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BIOGRAPHICAL SKETCH
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NAME
Marcantonio, Edward R.
POSITION TITLE
Professor of Medicine
eRA COMMONS USER NAME (credential, e.g., agency login)
Marcantonio
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Harvard College, Cambridge, MA
Harvard Medical School, Boston, MA
Brigham and Women’s Hospital, Boston, MA
Harvard School of Public Health, Boston, MA
Harvard Medical School, Boston, MA
Beth Israel Hospital, Boston, MA
DEGREE
(if applicable)
YEAR(s)
AB
MD
Residency
SM
Fellowship
Fellowship
1983
1987
1990
1992
1992
1994
FIELD OF STUDY
Biochemical Sciences
Medicine
Internal Medicine
Epidemiology
General Internal Medicine
Geriatric Medicine
A. Personal Statement
I serve as Section Chief for Research in the Division of General Medicine and Primary Care at Beth Israel
Deaconess Medical Center (BIDMC) and am a Professor of Medicine at Harvard Medical School. I am an
internationally recognized expert and clinical investigator in the area of delirium. I have conducted a series of
observational and interventional studies designed to improve delirium identification, target individuals at risk,
identify modifiable risk factors, and test intervention strategies to reduce the incidence, severity and duration of
delirium. I currently lead three NIH-funded studies in delirium research, including the Biomarker Discovery for
Delirium project within the first NIH-funded program project in the field of delirium research.
I am delighted to serve as the Associate Director of the Research Education Core (REC) of the Boston Older
Americans Independence Center (OAIC). Funding from the OAIC has been instrumental in my own career
development, and I am happy to be involved in providing similar support to the next generation of promising
new scientists in the field of aging. Working closely with the REC Director, Dr. Lewis Lipsitz, with whom I have
collaborated for over 20 years, and REC Associate Director Dr. Amy Wagers, I look forward to my involvement
in all REC activities. In particular, I will participate in the solicitation of REC proposals, selection of awardees,
and in their monitoring and mentoring over the course of their Awards. In addition, I will lead the Advanced
Aging Research Training Seminar Series, which will serve as one of the primary required didactic curricula for
all REC awardees. I look forward to working with overall OAIC PI Dr. Shallender Bhasin and the rest of the
OAIC leadership as we execute our Aims, which will result in the expansion of aging research in the Boston
community, thereby positively impacting the independence of older Americans nationwide.
Below are representative publications relevant to the OAIC theme of functional promoting therapies in older
adults. References b-d also involve the mentorship of junior investigators.
a. Marcantonio ER, Flacker JM, Michaels M, Resnick NM. Delirium is independently associated with poor
functional recovery after hip fracture. J Am Geriatr Soc 2000;48:618-24.
b. Givens JL, Sanft TB, Marcantonio ER. Functional recovery after hip fracture: the combined effects of
depressive symptoms, cognitive impairment, and delirium. J Am Geriatr Soc 2008;56(6):1075-79.
c. Rudolph JL, Inouye SK, Jones RN, Yang FM, Fong TG, Levkoff SE, Marcantonio ER. Delirium: an
independent predictor of functional decline after cardiac surgery. J Am Geriatr Soc 2010;58(4):643-9. PMCID:
PMC2856754
d. Fowler-Brown A, Wee C, Marcantonio E, Ngo L, Leveille S. The Mediating Effect of Chronic Pain on the
Relationship between obesity and physical function and disability in older adults. J Am Geriatr Soc. 2013; 61:
2079-2086. PMCID: PMC3973183
B. Positions and Honors
Positions and Employment
1994-1999
Instructor in Medicine, Harvard Medical School, Boston, MA
1999-2004
Assistant Professor of Medicine, Harvard Medical School, Boston, MA
2004-2012
Director of Research, Division of General Medicine and Primary Care, Beth Israel Deaconess
Medical Center, Boston, MA
2004-2012
200820122012-
Associate Professor of Medicine, Harvard Medical School, Boston, MA
Director, Aging Research Program, Division of General Medicine and Primary Care, Beth Israel
Deaconess Medical Center, Boston, MA
Section Chief for Research, Division of General Medicine and Primary Care, Beth Israel
Deaconess Medical Center, Boston, MA
Professor of Medicine, Harvard Medical School, Boston, MA
Other Experience and Professional Memberships
1989Member, American College of Physicians
1991Member, Society of General Internal Medicine
1992Member, American Geriatrics Society
1995Member, Gerontological Society of America
1997-2005
Director, Harvard National Training Center, Hartford-AFAR Medical Student Scholars Program
2000Editorial Board, Journal of the American Geriatrics Society
2001-2004
Research Committee, American Geriatrics Society
2003-2008
Aging Systems and Geriatrics Study Section, Center for Scientific Review, National Institutes of
Health, Ad hoc member 2003-2004, Empaneled Member 2004-2006, Chair, 2006-2008
2005-14
Distinguished Professor of Geriatrics Committee, Society of General Internal Medicine
2006Editorial Board, Journal of the American Medical Directors’ Association
2010Council of Mentors, Harvard Medical School
2011-14
Geriatrics Task Force, Society of General Internal Medicine
2011-14
NIA Beeson Career Development Award Review Committee, member
2012Editorial Board, Journal of Gerontology: Medical Sciences
2014
Co-Chair, AGS/NIA U13 Conference on Delirium Research
Honors
1983
1997
1999
2003
2005
2007
2009
2012
2014
A.B., Summa cum laude, Harvard College
New Investigator Award, American Geriatrics Society
Paul Beeson Physician Faculty Scholarship for Aging Research
Outstanding Scientific Achievement for Clinical Investigation Award, American Geriatrics Society
Best Doctors in America
Excellence in Mentoring Award, Beth Israel Deaconess Medical Center
A. Clifford Barger Excellence in Mentoring Award, Harvard Medical School
Lumlean Lectureship, Royal College of Physicians, London, United Kingdom
Elected Member, Association of American Physicians
C. Contributions to Science
1. Epidemiology of Postoperative Delirium: When I began my career in aging research in the early 1990’s,
the epidemiology of delirium was not well described. In the series of studies below, I defined the incidence and
risk factors for delirium after elective non-cardiac surgery (a) and cardiac surgery (c). It was also believed that
delirium was short-lived and had no impact on long term outcomes. Instead, we found that delirium was an
independent risk factor for poor functional recovery after hip fracture (b) and was associated with an acute
decline, prolonged recovery, and persistent decline in cognitive function after cardiac surgery (d). I conceived
and executed all of these studies, and served as first author or senior author on the resulting manuscripts.
a. Marcantonio ER, Goldman L, Mangione CM, Ludwig L, Muraca B, Haslauer CM, Donaldson MC,
Whittemore AD, Sugarbaker DJ, Poss R, Haas S, Cook EF, Orav EJ, Lee TH. A clinical prediction rule for
delirium after elective non-cardiac surgery. JAMA 1994; 271(2):134-9.
b. Marcantonio ER, Flacker JM, Michaels M, Resnick NM. Delirium is independently associated with poor
functional recovery after hip fracture. J Am Geriatr Soc 2000;48(6):618-24.
c. Rudolph JL, Jones RN, Levkoff SE, Rockett C, Inouye SK, Sellke FW, Khuri SF, Lipsitz LA, Ramlawi B,
Levitsky S, Marcantonio ER. Derivation and validation of a preoperative prediction rule for delirium after
cardiac surgery. Circulation 2009;119(2):229-36. PMCID: PMC2735244
d. Saczynski JS*, Marcantonio ER* (co-first), Quach L, Fong TG, Gross A, Inouye SK†, Jones RN† (co-last).
Cognitive trajectories after postoperative delirium. New Eng J Med. 2012; 367: 30-9. PMCID:
PMC3343229.
2. Interventions for Delirium: A second major emphasis of my career has been the development and testing
of interventions for the prevention or abatement of delirium. I first identified modifiable risk factors for delirium,
such as postoperative medications (a). Using these risk factors, I developed a model of proactive geriatrics
consultation for hip fracture patients, and tested it in a randomized trial that demonstrated a significant 36%
reduction in postoperative delirium and a greater than 50% reduction in the incidence of severe delirium (b). I
also developed a program for management of persistent delirium in post-acute skilled nursing facilities, and
tested it in cluster randomized trial (c). The program led to a greater than 3-fold improvement in recognition of
delirium, but did not result in a shortening of its course. I have also tested novel pharmacological interventions
for delirium, including performing a randomized trial of donepezil, a cholinesterase inhibitor commonly used for
treatment of dementia (d). While this did not show a benefit, the trial was a valuable contribution to the field in
that it led to reduced unnecessary exposure to these drugs in patients at risk for delirium.
a. Marcantonio ER, Juarez G, Goldman L, Mangione CM, Ludwig LE, Lind L, Katz N,Cook EF, Orav EJ, Lee
TH. The relationship of postoperative delirium with psychoactive medications. JAMA 1994;272(19):1518-22.
b. Marcantonio ER, Flacker JM, Wright JR, Resnick NM. Reducing delirium after hip fracture: a randomized
trial. J Am Geriatr Soc 2001;49(5):516-22.
c. Marcantonio ER, Bergmann MA, Kiely DK, Orav EJ, Jones RN. Randomized trial of a delirium abatement
program for post-acute skilled nursing facilities. J Am Geriatr Soc 2010; 58(6): 1019-26. PMCID:
PMC2924954
d. Marcantonio ER, Palihnich KA, Appleton P, Davis RB. Pilot randomized trial of donepezil hydrochloride for
delirium after hip fracture. J Am Geriatr Soc; 2011; 59 Suppl 2: S282-88. PMCID: PMC3233977
3. Improved Assessment Methods for Delirium: Delirium can be challenging to assess, both in research
and clinical settings. Another major focus of my career has been to develop better measurement tools for
delirium. Using a database of nearly 5000 detailed delirium assessments with cognitive testing, we used item
response theory, an innovative modern measurement approach, to identify the optimal screening items for
delirium (a). We used these data to develop both an improved severity instrument for delirium (the CAM-S) (b),
and a brief structured diagnostic interview for delirium that can be completed in 3 minutes or less (the 3DCAM) (c). The latter 2 tools are already being widely adopted in research. We are now pursuing new work to
develop strategies for clinical implementation, including development of an ultra-brief 2-item bedside screening
test of delirium (d). Getting both screening questions correct effectively rules out delirium.
a. Yang FM, Jones RN, Inouye SK, Tommet D, Crane PK, Rudolph JL, Ngo LH, Marcantonio ER. Selecting
optimal screening items for delirium: an application of item response theory. BMC Medical Research
Methodology. 2013 Jan 22;13:8. doi: 10.1186/1471-2288-13-8. PMCID: PMC3598414.
b. Inouye SK, Kosar CM, Tommet D, Schmitt EM; Puelle MR; Saczynski JS, Marcantonio ER*, Jones RN*
(co-last). The CAM-S, a new scoring system for delirium severity in 2 cohorts. Ann Int Med. 2014; 160: 52633. PMCID: PMC4038434.
c. Marcantonio ER, Ngo L, O’Connor MA, Jones RN, Crane PK, Metzger ED, Inouye SK. 3D-CAM: Validation
of a 3-Minute Diagnostic Interview for CAM-defined Delirium. Ann Int Med. 2014;161(8):554-61. PMCID:
PMC4319978.
d. Fick DM, Inouye SK, Guess J, Ngo LH, Jones RN, Saczynski JS, Marcantonio ER. Preliminary
development of an ultra-brief 2-item bedside test for delirium. J Hosp Med. 2015 Oct;10(10):645-50. PMCID
In Process.
4. Biomarkers and Mechanisms of Delirium: Despite its prevalence, morbidity, and cost, delirium remains a
wholly clinical diagnosis and very little is known about its underlying mechanisms. Moreover, there are no
biomarkers to guide its diagnosis or management. A relatively recent focus of my career has been to identify
blood and cerebrospinal fluid (CSF)-based biomarkers and genetic markers for delirium. We first conducted a
systematic review of the state of the field (a). Using serum collected from a cohort of cardiac surgery patients,
we identified chemokines, inflammatory markers that may regulate permeability of the blood-brain barrier, as
potential blood-based biomarkers of delirium (b). Using a large cohort of non-cardiac surgery patients free of
dementia, we found that Apo-E genotype was not associated with delirium (c). Finally, using the same cohort
and a matched, nested case-control design, we found that interleukin (IL)-6 at postoperative day 2 and IL-2
were significantly associated with delirium. This is an active area of investigation and I have several more
papers under review and in preparation in this general topic area.
a. Marcantonio ER, Rudolph JL, Culley D, Crosby G, Alsop D, Inouye SK. Serum biomarkers for delirium. J
Gerontol A Biol Sci Med Sci 2006;61(12):1281-86.
b. Rudolph JL, Ramlawi B, Kuchel GA, McElhaney JE, Xie D, Sellke FW, Khabbaz K,
Levkoff SE,
Marcantonio ER. Chemokines are associated with delirium after cardiac surgery. J Gerontol A Biol Sci
Med Sci 2008;63(2):184-9. PMCID: PMC2735245
c. Vasunilashorn S, Ngo L, Kosar CM, Fong TG, Jones RN, Inouye SK,* Marcantonio ER.* (co-last) Does
apolipoprotein E genotype increase risk for postoperative delirium? Am J Geriatr Psychiatry. 2015
Oct;23(10):1029-37. PMCID In Process.
d. Vasunilashorn SM*, Ngo L* (*co-first), Inouye SK, Libermann TA, Jones RN, Alsop DC, Guess J, Jastrzebski
S, McElhaney JE, Kuchel GA**, Marcantonio ER** (**co-last). Cytokines and postoperative delirium in
older patients undergoing major elective surgery. J Gerontol Med Sci. Epub ahead of print: 2015 July 27.
5. Delirium in Post-acute Care: With progressive shortening of hospital length of stay, and increasingly
recognition of the persistence of delirium, I sought out to examine the epidemiology of delirium in post-acute
skilled nursing facilities. Using secondary data from the Minimum Dataset, we found that delirium was common
in post-acute care, persisted for weeks in this setting, and was associated with poor functional recovery (a).
We proceeded to conduct our own primary data collection studies, which confirmed similar findings, and
demonstrated that delirium on post-acute admission was a potent risk factor increasing the likelihood of
hospital readmission and death, and decreasing the likelihood of return to the community (b). We further found
that persistent delirium in the post-acute setting impeded functional recovery (c) and greatly increased the risk
of mortality (d), while delirium resolution predicted functional recovery (c) and reduced mortality (d).
a. Marcantonio ER, Simon SE, Bergmann MA, Jones RN, Murphy KM, Morris JN. Delirium symptoms in
post-acute care: prevalent, persistent, and associated with poor functional recovery. J Am Geriatr Soc
2003;51(1):4-9.
b. Marcantonio ER, Kiely DK, Simon SE, Orav EJ, Jones RN, Murphy KM, Bergmann MA. Outcomes of older
people admitted to post-acute facilities with delirium. J Am Geriatr Soc 2005;53(6):963-9.
c. Kiely DK, Jones RN, Bergmann MA, Murphy KM, Orav EJ, Marcantonio ER. Association between delirium
resolution and functional recovery among newly admitted post-acute facility patients. J Gerontol A Biol Sci
Med Sci 2006;61(2):204-8.
d. Kiely DK, Marcantonio ER, Inouye SK, Shaffer ML, Bergmann MA, Yang FM, Fearing MA, Jones RN.
Persistent delirium predicts greater mortality. J Am Geriatr Soc 2009;57(1):55-61. PMCID: PMC2744464
Complete List of Published Work in Harvard Catalyst Profiles:
https://connects.catalyst.harvard.edu/Profiles/display/Person/3871
D. Research Support.
Ongoing Research Support
P01 AG031720 (Inouye)
4/15/2010-3/31/2016
NIH/National Institute on Aging
Interdisciplinary Study of Delirium and Its Long-Term Outcomes
The Program Project entitled “Interdisciplinary Study of Mechanisms and Long-Term Outcomes of Delirium”
seeks to elucidate the correlates of delirium and to examine delirium’s contribution to long-term cognitive and
functional decline. The project, also known as SAGES: Successful Aging after Elective Surgery, enrolled 566
patients undergoing scheduled non-cardiac surgery at Beth Israel Deaconess Medical Center (BIDMC) and
Brigham and Women’s Hospital, and 119 BIDMC primary care patients who serve as non-surgical controls.
The Epidemiology Core, led by Dr. Marcantonio, played a central role assembling, maintaining, and following
this cohort over the follow-up period. Project 2--Biomarker Discovery for Delirium, also led by Dr. Marcantonio,
integrated biomarker discovery into the project by collecting blood from the entire surgical cohort at 4 time
points and applying two state-of-the-art biomarker discovery techniques, 1) simultaneous assessment of
multiple inflammatory cytokines using a multiplex analyzer, and 2) proteomics using quantitative mass
spectrometry, in matched samples of surgical patients who developed and did not develop delirium.
Role: Project Leader, Core Leader
K24 AG035075 (Marcantonio)
9/30/2010-5/31/2016
NIN/National Institute on Aging
Mid-Career Mentoring Award for Patient-Oriented Research (POR) in Aging
The Specific Aims are: 1. To continue to build a research program around improving the quality and outcomes
of care for hospitalized older adults with delirium. This K24 enables me to leverage my currently funded studies
and other ongoing work to support the work of trainees, who in turn expand my research program. 2. To build a
mentorship program that expands POR in aging at BIDMC and HMS, with a focus on delirium and related
conditions. This objective is accomplished through structured, individual mentorship of young investigators with
a strong interest in POR. Protected time for mentorship is provided by the K24 award. 3. To expand my
mentorship program to include translational, interdisciplinary work around biomarker discovery for delirium, and
biomarker applications to improve risk stratification, diagnosis, and prognostication of older adults with
delirium. This objective is accomplished through my new research projects, career development activities, and
interdisciplinary collaborations that will be facilitated by receipt of the K24 award.
Role: Principal Investigator
R01 AG044518 (Inouye)
6/15/2014-2/28/2019
NIH/National Institute on Aging
Development and Validation of a Delirium Severity Toolkit
The goal of this project is to develop a Delirium Severity Toolkit, a dynamic set of six new measures developed
with expert clinical judgment and patient/family/nurse input using modern psychometric theory. Our measures
will capture the severity of delirium in various phenomenological presentations (e.g., hypoactive, hyperactive),
incorporate multiple perspectives (patient, family member, and nurse), will be useful to a broad array of
stakeholders (physicians, nurses, patients, family caregivers, researchers, and policy-makers), and will be
developed using state-of-the-art procedures that combine qualitative and quantitative approaches such as
those developed and utilized in current major NIH-supported measurement initiatives (e.g., PROMIS, NIH
Toolbox, Neuro-QOL). Moreover, our development work will be in compliance with FDA guidance on
instrument development to assure applicability for future clinical trials.
Role: Site PI, Co-Investigator
Completed Research Support (selected)
R01 HL085706-01 (Gruber-Baldini)
2/14/2008 - 1/31/2014
NIH/National Heart Lung and Blood Institute
FOCUS Hip Fracture Transfusion Trial: Delirium and Other Cognitive Outcomes
This is an ancillary study to a large clinical trial examining different thresholds for blood transfusion to treat
blood loss after hip fracture surgery. The ancillary study examined whether transfusion helps prevent shortterm (post-randomization) and long-term (30 day) changes in severity of delirium symptoms.
Role: Co-Investigator
R21 AG038994 (Xie)
9/1/2011 – 8/31/2014
NIH/National Institute on Aging
Role of Alzheimer’s-associated Abeta in POD and POCD
The objective of this research was to investigate the role of b-amyloid protein (Ab) and cytokine IL-6 in the
neuropathogenesis of post-operative delirium (POD) and post-operative cognitive dysfunction (POCD) in
humans. Specifically, we determined whether reduced Aβ levels and elevated IL-6 levels in the pre-operative
cerebrospinal fluid (CSF) are associated with higher incidence and greater severity of POD and POCD.
Role: Co-Investigator
R01 AG030618 (Marcantonio)
9/1/2008 - 6/30/2015
NIH/National Institute on Aging
3D-CAM: Deriving and Validating a 3-minute Diagnostic Assessment for Delirium
This project aimed to develop, refine, and validate the 3D-CAM: a 3-minute diagnostic assessment for delirium
using the CAM algorithm. Using a dataset of 4744 delirium assessments, we mapped items to key diagnostic
domains of delirium and used Item Response Theory to identify a subset of items that maximize the screening
efficiency for each of these domains. Using the items identified in Aim 1 and multivariable model selection
methods, we developed the 3D-CAM. We prospectively validated and tested the inter-rater reliability of the 3DCAM in a new cohort of 201 older hospitalized patients. We compared the performance of the 3D-CAM with
the CAM-ICU, another brief screening protocol for CAM-defined delirium that does not use verbal responses.
The 3D-CAM will be an invaluable tool for diagnosis of delirium in hospitalized older adults.
Role: Principal Investigator