FROM A HUMAN BRAIN. SO THAT'S ALL VERY WELL. SO WE NOW KNOW THAT THE ALZHEIMER'S BRAIN DIFFERS SIGNIFICANTLY FROM THE NORMAL BRAIN IN TERMS OF HOW MUCH IT ATROPHIES, HOW FAST IT ATROPHIES, WHAT STRUCTURES ATROPHY. BUT WHAT DOES ALL THAT HAVE MEAN IN TERMS OF BRAIN FUNCTION? DOES ATROPHY HAVE ANYTHING TO DO WITH HOW NERVE CELLS WORK IN ALZHEIMER'S DISEASE? WELL, WE CAN ANSWER THAT QUESTION BY DOING A SPECIAL?Y TYPE OF BRAIN IMAGING SCANS, AND HERE IS AN EXAMPLE OF SUCH A SCAN THAT'S CALLED A POSTRON TOMOGRAPHY SCAN RIGHT A PET SCAN FOR SHORT, A SPECIAL TYPE OF PET SCAN CALLED A GLUCOSE PET AND THE THEORY BEHIND THESE SCANS IS THAT BRAIN CELLS NEED GLUCOSE AS FUEL SO THAT'S WHAT THEY USE IN ORDER TO CARRY OUT THEIR FUNCTIONS IN THE BRAIN. SO IF YOU COULD INJECT SOMEBODY WITH A SMALL AMOUNT OF GLUCOSE AND LABEL THAT GLUCOSE WITH A TINY BIT OF RADIO ACTIVITY AND THEN COUNT THE RADIO ACTIVITY AS IT WAS TAKEN UP BY THE BRAIN WHEN THE PATIENT IS IN THE SCANNER, YOU CAN ESTIMATE AND WHICH PARTS OF THE BRAIN ARE ABLE TO USE THIS FUEL THAT YOU PROVIDE. THE ASSUMPTION IS THAT AS LONG AS YOUR CELLS ARE HEALTHY, ACTIVE, AND WORKING NORMALLY, THEY'LL EFFECTIVELY TAKE UP THE FUEL THAT YOU'VE GIVE THEM. SO HERE IS THE PET SCAN OF A NORMAL OLDER INDIVIDUAL WITHOUT ANY MEMORY PROBLEMS AND HERE IS AN ALZHEIMER'S BRAIN. SO WHAT I'D LIKE TO YOU FIRST APPRECIATE IS THE LITERALLY UNIFORM DISTRIBUTION OF RED COLOR ALL ALONG THE OUTER SURFACE OF THE BRAIN SOME IN SOMEBODY'S WHO IS NORMAL AND INDICATES REGIONS OF THE BRAIN THAT HAVE EFFECTIVELY AND EFFICIENTLY TAKEN UP THE GLUCOSE AND THE RADIO ACTIVITY SEEMS NICE AND EVENLY DISTRIBUTED. SO CONTRAST THAT IN SOMEBODY WITH AL ZIRLES DISEASE. YOU SEE REGIONS IN BOTH HALVES OF THE BRAIN THAT DO NOT SEEM TO BE ABLE TO TAKE UP THE FUEL THAT'S ESSENTIAL FOR THESE CELLS TO BE ACTIVE AND CARRY OUT THEIR NORMAL FUNCTIONS. AND IT'S ALSO IMPORTANT TO REALIZE THAT SOME OF THESE BRAIN REGIONS ARE THE VERY SAME REGIONS THAT WE'VE PREVIOUSLY SEEN UNDERGO ATROPHIC CHANGES OR SHRINKAGE. SO WHAT THEN HAPPENS TO NERVE CELLS IN ALZHEIMER'S DISEASE? SO WE WANT TO KNOW GO FROM LARGE STRUCTURES DOWN TO THE CELLULAR LEVEL. SO WHAT HAPPENS TO NERVE CELLS IN ALZHEIMER'S DISEASE? WELL, HERE IS A CARTOON THAT TELLS YOU ABOUT THE KINDS OF CHANGES THAT WE SEE IN ALZHEIMER'S DISEASE. SO YOU HAVE THREE HEALTHY-LOOKING NEURONS IN A NORMAL INDIVIDUAL. THE NEURON HAS WHAT WE CALL A CELL BODY, IT HAS A NUKE LOUIS. IT HAS THESE BRANCHING TREE-LIKE STRUCTURES THAT ARE CALLED DENDRITES SO CONNECTIONS BETWEEN DENDRITES ARE IMPORTANT FOR ONE NERVE CELL TO COMMUNICATE WITH ANOTHER AND YOU HAVE THIS LONG STEM-LIKE STRUCTURE CALLED THE AXON. SO CONTRAST THAT WITH WHAT HAPPENS IN ALZHEIMER'S DISEASE. SO YOU HAVE THREE NERVE CELLS IN SOMEBODY WITH ALZHEIMER'S DISEASE THESE ARE BRAIN SECTION THAT'S WE'RE LOOKING AT UNDER THE MICROSCOPE. YOU CAN IMMEDIATELY SEE THAT THERE ARE CLUMPS OF A STICKY SUBSTANCE IN BETWEEN THE NERVE CELLS AND THESE CLUMPS ARE CALLED AMLOID PLAQUES. THEY ARE FORMED BECAUSE OF ACCUMULATION OF A STICKY PROTEIN CALLED BETAAMLOID. INSIDE THE NERVE CELLS THEMSELVES, IF YOU TRY AND LOOK CLOSELY, YOU CAN SEE ABNORMAL CLUMPS OF ANOTHER PROTEIN CALLED TAU PROTEIN, WHICH FORMS STRUCTURES CALLED NEUROFLABLOID TANGLES. THE NEURONS THEMSELVES LOOK RATHER SICKLY. LOOK AT THE DENDRITES. THEY DON'T SEEM TO MAKE AS MUCH BRAMPS AS A NORMAL NERVE CELL DOES. THESE TWO STRUCTURES,S THE AM LOTT PLAQUES AND THE TANGLES, WERE DESCRIBED BY DR. ALLOYS ALZHEIMER'S MORE THAN 100 YEARS AGO IN GERMANY AND IT'S THAT DISCOVERY THAT ACTUALLY IS ASSOCIATED WITH DR. ALZHEIMER'S' DESCRIPTION OF THE DISEASE THESE TWO STRUCTURES ARE CONSIDERED THE PATHOLOGICAL HALLMARKS OF THE DISEASE. WHY IS IT IMPORTANT TO TALK ABOUT THESE ABNORMAL PROTEINS? WELL, THERE IS EVIDENCE THAT IF ACCUMULATED OVER SEVERAL YEARS THAT SEEMS TO SUGGEST THAT THE AGGREGATION OR ACCUMULATION OF BETAAMEL SKPOITED FORMATION OF PLAQUES MIGHT BE ONE OF THE EARLY EVENTS THAT TRIGGERS OF A WHOLE SET OF ABNORMAL CHANGES THAT EM LEADS TO NERVE CELL DYSFUNCTION AND NERVE CELL DEATH IN ALZHEIMER'S DISEASE. IT'S A THEORY THAT IS FAR FROM BEING PROVEEN CONCLUSIVELY BUT HAS GAINED INCREASING ACCEPTANCE OVER THE YEARS FROM THE SCIENTIFIC COMMUNITY. SO HERE IS A CARTOON THAT SHOWS YOU HOW THE BRAIN MIGHT BE DISRUPTED. SO YOU HAVE THREE NERVE CELLS HERE THAT ARE CONNECTED TO EACH OTHER AND YOU HAVE THIS BIG CLUMP OF AMELOID IN BETWEEN THE NERVE CELLS. AND WHAT THE AMELOID IS BELIEVED TO DO IS IT TRIGGERS OTHER CELLS NS BRAIN CALLED ATROCITES AND CELLS TO RELEASE A WHOLE SET OF INFLAMMATORY NEUROTOXIC COMPOUNDS THAT ARE TAJ DAMAGING TO THE NERVE CELLS. ANOTHER WAY THAT AN MANYELOID MIGHT WORK IN ALZHEIMER'S DISEASE IS BY THE COLLECTION OF SMALL BITS OF AMELOID IN BETWEEN NERVE CELL CONNECTIONS. AND THERE BY INTERFERING WITH THE WAY ONE NERVE CELL MIGHT COMMUNICATE WITH ANOTHER. SO THESE ARE EXAMPLES AS TO HOW ONE OF THE TOXIC PROTEINS MIGHT TRIGGER THE SERIES OF EVENTS THAT EVENTUALLY LEAD TO MEMORY LOSS, NEURAL DYSFUNCTION AND DEATH IN ALZHEIMER'S DISEASE. ONE OF THE MAJOR BREAKTHROUGHS SOME YEARS AGO WHEN SCIENTISTS AT THE UNIVERSITY OF PITTSBURGH DEVELOPED A WAY BY WHICH WE COULD ACTUALLY SEE AMELOID IN LIVING SUBJECTS AND THEY DID THIS BY DEVELOPING A DYE, A RADIOACTIVE DYE, WHICH WHEN INJECTED THROUGH THE VA-IN, IS TAKEN UP IN REGIONS OF THE BRAIN THAT HAVE AMELOID IN THEM AND WHEN YOU SCAN THAT SUBJECT IN A POSTRON PET SCANNER, YOU CAN SEE THAT BRAIN REGIONS THAT HAVE AMELOID SEEM TO TAKE UP THE RADIOACTIVE DYE MUCH MORE THAN NORMAL BRAIN REGIONS. SO HERE IS AN EXAMPLE OF AN AMELOID SCAN. THE RADIOACTIVE DYE THAT WAS DEVELOPED BY SCIENTISTS AT THE UNIVERSITY OF PITTSBURGH IS CALLED PITTSBURGH KMOUPD B. THIS IS A SCAN IN SOMEBODY WITH ALZHEIMER'S DISEASE AND A SCAN IN A COMPLETELY NORMAL INDIVIDUAL AND YOU CAN SEE REGIONS OF RED UPTAKE IN ALZHEIMER'S DISEASE THAT SEEM TO SIGNAL THE REGIONS IN THE BRAIN WHERE AMELOID DEPOSITION HAS OCCURRED. SO STRIKING DIFFERENCES IN THE AMELOID BURDEN IN ALZHEIMER'S DISEASE COMPARED TO A NORMAL INDIVIDUAL. SO WE'VE NOW LOOKED AT A WHOLE SET OF FACTORS THAT SEEM TO DIFFERENTIATE THE NORMAL BRAIN FROM ALZHEIMER'S DISEASE. WE'VE SEEN THAT THE NORMAL BRAIN IS RESISTANT TO ALZHEIMER'S DISEASE, TO ATROPHY. THE ALZHEIMER'S BRAIN UNDERGOES STRIKING ATROPHY IN CERTAIN BRAIN REGIONS IMPORTANT TO REMEMBER PROCESSES. WE KNOW THAT THE AM ZIRMS BRAIN IS NOT ABLE TO UTILIZE FUEL AS HE CAN'TIVELY AND WE KNOW THAT ABNORMAL PROTEIN AGGREGATIONS IN ALZHEIMER'S DISEASE CONSTITUTE THE PATHOLOGICAL HALLMARK. SO THE NEXT QUESTION THAT WE WANT TO ANSWER IS WHAT ARE THE FACTORS? WHAT ARE THE FACTORS THAT DETERMINE WHY A NORMAL BRAIN BECOMES A DISEASED BRAIN? WHAT ARE THE FACTORS THAT DRIVE THESE CHANGES? THERE REALLY ISN'T TIME TO GO THROUGH A WHOLE SET OF FACTORS THAT MIGHT NEED THESE CHANGES BUT WE'LL TALK ABOUT ONE VERY IMPORTANT FACTOR. AND THAT IS THE GENETIC RISK FACTOR FOR ALZHEIMER'S DISEASE, WHICH LIVES IN THE APPLE E LIPOPROTEIN GENE. SO FOR THOSE OF YOU WHO ARE NOT FAMILIAR WITH GENES AND GENETIC MATERIAL, HERE IS A QUICK PRIMA. SO ALL OF OUR GENETIC MATERIAL LIVES ANY INSIDE THE NUKE LOUIS OF EVERY CELL. IT'S SITUATED ON CHROMOSOMES IN THE FORM OF DOUBLE-STRANDED D.N.A. AND GENES ARE VERY IMPORTANT BECAUSE THEY CONTAIN THE CODING INFORMATION THAT'S NECESSARY FOR EVERY CELL TO MAKE PROTEINS, AND PROTEINS EVENTUALLY THE MOST IMPORTANT PLAYERS THAT CARRY OUT A CELL'S VITAL FUNCTIONS. SO IN ALZHEIMER'S DISEASE, THE DISCOVERY THAT THE GENE WAS A RISK FACTOR WAS MADE ALMOST ENTIRELY BY CHANCE IN 1993. THE GENE LIFSSES ON CHROMOSOME NO. 19, AND IT COMES IF IN THREE FLAVORS, IF YOU WILL. APPLE E 2 AND 3 AND 4. IT'S THE APPLE E 4 GENE THAT'S THE MOST IMPORTANT, MOST ROBUST RISK FACTOR FOR ALZHEIMER'S DISEASE AND WHAT DO I MEAN BY THAT? IN INDIVIDUALS WITH A FAMILY HISTORY -- SO IF YOU HAVE A FIRST PARENT OR A SIBLINGGrD WITH ALZHEIMER'S DISEASE, AND IF YOU HAVE NO COPIES OF THE APPLE E 4 GENE, YOUR LIFETIME RISK OF GETTING ALZHEIMER'S DISEASE IS ABOUT 20 PERCENT. SO A ONE IN FIVE CHANCE OF GETTING ALZHEIMER'S DISEASE. AND THE AVERAGE AGE AT WHICH YOU MIGHT DEVELOP SYMPTOMS OF MEMORY PROBLEMS IS ABOUT 84 YEARS. SO WHAT HAPPENS IF YOU HAVE JUST ONE COPY OF THE APPLE E 4 GENE? YOUR RISK GOES FROM 20 PERCENT TO 47 PERCENT. YOUR AGE OF ONSET DECREASES BY ABOUT TEN YEARS. AND IF YOU ARE AMONG THE SMALL GROUP OF INDIVIDUALS WITH TWO COPIES OF THE GENE, YOUR RISK INCREASES TO ABOUT 9 OPERCENT AND AGENT OF ONSET DOUGH CRESSS FERSFORTH. HAVING SAID THAT, IT'S VERY IMPORTANT TO BEAR THIS KARAT IN MIND. THE APPLE E 4 G BY ITSELF IS NEITHER NECESSARY OR SUFFICIENT TO CAUSE ALZHEIMER'S DISEASE AND THAT'S A VERY IMPORTANT DISCLAIMER TO ESTIMATES OF RISK IN ANYBODY THAT'S CONCERNED ABOUT APPLE E 4 AND RISK FOR ALZHEIMER'S DISEASE. SO HOW DOES THE GENE-TYPE INFLUENCE BRAIN FUNCTION? HERE IS AN EXAMPLE OF HOW WE CAN ANSWER THAT QUESTION. SO WE CAN DO THE SAME KINDS OF PET SCANS THAT WE JUST TALKED ABOUT. THE GOUKOSE -- GLUCOSE PET SCANS AND YOU'RE ALL EXPERTS IN WHAT GLUCOSE PET SCANS COULD LOOK LIKE. SO WE HAVE THREE INDIVIDUALS THAT UNDERGO PET SCANS OF THE BRAIN. YOU HAVE THE NORMAL INDIVIDUAL WITHOUT ANY APPLE E 4 GENES. HERE IS ANOTHER INDIVIDUAL WHO IS AGAIN COG NITIVELY NORMAL, NO MEMORY PROBLEMS. ABOUT THE SAME AGE AS THIS PERSON. AND HERE IS SOMEBODY WITH ALZHEIMER'S DISEASE. AND THEY'VE ALL UNDERGONE GLUCOSE PET SCANS. I'D LIKE TO YOU FOCUS ON THE LEFT HAND COLUMN. JUST IGNORE THE RIGHT HAND COLUMN FOR NOW. LOOK AT THE LEFT HAND COLUMN. NORMAL INDIVIDUAL SHOWS THIS NICE, UNIFORM PATTERN ALL OVER THE BRAIN. THIS INDIVIDUAL WHO IS STILL COG NITIVELY NORMAL, LOOK AT THE UPTAKE OF GLUCOSE IN THIS BRAIN. YOU CAN SEE A STRIKING DIFFERENCE. IT'S MUCH LOWER IN THE TEM PRINCIPAL AND PARITELAL LOBES. AND IF YOU COMPARE THE PATTERN TO SOMEBODY WITH ESTABLISHED ALZHEIMER'S DISEASE, YOU CAN BELIEVE THAT THIS INDIVIDUAL LOOKS MORE ALZHEIMER-LIKE THAN A NORMAL INDIVIDUAL. THESE SCANS ARE VERY IMPORTANT BECAUSE IT GIVES US AN HE WILL GANTS WAY OF MONITORING DISEASE PROGRESSION IN PEOPLE THAT ARE AT RISK BUT WHO HAVEN'T DEVELOPED SYMPTOMS YES. -- YET. SO HAVING TALKED ABOUT APPLE E GENEO-TYPE AND GENETIC RISK FACTORS FOR ALZHEIMER'S DISEASE, I THINK WE SHOULD ALSO MENTION -- TALK ABOUT HOW OUR KNOWLEDGE ABOUT RISK GENES FOR ALZHEIMER'S DISEASE HAS UNDERGONE AN EXPLOSION IN THE LAST COUPLE OF YEARS. SO WE'VE GONE FROM HAVING ONE ROBUST GENETIC RISK FACTOR FOR ALZHEIMER'S DISEASE TO NOW HAVING DISCOVERED TEN NEW GENES FOR ALZHEIMER'S DISEASE AND ALL OF THAT HAPPENED BETWEEN 2009 AND 2011. AND THESE FINDINGS ATTRACTED WIDE ATTENTION. SO HERE IS AN EXAMPLE OF WHAT TIME MAGAZINE CALLED THE MOST IMPORTANT AMONG THE MOST IMPORTANT MEDICAL BREAKTHROUGHS IN THE YEAR 2009, REFERRING TO THE DISCOVERY OF THESE NEW ALZHEIMER'S DISEASE RISK GENES. AND HERE IS AN EXAMPLE OF ANOTHER NEWS STORY FROM THE "NEW YORK TIMES" TALKING ABOUT THESE NEW GENETIC RISK FACTORS FOR ALZHEIMER'S DISEASE. SO THIS WAS A VERY EXCITING DEVELOPMENT. THE WHOLE RESEARCH COMMUNITIES WAS ENTHUSIASTIC ABOUT THESE FINDINGS. BUT AS A LOT OF MY NASHTS CLINICS WILL ASK ME WHAT RELEVANCE THESE GENETIC RISK FACTORS HAVE FOR THEM? I THOUGHT WE CAN LOOK AT THAT BY ANSWERING A SERIES OF QUESTIONS. SO WHAT WILL THE NEW ALZHEIMER'S DISEASE TELL US ABOUT ALZHEIMER'S DISEASE? WILL THEY HELP US IN PREDICTING RISKS FOR ALZHEIMER'S DISEASE? UNFORTUNATELY, NOT BECAUSE IT TURNS OUT THAT THESE GENES HAVE VERY, VERY SMALL EFFECTS IN COMPARISON TO THE APPLE E GENE, THE EFFECT IS VERY, VERY SMALL. SO LOOKING AT THEM AS ADDS VERY LITTLE TO OUR ABILITY TO PREDICT RISK FOR ALZHEIMER'S DISEASE IN SOMEBODY WHO CARRIES THESE GENES. WILL THESE GENES HELP US IN EFFECTIVE DIAGNOSIS OF ALZHEIMER'S DISEASE? AGAIN, THE ANSWER HAS TO BE NO FOR THE SAME REASONS. THEY HAVE VERY SMALL HE CAN'T SIZES AND ARE COMMONLY FOUND AND SO THEY ARE UNLIKELY TO BE USEFUL IN HELPING US BETTER DIAGNOSE ALZHEIMER'S DISEASE. WILL THEY TELL US SOMETHING ABOUT DISEASE MECHANISMS AND HERE I THINK THE ANSWER IS YES AND THAT IS WHY THE RESEARCH COMMUNITY IS ESPECIALLY ENTHUSIASTIC ABOUT THESE FINDINGS, BECAUSE STUDYING THESE GENES IN GREATER DETAIL MIGHT TELL US VERY IMPORTANT THINGS ABOUT DISEASE MECHANISMS, ABOUT DISEASE CAUSATION, ABOUT HOW THE DISEASE STARTS AND PROGRESSES AND THAT IS VERY CRITICAL BECAUSE IT IS THAT WHICH WILL EM HELP US DEVELOP EFFECTIVE TREATMENTS. AND THAT'S THE NOTE OF OPTIMISM THAT I'D LIKE FOR YOU TO TAKE HOME WHEN YOU THINK ABOUT THE NOVEL GENETIC RISK FACTORS FOR ALZHEIMER'S DISEASE THAT HAVE BEEN IN THE PRESS REAM. SO I'D LIKE TO STOP WITH -- RECENTLY. I'D LIKE TO START WITH POINTING OUT A WONDERFUL SOURCE OF INFORMATION HOSTING ON THE NIH WEBSITE CALLED WWW.ALZHEIMER'S.GOV. IT HAS LOTS OF INFORMATION FOR PATIENTS AND CAREGIVERS AND FAMILY MEMBERS. IT HAS USEFUL INFORMATION ABOUT CLINICAL TRIALS, ABOUT ONGOING RESEARCH THAT YOU COULD PARTICIPATE IN, AND I THINK I CAN'T SAY IT OFTEN ENOUGH. I'VE ONLY SHOWN A SNAP SHOT OF RESEARCH. THE TREMENDOUS ADVANCES WE'VE MADE IN UNDERSTANDING ALZHEIMER'S DISEASE, ABOUT HOW IT'S-T STARTS AND PROGRESSES, ABOUT HOW TO IDENTIFY AT-RICK INDIVIDUALS WOULD NEVER HAVE BEEN POSSIBLE BUT FOR THE SELFLESS CONTRIBUTION OF PATIENTS WITH THE DISEASE, THEIR CAREGIVERS AND FAMILY MEMBERS. SO I THINK YOU ALL -- THE WHOLE FIELD OWES A HUGE DEBT OF GRATITUDE TO THE ALZHEIMER'S COMMUNITY. AND HERE IS A SHANE NUMBER THAT YOU CAN CALL THAT WILL PUT YOU IN TOUCH WITH -- AN 1-800 NUMBER THAT YOU CAN CALL IF YOU ARE INTERESTED IN PARTICIPATING IN RESEARCH STUDIES AND CLINICAL TRIALS. THANK YOU VERY MUCH FOR YOUR ATTENTION. [APPLAUSE] >> THE DIRECTOR OF PSYCHIATRY HERE. I FEEL KIND OF AT HOME ACTUALLY. SO WELCOME TO DR. GILL'S HOME. [LAUGHTER] HE DID A WONDERFUL PREVIEW PRESENTATION -- THANK YOU SO MUCH -- I APOLOGIZE FOR MY ANT QALETED WAY OF TEACHING. ANTIQUATED WAY OF TEACHING. I WILL TALK A LITTLE BIT MORE ABOUT THE BRAIN AND WHY THE SLENAGE OF THE BRAIN AND WHAT HAPPENS IN ALZHEIMER'S DISEASE IS INDEED SO COMPLICATED. AND ONE OF THE TAKE-HOME MESSAGES I HOPE IS BEGINNING TO THINK ABOUT AGING AND ONSET OF ALZHEIMER'S DISEASE IN MORE COMPLICATED TERMS BEYOND JUST THE MEMORY LOSS AND BEYOND JUST THE MEMORY IMPAIRMENTS BECAUSE OFTENTIMES WE SEE PATIENTS THAT ARE BEGINNING TO DEVELOP ALZHEIMER'S AND PART OF THE COMPLEX AGENTING WITH REPRESENT WITH ANXIETY, REQUEST-W CONFUSION, WITH DEPRESSION, WITH A HOST OF SYMPTOMS THAT MAY BE IN FRONT AND HEND THEM AS THE MEMORY LOSS AND CHALLENGES WITH PROCESSING THIS INFORMATION. WITH THAT SAID, I'LL DRAW A LITTLE PICTURE THAT WILL -- THIS IS KIND OF A VERY FANCY DRAWING OF THE BRAIN, RIGHT? TO GET YOU ORIENTED, THAT'S AN I. SO THE HIPOCAMPI, THE PARTS OF THE BRAIN THAT SUPPORT MEMORY FUNCTIONING AND AS BEST AS WE KNOW HIPOCAMPUS IS CRITICAL AS A DOORWAY FOR MEMORIES SO IT'S BOTH THE WAY THAT WE ENCODE NEW MEMORIES AND THE WAY THAT WE RETRIEVE OLD MEMORIES. SO THAT DOORWAY, AS IT SHRINKS, AS YOU'VE SEEN IN PREVIOUS SLIDES, BEGINS TO BE INCREASINGLY MORE AND MORE SHUT. IN OTHER WORDS, THE ACQUISITION OF NEW MEMORIES GETS TO BE INCREASINGLY MORE DIFFICULT, AND RETRIEVAL OF NEW MEMORIES BEGINS TO BE MORE AND MORE DIFFICULT. OLD MEMORIES, AS YOU ALL KNOW, ARE WELL-SETTLED. THESE ARE STORIES THAT HAVE BEEN TOLD MANY, MANY TIMES AND THEY CAN LAST A REALLY LONG TIME. BUT AS THE ILLNESS PROGRESSES AND CONTINUES TO ATROPHY, THE DOORWAY INTO MEMORY CLOSES EM COMPLETELY. AND THE IMPORTANT ASPECT OF HOW MEMORY SYSTEMS AND INFORMATION PROCESSES WORK IS IT'S IMPORTANT TO THINK OF THE BRAIN AS A COMPLICATED SYSTEM IN WHICH EVERYTHING BEHIND THIS LINE, WHICH IS A SNARL SULCUS, ONE OF THE SUL CY DUCTOR. EVERYTHING HENDERSON IS DEVOTED TO INFORMATION PROCESSING SO HERE IS WHERE WE SEE THINGS, WE HEAR THINGS, WE FEEL THINGS WHEN WE TOUCH THEM, WHEN SOMEBODY TOUCHES US, AND VARIOUS INFORMATION SOURCES GET COHERENTLY PUT TOGETHER AND THE FRONTAL LOBE, WHICH IS THIS LARGE, LARGE FRONTAL PART IS CALLED THE FRONTAL LOBE. AND WE CAN ROUGHLY SUBDIBIDE THE FRONTAL LOBE INTO THIS LITTLE CIRCLE I JUST DREW. THE PREFONTAL LOBE AND THE REST OF IT IS THE MOERPD MAERPDER OF THE D REMAINEDER OF THE FRONTAL LOBE. IT LITERALLY LOOKS AT INFORMATION STREAMS AND ASSESSES THEM AND DECIDES WHAT TO DO WITH A PARTICULAR INFORMATION SET, WHETHER IT'S A NEWSPAPER ARTICLE OR IT'S A PHONE BILL OR IT'S A PHONE CALL FROM A RELATIVE OR A LOVED ONE. THE DECISION TO ACT IN A PARTICULAR WAY IS THEN EXECUTED BY THE FRONTAL LOBE. WHAT IT ALSO DOES, IT HAS A REALLY COMPLICATED TASK OF DECIDING AMONG EQUI PROBABLE ANSWERS. SO VERY SIMPLE THINGS LIKE I GOT A BILL IN THE MAIL AND WHAT AM I GOING TO DO WITH IT, WHICH IS SEEMINGLY VERY SIMPLE IT A NORMAL BRAIN, AS WE GET OLDER AND OLDER AND WE USE THOSE LITTLE TEASPOONS OF BRAIN, IT BEGINS TO BE MORE AND MORE COMPLICATED TO DECIDE WHAT TO DO WITH IT. AND WITH PATIENTS THAT ARE SUFFERING FROM INSIP YET AL ZIRLES DISEASE, THEY CAN BE QUITE ANXIOUS ABOUT ZAELING WITH EVERYDAY SCENARIOS AND SITUATIONS. PARTICULARLY SO BECAUSE THE PROCESSING OF NEW INFORMATION REQUIRES RETRIEVING OF THE OLD INFORMATION, MEANING THAT EACH TIME WE SEE SOMETHING NEW, THE BRAEN REACHES INTO THE HIPOCAMPUS -- BRAIN REACHES INTO THE HIPOCAMP HIPOCAMPUS -- -- IT TEACHES REACHES INTO THE HIPOCAMPUS TO FIGURE OUT WHAT IS IT THAT I'M LOOKING AT AND DECIDES THIS IS WHAT I'M LOOKING AT AND HAS TO DECIDE BASED ON PREVIOUS EXPERIENCES, THIS IS WHAT I SHOULD DO WITH IT. SO A SIMPLE OBLET OF GOING GROCERY SHOPPING BEGINS TO BE A FORMIDABLE TASK IF YOU THINK OF THE AMOUNT OF BRAIN TISSUE THAT GOT LOST AS THE BRAIN IS BEGINNING TO SHRINK. AND IT IS IMPORTANT TO BE AWARE OF THIS AS WE DEAL BOTH WITH NORMAL AGING PROCESS AS WELL AS APTS PATING THE ALZHEIMER'S ILLNESS PROGRESSION. SOME PATIENTS WITH ALZHEIMER'S LAST A VERY LONG TIME AND SOME PROGRESS VERY, VERY RAPIDLY. BUT BEING AWARE THAT THIS IS AN ORGAN THAT IS UNDERGOING THIS DEGENERATIVE PROCESSES WHERE THE NEURONS ARE DYING AND WHERE EVERLESS TISSUE IS AVAILABLE TO ACCOMPLISH THESE COMPLICATED TASKS, IT HELPS US TO THINK OF THE SYSTEMS WE HAVE TO PUT IN PLACE TO SUPPORT THE PERSON THAT IS GOING THROUGH THE PROCESS OF AGING. HAVING AN ONGOING RELATIONSHIP WITH A CLINICIAN THAT KNOWS THE PATIENT WELL, THAT KNOWS THE FAMILY SYSTEM REALLY WELL CAN USUALLY ESTABLISH AN EARLY DIAGNOSIS. GENES ARE USEFUL. PET SCANS ARE USEFUL BUT STILL NOTHING REALLY REPLACES THE CHILDRENICAL OBSERVATION OF THE PATIENT BY A FAMILY MEMBER, BY A LOVED ONE AND THEN BY A CLINICIAN THAT LOOKS AT THE PATIENT AND SEES THERE IS SOMETHING GOING ON WITH THIS PERSON. WHAT OFTENTIMES COMPLICATION PICTURE AS WELL IS THAT THE NORMAL SHRINKAGE OF THE BRAIN AND IN ALZHEIMER'S EVEN MORE PROGRESSIVE SHRINKAGE OF THE BRAIN IN THE FRONTAL REGIONS IS ALSO CONNECTED TO MOOD STATES. SO OFTENTIMES MELAN COLY, DEPRESSION AND ANXIETY CAN BE THE RESULT OF THIS BIOLOGICAL CHANGE IN THE TISSUE. WE ALSO SEE CHANGES IN THE SLEEP AND APPETITE CYCLE. THE DETERIORATION OF THE ABILITY TO SMELL FOODS, THE DETERIORATION OF ABILITY TO TASTE FOODS LEADS TO DECREASE IN APPETITE, DECREASED INTEREST IN EATING. THE SLEEP CYCLE ESSENTIALLY DETERIORATES DRAMATICALLY BOTH IN NORMAL AGENTING BUT PARTICULARLY IN ALZHEIMER'S. ALL OF THESE ARE THINGS TO BE AWARE OF AND TO ANTICIPATE AS WE TRY TO HELP MANAGE THIS. AS WE DON'T HAVE THE CURE FOR IT, WE ARE STILL MANAGE THIS ILLNESS IN TRYING TO PREVENT DETERIORATION AND PREVENT ANY OWE CURRENCES THAT WOULD FURTHER DISTRESS THE INDIVIDUAL. SO AS YOU CAN IMAGINE, THERE ARE EVENTS IN LIFE THAT WOULD SIGNIFICANTLY DISTRESS AN INDIVIDUAL WHO HAS DETERIORATION OF THE BRAIN TISSUE. SO ANYTHING THAT INVOLVES SIGNIFICANT CHANGE, WHETHER IT IS A CHANGE IN HOUSING OR IT'S A CHANGE IN WHERE THE SHOPPING TAKES PLACE, WHERE THERE IS A CHANGE IN THE FAMILY SYSTEM, OR THERE IS A NEW TELEVISION SET THAT NEEDS TO BE PROGRAMMED, A NEW REMOTE CONTROL THAT WE CANNOT OPERATE ANYMORE -- IT BEGINS TO INDUCE DRAMATIC DISSTRESS. I'D LIKE TO USE AS AN EXAMPLE OF A PATIENT THAT IBBEEN WORKING WITH FOR 11 YEARS, WHO VERY SLOWLY BUT SURELY IS PROGRESSING INTO PRETTY SIGNIFICANT ALZHEIMER'S DEMENTIA. AND AS WE1fu FOLLOWED THE PROGRESSION AND SHE'S AWARE OF WHAT'S GOING ON AND WE ARE SLOWLY DEVELOPING A SUPPORT SYSTEM AROUND HER, THE ONE EVENT THAT REALLY CAUSED DETERIORATION DRAMATICALLY WITHIN TWO WEEKS WAS THE FACT THAT HER GROCERY SHOP HAS CLOSED. AND SHE ALL OF A SUDDEN WAS LOST. SHE DID NOT KNOW WHERE TO GO TO BUY GROCERIES. SHE GOT VERY SIGNIFICANTLY ANXIOUS, MORE DEPRESSED, AND IT REALLY CAUSED A TUMBLE IN THE COLLEGEAL PRESENTATION. SO AS WE MANAGE PATIENTS WITH PROCESSING INFORMATION ISSUES, AND I THINK OF ALZHEIMER'S BOTH AS A MEMORY BUT INFORMATION PROCESSING DISEASE, WE WANT TO DIMINISH THE DISSTRESS, THE INFORMATION LOAD, AND GIVE THEM COPING STRATEGIES FOR DEALING WITH THE CHALLENGES THAT THEY'RE FACING. WE'RE TRYING TON GET THEM INTO HOSPITALS. WE TRY TO PROMOTE IN-PLACE AGING. WE TRY TO STIMULATE THEIR EXISTING MEMORY PATHWAYS. WE TRY TO KEEP THEM INTELLECT AOLLY CURIOUS AND ENGAGED. ANY HE WEREN'T PERSONAL INTERACTION IS HELPFUL. IT PROMOTES THE GROWTH OF NEW MEMORIES. ANYTHING THAT IS EMOTIONAL AND MEANINGFUL, WHETHER IT'S POSITIVE OR NEGATIVE, WILL LEAVE A MORE POWERFUL MEMORY TRACE. OBVIOUSLY, WE WANT IT TO BE A POSITIVE MEMORY TRACE RATHER THAN A NEGATIVE ONE. BUT THE AWARENESS OF THE CHANGES AND OBSERVING THEM IF A CLINICICAL WAY IS IMPORTANT FOR FAMILIES AS WELL BECAUSE THIS ILLNESS PROGRESSES CHANGES THE PERSON THAT WE KNEW IN ONE PARTICULAR WAY, PROVIDERS, WHETHER THERAPISTS OR PSYCHE TERRORISTS OR NEUROLOGISTS -- PSYCHIATRISTS OR NEUROLOGISTS, REALLY IS A COMPLICATED TASK TO HELP FAMILIES DEAL WITH SEPARATION ISSUES. THIS IS INITIALLY SEPARATION FROM THE PERSON WE THOUGHT WE KNEW, ULTIMATELY SEPARATION FROM THE PERSON ALTOGETHER BECAUSE OFTENTIMES THE ILLNESS IS SO SEVERE THAT IT EXCEEDS THE CAPACITY OF THE FAMILY AND THE SOCIAL SUPPORT SYSTEM. SO THAT PATIENTS NEED TO BE PLACED IN ASSISTED LIVING FACILITIES, EVENTUAL NURSING HOMES. AND THENˇ1 THE VERY PAINFUL AND COMPLICATED CONVERSATIONS ABOUT HOW HELPFUL IT IS TO HAVE FAMILY INVOLVED AND HOW NOT HELPFUL IT IS FOR FAMILIES TO CONTINUE TO BE INVOLVED, AT WHICH POINT IN TIME IS CONNECTIONS LOST OR STILL PRESENT? WE HAVE LOTS OF GOOD RESEARCH THAT SUPPORTS THE FACT THAT THERE IS INFORMATION PROCESSING THAT THE PERSON IS NOT EXPLICITLY AWARE OF BECAUSE THEIR PATHWAYS THAT ARE UNDER THE CORTEX WHERE THE BRAIN RECOGNIZES A FAMILIAR FACE AND THROUGH DATA POINTS LIKE SKIN CONDUCTION OR BREATHING, WE CAN DETECT THAT THE PERSON RECOGNIZES THAT THE LOVED ONE JUST WALKED INTO THE ROOM, EVEN THOUGH THEY MAY NOT RECOGNIZE THE LOVED ONE AND KNOW THEIR NAME. THEY'RE UNABLE TO NAME THE PERSON. SO THE PRESENCE OF THE FAMILY IS IMPORTANT. IT'S ALSO CRITICALLY IMPORTANT TO PRESERVE THE KNOWLEDGE OF THE PERSON AS THE PERSON ENGAGES IN THIS JOURNEY OF LIVING WITH ALZHEIMER'S DISEASE. PROVIDERS NEED TO KNOW WHAT KEPD OF -- KIND OF BEHAVIOR FROM THEIR CARETAKER THE PATIENT EXPECTED. WHAT KIND OF MUSIC DID THEY LIKE? WHAT COULD END OF ACTIVITIES DID THEY ENJOY BECAUSE ALL OF THOSE THINGS THE PATIENT SLOWLY BUT SURELY CAN NO LONGER EXPRESS AS A NEED AND DESIRE AND IF SOMEBODY REALLY, REALLY LIKED DUKE ELLINGTON, THEN LISTENING TO THAT KIND OF MUSIC IS VERY, VERY USEFUL AND VERY SOOTHING FOR THE PERSON. SIMILARLY, WE CAN CAPITALIZE ON THE UNFORTUNATE FACT THAT THE MEMORY SPAN CAN BE VERY SHORT AND AS IT GETS MORE AND THE INTO FIVE MINUTES, FOUR MINUTES, THREE MINUTES, ONE OF THE STRATEGIES THAT EXISTS IS THAT THE FAMILIES CAN TAPE, RECORD THEIR NARRATIVE FROM SOMEBODY THAT THE PATIENT KNOWS AND LOVES AND CARES ABOUT VERY MUCH. THEY CAN SIMPLY TALK INTO A MICROPHONE FOR ABOUT FOUR OR FIVE MINUTES AND TALK ABOUT THE FAMILY AND UPDATES THE FAMILY AND THE NEWS AND THAT RECORDING CAN BE LOOPED SO THAT THE PERSON THAT HAS A VERY SHORT MEMORY SPAN REALLY BY THE TIME A FIVE-MINUTE TAPE HAS ENDED, THEY NO LONGER REMEMBER WHAT WAS SAID AT THE BEGINNING OF THE TAPE SO THAT IT'S ALWAYS A NOVEL PIECE OF INFORMATION AND IT'S POSITIVE FROM A FAMILIAR VOICE, IT CAN BE VERY SOOTHING BECAUSE THE BRAIN THAT IS FRIGHTENED, THAT HAS A HARD TIME PROCESSING INFORMATION, THAT IS CONSTANTLY SURPRISED BY ITS ENVIRONMENT, IS A BRAIN THAT IS ALSO EASY TO PRODUCE AGITATION. IF SOMEBODY IS AT HOME WITH A CARETAKER THAT FROM ONE MEN TO THE NEXT THEY NO LONGER REMEMBER, WHEN THAT CARETAKER APPROACHES THE PATIENT -- THANK YOU -- WHENI7' THE CARETAKER APPROACHES THE PATIENT TO GIVE THEM A BATH, FOR EXAMPLE, THAT'S A USUAL COMPLICATED PLACE IN CARE OF PATIENTS -- THE PATIENT WILL EXPERIENCE THAT AS AN AFFRONT BY A STRANGER WHO IS TRYING TO DISROBE THEM. SO THIS IS REALLY A VERY COMPLICATED ACT OF DETOXIFYING SOMEBODY'S ANXIOUSITIS AND A COMPLETE STRANGER. OFTENTIMES IN ADVANCED ILLNESS WHEN THE MEMORY IS SO COMPLETELY GONE, PATIENTS WILL NO LONGER BE ABLE TO RECOGNIZE THEMSELVES, SO THAT IF THEY REPORT HALLUCINATION THIS THEY SAW A STRANGER IN THE BATHROOM, AS YOU UNPACK THE FACT THAT THEY SAW A STRANGE NERT BATHROOM YOU REALIZE THEY SAW THE MIRROR REFLECTION IN THE MIRROR BUT THEY NO LONGER RECOGNIZE THEMSELVES SO THEY PERCEIVE THAT AS A STRANGER IN THE BATHROOM. BUT THINKING ABOUT THE PERSON BEFORE THE ILLNESS STARTED REALLY HELPS US MANAGE THE PERSON AND TO BE AWARE OF AN ABILITY TO EXPRESS NEED. OFTENTIMES AGITATION MAY BE A DESIRE TO GO TO THE BATHROOM. IT CAN BE A THIRST. BUT INABILITY TO VERBALIZE WHAT IS GOING ON COMES ACROSS AS EPISODE OF AGITATION. SO HERE TASK FOR OUR‡ FIELD COMES IN BECAUSE WE ARE OFTENTIMES PSYCHIATRY IS INVITED TO DEAL WITH AGITATION AND OFTENTIMES WE RESPOND TO IT WITH MEDICATIONS BECAUSE THAT CALMS DOWN THE AGITATION. BUT WITHOUT REALLY UNDERSTANDING THE PATIENT, MEDICATIONS ARE OFTENTIMES A QUICK FIX. SIMILARLY, IN TREATMENT OF ALZHEIMER'S ILLNESS FOR WHAT WE HAVE, OFTENTIMES I PERSONALLY FEEL THATWE WE CONTINUE PRESCRIBING ANTI-ALZHEIMER'S MEDICATIONS WAY TOO LONG. THEY HAVE SIDE EFFECTS AND COSTS. RESEARCH DOES NOT SUPPORT THAT THEY REALLY HELP IN ADVANCED ALZHEIMER'S DISEASE. RESEARCH IS PRETTY MUCH CLUSIVE. ION IF YOU AGREE THAT IT HELPS MAYBE PRESERVE SOMEBODY IN THEIR ENVIRONMENT FOR ABOUT A YEAR OR TWO. BUT BEYOND THAT, IT IS REALLY NOT PARTICULARLY USEFUL. BUT WHAT IS USEFUL IS NOTICING SOMEBODY'S DEPRESSION, SOMEBODY'S ANXIETY, AND VERY AGGRESSIVE TREATMENT OF COMORBID DEPRESSIVE SYMPTOMS THAT CAN REPRESENT AS DIMENSIONA AND COMPLICATION DEMENTIA AND WORSEN MEMORY BECAUSE WITH DEPRESSION COMES LOSS OF MEMORY AND DIFFICULTY IN FOCUSING AND DIFFICULTY IN PROCESSING INFORMATION. IF WE DON'T TREAT DEPRESSION AGGRESSIVELY, THE PERSON IS MORE DEPARTMENT INED. SO REALLY, -- DEMENTED. SO WE'RE, WE'RE TALKING ABOUT MANY, MANY SYSTEMS OF THE BRAIN AND NEED TO BE THOUGHT OF BROADLY BEYOND JUST A MEMORY IMPAIRMENT AND ALSO LOOKING AT THE MANAGING OF THE ILINGS FROM THE -- ILLNESS FROM THE PERSPECTIVE OF MULTIDISCIPLINARY MANAGEMENT OF THE PATIENT. THERE ARE MEDICAL ISSUES. THERE ARE HEALTH ISSUES THAT CAN NO LONGER BE EXPRESSED ADEQUATELY SUCH AS PAIN, DISCOMFORT, AND TREATMENT OF THE MENTAL HEALTH COMORBID ISSUES AND GENERAL HELP WITH KAERNG THE FAMILY SYSTEM AND THE PROVIDER SYSTEM. THIS ILLNESS IS VERY, VERY DRAINING ON THE SYSTEM THAT SUPPORTS THE PATIENT WHETHER IT'S A FAMILY SYSTEM OR WHEN THE PATIENT IS ENTHE ASSISTED LIVING FACILITY OR NURSING HOME. IT IS VERY DIFFICULT TO KEEP EVERYBODY SUPPORTIVE, POSITIVE AND ORGANIZED AROUND SOMETHING THAT ULTIMATELY IS DETERIORATING AND EVENTUALLY ENDS IN DEATH. SO WE HAVE VERY COMPLICATED SYSTEMS OF CARE IN PLACE, IN WHICH PROVIDERS ACTUALLY THAT ARE INTERESTED IN HELPING PATIENTS ARE GETTING ADDITIONAL TRAINING -- ACTUALLY, I'LL PUT A PLUG IN AND THE DIRECTOR OF THE SCHOOL OF PSYCHOLOGY ARE LAUNCHING A TWO-YEAR PROGRAM FOR THERAPISTS, PSYCHIATRISTS WHO AND NURSING PROVIDERS6 THROUGH TWO YEARS, WILL LEARN BOTH TO THINK ABOUT THE ILLNESS IN A COMPLEX WAY BUT ALSO LEARN ABOUT WAYS TO MANAGE AN ILLNESS AND TO HELP GUIDE FAMILIES THROUGH THIS PROCESS. SO MEDICATIONS -- EVERYBODY ALWAYS WANTS TO KNOW ABOUT MEDICATIONS. AS I SAID, ALZHEIMER'S MEDICATIONS ALL ARE BASED ON THE PRINCIPLE OF LIGHTING UP THE CORT ESHG. AS YOU SAW -- CORTEX. THE CORTEX IS THIS OUTER LAYER OF THE BRAEN, WHERE NERVE -- BRAIN, WHERE NERVE CELLS LIVE AND FUNCTION. IT TENDS TO BE HYPOACTIVE. SO MOST OF THE ALZHEIMER'S MEDICATIONS TEPID TO LIGHT UP THE BRAIN A -- TEND TO LIGHT UP THE BRAIN A LITTLE BIT. TO KIND OF EEK OUT THAT LAST OUNCE OF PERFORMANCE FROM THE BRAIN. BUT EM, YOU -- EVENTUALLY, YOU GET EVERYTHING YOU CAN OUT OF THE TISSUE AND MANAGE THE ILLNESS -- ANXIETY, DEPRESSION AND AGITATION, AS NEEDED. EVENTUALLY PSYCHEOSIS, WHICH IS DIFFICULTY IN TESTING REALITY TETSSETS IN, WHICH USUALLY STARTS VERY SIMPLE THINGS LIKE -- IT'S REALLY HARD TO BE STUCK HERE. I USUALLY MOVE A LOT. SO LET'S SAY I'M AN OLDER PERSON THAT HAS PUT THIS PEN HERE. AND LET'S SAY THEN TWO MINUTES LATER I MOVE THE PEN OVER HERE. AND HA SECONDS LATER I -- 45 SECONDS LATER I FORGOT THAT I MOVED THE PEN BUT THIS PEN MOVED, SOMEBODY MOVED THE PEN OR LAUNDRY IS TAKEN FOR A WASH AND YOU FORGET TO PICK UP THE LAUNDRY. SOMEBODY STOLE MY LAUNDRY. SO THE BRAIN ALWAYS, EVEN IN ITS IMPAIRED STATE, TRIES TO GENERATE MEANING AND TRIES TRIES TO UNDERSTAND. SO WHEN THEY'RE MISSING DATA POINTS, BRAIN WILL FILL IN THE BLANKS AND BECAUSE OF THE RIDGEDY. WHERE THERE USED TO BE MILLIONS OF NERVE CELLS, THERE ARE FEWER AND FEWER TO PROCESS INFORMATION, YOU TRY TO EXPLAIN TO THE PERSON WHAT HAS HAPPENED BUT THEY DON'T UNDERSTAND ANYMORE. JUST LIKE THEY THEY CAN'T PROGRAM THE VCR ANYMORE THAT THE BRAIN CAN NO LONGER ACCEPT THAT DATA SET SHIFT. AND ANOTHER IMPORTANT THING THAT PEOPLE FORGET, BECAUSE WE ALL ARE ORGANIZED AROUND REALITY, AROUND SAYING TO THE OTHER, AS IF THEIR BRAIN OPERATES LIKE OURS. SO WE OPERATE ON THE PRINCIPLE DON'T YOU KNOW AND DON'T YOU REMEMBER? AND NONE OF THOSE ARE USEFUL. ANY SENTENCE THAT BEGINS WITH THAT IS JUST NOT USEFUL BECAUSE TO THE PERSON THAT'S IN THE EARLY STAGES OF ILLNESS, IT'S A REMINDER THAT THEIR MEMORY IS GOING SO IT'S POWERFULLY DISTRESSING AND REALLY DEPRESSING. BUT EVENTUALLY IT BEGINS IN SOME EXAMPLES TO BE HARMFUL SO THAT IF THERE IS A DRAMATIC LOSS THAT THE PERSON SUFFERED, FOR EXAMPLE, OFTENTIMES IF THE COUPLE MOVED TO AN ASSISTED LIVING FACILITY AND DIES, THE OTHER SPOUSE MAY FORGET THAT HER PUS OR -- HUSBAND OR HIS WIFE DIED. IT IS PATENTLY NOT USEFUL TO TELL THEM REMEMBER YOUR WIFE DIED, BECAUSE THE MEMORY LOSS ERASES THE LOSS ALTOGETHER, SO TO TELL A PERSON AND MOERND THEM THAT THEIR LOVED ONE HAS DIED -- IT'S LIKE MAKING THEM REMEMBER OR OF TELLING THEM THAT THEY DIED FOR THE FIRST TIME OVER AND OVER AND OVER AGAIN. SO TO REALLY THINK OF ALZHEIMER'S DISEASE IS TO THINK ABOUT THE OTHER IN VERY DIFFERENT WAYS THAN WHAT WE NORMALLY DO. AND SITTING WITH A PROVIDER THAT KNOWS HOW TO THINK ABOUT THE PERSON IN THOSE PARTICULAR WAYS IS OFTENTIMES VERY USEFUL. SO NO MORE PICTURES. I'LL STOP HERE. THANK YOU. [APPLAUSE] >> WOW. WHAT INCREDIBLE, INCREDIBLE INFORMATION. I KNOW THERE ARE A BUNCH OF QUESTIONS IN THE AUDIENCE FOR OUR TWO SPEAKERS. FIRST, WE'D LIKE TO THANK BOTH DR. BISETI AND DR. GILL FOR BRINGING US REALLY INSIGHTFUL, ENLIGHTENING INFORMATION IN A WAY THAT THE PUBLIC CAN UNDERSTAND. THANK YOU. WHAT WE'D LIKE TO ASK BOTH OF YOU TO DO IS TO COME UP AND FOR OUR Q&A PANEL AND BECAUSE WE'RE VIDEO CASTING THE LECTURE, WE HAVE TO ASK YOU TO STAY CLOSE TO THE MICROPHONE, IF YOU WOULD. MONIQUE HAS A MICROPHONE IN THE AUDIENCE FOR ANYONE WHO HAS A QUESTION FOR EITHER ONE OF OUR EXPERTS. AND YES, IF YOU WOULD RAISE YOUR HAND, SHE'LL COME AROUND AND WE'LL BEGIN THAT WAY. >> WHY IS THE PATIENT ABLE TO REMEMBER THE QUESTION BUT CANNOT REMEMBER THE ANSWER? WOULDN'T TO BE POSSIBLE TO FIND OUT? >> THERE IS A SPACE IN THE MIND THAT IS CALLED A BUFFER, SO THERE IS A MEMORY THAT THERE ARE VARIOUS KINDS OF MEMORIES. WHERE DID THE QUˇ COME FROM? I'M NOT SURE. OKAY. SO CERTAIN SETS OF INFORMATION WE CAN CALL A HOLD IN OUR MIND, A BUFFER, FOR A LIMITED AMOUNT OF TIME. SO THE QUESTION THAT COMES IN CAN EXIST IN THIS BUFFER FOR A SMALL PERIOD OF TIME. THAT THE ANSWER EXISTS SOMEWHERE ELSE. AND TO ACTUALLY TAKE IN THE QUESTION, HOLD THE INFORMATION, AND REMEMBER THE ANSWER AND PUT IT TOGETHER IS A TASK OF THAT PREFRONTAL PART OF THE BRAIN THAT'S RIGHT UPFRONTS HERE. SO AS YOU CAN SEE, AS YOU TAKE EACH SIMPLE TASK INTO ITS COMPONENT, IT'S ACTUALLY NOT SIMPLE AT ALL. SO WHEN YOU ASK A QUESTION, SOMEBODY CAN MIRROR THE QUESTION BACK TO YOU BUT ALL THIS OTHER COMPLICATED SUCH, IT'S MUCH MORE DIFFICULT. STUFF, IT'S MUCH MORE DIFFICULT. >> HOW DOES A PERSON GET OR END UP WITH TWO COPIES OF THE APO 4 GENE? >> SO IT DEPENDS UPON THE -- HOW DOES -- WHY DO INDIVIDUALS DIFFER IN THE NUMBER OF APO E 4 COPIES? I GUESS THAT WAS THE QUESTION, CORRECT? SO IT DEPENDS UPON THE APO E GENEOTYPE OF THAT INDIVIDUAL'S PARENTS AND HOW DURING CELL DIVISION, THOSE COPIES OF THE GENE PASS FROM ONE GENERATION TO ANOTHER. SO IT DEPENDS ON THE APO E GENE-TYPE OF THE PARENTS OF THAT INDIVIDUAL. GENEO-TYPE. >> ONE QUESTION I HAVE HERE WHAT CAUSES ALZHEIMER'S OR MAYBE YOU DON'T KNOW, TO PROGRESS MORE QUICKLY IN SOME PEOPLE AND MORE SLOWLY IN OTHERS? >> SO THAT'S A GREAT QUESTION. IT'S SOMETHING THAT A LOT OF US ARE KEEN ON FINDING THE ANSWER TO. AND ONE OF THE MOST IMPORTANT QUESTIONS IS EXACTLY THAT. HOW DO YOU PREDICT WHICH GROUP OF PATIENTS WITH MEMORY PROBLEMS WILL PROGRESS FASTER AND WHO IS LIKELY TO STAY STABLE? AND IT'S RESEARCH THAT I ESPECIALLY— AND IT GETS TO THE QUESTION OF WITH WHY WE NEED BIOMARKERS AND BIOMARKERS ARE A FANCY TERM FOR SIMPLE TESTS. SO IF WE COULD DEVISE A TEST, FOR INSTANCE, A BLOOD TEST, THAT COULD TELL US WHICH GROUPS OF PATIENTS WITH THE SAME KINDS OF MEMORY SYMPTOMS WILL PROGRESS MUCH FASTER, SAY A YEAR FROM NOW OR TWO YEARS FROM NOW, WE MIGHT BE ABLE TO BETTER TARGET TREATMENTS OR SUPPORT SYSTEMS FOR THAT PARTICULAR GROUP OF PEOPLE. BUT AS OF NOW, WE REALLY DON'T HAVE A GOOD HANDLE ON THAT QUESTION. IT'S SOMETHING THAT A LOT OF US ARE INVOLVED IN FINDING THE ANSWER TO, TRYING TO PREDICT WHO WILL DEVELOP ALZHEIMER'S DISEASE SYMPTOMS PROGRESSION AT A MUCH FASTER RATE THAN SOMEBODY ELSE. >> JUST TO ADD TO THAT A LITTLE BIT. EVERYTHING IS A COMBINATION OF GENETIC PREDISPOSITION AND ENVIRONMENT. I BELIEVE, SO SOME PEOPLE HAVE GENETIC DISPOSITION TARAPID PROGRESSING ILLNESS. BUT CLINICICALLY WHAT WE DO SEE IS THE PATIENTS WHO SUCCESSFULLY AGE IN PLACE, THAT ARE NOT MOVED AROUND, THAT ARE WITHIN FAMILIAR ENVIRONMENTS THAT ARE NOT EXPOSED TO OTHERWISE PSYCHOSOCIAL STRESSES, THEY TEPID TO STAY STABLE LONGER. >> GO AHEAD. >> DR. GILL MENTIONED AT THE BEGINNING OF HIS TALK THAT WE SHOULD KEEP THE PERSON INTELLECTUALLY ACTIVE. MY QUESTION IS DO EITHER ONE OF YOU HAVE ANY EXPERIENCE WITH WHETHER BRAIN GAMES HELP. I NOTICE, FOR EXAMPLE, THERE IS A MARBLES, A NEW SHOP IN THE MONTEGOMERY MALL THAT SPECIALIZES ONLY IN BRAIN GAMSSES AND THERE IS A LOT OF THEM THAT CAN BE DOWNLOADED. YOU CAN TRY THEM OUT, ET CETERA. DO YOU HAVE ANY EXPERIENCE IN WHETHER THAT REALLY MAKES A DIFFERENCE AND IS IT ONLY IN THE BEGINNING STAGES? IF IT DOES REALLY HELP. BUT IF YOU DO IT ON A REGULAR BASIS, LIKE THREE TIMES A WEEK OR SOMETHING? >> SO THAT'S A GREAT QUESTION. IT'S SOMETHING THAT I'M ASKED BY PATIENTS ALL THE TIME. THERE IS TWO WAYS OF LOOKING AT IT. SO YOU ARE ESSENTIALLY ASKING THE QUESTION ARE THERE FACTORS THAT PROTECT AGAINST ALZHEIMER'S DISEASE AND IF INDULGING -- ENGAGING IN COGNITIVE ACTIVITIES PROTECT US AGAINST ALZHEIMER'S DISEASE? UNFORTUNATELY, WAIT WE LOOK AT PSYCHE EVIDENCE, IT'S A VERY TEDIOUS AND BORING WAY OF LOOKING AT SCIENTIFIC EVIDENCE, AND THAT IS BY LOOKING AT ALL THE PUBLISHED RESEARCH THAT'S OUT THERE. AND LOOKING AT IT IN A VERY UNBIASED, IN A VERY OGNOSTIC WAY AND ASKING WHAT EVIDENCE IS OUT THERE THAT SUPPORTS OR DISPROVES A CERTAIN BELIEF? SO BACK IN 2011, THE NIH HOSTED A CONFERENCE CALLED A STATE OF THE HEALTH CONFERENCE WHERE AN EXPERT PANEL WAS CONSTITUTED TO ANSWER EXACTLY THOSE KINDS OF QUESTIONS. WHAT ARE THE RISK FACTORS? WHAT ARE THE PROTECTIVE FACTORS AGAINST ALZHEIMER'S DISEASE? AND THEY LOOKED AT 25 YEARS' WORTH OF PUBLISHED RESEARCH TO ANSWER EXACTLY THOSE KINDS OF QUESTIONS. AND THEY CONCLUDED THAT THE EVIDENCE EITHER FOR RISK FACTORS OR FOR PROTECTIVE FACTORS WAS VERY LOW, WHICH MEANS YOU REALLY CANNOT DRAW FIRM CONCLUSIONS, WHETHER THEY ARE GOOD OR BAD. BUT HAVING SAID THAT, THEY CONCLUDED THAT THERE WAS SOME EVIDENCE THAT ENGAGING IN COG NITIVELY ESTIMATING ACTIVITIES MIGHT IN FACT REDUCE YOUR RICK FOR ALZHEIMER'S DISEASE, JUST AS ENGAGING IN MODERATE AMOUNTS OF PHYSICAL ACTIVITY MIGHT BE PROTECTIVE. BUT THE EVIDENCE IS LOW, BUT IT'S STILL SUGGESTIVE. >> A COUPLE OF OTHER INTERESTING PIECE OF EVIDENCE ARE THERE IS A PROTECTIVE FACTOR. ALSO RISK FACTORS. THIS IS TONGUE-AND-CHEEK BUT IT'S AN ACTUAL STUDY. APPARENTLY WATCHING DAY TIME TELEVISION ROTS YOUR BRAIN. SKIP OPRAH. AND SOME EVIDENCE OF PEOPLE THAT ARE REALLY, REALLY THIN ARE MORE AT RISK FOR ALZHEIMER'S. >> TO PARAPHRASE THE TOPIC FOR THIS EVENING AS IT WAS TITLED, THE MINUTE I FORGET SOMETHING, IT'S LIKE OH, NO. IS THIS NORMAL? IS THIS THE BEGINNING? HOW DO YOU ADDRESS THAT? WHAT CAN YOU TELL US THAT WOULD MAKE US KNOW WHAT'S NORMAL MEMORY LOSS? >> WELL, THERE IS A NORMAL PROCESS OF AGING AND BRAIN SHRINKS. AND I CAN ASSURE YOU I USED TO HAVE AN ENCYCLOPEDIC MEMORY AND I DIDN'T NEED A MEDICAL RECORD. NOT THE CASE ANYMORE BUT SLOWLY OUR BRAINS GETS LESS PLASTIC. WITH IT BECOMES ABNORMAL IS REALLY WHEN THE SYSTEM AROUND YOU NOTICES THAT YOU ARE REALLY REPEATING YOURSELF OR A PIECE OF INFORMATION THAT SOMEBODY JUST GAVE YOU YOU ARE ASKING FOR AGAIN. SO USUALLY AN ENVIRONMENT THAT INFORMS THAT SOMETHING OUT OF THE ORDINARY IS CHANGING. AND ALSO THERE IS A PARAMATER OF DYSFUNCTION OF HOW MUCH IS RAILED TO MEMORY LOSS. >> WHY IS THERE A DIFFERENTIATION BETWEEN CARDIOVASCULAR DEMENTIA AND ALZHEIMER'S OR IS IT TOO BROAD A TOPIC, ALZHEIMER'S -- I AM TRYING TO DETERMINE WHY ISN'T THERE A BREAKDOWN BECAUSE THEY'RE TWO DIFFERENT SITUATIONS? >> DEMENTIA IS OBVIOUSLY A VERY BROAD TERM AND ALZHEIMER'S HAS GOTTEN POLITICALLY CORRECT. BUT THE TERM IS SEXY SO IT'S PLAMPLET BUT THERE ARE OTHER ALSO DEMENTIAS AS WELL. ANYTHING THAT DAMAGES THE BRAIN PARTICULARLY IS A FINE WILL CAUSE A VERY SIMILAR SYMPTOM SPECTRUM. SO BREAKDOWN IS USEFUL FOR US DIAGNOSEICALLY, CLINICALLY. FOR THE PATIENT IT'S NOT PARTICULARLY USEFUL BUT MANAGEMENT IS ALSO VERY DIFFERENT. WE DO WANT TO DIAGNOSE PARTICULARLY CARDIO VASC COLLAR DEMENTIA. >> AND THERE ARE DISTINCTIONS OF WHAT IS ALZHEIMER'S DISEASE AND WHAT IS VASCULAR DEMENTIA IS. IN SOME INSTANCES IT'S QUITE ARTIFICIALF YOU LOOK AT SOME OF THOSE BRAIN SECTIONS IN SOMEBODY THAT HAD A CLINICAL DIAGNOSIS OF ALZHEIMER'S DISEASE WHEN THEY WERE ALIVE AND IF YOU LOOK AT THEIR BRAINS AFTER DEATH, IT'S DIFFICULT TO FIEND SOMEBODY WITH ONLY ALZHEIMER'S DISEASE PATHOLOGY IN THE BRAIN. THE MOST COMMON PATHOLOGY THAT THE CHANGES ARE CHANGES RELATED TO VASCULAR DEMENTIA AND STROKES IN THE BRAEN. SO THOSE TWO PATHOMGS OFTEN BOHAND IN HAND. PATHOLOGIES GO HAND IN HAND. OUR DISTINCTION IS A DISTINCTION OF CONVENIENCE BUT THEY OVERLAP TO A LARGE EXTENT. >> MOVING BACK TO RISK FACTORS. NOTICING MY ELDERLY RELATIVES, I NOTICED THE ONES THAT HAD THE MOST SERIOUS DECLINES SEEM TO ACCELERATE AFTER THEY LOST THEIR SIGHT OR HEARING OR SENSE OF SMELL -- THINGS OF THAT SORT. AND SO IT SEEMS TO ME I'D BE INTERESTED TO HEAR YOUR COMMENTS ON LOSS OF INPUT. >> ABSOLUTELY. I THINK HEARING LOSS IS ONE OF THE MOST DRAMATIC PRECIPITATING FACTORS AND AS WE SEE CLINICALLY IS PART OF THE HUMAN VANITY, IF YOU WILL. PEOPLE ARE REALLY RESISTANT TO WEARING HEARING AIDS AND THAT REDUCED INPUT BEGINS TO BE THE MOVING PIN. YOU DON'T HEAR THE BEGINNING OF THE A SENTENCE AND THE ENOF THE SENTENCE AND MAKE UP WHAT HAPPENED IN BETWEEN. SO THERE IS A LOT OF CONFAB LATING THAT THE PATIENT DOES AND INCREASINGLY THERE IS MORE AND MORE INTERNAL PROCESSING VERSUS INTERACTING WITH THE OTHER. THE BEST PROTECTIVE FACTOR THAT I CAN THINK OF IS INTERACTING WITH THE OTHER. IT IS CONTINUING MEANINGFUL INTERACTION WITH ANOTHER HUMAN BEING. THAT'S WHAT KEEPS US GOING. SO OFTENTIMES AGING DOES INCLUDE THAT FAMILIES MOVING DOWN IN SEPARATE DIRECTION. THE SINGLE PERSON BEGINS TO BE INCREASINGLY LONELY. REMEMBER, THEY CAN'T DRIVE ANYMORE REALLY. THEY CAN'T TAKE A BUS AND FOLLOW THE TRAFFIC PATTERNS -- ALL OF THAT IS SCARY AND FRIGHTENING AND OFTENTIMES LIKE IN CASE OF MY PATIENT, THE ONLY TIME SHE GETS OUT OF THE HOUSE IS TO SEE ME TWICE A WEEK SO SHE GETS DRESSED UP AND HAS A CAB THAT PICKS HER UP AND SHE COMES TO HER SESSION TO SEE ME. WHEN THAT GROCERY STORE CLOSED, SHE STARTED FORGETTING OUR APPOINTMENTS, WHICH WAS THE BEGINNING OF A REAL DOWNTURN. BUT INPUT IS VERY IMPORTANT. HEARING AIDS, SUPPORT. TASTY FOODS, NOT BLAND FOODS, TO KEEP THE INPUT GOING, IF YOU WILL. >> HI. I AM WONDERING IF SOME OTHER PEOPLE HERE, LIKE MYSELF, ARE WONDERING IF YOU CAN TELL US ANYTHING VAGUELY HOPEFUL. IF EITHER OR BOTH OF YOU COULD SPEAK A LITTLE BIT TO SOME OF THE RESEARCH THAT'S COMING ALONG F IT'S COMING ALONG, ABOUT TREATMENTS, PREVENTION, MORE EFFECTIVE WAYS OF STALLING OUT THE PROCESS? THANK YOU. [LAUGHTER] >> SO EXACTLY A WEEK AGO, THE NATIONAL ENSTITUTE ON AGING HOSTED AN ALZHEIMER'S DISEASE SUMMIT ON THE MEAN KARPS -- CAMPUS IN BETHESDA. MY SKBROSHGS THE HEALTH SECRETARY WAS THERE AS WELL AND UNVEILED A VERY AMBITIOUS PLAN TO HE CAN'TIVELY TREAT ALZHEIMER'S DISEASE IN THE COMING FUTURE. THERE IS A LOT OF RESOURCES THAT ARE NOW GOING TO BE AVAILABLE FOR PROMISING RESEARCH, AND THIS, BELIEVE IT OR NOT, IS A VERY EXCITING TIME, BECAUSE WE ARE GOING TO BE IN A POSITION FOR THE VERY FIRST TIME, TO BE ABLE TO TEST TREATMENTS IN PEOPLE AT MUCH, MUCH EARLIER STAEJS OF DISEASE. SO WHAT WE'VE HAD UNTIL NOW ARE DRUG TRIAL AFTER DRUG TRIAL THAT HAS FAILED IN TREATING PEOPLE WITH ESTABLISHED ALZHEIMER'S DISEASE. SO WE ARE NOW GOING TO BE ABLE TO TEST SOME OF THESE DISEASE-MODIFYING TREATMENTS IN PATIENTS THAT WE KNOW ARE AT EXTREMELY HIGH LISK FOR ALZHEIMER'S DISEASE BECAUSE THEY CARRY A RISK GENE. WE KNOW THAT THEY ARE GOING TO GET THE:Oy DISEASE IN ABOUT TEN YEARS FROM NOW. AND THERE HAS BEEN A LARGE TRIAL THAT IS GOING TO BE FUNDED IN PART BY THE NIH, THAT IS GOING TO TEST AN ANTIBODY AGAINST AMELOID. IN A COLOMBIAN COHORT OF PEOPLE THAT HAVE A KNOWN GENETIC RISK BUT WERE COGNITIVE NORMALLY AS OF NOW. SO IT'S A VERY EXCITING TIME. IT'S GS GOING TO BE FIRST TIME. THERE IS GOING TO BE A ANOTHER STUDIED THAT IS GOING TO LOOK AT THE EFFECTS OF NASAL INSULIN IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT, WHICH IS ALZHEIMER'S DISEASE-LIGHT, IF YOU WILL. SO IT'S A VERY EXCITING TIME. AND TEN YEARS AGO, WHEN I WAS STARTING OUT DOING MY RESIDENCEY, SOMEONE TOLD ME THAT WE'D BE TESTING THESE DRUGS FOR PREVENTION OF EARLIER TREATMENT OF ALZHEIMER'S DISEASE. I WOULD HAVE FOUND IT VERY HARD TO BELIEVE THEM. SO I HOPE YOU WILL TAKE WAY THAT THIS IS THE TIME OF GREAT EXCITEMENT AND KEEP OUR FINGERS CROSSED. >> BUT WHILE WE'RE WAITING, I THINK IT'S ALSO REALLY IMPORTANT TO REMEMBER THAT THIS DISEASE IS OFTENTIMES MORE TRAGIC FOR THE ENVIRONMENT THAN THE PERSON THEMSELVES, BECAUSE IF WE ARE VERY SUCCESSFUL IN MANAGING THE PERSON, MANY, MANY YEARS OF CLINICICAL EXPERIENCE ON ALL LEVELS OF CARE AND A LOT OF NURSING HOME WORK AND IT'S ALWAYS IMPRESSIVE TO SEE HOW A SUCCESSFUL PLACEMENT AND A SUCCESSFUL SYSTEM CAN REALLY MAINTAIN A SIGNIFICANT AMOUNT OF JOY IN THE EXISTENCE THAT IS VERY DIFFERENT AND IT'S VERY CHANGED FROM WHERE YOU MET THE PERSON OR THE WAY YOU KNEW THEM BEFORE. BUT IT IS NOT TRAGIC IN AND OF ITSELF. IT'S JUST A VERY DRAMATIC CHANGE. SO IT'S USEFUL TO THINK OF JOY THAT CAN EXIST WITHIN THIS NEW STATE, WHILE WE'RE WAITING FOR THE CURE. >> YOU MENTIONED EARLIER -- I CAN'T REMEMBER WHICH ONE OF YOU -- THAT IF A PERSON IS DEPRESSED OR ANXIOUS, THAT CAN CAUSE IT TO PROGRESS FASTER. WHAT ABOUT IF A PERSON IS DEPRESSED AND IS UNTREATED KIND OF BEFORE? DOES THAT -- I KNOW YOU DON'T KNOW CAUSES BUT I AM JUST WONDERING THE RELATIONSHIP BETWEEN THAT. AND ALSO, ON TOP OF THAT, ADD, BECAUSE ADD CAUSES RETENTION -- YOUR ATTENTION TO BE DISTRACTED MORE. SO IF YOU HAVE THESE COMBINATION OF THINGS, DOES THAT -- DOES THAT IMPACT GETTING IT? >> SIGNIFICANT DEPRESSION CAN BE CALLED PSEUDODEMENTIA IN ELDERLY BECAUSE IT CAN LOOK LITERALLY LIKE A DEPARTMENT INING ILLNESS. SO DIAGNOSING DEPRESSION IS REALLY IMPORTANT BECAUSE IT'S WHAT WE WOULD CALL REVERSIBLE CAUSE OF DEMENTIA IN THIS PARTICULAR SITUATION IT'S BASED ON HISTORY OR STRESSORS OR FAMILY HISTORY AND AN ATTEMPT TO TREATMENT WILL REVEAL IF WE ARE SUCCESSFUL AT TREATING DEPRESSION, THE PERSON WILL GET COGNITIVELY SIGNIFICANT BETTER. A.D.H.D. IS A CONSEQUENCE OF THE FRONTAL LOBE THAT DRIVES WHO WE ARE SO ONE OF THE MANIFESTATIONS OF DEMENTIA, DEPRESSION, BIPOLAR ILLNESS AND SKITS FRAEN -- SKITS FRENIA IS DIFFICULT IN FOCUSING AND THEY HAVE A HARDER TIME ENCODING MEMORIES BECAUSE THEY CANNOT DO THE INTERNAL REHEARSAL AND REPETITION THAT IS REQUIRED TO REALLY SET THAT MEMORY DOWN. SO THAT THERE IS A FLEETING IMPRESENT IN THIS BUFFER THAT I MENTIONED EARLIER THAT EVAPORATES AND IS GONE. SO AND THAT'S WHAT COULD END OF THE MULTIPEOPLE TEAM THAT MANAGES THE PERSON COMES INTO PLAY. ION IF YOU HAVE ANY THOUGHTS ON IT.1¨ >> I KNOW I COMPLETELY AGREE AND NOT ONLY IS IT IMPORTANT TO RULE OUT DEPRESSION AS A CAUSE FOR THE MEMORY SYMPTOMS THAT BRING A PATIENT INTO CLINIC. THERE IS EMERGING EVIDENCE NOW THAT TREATING DEPRESSION EARLY ON MIGHT, IN FACT, SLOW THE PROGRESSION OF THAT+++ I DON'T KNOW IF THAT ANSWERS YOUR QUESTION, BUT THAT'S ABOUT ALL THAT WE CAN SAY AT THIS TIME AS FAR AS THE ROLE OF DIET AS A PROTECTIB AGENT IS CONCERNED. THERE IS SOME SUGGESTIVE EVIDENCE THAT EAG THE KINDS OF DIET THAT YOU MENTIONED MIGHT BE PROTECTIVE. >> AND THE CLINICIANS WILL SAY IT'S NOT GOING TO HURT YOUT CAN ONLY HELP SO GO FOR VEGGIE. >> WHEN I WAS YOUNG, I HAD HEAD INJURY, SOION WHEN I'M 18, WILL THAT CAUSE -- 80 TO ME? THAT HEAD INJURY, WILL THAT CAUSE ALZHEIMER'S DISEASE OR NOT? >> SO REPEATED HEAD TRAUMA IS AN ESTABLISHED RISK FACTOR FOR ALZHEIMER'S DISEASE IN GERM, YES, WHICH IS WHY IN TERMS OF LOOKING AT YOUR GENETIC RISK FACTORS, ONE OF MY ATTENDANTS IN MEDICAL SCHOOL USED TO SAY IT'S POSSIBLY BEST FOR YOU NOT TO BECOME A PROFESSIONAL BOXER. IT'S A FLIPPANT COMMENT BUT IT KIND OF DISTILLS HOW WE LOOK AT RISK FACTORS ALONE OR IN COMBINATION. THE SHORT ANSWER TO YOUR QUESTION IS REPEATED HEAD INJURY IS OFTENTIMES A RISK FACTOR FOR ALZHEIMER'S DISEASE. BUT I WOULDN'T WORRY TOO MUCH ABOUT IT IN YOUR CASE UNTIL YOU ACTUALLY TALK ABOUT YOUR SPECIFIC CLINICAL HISTORY WITH YOUR MEDICAL CARE PROVIDER. >> SOMEONE -- SNA >> [INAUDIBLE] >> SIR, YOU'VE ALREADY SPOKEN ONCE. >> WE HAVE OVER FIVE MILLION PEOPLE WITH ALZHEIMER'S IN THE U.S. HOW DOES THIS COMPARE WITH COUNTRIES THAT HAVE MORE COMPLICATED LANGUAGE THAN ENGLISH AND THE REASON PERHAPS I'M ASKING THIS IS I WAS TOLD IF YOU DO CROSSWORD PUZZLES YOUR MEMORY IS LIKELY TO LAST LONGER. THANK YOU. >> SO IT'S A VERY INTERESTING QUESTION. WE'VE SORT OF ADDRESSED THAT WHEN SOMEBODY ASKED ABOUT HOW ENGAGING IN COGNITIVE ACTIVITIES MIGHT BE PROTECTIVE. SO THERE IS SOME EVIDENCE TO SUGGEST THAT ENGAGING IN COG NITIVELY ESTIMATING ACTIVITIES MIGHT BE PROTECTIVE. BUT THE EVIDENCE FOR THOSE KINDS OF OBSERVATIONS IS LOW. >> AND I'M NOT AWARE OF ANY CROSS CULTURAL DIFFERENCES BASED ON COMPLEXITY OF LANGUAGE OR LIFESTYLE THAT WOULD HELP PROTECT FROM ALZHEIMER'S. >> IN SOMEONE THAT IS NOT EXHIBITING SENS OF DEPRESSION, IS THERE -- WHAT WOULD BE YOUR RECOMMENDATION FOR A FIRST STEP TO SEE IF IT'S ACTUALLY MEMORY LOSS OR ALZHEIMER'S? IS THERE A TEST FOR THIS APO E 4 GENE OR ANYBODY COULD GET THAT TEST OR THROUGH A BLOOD TEST TO FEPD OUT WHEN I GET TO SUCH AND OFF AN AGE I AM GOING TO BE MORE OR WHAT WOULD BE YOUR FIRST STEP? TO SIT DOWN WITH SOMEBODY TO HAVE AN MRI OR A BRAIN SCAN OR -- >> SO ACTUALLY A LOT OF PRETTY PICTURES. A LOT OF FANGSY BRAIN SCANS. A LOT OF VERY SOPHISTICATED IMAGING METHODS. WE'VE LOOKED AT MRI SCANS AND PET SCANS BUT THE MOST USEFUL DIAGNOSTIC TEST FOR SOMEBODY WITH MEMORY PROBLEMS THAT COMES TO MY CLINIC IS TO SIT DOWN WITH THE PATIENT, MEET THEIR FAMILY MEMBER AND GET A DETAILED CLINICAL HISTORY. ASK ABOUT WHAT KINDS OF MEMORY PROBLEMS THEY HAVE, HOW DID THEY START, HOW DID THEY PROGRESS? DOES THE MEMORY PROBLEM AFFECT THEIR DAILY FUNCTIONING? HOW HAS THEIR ABILITY TO DO CHORES AROUND THE HOUSE CHANGED OVER THE LAST ONE YEAR AND TEN YEARS? THAT IS THE FIRST POINT AT WHICH YOU GAIN INFORMATION THAT HELPS YOU TO A DIAGNOSIS. EVERYTHING ELSE, INCLUDING ALL THE FANCY BRAIN SCANS I'M SHOWING YOU, ALL THE BLOOD TESTS, ARE ONLY HELPFUL IN CONTRIBUTING TO THAT PROCESS. BUT THE MOST CRITICAL STEP I WOULD ARGUE, IS TO ACTUALLY GET A CLINICAL HISTORY, BOTH FROM THE PATIENT, AS WELL AS THE CAREGIVER. >> AS WELL AS I AGREE TO THAT COMPLETELY. A FAMILY HISTORY AS WELL. IF YOU HAD A MOTHER WHO DIED OF ALZHEIMER'S OR IF A GRANDMOTHER DIED -- IF IT RUNS IN THE FAMILY, WY SAY DEFINITELY BUY LONG TERM CARE INSURANCE. BUT IF YOU HAVE A LONG LONGEVITY WITH NO COGNITIVE ISSUES IN THE FAMILY, THAT WOULD BE ALSO AN IMPORTANT DATA POINT. >> CAN YOU COMMENT ABOUT RESEARCH BEING DONE WITH KIR CUMIN? >> SO THERE IS A LOT OF INTERESTING RESEARCH ON KIR CUMIN. FOR THOSE WHO DON'T KNOW IS THE CURRY SPICE IN INDIAN FOOD. IT'S A YELLOW SPICE THAT GOES INTO VIRTUALLY EVERYTHING TO DO WITH INDIAN CUISINE. THERE IS A LOT OF EVIDENCE FROM THE BASIC SCIENCE LABS. THESE ARE EXPERIMENTS PERFORMED IN TRANSGENIC ANIMAL MODELS WITH THE DISEASE. WHERE CUMIN HAS BEEN SHOWN TO HAVE A PROTECTIVE PATROL AND -- ROLE AND THERE IS SOME EPIDEMIOLOGICAL EVIDENCE THAT DIETS RICH IN KIR CUMIN, FOR INSTANCE, INDIAN DIETS MIGHT ACTUALLY BE PRECIVE. BUT AGAIN, WE HAVEN'T DONE A RIGOROUS STUDY TO ESTABLISH WHETHER THAT IS A PROTECTIVE FACTOR OR NOT DEFINITIVELY. BUT THERE IS BASIC RESEARCH, LOTS OF PEOPLE INTERESTED IN ASKING THAT QUESTION. AND FROM BASIC SCIENTIFIC EXPERIMENTS, IT DOES LOOK AS IF IT MIGHT BE A PROMISING AGENT FOR FURTHER STUDIES. >> THANK YOU. REGARD THIS TIME I'D LIKE TO MOVE TOWARDS THE CONCLUSION OF OUR EVENING. I AM SURE THAT BOTH OF OUR PHYSICIANS WILL BE HAPPY TO STAY A FEW MINUTES AFTER, IF YOU HAVE A SPECIFIC QUESTION, BUT PLEASE REMEMBER TO TURN IN YOUR EVALUATIONS AND WE HOPE YOU HAVE A VERY SAFE DRIVE HOME. PLEASE GIVE OUR PHYSICIAN EXPERTS A HUGE ROUND OF APPLAUSE. [APPLAUSE] CLEARLY, THIS EVENING WAS ENGAGING FOR EVERYONE. I THINK WE COULD STAY A LOT LONGER, AND AGAIN, THANK YOU FOR TAKING YOUR TIME. WE'RE GRATEFUL FOR THE EXPERTISE AND YOU WERE HERE TO SHARE AND ON BEHALF OF THE NIH, SUBURBAN HOSPITAL, JOHNS HOPKINS MEDICINE, WE WELCOME YOU BACK AND DAYS TO COME WITH MORE GREAT EDUCATION SESSIONS. THANK YOU.