Paul B. BeesonCareer Development AwardsIn Aging Research Program

2009 ReportFeaturing the 2007 Scholars

Sponsors:

National Institute on AgingThe Atlantic PhilanthropiesThe John A. Hartford FoundationThe Starr FoundationThe National Institutes of Health

Office of Dietary Supplementsand an anonymous donor

Administered by:

National Institute on AgingAmerican Federation for Aging

Research

Sponsors:

National Institute on Aging

The Atlantic Philanthropies

The John A. Hartford Foundation

The Starr Foundation

The National Institutes of HealthOffice of Dietary Supplements

and an anonymous donor

Administered by

National Institute on Aging

American Federation for AgingResearch

The Paul B. BeesonCareer DevelopmentAwards in Aging ResearchProgram

All inquiries and correspondenceshould be directed to:

American Federation for Aging Research55 West 39th Street, 16th FloorNew York, NY 10018T: 212.703.9977F: 212.997.0330E: grants@afar.orgwww.afar.org, www.beeson.orgwww.infoaging.org, and www.healthcompass.org

Stephanie LedermanExecutive Director

Katherine Kelly AppleCommunications and Development Associate

Catherine CullarAdministrative Manager

Stacey HarrisDirector, Communications

Hattie HermanProgram Officer

Nancy O’LearyDirector, Development

Jacalyn SchwartzDirector, Finance

Veronica SmithProgram Associate

Odette van der WillikDirector, Grant Programs

About the American Federationfor Aging Research (AFAR)

AFAR is a nonprofit organization whosemission is to support biomedical researchon aging. It is devoted to creating theknowledge that all of us need to live healthy,productive, and independent lives. Since1981, AFAR has awarded more than $113million to nearly 2,500 talented scientists aspart of its broad-based series of grantprograms. Its work has led to significantadvances in our understanding of agingprocesses, age-related diseases, and healthyaging practices. AFAR communicates news ofthese innovations through its organizationalweb site www.afar.org and educational websites Infoaging (www.infoaging.org) andHealth Compass (www.healthcompass.org).

Editorial direction was provided byStacey Harris

We would like to thank the BeesonScholars for reviewing this reportfor scientific accuracy.

About Paul B. Beeson, MD(1908-2006)

Paul B. Beeson, a distin-guished physician, researcher,and teacher, was the inspira-tion behind the creation of thePaul B. Beeson CareerDevelopment Awards in AgingResearch Program. It was hisvision to increase the numberof physicians with a combinedclinical, academic, and scien-tific expertise to care for agrowing older population.

At the time of his death,Dr. Beeson was professoremeritus of medicine at theUniversity of Washington.

Though “retired,” he remained active in thefield of aging research, attending meetingsand advising many Beeson Scholars. In hislong and distinguished career, he profoundlyinfluenced the career paths of many physiciansand was stalwart in his concern for the careand dignity of patients.

It is a tribute to him that to date, 152 physi-cian-scientists throughout the United Statesand the Island of Ireland have emerged asleaders in the field, changing the landscape ofgeriatric medicine and aging research. Hisenduring legacy is that these leaders will notonly provide the best possible care for olderadults, but will also go on to train the nextgeneration of leaders.

12009 Report

This report celebrates the 14th yearof the Paul B. Beeson CareerDevelopment Awards in AgingResearch Program and introducesthe 2007 Beeson Scholars, whosework, already in progress, is enhanc-ing academic careers in agingresearch, teaching, and practice.

Every year, we take pride in theextraordinary men and womenwhose innovative research have

been selected from 40 of the nation’s most prestig-ious medical schools and research institutions. Theprogram remains competitive; only 152 physician-scientists have been named Beeson Scholars since1995, an award of utmost standing in the agingresearch and geriatric medicine communities.

The Beeson program has become a model ofcooperation between foundations and government.Our partnership with the National Institute on Aging

Message from AFAR’s Executive Director

(NIA), now in its fifth year, has allowed the program toexpand and evolve into a leadership powerhouse inaging research and clinical care.

Past Beeson Scholars have made their mark inacademic medicine, research, and clinical practice andwe expect no less from our 2007 Scholars. Their innova-tive research — from the role of cognitive function infalls and depression in the elderly, to the connectionbetween cardiac health and brain aging, to racialdisparities in hospice use — already stand on their own,but combined with the work of their peers will greatlyimpact the health and quality of life of older adults.

Stephanie Lederman

StephanieLederman

“TheBeesonprogramhasbecomeamodelof cooperation

between foundationsandgovernment.”

independence in old age, diseasesand disabilities of old age, andissues in clinical management andsystems of care. Each year, up to 10clinically trained investigators are

selected in the U.S. and one in the Island of Ireland.The benefits of the award for Beeson Scholars arenumerous and career-changing, helping them developresearch during a critical period in which funding islimited. They include:

• Flexible, generous funding with ample resources topursue an innovative research program;

• Protected time for research;

• An outstanding support system with senior facultyat each Scholar’s institution serving as mentors, andScholars matched with members of the BeesonProgram Advisory Committee;

• Extensive networking opportunities within the vastnetwork of Beeson Scholars; and

• Alumni participation through annual meetings,where Scholars can assume leadership roles in theprogram, including becoming mentors to the nextgeneration of Beeson Scholars.

Since the first group of Beeson award recipients wasselected, the program has blossomed into one of thenation’s most well-respected career development

From Innovation to Revelation:The Paul B. Beeson Career Development Awards inAging Research Program

The rapidly expanding aging population in the U.S.and beyond requires a forward-thinking approach toaddressing the strains that will be placed on ournation’s healthcare system in the years ahead. Thisapproach requires more geriatrics research andtraining, integrating high-quality medical andsupportive careservices withsupport ofscientific researchto ensure that welive healthierlonger, lesssusceptible todisease anddisability.

Nearly 15 yearsago, severalphilanthropiesrealized the needto develop aprogram to assistin the development of future leaders in the field ofaging, encouraging physician-scientists to pursueindependent, ground-breaking, clinically relevantresearch, and deepen the commitment of academicmedicine to research in aging that would translateresearch outcomes into advances in treatment,prevention, and service. Together, they created whattoday is known as the Paul B. Beeson CareerDevelopment Awards in Aging Research Program, oneof the largest programs in the U.S. that supports agingresearch and geriatric medicine. Generously supportedby the National Institute on Aging, The AtlanticPhilanthropies, The John A. Hartford Foundation, TheStarr Foundation, the National Institutes of HealthOffice of Dietary Supplements and an anonymousdonor, and administered by the American Federationfor Aging Research with the NIA, the Beeson award hasprovided nearly $80 million to 152 researchers since1995.

With the addition of the National Institute on Aging aspartner in 2004, Beeson Scholars receive between$600,000 and $800,000 over three to five years tostudy the biology of aging, maintenance of health and

Paul B. Beeson Career Development Awards In Aging Research Program2

2008 Annual Meeting Poster Session

programs, attracting and supporting some of thebrightest minds not only in aging but also in scienceas a whole. “The Beeson Scholars are an extraordinarygroup of people,” says Christopher A. Langston, PhD,program director of The John A. Hartford Foundation,one of the program’s founding sponsors. “All theScholars are outstanding researchers, and in manycases, leaders in their respective disciplines.”

Florence A. Davis, president of The Starr Foundation,adds that, “The Beeson award permits investigators toexplore problems that previously have been neglectedfor lack of funding. That can make a big difference inhow long and how well a person lives. The programmay also encourage more scientists to pursue careersin geriatrics and gerontology.”

The Beeson program has evolved to includeexpansion to the Island of Ireland as well as thecreation of a collaborative grants programencouraging Beeson Scholars to partner and expandon their primary Beeson-supported research (see boxpage 5).

With funding from The Atlantic Philanthropies, theBeeson program expanded internationally in 2007,supporting junior physician faculty on the Island ofIreland, with the goal of helping to train physicians ingeriatrics, build Ireland’s capacity to provide high-quality care for older adults, and advance knowledge ofeffective geriatric care. Three physician-scientists havebeen named Beeson Ireland Scholars so far. “Our goalsfor the Beeson Ireland program are similar to the U.S.program: to take academic stars who are conductingresearch relevant to aging and firmly ground theircareers in geriatrics,” says Brian F. Hofland, PhD,director of the Ageing Programme at The AtlanticPhilanthropies, also a founding partner. “Both thepopulations of Northern Ireland and the Republic ofIreland are rapidly aging and we want to furtherdevelop the human capital in this important field byproviding an opportunity for talented faculty to maketheir mark and work in areas of increasing importance.”

2009 Report 3

Point of View – NIAWe joined the Beeson program because of aconfluence of needs, one being our alarm at thedecline in professionally trained researchersobtaining NIA and NIH funding. We saw theBeeson program as a way to address that gap. Webelieved that the resources offered through theprogram coupled with the annual meetings andnational mentoring would be particularly attractiveto relatively newly trained clinician-scientists.

We are very pleased with the success of theprogram to date. At the application and awardstage we continue to see a strong response to eachyear’s solicitation and are impressed that thereviewers of the applications frequently commenton the overall strength of the applications. As wehad hoped, most of the awardees are the kind ofclinician-scientists that we intended to attract. Everyyear, the program has had awards going to all broadscientific areas in the NIA’s mission – from the verybasic to clinical and translational research. In terms

of outcomes we have seenincreasing numbers of Beesonawardees compete successfullyfor R01 and other research grantfunding both from NIA and fromother NIH Institutes and Centers.

The vibrancy in the program iswell captured at the annualmeetings. These awardees sharetheir research findings with eachother and often form

collaborations. Attendance from former Beesonawardees is high, showing a healthy continuingidentification with the program and a welcomedesire to give back, both through formal mentoringand through informal advice.

Robin A. Barr, DPhilDirector, Division of Extramural ActivitiesNational Institute on Aging

Robin A. Barr

I was fortunate to be among the firstBeeson Scholars selected in 1995.Looking back, this was a pivotalmoment in my career as it allowedme to pursue my ongoing researchprojects and initiate new projectsunencumbered with worries aboutsources of funding and administrativeresponsibilities during a critical periodof transitioning from a junior investig-ator to a more established one.

The Beeson program has grown dramatically to includemore collaboration among the Scholars, addressing themultiple influences at play in aging research from thecellular to societal that require novel approaches andgreater interactions among disciplines. This sharedrepository of information will only enhance human healthas we age. An example of this is the Hartford/AFARCollaborative Research Awards that specificallyencourage collaborations between Beeson Scholars. Inmy case, the Beeson program brought Todd Golde, a1997 Scholar, and me together for one of the mostproductive projects in my professional career. Whilepresenting at a Beeson-sponsored symposium, werealized that our shared research interests werecomplementary and ripe for partnership. This led to thediscovery of a new class of compounds, gamma-secretase modulators, that are now being pursued byacademic laboratories and the pharmaceutical industryas a potential Alzheimer’s disease treatment.

Now as chair of the Beeson Program AdvisoryCommittee, I am honored to remain involved with theprogram. Funding for this distinctive program is always

a top priority and in the current financial climate, theremay be challenges. I have seen a number ofcolleagues forced to leave academic medicine duringtheir critical formative years — the period aftersecuring their first faculty position – with so muchpromise leaving with them.

Another priority is to continue the strong emphasis onmentoring, a key factor to ensuring academic successamong the Scholars. Due to the lack of mentors, juniorfaculty members are sometimes left to succeed ontheir own without a strong network of teachingsupport. One of the duties of the Advisory Committeeis to mentor incoming Beeson Scholars, providingtimely professional and personal advice outside of theScholars’ institutions. The combination of funding andmentorship has a direct impact on whether talentedinvestigators advance in their academic careers.

Lastly, we participate in the selection process that is ledby the National Institute on Aging review section. Wehope to continue attracting the very best clinician-investigators from some of the nation’s leading academicinstitutions combining basic, clinical, and translationalresearch in aging and age-associated diseases.

It is my pleasure to introduce you to the 2007 Scholars.

Edward H. Koo

Letter from Edward H. Koo, MDChair of the Program Advisory Committee

Edward Koo

4 Paul B. Beeson Career Development Awards In Aging Research Program

52009 Report

As physician-scientists, the Beeson Scholars areuniquely positioned to play a crucial role in thetransfer of findings that can transform scientificknowledge and institute changes in medicalresearch necessary to improve the health care andindependence of older Americans.

Often, the success of research efforts depends on thecollaboration and exchange among researchersengaged in numerous disciplines. The Hartford/AFARCollaborative Research Awards – created as a onetime grant program — stimulates collaborationsamong Beeson Scholars to move beyond theconfines of their own disciplines and explore newmodels of interdisciplinary research.

In 2007, five research teams of Beeson Scholarsreceived $400,000 each to investigate cognition and

Hartford/AFAR Collaborative Research Awards: Expansion of thePaul B. Beeson Career Development Scholars Program

physical rehabilitation; novel forms of therapy in theprevention and treatment of Alzheimer’s disease;memory decline; the role of inflammation incognitive decline; and the protective benefits of apreviously considered toxic metabolite in aginghearts and brains.

“There are major opportunities and gaps in researchon aging that no single investigator could tacklealone,” said Corinne Rieder, EdD, executive directorof The John A. Hartford Foundation. “Research onaging encompasses many areas of investigation andcare: from the very basic biology of aging processesto the clinical and social care needs. Our BeesonScholars are the top scientists in the nation – a braintrust to help tackle the many research and clinicalchallenges of geriatric medicine. The prospects forthis collaborative effort are great.”

“This award has enabled us to establish amultidisciplinary working group that includesgeriatricians, psychiatrists, anesthesiologists, andsurgeons who are all focused on improvingoutcomes in vulnerable older adults who areundergoing surgery and anesthesia. No onemember of this investigative team could do thisresearch alone. The Beeson support has allowedideas that we developed together to flourishoutside of our perceived boundaries.”

Laura L. Dugan, MDUniversity of California, San DiegoJeremy D. Walston, MDJohns Hopkins University School of Medicine

Research Focus:Systemic Inflammation and Central NervousSystem Dysfunction: A Mechanistic andTranslational Pilot

“The Hartford/AFAR Collaborative ResearchAward encouraged us to realize that theapproaches we had separately developed forpromoting neurogenesis might be combined in asynergistic way. The award has made it possiblefor us to apply the first generation of smallmolecule growth factor mimetics developed in theStanford lab in the context of the novel imagingand exercise protocols that were pioneered atColumbia University’s lab. This combinedapproach might allow us to reverse the decline inneurogenesis that occurs during aging.”

Frank M. Longo, MD, PhDStanford University School of MedicineScott A. Small, MDColumbia University School of Physicians andSurgeons

Research Focus:Ameliorating Age-related Memory Decline

The dominant risk factor forAlzheimer’s disease is increasingage. And yet, researchers knowagonizingly little about themechanism that doubles the riskevery 5.5 years after a personreaches the age of 60. At least 5.2million adults in the United Statesare now living with the disease,according to the Alzheimer’s

Association. By 2050, that number could triple. Ifresearchers hope to reverse that trend, they mayneed considerable assistance from neurologists likeDr. Randall Bateman, whose research on the cause,diagnosis, and treatment of Alzheimer’s focuses onhow an unusual protein called amyloid-beta (Aß) ismetabolized in the human brain.

“What we know is that in Alzheimer’s, the protein is1,000-fold above its normal level,” Dr. Bateman says.“What we don’t know is why that build-up occurs, butwe’re fairly confident that it leads to a cascade ofevents that leads to dementia.” Recent research byDr. Bateman has uncovered some tantalizing cluesabout how humans metabolize Aß. Younger adults, forexample, can clear away about eight percent of theprotein from the brain every hour, based on measuringlabeled Aß in the cerebrospinal fluid.

“Our hypothesis is that as we get older, that percentagerate changes,” Dr. Bateman says. “You make too much,or there’s a decrease in the clearance of the Aß.” To testthat hypothesis, he is studying the clearance rates andcerebrospinal fluid contents in volunteers ranging fromtheir 20s to their 90s. “By looking at all these differentages, we think we’ll be able to see the effect that aginghas on the protein in the brain.”

For his Beeson project, Dr. Bateman will be comparingAß metabolism in 30 healthy young adults with that of30 healthy middle-aged adults. An in vivo labeling

process will allow his team to tag the Aß protein as ithas been made in the brain, while a lumbar catheter(similar to that used for an epidural) will sample theprotein levels in the cerebrospinal fluid every hour for36 hours. A specialized mass spectrometry techniquecan then sort out the slightly heavier tagged version ofthe protein from pre-existing Aß.

Dr. Bateman compares the challenge to calculatingthe flow and clearance rate of water as it enters a sinkthrough a faucet and leaves through an open drain.Without labeling, an observer could only gauge theoverall water level. But Dr. Bateman’s method, akin todyeing the water blue as it flows in from the faucet,should help his team track the Aß protein. In aseparate but related study, he will compare theprotein contents of cerebrospinal fluid samples takenfrom 50 people with Alzheimer’s disease to the fluidcontents of 50 comparably aged but healthy people.

Armed with the new information, Dr. Bateman hopesto learn why aging carries such a large increase in riskfor Alzheimer’s, and how to devise a better way oftesting therapeutics to ensure they hit the right targetsin the brain. “If you develop therapies where you wantto lower the production rate of Aß,” he says, “at leastyou’ll know that your drug is doing what it is designedto do.”

The Beeson award, Dr. Bateman says, has given himthe practical means to follow his long-standing interestin how the brain works. He is especially thankful for theprogram’s strong focus on career development and forannual meetings that he calls a highlight of his year.“You get a chance to sit down with scientists who arenot in your field. There’s a lot of brainstorming, think-tank activities, and that’s incredibly enriching,” he says.“That really brings a lot of new ideas and newexcitement. The other big advantage is that you get tonetwork with other leaders in the field. In my opinion,it’s a major part of the program, which is invaluable.”

Abeta and Proteomic Analysis of Cerebrospinal Fluid inAlzheimer’s Disease and Aging

Randall J. Bateman, MDAssistant Professor of NeurologyWashington University School of Medicine

MENTORS:John C. Morris, MDDavid M. Holtzman, MD

Bateman

6 Paul B. Beeson Career Development Awards In Aging Research Program

72009 Report

An 85-year-old woman may notwant to live forever, but may carevery deeply about how she dies andwhether she can continue living athome until then. What would high-quality healthcare mean for her?Unfortunately, few measures exist toprovide even basic indicators ofquality for the nation’s oldestpatients, a compelling reason for

Dr. Julie Bynum to ramp up her own research examininghow such healthcare is delivered. “We don’t know fromclinical trials,” she says. “And the goals of care are quitedifferent for older people.”

The key, according to Dr. Bynum, is providing care thatmatches a patient’s stated goals. “My basic idea isthat every treatment choice includes both harm andbenefit. The only way to know what is right for theindividual is to make sure that the individual isinfluencing the choice,” she says. To that end, she isexploring how the United States healthcare systemshapes treatment choices and care among the elderly.“The reason is that we don’t have a lot of evidence forwhat’s harmful and what’s beneficial.”

Even before she became a physician, Dr. Bynum knewshe wanted to take care of older adults. While in medicalschool at Johns Hopkins University in Baltimore, shereceived a Medical Student Training in Aging Researchaward and after graduation, a John A. Hartford/AFARAcademic Geriatrics Fellowship grant to analyze Medicareexpenditures and hospital use among Alzheimer’spatients. Because of her early participation in two AFARprograms and contact with mentors in geriatrics, she says,the Beeson award became a goal very early in her career.Now that she is a Beeson Scholar, the award has kept herwell-connected with peers and spurred “incrediblygreat” contacts with other experts – an important benefitto someone whose work straddles both healthcare policyand gerontology.

For one arm of her Beeson project, Dr. Bynum islooking at how older patients receive care from anetwork that can include primary doctors, clinics,

hospitals, and nursing homes, among other providers.Most performance measures focus on locations, suchas what happens within a hospital. “But I think themost important question is what happens to people,no matter where they are,” she says.

Dr. Bynum has used Medicare claims to identifycaregiver groups and assess a patient’s overallexperience. “The long-term goal is to be able to comeup with measurements that can evaluate thesephysicians’ groups in treating the oldest old,” she says.But because the field of research is still in its infancy,she is building many of her own measures of care.

For a second arm of her project, Dr. Bynum isinterviewing about three dozen people – all at least 80years old – about recent doctor visits and whether theyhave received enough support to make informedchoices. Answers from the one-on-one interviewsessions may help doctors better tailor treatmentoptions to the goals of their patients, an importantconsideration when weighing medical interventionsthat carry short-term risks or benefits that may notmaterialize until far into the future. Studies haverevealed a surprisingly high rate of prostate-specificantigen screening among men older than 80, forexample, even though the prostate cancer screens arenot recommended for men older than 75. And unlikeyounger age groups, Dr. Bynum says, people olderthan 80 tend to do worse with carotid artery stentsthan without them.

So far, her interviews suggest that older patients knowthey have choices regarding surgery. “What they don’tunderstand is that they have a role in deciding whichmedications are good for them or not,” she says.Understanding of screening choices has been decidedlymixed. The interviews also suggest specific end-of-lifeissues carry more weight. “They care about how theydie. They care about whether they’re in and out of thehospital,” she says. In short, their goals may differmarkedly from other patients, and understanding thosedistinctions could be crucial for providing the elderlywith the best possible care.

Improving the Quality of Health Systems for the Very Old

Julie P.W. Bynum, MD, MPHAssistant Professor of Medicine andCommunity Family MedicineDartmouth Medical School

MENTORS:Elliott S. Fisher, MD, MPHStephen J. Bartels, MD

Bynum

Nearly 60 percent of older peoplein the United States take more thanfive medications every week,according to a 2006 study by theSlone Epidemiology Center at BostonUniversity. But if pharmaceuticalclinical trials never include theoldest and the sickest, how candoctors know whether benefitsoutweigh the risks for their

complicated patients? “You have to be able to look atdata in the real world,” says Dr. Sascha Dublin, who isdoing just that in a big way. An epidemiologist bytraining, Dr. Dublin is tapping the patient database ofSeattle’s Group Health for her research. “We can lookat what people are actually taking, and what thingshappen to them,” she says.

Her goal, she says, is to encourage researchers toconduct better studies on drug safety for the elderly.Given their disproportionate burden of prescriptiondrugs and vulnerability, older people need to makeinformed choices. “But to make better choices, youneed solid data,” Dr. Dublin says. “In many cases,there isn’t any data to make decisions.” As a result,she says, patients may be filled with false hope or fear.For her Beeson project, she says, “one of myquestions is: What do we need to know about thesepeople, about their cognitive status, their physical andfunctional status, to get accurate results?”

One way Dr. Dublin is tackling that question is byassessing the impact of prescription drugs oncommunity-acquired pneumonia risk, a particularconcern for older people and those with conditionslike heart and lung disease. A 2004 study suggestedthat acid-suppressing medications used to treatgastroesophageal reflux disease, or GERD, mayincrease the risk for pneumonia in the generalpopulation. The drugs work by making the stomachless acidic, but a more permissive environment forbacteria could raise the risk of aspirating pneumonia-

causing bacteria into the lungs. Dr. Dublin’s analysis,however, suggests the risk may be inflated by failingto adjust for factors like higher prescription ratesamong frailer people – including those with lungdisease. “The pneumonia risk may not be that themedicine increased risk, it may be that the users havechronic lung disease, which puts them at increased risk.It may not really be about aspirating stomach contents.”

Dr. Dublin is also accounting for a long list ofvariables to critically examine the suggestion thatstatin drugs, prescribed to control cholesterol levels,carry added infection and pneumonia-fightingbenefits. Patients on statins are more likely to surviveand less likely to get infections. But people on statinsalso tend to be younger and healthier, she notes,suggesting the possibility of a “healthy user bias” inwhich those patients are more likely to pursue healthierchoices in general.

One of Dr. Dublin’s favorite aspects of the Beesonprogram is how it promotes a cross-fertilization of ideasfrom all areas of aging research. “Every time I go to theBeeson meeting,” she says, “I come home with newideas and potential collaborations.” Among her newcollaborators is 2006 Beeson Scholar Dr. Margaret Fang,an assistant professor of medicine at the University ofCalifornia at San Francisco. “We realized very quicklythat we had tremendously overlapping interests, sowe’re doing a sub-project among elderly people with acertain heart condition and are looking at who getswarfarin and who doesn’t,” Dr. Dublin says. The bloodthinner marketed as Coumadin carries the risk ofexcessive bleeding. But without it, patients risk a stroke.

Clarifying a drug’s risks and benefits can lead to arapid response, like pulling a dangerous product frompharmacies or reevaluating its use among certainpatients. Some risk factors are hard to change, shesays, “but it’s not that hard for someone to quit usinga prescription drug.”

Pharmacoepidemiology in the Elderly: Medications, Pneumonia Riskand Confounding

Sascha Dublin, MD, PhDAssistant InvestigatorUniversity of Washington Group Health Cooperative

MENTORS:Eric B. Larson, MD, MPHNoel S. Weiss, MD, DrPH

Dublin

8 Paul B. Beeson Career Development Awards In Aging Research Program

92009 Report

When Dr. Roee Holtzer published a2006 study that associated walkingspeed with multiple cognitivefunctions in healthy older adults, hesoon began fielding calls fromaround the United States. Heremembers one in particular: anIndiana woman who confided thatshe had never before thought to linktogether the simultaneous decline

of her husband’s cognitive and walking abilities.

She was not alone. Most people understand that beingable to walk to the bus stop or grocery store stronglyinfluences whether older adults can continue livingindependently. Likewise, many public health programstargeting the same age group focus on the risk of fallsand minimizing that risk. Nevertheless, Dr. Holtzer says,“typically, one would not think to administer a cognitivebattery of tests as part of a risk assessment for falls.”

Due in large part to his research, that mindset may bechanging. “Walking has been associated with a rangeof outcomes, anywhere from risk of dementia to risk fordisability, so gait speed has been divined by severalgroups of researchers as a very important index ofphysical disability or frailty,” Dr. Holtzer says. After his2006 study in Neuropsychology strengthened that link,a follow-up showed that older individuals scoring betterfor a cluster of cognitive functions including attentionand processing speed were at reduced risk for falling,while those who scored worse had a significantly higherrisk. More recently, Dr. Holtzer has homed in on agenetic factor that may underlie gait speed.

The Beeson award, he says, has given him new ideasthrough meetings with other scientists and theflexibility to expand his work to include predictors ofdementia through the well-respected Einstein AgingStudy. A prime source of inspiration, in fact, has comefrom within the same building at Yeshiva University’sAlbert Einstein College of Medicine. Upon his facultyappointment there in 2004, he met Beeson ScholarDr. Joe Verghese, who was conducting work on gaitdisorders and their links to aging and dementia.

Predictors of Gait and Falls in Aging: Linking Cognitive Controlto Genes

Roee Holtzer, PhDAssistant ProfessorAlbert Einstein School of Medicine

MENTORS:Joe Verghese, MDRichard B. Lipton, MDLaurie J. Ozelius, MD

Holtzer

“We began to talk and discover that we have a sharedinterest. And then the ball just got rolling from there,”Dr. Holtzer says. Their collaboration has yielded morethan a half-dozen studies so far.

For his Beeson project, Dr. Holtzer has adopted athree-level plan to tease apart the tangled relation-ships among declining gait, falls, and aging. Beyondadministering clinical neuropsychological tests toassess deficits in specific cognitive abilities, he ispursuing a more focused computer-aided strategythat precisely measures attention by dividing it into itsthree subcomponents of alerting, orienting andexecutive attention, or conflict-resolution.

“We have demonstrated that these three attentionnetworks do exist in aging, that they are separateand that they can be measured reliably in allpeople,” he says. “This was not a trivial issue becausein all people, with aging, the brain goes throughmajor, major changes.” That success has led to a thirdlevel of questioning: what is it about attention thatpredicts gait in older adults? “It’s important in terms ofthe behavior, but also because these networks aremediated by different brain regions and also havebeen related to different genes,” Dr. Holtzer says.

One gene in particular, COMT, has attracted notice asa potential regulator of gait in healthy older adults dueto its role in degrading dopamine, a neurotransmitterthat controls both cognition and movement. In a 2008Neurobiology of Aging study, Dr. Holtzer and hiscollaborators showed for the first time that the genemay act through separate pathways in the brain’sstriatum and prefrontal cortex to influence gait andattention, respectively.

“I’m interested in not just understanding cognitivefunction for healthy individuals but relating it tooutcomes and functions in an individual’s daily life,from depression to the ability to functionindependently,” he says. Ultimately, better riskassessments and interventions could help with theoutcome that matters most: a better quality of life forolder adults.

As a graduate student at DrexelUniversity in Philadelphia, Dr. AngelaJefferson was studying the differentialdiagnosis of Alzheimer’s disease andvascular dementia when an unusualclinical case crystallized the potentrelationship between blood flow andbrain function. A 48-year-old patientwith a rare vascular disorder calledmoyamoya syndrome was referred to

a specialist at the Hospital of the University ofPennsylvania, where Dr. Jefferson was completing apracticum. Already impacted by a stroke, the patient hadso many blocked blood vessels in her brain thatsurgeons had to reroute her right superficial temporalartery past all the obstructions. After the surgery, Dr.Jefferson recalls, “her blood flow values practicallydoubled on both sides of her brain.” Likewise, thepatient’s cognitive test scores dramatically improved.

The case, which Dr. Jefferson eventually published withfour co-authors in the American Journal of Neuroradiology,led to her interest in studying blood flow from the heartto the brain and how it can reveal important clues aboutwhat can go wrong during the cognitive aging process.Now at Boston University School of Medicine, she isstudying how a subtle reduction in heart function mayaccelerate cognitive decline. “We know that people withheart failure are at increased risk for Alzheimer’sdisease,” Dr. Jefferson says. Other studies suggest thatbefore receiving heart transplants, patients with end-stage heart disease have reduced blood flow in thebrain and lower memory and cognition scores. After thetransplant, cerebral blood flow can increase by 50percent, accompanied by an increase in cognitivefunction. “These studies suggest that there’s arelationship between heart function and brain functionin patients with end-stage disease,” she says. “Myresearch focuses on what happens when you don’t haveend-stage heart disease. Are these relationships presentwhen you have subtle reductions in heart function?”

To find out, Dr. Jefferson is looking for potential linksbetween systolic function – a measure of the heart’s

pumping efficiency – and brain aging among 1,500relatively healthy adults ranging in age from 35 to 85who are participating in Boston University’s famedFramingham Heart Study. For a second project, she iscollecting data from people with mild cognitiveimpairment to see if systolic function is associatedwith MRI markers of early Alzheimer’s disease. “We’relooking for global neuronal loss, but we’re alsolooking for neuronal loss in the hippocampus, wherethe earliest signs of Alzheimer’s can be visualized byMRI,” she says. The study also will test if systolicfunction is associated with vascular disease in thebrain and test patients’ cognitive abilities.

Dr. Jefferson credits the Beeson award for not onlyallowing her to spend more time on her scientificinterests, but also for helping her secure a major grantfrom the Alzheimer’s Association to expand herresearch. With the Beeson award in hand, she has beenfree to attend more career-enhancing lectures andclasses. And through the extended Beeson network, shesays, she has found numerous potential collaboratorswhom she likely would not have met otherwise.

The combined resources could go far in resolvinglingering uncertainties over the impact of the vascularsystem on cognition. Most medical textbooks, Dr. Jeffersonsays, suggest that an auto-regulatory system preservesblood flow in the brain, meaning that reductions insystolic function don’t impact blood flow in the brain.Although that phenomenon may be true in acuteinstances of reduced heart function, research inmonkeys suggests that reductions in systolic functiondirectly reduce blood flow in the brain. The bigquestion, of course, is whether these relationships aretrue for humans.

So far, Dr. Jefferson’s early results agree that systolicfunction may indeed be related to the brain’s integrity.With subtle reductions, she says, lower blood flowfrom the heart could contribute to microvasculardisease in the brain, contributing to vascular andAlzheimer’s disease pathology in the elderly. With herresearch as a guide, perhaps such cases will enddifferently in the not-so-distant future.

Cardiac Integrity and the Aging Brain

Angela L. Jefferson, PhDAssistant Professor of NeurologyBoston University School of Medicine

MENTORS:Emilia J. Benjamin, MD, ScMRebecca A. Silliman, MD, PhD

Jefferson

10 Paul B. Beeson Career Development Awards In Aging Research Program

112009 Report

Studies show that African Americansuse hospice services at a lower ratethan Caucasians in the UnitedStates, even though the AfricanAmerican population shoulders ahigher burden of terminal cancerand heart disease, the two mostcommon conditions among thosereceiving end-of-life care. Researchalso suggests that African Americans

are more likely than Caucasians to receive inadequatepain management and report poor provider communi-cation, contributing to a lower overall satisfaction withsuch care. “Because hospice use is associated withimprovements in the quality of end-of-life care,” saysDr. Kimberly Johnson, “increasing the use of hospicecare among African Americans could decrease some ofthe racial disparities in that care.”

With her Beeson research, Dr. Johnson is shifting thefocus from changing the individual to changing theservice organization. “Rather than focus on why olderAfrican Americans do not use hospice care, my researchlooks at how hospice organizations can better meet theneeds of dying African Americans,” she says.

The first part of her study, a database analysis ofMedicare claims in North Carolina and South Carolina,will help determine variability among individual hospices.“Some hospice organizations are reaching a largerpercentage of African Americans in their service areathan others,” she says, and a thorough inspection of thedatabase will help her describe that variability and beginto understand the causes. A second, complementaryproject will consist of surveys and qualitative interviewswith the 131 hospice care providers in both states to helpidentify best practices geared toward reaching moreAfrican Americans.

Although her analysis is just beginning, anecdotal dataand expert opinion have suggested some practices thatare likely to work. “Number one is partnerships,” shesays, especially between hospices and institutions in theAfrican American community like churches. Church-

based outreach and education are critical for buildingtrust, she says, “because spirituality is such an importantpart of African American culture.” The presence of adiverse staff that reflects the community it serves alsomay make a big difference. “Some terminally ill patientsmay be more comfortable with care providers who sharetheir beliefs, values, and culture,” Dr. Johnson says.

Reaching out to African American media also may helpincrease access to hospice care for older members ofthe community, as can backing flexible hospice policieswith regard to chemotherapy and radiation therapy,hospitalizations, feeding tubes, and transfusions. Hospicesthat do not restrict those interventions, Dr. Johnson says,may be more attractive to African Americans who valuesuch end-of-life services more than other patient groupsfor spiritual or cultural reasons.

Prior to receiving the Beeson award, Dr. Johnsonconducted a number of small projects while spendingthe bulk of her time in geriatrics and palliative care.Through her work, she saw how the beliefs andpriorities of older African American patients and theirfamilies were often at odds with those of the medicalteam, and she frequently found herself being soughtout as a mediator to help resolve conflicts. The Beesonaward, she says, has given her the protected time andresources to pursue a research agenda delving moredeeply into how those conflicts might be avoidedwithin a hospice setting. “I like to think of the Beesonaward as a toolkit that provides everything necessaryto build a career as a successful researcher,” she says.“The Beeson award has thought of everything.”

As her research expands, she says, “I’m hoping toengage more in community-based research, to helphospices implement interventions which include bestpractices in reaching older African Americans.” NorthCarolina and South Carolina are convenient places forher to begin applying what she has learned. “But thehope is that we will develop a model of best practicesthat can be used anywhere,” she says, “and ultimatelyhave a significant impact in improving the quality ofcare for African Americans facing terminal illnesses.”

Organizational Variability and Racial Disparities in Hospice Use

Kimberly S. Johnson, MDAssistant Professor of MedicineDuke University Medical Center

MENTORS:James A. Tulsky, MDRichard Payne, MD, PhD

Johnson

Dr. Kejal Kantarci has beenfascinated with medical imagingever since she was a buddingradiologist at Marmara UniversityMedical School in Turkey. Now anassistant professor of radiology atthe Mayo Clinic, she has calledupon her neuroimaging expertise toidentify the danger signs of earlycognitive decline. “What I’m after is

identifying quantitative imaging markers for the earlydiagnosis of dementia,” Dr. Kantarci says. Amongpeople with mild cognitive impairment, early detectioncould lead to interventions for a range of dementias,but only if the warning signs are truly predictive.

One of the best bets for reaching that goal may beproton magnetic resonance spectroscopy (1H MRS).In 2000, Dr. Kantarci and colleagues used the imagingtechnique to show that an inflammation-associatedmetabolite known as myo-inositol is present at higherthan normal levels in mildly cognitively impaired patientsat increased risk for developing Alzheimer’s disease.Initially, she focused on imaging only one or a few selectregions of the brain. “Now I’m expanding that to fiveregions of the brain because there are other earlydementia pathologies in patients with mild cognitiveimpairment that may progress to more serious conditions,and we need to look at different regions of the brain todetect them,” she says. “When we are supplyingtreatment, we need to know which dementia pathology isthe underlying cause of the mild cognitive impairment.”

Metabolites, or the biochemical products ofmetabolism, contain protons that render themdetectable by 1H MRS. When properly tuned, a singleimaging run can detect five or six of the biochemicalsand measure how a specific metabolite’s levelschange early in the course of declining cognitivefunction. “So it’s a quantitative marker that we can trackin individuals who don’t yet have dementia,” Dr. Kantarcisays. The big question is whether the metabolites havea future in prediction and early diagnosis of thatdementia. Then, can they be used as reliable markersfor disease progression and for the effectiveness of

treatments in clinical trials? “We’re hoping thesebiological markers that are more closely related to thepathology in the brain will more precisely detectdisease progression than our standard clinicalmeasures,” she says.

To get at the metabolite levels, Dr. Kantarci has zeroedin on precisely framed regions of the brain that can beimaged with 1H MRS. Among her targets, she isfocusing on the medial temporal lobe and theposterior cingulate gyrus, areas involved in memoryfunction and linked to Alzheimer’s. Another area, thefrontal lobe, has been associated with frontotemporaldementia. Metabolites in yet another, the occipitallobe, can change in people diagnosed with what isknown as dementia with Lewy bodies.

Despite the advanced nature of neuroimaging,Dr. Kantarci believes the technology has yet to reachmaturity – an exciting opportunity to help shape anopen field. Having abundant resources at her disposalcertainly helps. Her Beeson mentor, Dr. Ronald Petersen,is director of the Mayo Clinic Alzheimer’s DiseaseResearch Center, one of the nation’s largest centers andher other mentor, Dr. Clifford Jack, is the director of theAging and Dementia Imaging Laboratory at the MayoClinic. Dr. Kantarci also has direct access to data fromthe Mayo Study of Aging, which is analyzing theincidence and prevalence of mild cognitive impairmentin Minnesota’s Olmstead County.

Even so, a project of such magnitude would have beenhard to pull off without the support of the Beesonaward. With it, she says, “I was able to write new grantsto continue my funding and to put together a solidfoundation for the future.” Having a majority of hertime protected for Beeson-funded research and training“is definitely crucial to be able to do something likethis.” The award also has spurred new collaborations,including a proposal she recently submitted with amentor to another Beeson Scholar, Dr. Sanjay Asthana,associate director of the Wisconsin Alzheimer’s Instituteat the University of Wisconsin School of Medicine andPublic Health. Receiving the Beeson award, Dr. Kantarcisays, “has definitely lifted my career in many ways.”

Proton MRSMarkers of MCI Syndromes and Common Dementias

Kejal Kantarci, MDAssistant Professor of RadiologyMayo Clinic College of Medicine, Rochester

Kantarci

MENTORS:Ronald C. Petersen, MD, PhDClifford R. Jack, Jr., MD

12 Paul B. Beeson Career Development Awards In Aging Research Program

132009 Report

A straightforward lesson in saltreduction fueled Dr. PatriciaKearney’s faith in the power ofpreventive medicine. As a medicalstudent at University College Cork,Ireland, Dr. Kearney took an electivein epidemiology at Johns HopkinsUniversity, where Irish native Dr. PaulWhelton explained how a programencouraging hospital patients to

reduce their salt intake could have a huge impact onreducing cardiovascular disease. “It just stuck with meas a medical student: The recognition that preventionis incredibly powerful.”

Now a doctor herself, Dr. Kearney says, “I find thatapproach in promoting health to be incredibly exciting.”Her excitement over preventive medicine could receive asignificant boost with The Irish Longitudinal Study onAgeing, or TILDA, a groundbreaking study spearheadedby Trinity College Dublin that aims to enroll 7,000 to10,000 Irish adults over the age of 50. Her participation inthe study could yield a gold mine of information aboutthe factors contributing to cardiovascular disease, aparticular risk for older people. Most of the focus to datehas been on known risk factors like higher bloodpressure, smoking, obesity, diabetes, and lack of physicalexercise, she says, “but there’s also the social gradient,and that’s what I want to explore.” With the TILDA study,she says, “we’ll have all that data, and be able to look athow those factors interact with each other.”

One of the potentially critical elements that Dr. Kearneyhopes to address is whether study participants areminimizing risk factors such as hypertension. The gapbetween self-reporting and objective measures is thoughtto be higher among people who are less educated andbelong to a lower social class, she says. A combination ofobjective measures – including height, weight, and bloodpressure – and a thorough questionnaire collectingeconomic, social, and behavioral data may help herbetter understand whether education, social class, orother factors influence any self-reporting discrepancies.

Why all the attention to social or economic status andself-reporting? “There has been a perception that a lotof cardiovascular risk is well-explained,” Dr. Kearney says.But for all the accumulated knowledge, many people stillcarry a heavy load of risk factors and are not beingtreated for them, or are being treated inappropriately.For any public health programs to succeed, researcherswill need to understand what is blocking adherence to atreatment regimen and how to overcome it. Is socialisolation, for example, a true risk factor, or is it a markerfor a deeper problem? The question is especiallyimportant for older adults, because loneliness and socialisolation tend to increase with age.

In the face of the study’s magnitude, Dr. Kearneycredits the Beeson award with helping her maintain herenthusiasm and focus. At the 2008 annual meeting, shewas particularly struck by a group brainstormingsession in which participants presented their researchchallenges and solicited advice. One of her concernswas being able to answer enough questions in thegrant’s allotted three-year timeframe. The feedback,she says, sent a clear message. “The Beeson programhad invested in me, not just in my research, but in meas a clinical researcher, as someone who is going tocontribute to the future.”

With fewer medical researchers in Ireland to call upon foradvice, Dr. Kearney says she particularly welcomed themeeting’s “incredibly nurturing” atmosphere and senseof community. “I came back from the meeting totallyrevved up for my research and incredibly invigorated.”A second pilot study for TILDA is now underway, andwith the larger study’s eventual results, she says, shehopes to help older adults chart out a better course forcontaining their hypertension and diabetes risk and forfollowing through on sound prevention advice. “Thebottom line is that we’re trying to improve the health ofpeople as they age,” she says. “And we are going tohave more and more older people.”

Biopsychosocial Factors and Vascular Disease in an Ageing Cohort ofIrish Adults

Patricia M. Kearney, MBBChBAO, PhD, MPHClinical Research FellowTrinity College Dublin

MENTORS:Rose Anne Kenny, MDIvan Perry, MD, PhD

Kearney

As a specialist in geriatric medicine,Dr. McGuinness has long beenattracted to caring for older people.After receiving her medical degree,she began studying the neuropsycho-logical changes in patients with vascu-lar dementia and Alzheimer’s disease(AD) – and more recently, to develop-ing an early indicator for elevatedAlzheimer’s risk. “My emphasis is on

early diagnosis or detection, and correctly classifyingpatients with mild cognitive impairment,” Dr. McGuinnesssays. “If we can devise methods of finding those patientsmost at risk of disease progression, that would be veryuseful. This would be particularly exciting if new treat-ments become available.”

For her Beeson research, she is zeroing in on an enzymecalled ß-secretase. Initial work by her research team atQueen’s University Belfast led to the development of anovel quantitative assay of platelet ß-secretase activity.This enzyme is involved in cleaving amyloid precursorprotein to produce beta-amyloid, which is deposited inthe brains of people with AD. Activity of this enzyme wassignificantly higher in patients with AD but did not corre-late with cognitive decline as measured by the MiniMental State Examination (MMSE). This led Dr.McGuinness and her colleagues to wonder if activity waselevated before the onset of symptoms.

In a small pilot study, Dr. McGuinness and her colleaguesfound that ß-secretase activity was 27 percent higher inpatients with mild cognitive impairment (MCI) than in age-matched controls, suggesting the enzyme may indeed bea marker of early disease. This straightforward test thatmeasures enzyme’s activity in blood platelets sparespatients frommore invasive cerebrospinal fluid sampling.Could the assay pave the way for a blood test gaugingAlzheimer’s risk? “That would be the hope,” she says.

With the Beeson award, Dr. McGuinness says, she is well-positioned to reach that goal. “This is the first time it wasgiven in Ireland, so it means a lot to the university, and

it’s also enabled me to meet a lot of influentialresearchers in America through the annual meeting,” shesays. “It’s given me a better foundation in the university.”Building on her earlier findings, she has launched amajor study in which she is carefully classifying patientswith MCI, a very heterogenous disorder that may be theunderlying cause of AD, vascular dementia, depression,and other forms of dementia.

Dr. McGuinness will perform a battery of neuropsycholog-ical tests on 150 recruited patients to more accuratelydefine their cognitive deficits. One hundred fifty controlswill also be recruited. The patients will be tested forplatelet ß-secretase activity and be genotyped for theAPOE gene, one form of which has been associated witha higher risk for late-onset Alzheimer’s. The rigorous sort-ing and follow-up over the course of a year, she hopes,may better define those most at risk, such as patients withamnestic mild cognitive impairment. Studies suggest that12 percent of these memory-deficient patients progressto Alzheimer’s disease every year. “The ones with forget-fulness – are they the ones who have the highest ß-secre-tase activity, or is ß-secretase activity higher in all patientswith mild cognitive impairment?” Dr. McGuinness asks.“We don’t know the answer.” Patients will be followedyearly with repeat neuropsychological and blood tests sowe can ascertain what happens over time.

In a similar vein, she is pursuing an imaging techniqueabbreviated FDG-PET, which uses an analog of glucosethat can be radioactively labeled and then used to scan thebrain. “The whole brain is imaged, and if there is reducedtracer uptake in the medial-temporal lobe, that would be inline with mild cognitive impairment and patients who aremore at risk of Alzheimer’s disease,” she says. With theneuropsychological results, the FDG-PET and the ß-secre-tase platelet assays, she hopes to more accurately predictthose at risk of progression. “I suppose in dementiaresearch, there’s not going to be one test that you canuse,” she says. But together, they could be invaluable.

Platelet ß-secretase in Mild Cognitive Impairment

M. Bernadette McGuinness, MD, MRCPSenior Clinical Research FellowQueen’s University Belfast

MENTORS:Anthony P. Passmore, BSc,MD, FRCP

Janet A. Johnston, PhD

McGuinness

14 Paul B. Beeson Career Development Awards In Aging Research Program

152009 Report

Insulin resistance is a majorcontributor to type 2 diabetes, thefifth leading cause of death in theUnited States. Research has likewiselinked aging to a higher risk fordiabetes, due to factors such as adecline in the amount and functionof muscle mass and a drop in theability of the muscle to metabolizefuels like sugars and fat. The big

question, according to Dr. Nicolas Musi, is what agehas to do with it at a molecular level.

Some key answers could be forthcoming from Dr. Musi’sBeeson research comparing adults between the ages of18 and 30 with adults older than 65. “Basically, we aretaking tissue from both groups and we are comparing aseries of genes and proteins that are responsible formaintaining muscle mass and metabolizing sugars andfats,” he says. “We hypothesize that the older group willhave altered function of certain genes and proteins thatare important to maintain muscle mass and function.”

The underlying abnormality, he believes, is an age-associated dysfunction among the muscle cells’ energy-producing mitochondria, whose decline triggers a seriesof cellular cascades leading to a reduction in musclemass, function, and glucose metabolism. Preliminarystudies in rodents and humans suggest that agingtriggers the excessive activation of a cellular pathwayabbreviated IKK/lkB/NFkB, and that the pathway’smolecules negatively impact muscle cell function.

Insulin normally stimulates the transport of sugar fromthe blood into the muscle cells, thereby helping tomaintain blood sugar levels within a controlled range.With mitochondrial dysfunction leading to an over-activation of the IKK/lkB/NFkB pathway, Dr. Musi says,the muscle becomes resistant to insulin and too muchsugar remains in the blood, instead of moving into themuscle reservoir. Decreasing the muscle mass onlycompounds the problem. “If you have less muscle,then you have less space where the glucose is goingto get in and be metabolized,” he says.

A second aspect of the research will test whetherexercise can reset the normal mitochondrial functionand whether that correction restores the normalactivity of the molecular pathway. Exercise is alreadyknown to help maintain muscle mass, muscle function,and the ability to metabolize sugars, and although theability of muscle to respond to insulin declines withage, Dr. Musi says, “most often, the patients’ musclewill respond to exercise in terms of improving insulinsensitivity.” Under the training regimen, patients willexercise on a stationary bicycle three to four times aweek for three months. Studies suggest the agingpopulation adheres well to exercise and lifestyleinterventions, raising his hope that the Beeson-fundedresearch will point toward a significant diabetesmitigating factor among the elderly.

Ultimately, Dr. Musi says the underlying mechanismmust be deciphered. “If we’re going to intervenepharmacologically, we need to understand what’shappening at the molecular level,” he says. “Noteveryone can exercise. Exercise is always promoted,but perhaps finding new treatments that have anexercise-like effect would be very desirable.”

Dr. Musi’s research has merged his interests ingerontology, endocrinology, and exercise physiology,and he credits the Beeson award as a “fundamental”support in helping him create a successful blend.“This study could not have been done without theBeeson award,” he says, noting that it has fosteredother aspects of his work, including careerdevelopment and networking with annual meetingparticipants. The support, he hopes, will help himfurther demonstrate how exercise “really has a seriesof very robust effects on our bodies, and that some ofthese effects can be seen from the very first exercisesession.” With evidence that it works like medicine –or better, perhaps people will be encouraged toexercise more and healthcare providers will designbetter exercise interventions that truly make adifference between life and death, whether fordiabetes or for some other disease.

Role of IKK/IkB/NFkB Signaling in Insulin Resistance in Aging Muscle

Nicolas Musi, MDAssociate Professor of MedicineUniversity of Texas Health Science Center at San Antonio

MENTORS:Arlan G. Richardson, PhDRalph A. DeFronzo, MD

Musi

In college, Dr. Neil Segal volunteeredto spend evenings with residents of anursing home, who were more thanhappy to get out of their rooms anddo something active. He beganthinking about mobility, an idea thatgrew during his year as a FulbrightScholar in Japan, where he studied 14types of health and welfare facilitiesfor the country’s elderly. “When I

compared all of those at the end of the year, I noticedthat the facilities that focused on mobility and functionalactivity were the ones that were more successful ingetting people back to their homes,” he says.

A medical career was born. Dr. Segal initially focused onhow central and lower body obesity – an “apple” versusa “pear” body shape – might put someone’s knees at abiomechanical disadvantage. Eventually, he becameinterested in how knees function in people withosteoarthritis and used computerized motion analysis todetermine what people who walk better do that lower-functioning people with knee osteoarthritis do not.

For his Beeson research, Dr. Segal is expanding on hisstudies to determine the benefits of two intensiverehabilitation interventions for adults over the age of 60who have painful knee osteoarthritis. Specifically, he isexamining whether functional activities with a weightedvest or a physical therapy program to reduce knee jointforces during walking are effective in improvingmobility. The findings, he says, could lead to betterrehabilitation and more accurate indicators of whicholder adults might benefit from each type of therapy.

The first of three arms in the randomized year-longstudy is a gait-training program that uses a high-techtreadmill. “We use a computerized camera to trackwhere their body is in space. From sensors, we canstudy the forces touching the treadmill, and so gaugethe forces on the knees, ankles, hip joints, and back.”

As a patient walks, so does a stick figure on a computerscreen, displaying the real-time force in the knee joints.“So if a therapist tells the patient to turn his toesoutward more, he would be able to see the real-timereduction in the force on his knees,” Dr. Segal says.

In the power-training intervention, other studyparticipants wear a weighted vest and do mobilityexercises, like walking up stairs or standing up from achair. “With resistance training or strength training,you’re activating the muscle for a specific force. If yourvest is 10 pounds, you’re just lifting the vest,” Dr. Segalsays. “But power training adds velocity, encouraging thepatients to stand up from a chair or walk up stairs asquickly as they can.”

Dr. Segal’s hypothesis is that either intervention willdeliver a better outcome than the study’s third arm, inwhich knee osteoarthritis patients receive no specialtraining at all. “It would be great, though, if the low-resource weighted vest intervention showed good resultsfor some participants,” he says. That would meanpatients wouldn’t need to rely on a technologicallyadvanced treadmill that exists in few places.

Becoming a Beeson Scholar, Dr. Segal says, has“affected every aspect of what I’m doing. I leveragedfunding from this award to obtain matching funding tohire more assistants. And that allowed me to successfullycompete for several other grants. My whole program justblossomed.” Meeting other Beeson Scholars, he says,has been another “amazing opportunity.” From talkingwith 2004 Beeson Scholar Dr. Catherine Sarkisian atUCLA, “I was able to develop an interview protocol tomotivate patients to continue to do the exercises thatI’ve been teaching them.” They’re not alone in beingnewly inspired. “I feel more motivated seeing Scholarsat every level of the Beeson program,” Dr. Segal says.“It also motivates me to help others with less researchexperience. I get so much help from the Beeson familythat I want to help others.”

Optimizing Mobility in Elders With Knee Osteoarthritis:Gait and Power Training

Neil A. Segal, MDAssistant Professor of Orthopaedics and RehabilitationUniversity of Iowa College of Medicine

MENTORS:Robert Wallace, MDJames C. Torner, PhDH. John Yack, PhD

Segal

16 Paul B. Beeson Career Development Awards In Aging Research Program

172009 Report

Dr. Manjula Kurella Tamura’sresearch really emerged from agrowing frustration in her clinicalpractice as a nephrologist. “I wasseeing more and more elderlypatients in my clinic with advancedchronic kidney disease andinevitably we would address theissue of dialysis and whether theyshould start,” she says. “I really felt

ill-prepared to talk to them about the pros and cons ofdialysis.” How would it affect her patients’ quality oflife? What were the other downsides? In short, whatwas the bigger picture?

By studying the oldest and sickest patients, Dr. KurellaTamura hopes to better illuminate how dialysis mayaffect that small but rapidly growing group. In 2007,she co-authored a study in the Annals of InternalMedicine concluding that for patients 80 and older,dialysis initiation rates increased 57 percent between1996 and 2003. Nearly half of those patients died withinone year of beginning the procedure. “The operativeangle of this is that the vast majority of people startingdialysis in the United States are elderly,” she says. “Andwe really don’t have a good handle on what some ofthe functional consequences of being on dialysis are.”

As she became more interested in the geriatricsaspects of her specialty, Dr. Kurella Tamura had astartling realization. Patients with kidney failure arepredisposed to early heart disease, stroke, bonefractures, menopause, and muscle wasting, amongother complications, suggesting a faster rate of agingin these patients. To understand how chronic kidneydisease may contribute to this phenomenon, she hasnow focused on studying the link between kidneyfailure and cognitive decline. Studies by her andothers have demonstrated that up to 30 percent ofpatients with chronic kidney disease on dialysis have

impaired cognitive function, though the reasons whyare unknown. Perhaps more surprisingly, even patientswith very mild chronic kidney disease not on dialysisappear to be at higher risk for cognitive decline.

With her Beeson award, Dr. Kurella Tamura is usingMRI scans to image the brains of older patients withchronic kidney disease on dialysis and collectingblood samples to measure metabolic waste productsthat accumulate because of the disease and that maycontribute to inflammation and brain dysfunction.“There are very few data right now on what the brainlooks like in those patients,” she says. With more datain hand, she hopes to find new connections betweenchronic kidney disease and cognitive decline.The award, she says, has provided a big boost towardthat goal by providing funds for the expensive butinformative MRI scans and granting invaluable accessto experts in geriatrics who have offered her guidanceand new insights. To develop this area of research,Dr. Kurella Tamura has worked closely with her mentor,Dr. Kristine Yaffe, also a Beeson Scholar and a leadingclinical researcher in dementia and cognitive impairmentat the University of California, San Francisco. “Dr. Yaffe’swork, especially in diabetes and cognitive impairment,has really provided a framework for some of my studies.”

For a second study, part of a larger National Institutesof Health-backed effort, Dr. Kurella Tamura isexamining the link between dietary protein intake,levels of metabolic waste products, and cognitivefunction in a randomized trial of dialysis done threetimes a week versus six times a week.

Although the number of patients on dialysis in the U.S.is still relatively small, more than eight million Americanadults have chronic kidney disease not yet requiringdialysis, and Dr. Kurella Tamura’s studies may ultimatelyhelp to reduce the risk for cognitive decline in thislarger group as well. A holistic view indeed.

Mechanisms of Cognitive Impairment in Chronic Kidney Disease

Manjula Kurella Tamura, MD, MPHActing Assistant Professor of MedicineStanford University School of Medicine

MENTORS:Kristine Yaffe, MDGlenn M. Chertow, MDC. Seth Landefeld, MD

Tamura

As a geriatric neurologist in China,Dr. Lihong Wang saw numerouspatients incapacitated by stroke orParkinson’s disease at HebeiProvincial Hospital. “Many of themhad frontal lobe dysfunction and Ididn’t know how to deal with it,”she recalls. The more she thoughtabout it, though, the moreintrigued she became – a growing

interest that led her to Yokohama City UniversitySchool of Medicine in Japan to study how Parkinson’sdisease affects the brain’s frontal lobe. Fascinated withthe ability of neuroimaging techniques to highlightbrain function and dysfunction, she eventually movedon to Duke University as a post-doctoral fellow underthe supervision of Dr. Gregory McCarthy where shehas used functional magnetic resonance imaging(fMRI) to scrutinize the cognitive and emotionalsystems of patients with depression.

For her current Beeson research, she is working closelywith her mentors Drs. David Steffens and RangaKrishnan. Dr. Wang hopes to sort out the fuzzyrelationship between depression and mild cognitiveimpairment, both of which are common among theelderly, and each of which may influence the other. Inparticular, she is interested in using fMRI to predict mildcognitive impairment in older patients with depression.As she notes, the imaging technique can revealalterations in the neural system long before any clinicalsymptoms appear. So far, fMRI has not been applied as aclinical diagnostic tool, but Dr. Wang believes it is moresensitive to cognitive changes than neuropsychologicalassessments and that it shows great potential for reliablypredicting cognitive impairments.

In people diagnosed with depression, alteredactivation in the brain’s prefrontal cortex has beenlinked to abnormal executive function, which controlshigher-order processes such as working memory,planning, and decision-making. Abnormalities in

another area called the hippocampus have been tiedto mild cognitive impairment. And changed activity inthe limbic system, including the amygdala, has beenassociated with deficits in emotional processing – andmore recently, in emotional memory. Dr. Wang’s workcould clarify those links and whether changes in theamygdala and hippocampus of patients withdepression might help predict mild cognitiveimpairment. The overall goal, she says, is to identifywhich neuroimaging markers are most predictive sothat effective early interventions can be pursued.

To reach that point, she will examine how fMRIcompares to the gold standard of a neuropsychologicalbattery of tests in detecting and predicting cognitivedecline in older patients being treated for depression.During an initial phase, the patients are asked toremember a group of pictures depicting positive,negative, or neutral emotions. Three hours later, thepatients undergo fMRI scans while viewing the oldpictures mixed with a set of new ones, some of whichare repeated once. “We ask them which ones they’veseen previously outside the scanner, and which oneshave just been repeated recently,” Dr. Wang says.

The experiment gauges working memory as well asemotional response. In depressed patients, thehippocampus and amygdala light up less for positiveor emotionally neutral pictures, but more for negativeones. Newly repeated pictures, meanwhile, elicit alower activation of the prefrontal cortex. Repeatingthe same test with different pictures one year latercould identify patients whose cognitive impairmentremains even after successful treatment fordepression. “As you treat depression, the depressivesymptom is improved but those who still have memorydysfunction may fall into mild cognitive impairment,”Dr. Wang explains. Importantly, a low baselineactivation in the amygdala and hippocampus ofpatients viewing old negative and positive picturesduring the experiment’s first phase could predict whomight develop mild cognitive impairment.

fMRI Prediction of Mild Cognitive Impairment in Geriatric Depression

LihongWang, MD, PhDAssistant Professor of PsychiatryDuke University Medical Center

MENTORS:David C. Steffens, MDRanga R. Krishnan, MB ChB

Wang

18 Paul B. Beeson Career Development Awards In Aging Research Program

192009 Report

Beeson Scholars: News from the Bench

Family Surrogates and Informed Consent

With their decision-making abilities impaired, manyaging patients with Alzheimer’s are unable to giveinformed consent to participate in research studies.Beeson Scholars Jason Karlawish, MD (2000), andKenneth Langa, MD, PhD (2003), investigated the issueof surrogate consent in a study published in theJanuary 2009 Neurology. Drs. Karlawish and Langasurveyed older Americans, finding that the majority ofsubjects would allow a family surrogate to give consentand would participate in surrogate-based research.Since Alzheimer’s research is often stalled by thecomplicated issue of consent, this study could be animportant indicator of the general acceptance of familysurrogates and move the process forward. Dr. Karlawish,of the University of Pennsylvania, and Dr. Langa, of theUniversity of Michigan also had their work featured in aJanuary 14, 2009, article by Insciences.

Cheers! To a Longer Life

On January 21, 2009, CNN highlighted the research of1998 Beeson Scholar Alison Moore, MD, MPH, of theUniversity of California, Los Angeles. Dr. Moore’s studyfound that moderate alcohol consumption had positiveeffects for seniors. By analyzing self-reported data frommen and women over 50, Dr. Moore saw that healthyseniors who drank fewer than 15 alcoholic beverages aweek had reduced odds for developing physicaldisabilities or dying in the next five years. Furtherinvestigation is necessary to explore the specific causeof this relationship, but researchers suggest thatalcohol’s effect of decreasing atherosclerosis or raisinggood cholesterol levels may explain the connectionbetween alcohol consumption and improved health.Dr. Moore’s study was recently published in the January15, 2009 issue of the American Journal of Epidemiology.

Understanding Diabetes, Body and Mind

The research of 2000 Beeson Scholar Scott Small, MD,of Columbia University, was cited in a January 6, 2009,New York Times story about links between blood sugarlevels and declining memory. Dr. Small led a team ofinvestigators to explore the neurological effects ofblood sugar spikes, which appear to influence aparticular part of the brain connected to memory-formation. Using MRIs to examine brain activity,

researchers found that elevated blood sugar levelscorresponded with reduced blood flow in the dentategyrus, a region of the hippocampus. Not only does thisstudy have implications for understanding therelationship between diabetes and aging, but Dr. Small’sresearch also emphasizes the importance of physicalexercise to regulate glucose levels and care for theaging brain. Dr. Small’s research about memory andaging has also been highlighted in Time.

Prescribing a New Direction for Treatment

In a study published in the December 2008 issue ofClinical Interventions in Aging, research led by 2005Beeson Scholar Malaz Boustani, MD, MPH, reviewedclinical trials of cholinesterase inhibitors to assess theirvalue in treating behavioral problems exhibited byAlzheimer’s patients. Dr. Boustani and colleagues atIndiana University found that cholinesterase inhibitors,typically prescribed for cognitive symptoms ofAlzheimer’s disease, were also effective in managingpatients’ accompanying psychological and behavioralsymptoms. Dr. Boustani is eager to use this study toconnect physicians with progressive treatments for theirAlzheimer’s patients. Dr. Boustani’s study findings wereprofiled in several publications, including Science Dailyand U.S. News & World Report.

Inheriting Good Health

A November 25, 2008, article in the New York Timesprofiled the research of 2005 Beeson Scholar DellaraTerry, MD, MPH. Dr. Terry’s investigations showed thatolder adults whose parents lived 100 years or longerwere healthier than others their age and were at muchlower risk for heart attacks, strokes, or diabetes. Thestudy monitored the health of centenarian offspring overthree to four years and found that this group had 78%lower risk for heart attack, 83% lower risk of stroke, and86% lower risk for diabetes than their peers. Theseresults, published in the September 2008 Journal of theAmerican Geriatrics Society, are consistent with Dr. Terry’sprevious research, which suggested that the avoidanceor delay of cardiovascular disease and cardiovascular riskfactors may play an important role in living to a very oldage. Dr. Terry, of the Boston University School ofMedicine, co-authored this research with 1996 BeesonScholar Thomas Perls, MD, PhD.

Beeson ScholarsTo learn more go to www.beeson.org

2008

Sarwat Chaudhry, MDAssistant Professor of MedicineYale University School of Medicine

Stephanie Cosentino, MDAssistant Professor of NeuropsychologyColumbia University College of Physicians and Surgeons

XinQi Dong, MDAssistant Professor of MedicineRush University Medical Center

Susan E. Hardy, MD, PhDAssistant Professor of MedicineUniversity of Pittsburgh

Paul B. Rosenberg, MDAssistant Professor of Psychiatry & Behavioral SciencesJohns Hopkins University School of Medicine

Joseph S. Ross, MDAssistant Professor of Geriatrics and Adult DevelopmentMount Sinai School of Medicine

Steven J. Russell, MD, PhDInstructor in MedicineHarvard Medical School/Joslin Diabetes Center

Arthur A. Simen, MD, PhDAssistant Professor of PsychiatryYale University School of Medicine

Farzaneh A. Sorond, MD, PhDAssistant Professor of NeurologyHarvard Medical School/Brigham and Women’s Hospital

20 Paul B. Beeson Career Development Awards In Aging Research Program

Program Advisory Committee

Edward H. Koo, MD, ChairUniversity of California, San Diego School of Medicine

Itamar B. Abrass, MDUniversity of Washington School of Medicine

Nir Y. Barzilai, MDAlbert Einstein College of Medicine

Christopher M. Callahan, MDIndiana University School of Medicine

Laura L. Dugan, MDUniversity of California, San Diego School of Medicine

Thomas M. Gill, MDYale University School of Medicine

William B. Hazzard, MDUniversity of Washington School of Medicine

Mark S. Lachs, MDWeill Medical College of Cornell University

From left to right: Mary Tinetti*, Itamar Abrass, William Hazzard,Laura Dugan, Richard Loeser, Thomas Gill, Dan Blazer*, LewisLipsitz, Edward Koo, Christopher Callahan.

*member through 2008

* Paul Beeson Career Development Awards in Aging Research Program for the Island of Ireland

Lewis A. Lipsitz, MDHarvard Medical School

Richard F. Loeser, Jr, MDWake Forest University School of Medicine

Alan R. Shuldiner, MDUniversity of Maryland School of Medicine, Baltimore

Kristine Yaffe, MDUniversity of California, San Francisco School of Medicine

Michael A. Steinman, MDAssistant Professor of Medicine in ResidenceUniversity of California, San Francisco School of Medicine

Stephen A. Todd, MD, MRCP *Senior Clinical Research FellowQueens University of Belfast

Douglas B. White, MDAssistant Professor in Pulmonary and Critical CareUniversity of California, San Francisco School of Medicine

Heather E. Whitson, MDMedical InstructorDuke University School of Medicine

2007

Randall J. Bateman, MDAssistant Professor of NeurologyWashington University School of Medicine

Julie P.W. Bynum, MD, MPHAssistant Professor of Medicine and Community Family MedicineDartmouth Medical School

Sascha Dublin, MD, PhDAssistant InvestigatorUniversity of Washington Group Health Cooperative

Roee Holtzer, PhDAssistant ProfessorAlbert Einstein College of Medicine

Angela L. Jefferson, PhDAssistant Professor of NeurologyBoston University School of Medicine

Kimberly S. Johnson, MDAssistant Professor of MedicineDuke University Medical Center

Kejal Kantarci, MDAssistant Professor of RadiologyMayo Clinic College of Medicine, Rochester

Patricia M. Kearney, MBBChBAO, PhD, MPH *Clinical Research FellowTrinity College Dublin

M. Bernadette McGuinness, MD, MRCP *Senior Clinical Research FellowQueen’s University Belfast

Nicolas Musi, MDAssociate Professor of MedicineUniversity of Texas Health Science Center at San Antonio

Neil A. Segal, MDAssistant Professor of Orthopaedics and RehabilitationUniversity of Iowa College of Medicine

Manjula Kurella Tamura, MD, MPHActing Assistant Professor of MedicineStanford University School of Medicine

Lihong Wang, MD, PhDAssistant Professor of PsychiatryDuke University Medical Center

2006

Katrin F. Chua, MD, PhDAssistant Professor of MedicineStanford University School of Medicine

Margaret C. Fang, MD, MPHAssistant Professor of Medicine in ResidenceUniversity of California, San Francisco School of Medicine

Alex D. Federman, MD, MPHAssistant Professor of MedicineMount Sinai School of Medicine

Emily V.A. Finlayson, MD, MSAssistant Professor of SurgeryUniversity of Michigan Medical School

Stacy M. Fischer, MDAssistant Professor of MedicineUniversity of Colorado Denver

Alfred L. Fisher, MD, PhDAssistant ProfessorUniversity of Pittsburgh School of Medicine

Sean X. Leng, MD, PhDAssistant Professor of MedicineJohns Hopkins University School of Medicine

Ann M. O’Hare, MD, MAAssistant ProfessorUniversity of Washington School of Medicine

Caterina Rosano, MDAssistant Professor of EpidemiologyUniversity of Pittsburgh Graduate School of Public Health

Manish N. Shah, MD, MPHAssociate Professor of Emergency Medicine, Community andPreventive Medicine and Geriatrics

University of Rochester School of Medicine and Dentistry

2009 Report 21

Consuelo H. Wilkins, MDAssistant Professor of Medicine and PsychiatryWashington University School of Medicine

2005

Liana G. Apostolova, MDAssistant Professor of NeurologyDavid Geffen School of Medicine at University of California, LosAngeles

Malaz A. Boustani, MD, MPHAssistant Professor of MedicineIndiana University School of Medicine

Jennifer S. Brach, PhDAssistant Professor of Physical TherapyUniversity of Pittsburgh School of Health and RehabilitationSciences

Arleen F. Brown, MD, PhDAssociate Professor in ResidenceDavid Geffen School of Medicine at University of California, LosAngeles

Cynthia M. Carlsson, MD, MSAssistant Professor of MedicineUniversity of Wisconsin School of Medicine and Public Health

Daniel R. Goldstein, MDAssociate Professor of Internal MedicineYale University School of Medicine

Wendolyn S. Gozansky, MD, MPHAssistant Professor of MedicineUniversity of Colorado Denver

Leanne Groban, MDAssociate Professor of AnesthesiologyWake Forest University School of Medicine

Arti Hurria, MDDirector of the Cancer and Aging Research Program andAssistant Professor

City of Hope

Pearl H. Seo, MD, MPHAssistant Professor of Hematology/OncologyMiller School of Medicine at University of Miami

Dellara F. Terry, MD, MPHAssistant Professor of MedicineBoston University School of Medicine

2004

Sandy Chang, MD, PhDAssociate Professor of Cancer Genetics and HematopathologyUniversity of Texas MD Anderson Cancer Center

Cathleen S. Colon-Emeric, MDAssociate Professor of MedicineDuke University Medical Center

William Dale, MD, PhDAssistant Professor of MedicineUniversity of Chicago School of Medicine

Lee E. Goldstein, MD, PhDAssociate Professor of Psychiatry, Ophthalmology, Neurology,Pathology and Laboratory Medicine, and Bioengineering

Boston University School of Medicine

Cary P. Gross, MDAssociate Professor of MedicineYale School of Medicine

John J. Lehman, MDAssistant Professor of MedicineWashington University School of Medicine

Andrew P. Lieberman, MD, PhDAssociate Professor of PathologyUniversity of Michigan Medical School

Atul Malhotra, MDAssistant Professor of MedicineHarvard Medical School/Brigham and Women’s Hospital

Martin J. Sadowski, MD, PhDAssistant Professor of Neurology and PsychiatryNew York University School of Medicine

Catherine A. Sarkisian, MD, MSPHAssociate Professor of MedicineDavid Geffen School of Medicine at University of California, LosAngeles

Clemens R. Scherzer, MDAssistant Professor of NeurologyHarvard Medical School/Brigham and Women’s Hospital

Lisa C. Silbert, MDAssistant Professor of NeurologyOregon Health and Sciences University

Joe Verghese, MDAssociate Professor of NeurologyAlbert Einstein College of Medicine

2003

Meredith A. Hawkins, MDProfessor of MedicineAlbert Einstein College of Medicine

Michael C. Irizarry, MDDirector, EpidemiologyGlaxoSmithKline

Kenneth M. Langa, MD, PhDAssociate Professor of Internal MedicineUniversity of Michigan

Sarah H. Lisanby, MDProfessor of Clinical PsychiatryColumbia University College of Physicians and Surgeons

Jack M. Parent, MDAssociate Professor of NeurologyUniversity of Michigan Medical School

Henry L. Paulson, MD, PhDProfessor of NeurologyUniversity of Michigan Medical School

Elizabeth A. Phelan, MDAssociate Professor of MedicineUniversity of Washington School of Medicine

Wendy S. Post, MD, MSAssociate Professor of Medicine and EpidemiologyJohns Hopkins University

Norman E. Sharpless, MDAssociate Professor of Medicine and GeneticsUniversity of North Carolina at Chapel Hill, School of Medicine

Michael G. Shlipak, MD, MPHAssociate Professor of Medicine, Epidemiology and BiostatisticsUniversity of California, San Francisco School of Medicine

Reisa A. Sperling, MDAssociate Professor of NeurologyHarvard Medical School/Brigham and Women’s Hospital

2002

David J. Casarett, MDAssociate Professor of MedicineUniversity of Pennsylvania School of Medicine

James E. Galvin, MDAssociate Professor of Neurology, Psychiatry and NeurobiologyWashington University School of Medicine

F. Brad Johnson, MD, PhDAssistant Professor of Pathology and Laboratory MedicineUniversity of Pennsylvania School of Medicine

Albert R. La Spada, MD, PhDAssociate Professor of Laboratory Medicine, Medicine and NeurologyUniversity of Washington

Michael T. Lin, MDAssistant Professor of Neurology and NeuroscienceWeill Medical College of Cornell University

Robert A. Marciniak, MD, PhDAssistant Professor of Medicine and Cell and Structural BiologyUniversity of Texas Health Science Center at San Antonio

Laura E. Niklason, MD, PhDAssociate Professor of Anesthesiology and Biomedical EngineeringYale University School of Medicine

Michael A. Schwarzschild, MD, PhDAssociate Professor of NeurologyHarvard Medical School/Massachusetts General Hospital

Jürgen Ünützer, MD, MPH, MAProfessor and Vice Chair of Psychiatry and Behavioral SciencesUniversity of Washington School of Medicine

2001

Asa Abeliovich, MD, PhDAssociate Professor of Pathology and NeurologyColumbia University College of Physicians and Surgeons

Katrin Andreasson, MDAssociate Professor of Neurology and Neurological SciencesStanford University School of Medicine

Eric A. Coleman, MD, MPHProfessor of Geriatric MedicineUniversity of Colorado Denver

Jay M. Edelberg, MD, PhDGroup Director, Clinical BiomarkersBristol-Myers Squibb Company

E. Wesley Ely, MD, MPHProfessor of MedicineVanderbilt University

Paul B. Beeson Career Development Awards In Aging Research Program22

Roger J. Hajjar, MDProfessor of MedicineMount Sinai School of Medicine

James A. Mastrianni, MD, PhDAssociate Professor of NeurologyUniversity of Chicago School of Medicine

Michael C. Naski, MD, PhDAssociate Professor of PathologyUniversity of Texas Health Science Center at San Antonio

M. Carrington Reid, MD, PhDAssociate Professor of MedicineWeill Medical College of Cornell University

Mary Whooley, MDProfessor of Medicine, Epidemiology and BiostatisticsUniversity of California, San Francisco

Kristine Yaffe, MDProfessor of Psychiatry, Neurology and EpidemiologyUniversity of California, San Francisco

2000

Brock Beamer, MDAssistant Professor of MedicineJohns Hopkins University

Gunnar K. Gouras, MDProfessor of Neurology and NeuroscienceWeill Medical College of Cornell University

Mary Beth Hamel, MD, MPHAssociate Professor in MedicineHarvard Medical School/Beth Israel Deaconess Medical Center

Joshua M. Hare, MDProfessor of Medicine and Chief of CardiologyMiller School of Medicine at University of Miami

Fuki M. Hisama, MDAssociate Professor of PediatricsHarvard Medical School/Children’s Hospital Boston

Jason H. Karlawish, MDAssociate Professor of Medicine and Medical EthicsUniversity of Pennsylvania School of Medicine

Jean S. Kutner, MD, MSPHAssociate Professor and Division Head of General InternalMedicine

University of Colorado Denver School of Medicine

Brett Lauring, MD, PhDAssociate Director, Clinical PharmacologyMerck Research Labs

Frank S. Lee, MD, PhDAssociate Professor of Pathology and Laboratory MedicineUniversity of Pennsylvania School of Medicine

R. Sean Morrison, MDProfessor of Palliative Care, Geriatrics and MedicineMount Sinai School of Medicine

Scott A. Small, MDAssociate Professor in NeurologyColumbia University College of Physicians and Surgeons

2009 Report 23

1999

Kenneth E. Covinsky, MD, MPHProfessor of MedicineUniversity of California, San Francisco School of Medicine

Matthew P. Frosch, MD, PhDAssociate Professor of PathologyHarvard Medical School/Massachusetts General Hospital

Daniel T. Laskowitz, MDAssociate Professor of Medicine (Neurology) and AssistantProfessor of Anesthesiology and Neurobiology

Duke University Medical Center

Dale Leitman, MD, PhDAssociate Professor in Residence Obstetrics, Gynecology andReproductive Sciences

University of California, San Francisco School of Medicine

Richard Z. Lin, MDAssociate Professor of Medicine and Physiology and BiophysicsStony Brook University Medical Center

David R. Lynch, MD, PhDAssociate Professor of NeurologyUniversity of Pennsylvania School of Medicine

Edward R. Marcantonio, MD, MScAssociate Professor of MedicineHarvard Medical School/Beth Israel Deaconess Medical Center

Mitchell S. Nobler, MDAssociate Professor of Clinical PsychiatryNew York State Psychiatric Institute/Columbia University Collegeof Physicians and Surgeons

Anne Louise Oaklander, MD, PhDAssociate Professor of NeurologyHarvard Medical School/Massachusetts General Hospital

Thomas A. Rando, MD, PhDAssociate Professor of NeurologyStanford University School of Medicine

1998

Helene Benveniste, MD, PhDProfessor of AnesthesiologyStony Brook University Medical Center

Laura L. Dugan, MDAssociate Professor and Chief, Division of GeriatricsUniversity of California, San Diego School of Medicine

Terri R. Fried, MDAssociate Professor of MedicineYale University School of Medicine

Anne M. Kenny, MDAssociate Professor of MedicineUniversity of Connecticut Health Center

Alison A. Moore, MD, MPHAssociate Professor of Medicine and PsychiatryDavid Geffen School of Medicine at University of California,Los Angeles

Thomas T. Perls, MD, MPHAssociate Professor of MedicineBoston University School of Medicine

P. Murali Doraiswamy, MDAssociate Professor of Psychiatry and MedicineDuke University Medical Center

Harlan M. Krumholz, MD, SMProfessor of Medicine and Epidemiology and Public HealthYale University School of Medicine

Makau Lee, MD, PhDClinical Professor of MedicineUniversity of Mississippi Medical Center

Richard F. Loeser, Jr., MDProfessor of Internal MedicineWake Forest University School of Medicine

Karen M. Prestwood, MDAssociate Professor of MedicineUniversity of Connecticut Health Center

May J. Reed, MDAssociate Professor of MedicineUniversity of Washington School of Medicine

R. Glenn Smith, MD, PhDAssociate Professor of NeurologyUniversity of Texas Medical Branch

1995

Ashley I. Bush, MD, DPM, PhDProfessor of PathologyMental Health Research Institute of Victoria, Australia

Ted M. Dawson, MD, PhDProfessor of Neurology and NeuroscienceJohns Hopkins University School of Medicine

David M. Holtzman, MDProfessor and Chair of NeurologyWashington University School of Medicine

Edward H. Koo, MDProfessorUniversity of California, San Diego School of Medicine

Mark S. Lachs, MD, MPHProfessor of MedicineWeill Medical College of Cornell University

Frank M. Longo, MD, PhDProfessor and Chair of Neurology and Neurological SciencesStanford University School of Medicine

Richard A. Marottoli, MD, MPHAssociate Professor of MedicineYale University School of Medicine

Lina M. Obeid, MDProfessor of MedicineMedical University of South Carolina

Peter Reaven, MDProfessor of Clinical MedicineUniversity of Arizona School of Medicine

Alan R. Shuldiner, MDProfessor of MedicineUniversity of Maryland School of Medicine, Baltimore

24 Paul B. Beeson Career Development Awards In Aging Research Program

Eric D. Peterson, MD, MPHProfessor of MedicineDuke University Medical Center

R. Scott Turner, MD, PhDProfessor of NeurologyGeorgetown University Medical Center

Jeremy D. Walston, MDAssociate Professor of MedicineJohns Hopkins University School of Medicine

Raymond L. Yung, MDAssociate Professor of Internal MedicineUniversity of Michigan Medical School

1997

Nir Y. Barzilai, MDProfessor of Medicine and Molecular GeneticsAlbert Einstein College of Medicine

Michele F. Bellantoni, MDAssociate Professor of MedicineJohns Hopkins University School of Medicine

James R. Burke, MD, PhDAssociate Professor of MedicineDuke University Medical Center

Mark D’Esposito, MDProfessor of Neuroscience and PsychologyUniversity of California, Berkeley School of Medicine

Thomas M. Gill, MDProfessor of Medicine, Epidemiology and Public HealthYale University School of Medicine

Bernard F. Godley, MD, PhDProfessor and Chair of OphthalmologyUniversity of Texas Medical Branch

Todd E. Golde, MD, PhDProfessor and Chair of NeuroscienceMayo Clinic, Jacksonville

Helen Hoenig, MD, MPHAssociate Professor of MedicineDuke University Medical Center

Elan D. Louis, MD, MScProfessor of Neurology and EpidemiologyColumbia University College of Physicians and Surgeons andMailman School of Public Health

Charles A. Thornton, MDProfessor of NeurologyUniversity of Rochester School of Medicine and Dentistry

1996

Christopher M. Callahan, MDProfessor of Medicine and DirectorIndiana University Center for Aging Research

Robert W. Doms, MD, PhDProfessor and Chair of MicrobiologyUniversity of Pennsylvania School of Medicine

Sponsors:

National Institute on Aging

The Atlantic Philanthropies

The John A. Hartford Foundation

The Starr Foundation

The National Institutes of HealthOffice of Dietary Supplements

and an anonymous donor

Administered by

National Institute on Aging

American Federation for AgingResearch

The Paul B. BeesonCareer DevelopmentAwards in Aging ResearchProgram

All inquiries and correspondenceshould be directed to:

American Federation for Aging Research55 West 39th Street, 16th FloorNew York, NY 10018T: 212.703.9977F: 212.997.0330E: grants@afar.orgwww.afar.org, www.beeson.orgwww.infoaging.org, and www.healthcompass.org

Stephanie LedermanExecutive Director

Katherine Kelly AppleCommunications and Development Associate

Catherine CullarAdministrative Manager

Stacey HarrisDirector, Communications

Hattie HermanProgram Officer

Nancy O’LearyDirector, Development

Jacalyn SchwartzDirector, Finance

Veronica SmithProgram Associate

Odette van der WillikDirector, Grant Programs

About the American Federationfor Aging Research (AFAR)

AFAR is a nonprofit organization whosemission is to support biomedical researchon aging. It is devoted to creating theknowledge that all of us need to live healthy,productive, and independent lives. Since1981, AFAR has awarded more than $113million to nearly 2,500 talented scientists aspart of its broad-based series of grantprograms. Its work has led to significantadvances in our understanding of agingprocesses, age-related diseases, and healthyaging practices. AFAR communicates news ofthese innovations through its organizationalweb site www.afar.org and educational websites Infoaging (www.infoaging.org) andHealth Compass (www.healthcompass.org).

Editorial direction was provided byStacey Harris

We would like to thank the BeesonScholars for reviewing this reportfor scientific accuracy.

About Paul B. Beeson, MD(1908-2006)

Paul B. Beeson, a distin-guished physician, researcher,and teacher, was the inspira-tion behind the creation of thePaul B. Beeson CareerDevelopment Awards in AgingResearch Program. It was hisvision to increase the numberof physicians with a combinedclinical, academic, and scien-tific expertise to care for agrowing older population.

At the time of his death,Dr. Beeson was professoremeritus of medicine at theUniversity of Washington.

Though “retired,” he remained active in thefield of aging research, attending meetingsand advising many Beeson Scholars. In hislong and distinguished career, he profoundlyinfluenced the career paths of many physiciansand was stalwart in his concern for the careand dignity of patients.

It is a tribute to him that to date, 152 physi-cian-scientists throughout the United Statesand the Island of Ireland have emerged asleaders in the field, changing the landscape ofgeriatric medicine and aging research. Hisenduring legacy is that these leaders will notonly provide the best possible care for olderadults, but will also go on to train the nextgeneration of leaders.

Paul B. BeesonCareer Development AwardsIn Aging Research Program

2009 ReportFeaturing the 2007 Scholars

Sponsors:

National Institute on AgingThe Atlantic PhilanthropiesThe John A. Hartford FoundationThe Starr FoundationThe National Institutes of Health

Office of Dietary Supplementsand an anonymous donor

Administered by:

National Institute on AgingAmerican Federation for Aging

Research