DUKE UNIVERSITY MEDICAL CENTER
Claude D. Pepper Older Americans Independence Center

Kenneth Schmader, M.D.
Principal Investigator		   919-660-7500   kenneth.schmader@duke.edu
Michelle Cooley
Program Administrator		   919-660-7551   michelle.cooley@duke.edu
     
CENTER DESCRIPTION

The overall goal of the Duke Claude D. Pepper Older Americans Independence Center (Duke OAIC) is to support research and training that improves the independence of older Americans by focusing on our theme to understand and optimize reserve and resilience. This theme is founded on the insight that independence in older adults is related to an individuals ability to withstand or recover from functional decline following acute or chronic health stressors. We conceptualize resilience as a dynamic response observed and measured after a stressor is applied.  We define resilience as the ability to resist or recover from adverse effects of a stressor; reserve is the pre-stressor capacity, in multiple domains, to adapt to a stressor.  Our approach includes better understanding of the underlying mechanisms as well as the creation of new interventions for optimizing reserve and resilience across the lifespan

Our overall strategy for the OAIC is to serve as a sustained resource to our investigators through a broad range of training and research studies; the goal is to address knowledge gaps in our focus with an emphasis on translational and interdisciplinary research. We recruit and develop early stage investigators in aging research related to our focus and utilize the substantial strengths of the Duke academic and health system environment to advance our focus. 

The Duke Pepper Center has been at the forefront of geriatric research and training focused on the development of interventions to improve the functional status of older adults and the support of research that identifies risk factors predictive of functional decline. The Duke Pepper Center originally began its funding as a Geriatric Research and Training Center (GRTC) in 1991. The GRTC was originally funded with three research cores and support for junior faculty and pilot projects, which reflects the organization of the current OAIC structure. One year later, Duke was awarded a Pepper Center and, at the direction of the National Institute on Aging, the two programs were combined into one. Initial Pepper Center support focused on the development of promising interventions to promote the independence of older Americans and faculty development. Since then, the Duke OAIC has produced an impressive portfolio of relevant research and innovations in faculty development.

The specific goals of the Duke Pepper Center are:

  1. To advance our knowledge of measures, mechanisms and analyses of reserve and resilience in older adults through an integrated research program
  2. To develop and evaluate interventions that optimize reserve and resilience in older adults.   
  3. To identify and develop the next generation of researchers who will become leaders in aging and geriatrics research related to the Duke OAIC focus.
  4. To support pilot studies needed to design successful, more definitive research studies related to the Duke OAIC focus. 

CORES
Leadership and Administrative Core (LAC)
Leader 1:    Kenneth Schmader, MD   kenneth.schmader@dm.duke.edu
The Leadership and Administrative Core (LAC) provides the scientific leadership and administrative infrastructure to create a robust environment for aging and geriatrics research in our theme. The Leadership and Administrative Core promotes the development of early investigators with interests in aging and geriatrics research and ensures the coordination, integration, funding, and translation of research within the Duke OAIC, a mission that supports our ultimate goal of improving the independence of older adults. The specific aims of the Leadership and Administrative Core are to: 1) to provide overall coordination and administration of the Duke OAIC 2) to stimulate, monitor, sustain and evaluate the progress of the OAIC towards achieving its research and education goals 3) to assess scientific opportunities for innovative research in our theme with an emphasis on translational and interdisciplinary research 4) to utilize and develop resources effectively to meet the goals of the Duke OAIC.

Research Education Component (REC)
Leader 1:    Cathleen Colon-Emeric, M.D.   colon001@mc.duke.edu
Leader 2:    Kimberly Johnson, M.D.   kimberly.s.johnson@duke.edu
Leader 3:    Barrett Bowling, M.D.   barrett.bowling@duke.edu
The objective of the Research Education Component (REC) is to develop the next generation of researchers who will become leaders in integrating basic science and clinical insights into innovative interventions promoting reserve and resilience in late life. Guided by educators in the Aging Center with nationally recognized expertise in curriculum development and evaluation, the REC measures the impact of OAIC programs on Scholars' career progression using innovative evaluation methods such as nominal group sessions. We have well established, close partnerships with multiple partner programs across the university (e.g., the Duke Clinical Translational Science Award Center (CTSA) KL2 program, NIA T32 aging training grant, NIA Roybal Center, NIMHD REACH EQUITY Center) . The School of Medicine offers excellent professional development programs, research leadership training, and grant-writing education and support services that are utilized by our scholars. Examples of REC training activities include our Intervention Development in Elderly Adults (IDEA) Workshop, Works-In-Progress sessions, Health Care Disparities Research Curriculum and “Pepper Shakers” networking events with faculty and scholars The specific aims of the Research Education Component are to: 1) to deliver an aging research curriculum around promoting physical reserve and resilience, while providing multiple opportunities for feedback, networking, and peer support; 2) to train and support mentors to enhance the quality of translational research mentoring across disciplines; 3) to provide mentored research experiences to prepare a diverse group of aging researchers focusing on physical resilience in older adults

Pilot and Exploratory Studies Core (PESC)
Leader 1:    Heather E. Whitson, MD   heather.whitson@duke.edu
Leader 2:    S. Nicole    susan.hastings@duke.edu
The Pilot/Exploratory Studies Core (PESC) emphasizes physiological reserve at the cell/tissue/organ level, which we hypothesize is a key contributor to resilience at the whole person level. The PESC impacts public health by performing studies that develop knowledge to maintain or recover independence in older Americans, by promoting reserve and resilience in the face of chronic and acute stressors. The PESC places emphasis on the development of novel interventions that will bolster resilience. PESC continues to support studies that conduct crucial resilience-related pilot work prior to the stage of intervention (e.g., development of measures or model systems). Our mentoring approach and OAIC environment train awardees to strategize as to how their lines of research may translate into improved human outcomes. We use small exploratory pilot monies as a rapid response mechanism to take advantage of cutting edge areas. The PESC solicits and selects high quality pilot studies from across Duke University Medical Center using a rigorous, multi-stage process that incorporates internal and external review. The PESC carefully monitors study progress and assists in the development of larger grant proposals from pilot study findings. The Duke PESC includes several highly innovative features: 1) the Pilot Grants Workshop, developed by OAIC Director Kenneth Schmader and frequently requested in national venues, 2) the inclusion of patient/community representatives on the Review Panel that selects pilots, 3) the Data Integration Working Group, which is a central hub for scientific development, oversight, and translation, and 4) mechanisms that support the science and careers of unfunded pilot study applicants. The specific aims of the Pilot/ Exploratory Studies Core are to: 1) to advance top quality science related to late-life reserve and resilience; 2) to attract and nurture a diverse cadre of outstanding investigators equipped to pursue promising new directions in aging research related to our theme; 3) to build and sustain relationships with critical stakeholders to maximize the impact and translation of the work conducted through this and future OAICs

Analysis (AC)
Leader 1:    Carl F. Pieper, DPH   carl.pieper@dm.duke.edu
Leader 2:    Jane F. Pendergast, Ph.D.   jane.pendergast@duke.edu
The Analysis Core (AC) serves as the central resource for data management and biostatistical analyses for research to understand and optimize reserve and resilience. The AC provides specialized research expertise in study design, data collection and management, development of statistical analysis plans, analytic support, and interpretation/dissemination of results to OAIC scholars and faculty. The AC promotes novel lines of research by developing new methods specifically targeted to detect and measure reserve and resilience. Finally, the AC supports training objectives by developing fellow and faculty understanding of biostatistics and research methodology—critical areas of the research enterprise that are typically a knowledge gap in basic, translational, and clinical researchers. The AC works closely with OAIC investigators, the two Resource Cores (Molecular Measures Core and Physical Measures Core), the PESC and REC to direct study design and analysis and to insure studies are properly powered and address targeted research questions. Furthermore, the AC is uniquely positioned to expand studies to evaluate additional or emerging hypotheses, including those that support methodologic investigations in statistical science, a unique goal of this Core. The specific aims of the Analysis Core are to: 1) to provide data management and analytic support to funded and proposed projects, pilots, and OAIC investigations 2) to provide training and mentoring to OAIC Scholars and faculty 3) to develop and disseminate biostatistical analytic methodologies to advance the study of resilience and reserve.

Health and Mobility Measures Core (HMC)
Leader 1:    Katherine Hall, Ph.D.   katherine.hall@duke.edu
Leader 2:    Amy Pastva, PT, MA, PhD   amy.pastva@duke.edu
The Health and Mobility Measures Core (HMC) provides whole-person health and mobility measurement capabilities to advance our theme of understanding and optimizing physical reserve and resilience. The HMC serves as a central resource for Duke OAIC investigators and the broader Duke community seeking consultation, mentoring, training, and innovation for valid, sensitive, and reliable whole-person level health and mobility measures. A panel of 8 members, with complementary expertise in measurement across multiple domains, comprises the Core and provides highly integrated, customized support to investigators supported by our Research Education Component, Pilot/Exploratory Studies Core, Externally Funded Projects, and the larger Duke Community engaged by the Duke OAIC. The HMC supports investigators by meeting regularly throughout the full spectrum of project development, from early phase planning, to final interpretation of findings, to subsequent grant preparations, to dissemination and/or implementation. These meetings concurrently involve members of the Analysis and Molecular Measures Cores to assure maximal synergy. The specific aims of the Health and Mobility Measures Core are to: 1) to provide centralized intervention development and measurement expertise, including consultation and mentoring to advance our thematic investigations of physical reserve and resilience 2) to develop measurement protocols and train personnel in administration and data collection 3) to identify gaps in reserve and resiliency measures and develop and/or adapt innovative new measurement approaches for related outcomes

Molecular Measures Core (MMC)
Leader 1:    Virginia B. Kraus, MD, PhD   vbk@duke.edu
Leader 2:    James Bain, PhD   james.bain@duke.edu
Molecular profiling can uniquely discover biomarkers, and predict and monitor traits and processes to understand and optimize reserve and resilience. The goal of the Molecular Measures Core (MMC) is to promote an understanding of the means to optimize whole person reserve and resilience through analyses of molecular factors indicative of cellular and tissue level ability to withstand and recover from stressors. The MMC complements the whole person level analyses offered through the Health and Mobility Measures Core and is inter-dependent with the Analysis Core, which is responsible for statistical analysis and modeling of data generated by the Health and Mobility Measures Core and MMC. The MMC has extensive molecular profiling capabilities for body and cell-culture fluids and tissue extracts, including inflammatory, metabolic, biochemical, senescent, genomic/epigenomic, and extracellular vesicle markers. The MMC has capabilities to expand and adapt existing core capabilities to facilitate the many needs of the novel investigator-initiated research projects affiliated with our Duke OAIC. The current development project is a translational research project to test in vivo and in vitro resilience to stressors that uses a senescent model system to test interventions to promote resilience, The specific aims of the Molecular Measures Core are to: 1) to perform molecular analyses to support researchers and scholars, and harmonize markers across Duke OAIC research projects 2) to develop new molecular profiling and testing capabilities to evaluate resiliencies in the setting of stressors including SARS-CoV2 3) to conduct systems pathway analyses to identify biological pathways indicative of resilient phenotypes 4) to provide research-oriented mentorship, consultation and training on principles and methods of molecular analyses, in collaboration with PESC and REC

CAREER DEVELOPMENT
REC Scholar, Research & Grants Funded During Pepper Supported Time Years /
Publications
 
Sonali Advani, MBBS, MPH
Assistant Professor of Medicine / Department of Medicine
Deprescribing intervention to reduce inappropriate antibiotic exposure and improve resilience in older adults
Specific Aim 1: To develop and implement a deprescribing intervention to reduce inappropriate treatment of ASB in hospitalized older adults. Hypothesis 1: Our deprescribing intervention leveraging the UA with pharmacist support will reduce inappropriate antibiotic use in older adults with ASB. Specific Aim 2: To assess the feasibility, safety, and acceptability of this deprescribing intervention in older adults. Hypothesis 2: Our deprescribing intervention focusing on older adults with ASB will be safe, feasible, and acceptable. Reducing inappropriate treatment of ASB is a key priority for the American Geriatrics Society, CDC, and AHRQ. The CDC has identified "urinalysis" as a key opportunity to improve antibiotic use, and recommends developing criteria to differentiate between ASB and symptomatic urinary tract infection (UTI).
  • SHEA Research Scholar Award (Society for Healthcare Epidemiology of America)

 2022-2024 /
0 (total)
0 (1st/Sr)
 
Leah Acker, MD, PhD
Medical Instructor / Department of Anesthesiology
Pilot testing of a non-invasive neuroimmune modulation tool— transcutaneous auricular vagus nerve stimulation (taVNS)—to enhance perioperative cognitive resilience in older adults
The objective of this pilot proposal is to identify and quantify barriers to a feasible, high-fidelity randomized controlled trial (RCT) of self-administered taVNS to prevent POD in older surgery patients. The rationale for this pilot study is that understanding feasibility challenges early will allow us to carefully design a future RCT with maximal clinical impact. Aim 1: Measure the fidelity and tolerability of preoperative self-administered taVNS in anxious surgery patients age = 65. Aim 2: Quantify the feasibility of recruiting and retaining anxious surgery patients age = 65 to self administer preoperative taVNS with high fidelity. Exploratory aim: Assess the dose-relationship between taVNS and anxiety, heart rate, and inflammation.
 2022-2024 /
0 (total)
0 (1st/Sr)
 
Kimberly Hreha, EdD, OTR/L
Assistant Professor / Department of Orthopaedic Surgery
Evaluating Physical Resilience and Best Practices in Vision Rehabilitation of Stroke Patients: A Mixed Methods Approach
Aim 1: Identify which strategies best support accessibility and tolerability of assessment and study enrollment protocols. Aim 2: Obtain feasibility data and explore facilitators and barriers of physical resilience measurement.
 2022-2024 /
0 (total)
0 (1st/Sr)
 
Past Scholars
Corey Simon, Orthopaedic Surgery (2018-2020)
Nazema Siddiqui, MD, MHS, Obstetrics and Gynecology (2018-2020)
Anthony Sung, MD, Senior Fellow in the Duke Center for the Study of Aging and Human Development, Center for the Study of Aging and Human Development, Institutes and Centers (2018-2020)
Brian James Andonian, MD MHSc, Department of Medicine, Division of Rheumatology and Immunology (2020-2022)
Ming-Feng Hsueh, PhD, Department of Orthopaedic Surgery (2020-2022)
Daniel Parker, MD, Department of Medicine (2020-2022)

PILOT/EXPLORATORY PROJECTS (8 Pilot Projects Listed)
1. Project Title: ApoE: A new target to improve aged bone healing
  Leader: Gurpreet Baht, PhD
  Aim 1: Develop a therapeutic intervention to improve aged bone fracture healing. In our recent study, we showed that lowered circulating ApoE levels in knockout mice were associated with improved aged fracture repair. To test whether temporarily lowering circulating ApoE levels during fracture healing will improve fracture outcome, we will perform fracture studies with small molecule reverse agonists to a nuclear receptor that controls ApoE expression. Aim 2: Identify the immunophenotypic differences in the fracture calluses of aged mice treated with inhibitors of ApoE expression. We hypothesize that ApoE-based age-associated changes in fracture repair are due to changes in the immunophenotype of the fracture callus.
 
2. Project Title: Resilience after heart transplant or LVAD in patients with advanced heart failure
  Leader: Adam DeVore, MD MHS
  Aim 1: Determine the feasibility of a comprehensive assessment to predict resilience and to describe normative values in patients with advanced heart failure. We will enroll approximately 50 patients undergoing evaluation for heart transplant or LVAD at Duke. We will collect information on the completion rate of each assessment during the study protocol and collect qualitative data from the study teams on feasibility and study burden. Aim 2: Describe at what time point after surgery patients with advanced heart failure recover using assessments of physical, cognitive and psychosocial health.
 
3. Project Title: Mechanisms underlying variation in primate physiological reserve
  Leader: Elaine Gomez Guevara, PhD
  Aim 1: Measure oxidative stress and telomere dynamics across the lifespan in species of Lemur (fast maturation, shorter lifespan than Propithecus, while sympatric) and Propithecus (extreme longevity for body size in nature, very slow development, low rate of actuarial senescence, evidence for enhanced somatic maintenance). Lemur catta, the ring-tailed lemur, and Propithecus coquereli, Coquerel’s sifaka, will be monitored at the Duke Lemur Center. Aim 2: Validate inflammatory biomarkers as age-related markers in these models.
 
4. Project Title: Understanding the role of IL-15 signaling in podocyte resilience and survival
  Leader: Gentzon Hall, MD PhD
  Hypothesis: A functioning IL-15/IL-15R axis is essential for homeostatic prosurvival signaling in podocytes, and impaired IL-15 signaling reduces podocyte resiliency to proapototic stimuli, increasing risk of glomerulosclerosis .Aim 1: To characterize the effects of IL-15/IL-15R knockdown a) on podocyte resiliency and loss in response to proapoptotic stimuli and b) on signaling through three prosurvival transcriptional regulatory pathways. Aim 2: To characterize the effects of targeted IL-15/IL-15R KD on pronephric integrity and function in DBP-GFP zebrafish.
 
5. Project Title: Personalized Targeted Nutrition via StructurEd Nutrition Delivery Pathway to Improve Resilience in Older Adult Trauma Patients – SeND Home
  Leader: Krista Haines, DO, MABMH
  Our long-term goal is to improve resilience for critically ill older adults who suffer trauma. The overall objective of the current proposal is to fully develop the SeND Home program through a formal feasibility, acceptability, and fidelity trial using an iterative design. We will accomplish our goals through the following aims: Aim 1: Assess the feasibility, fidelity, and acceptability of SeND Home for older adult trauma patients. We will enroll 40 older patients and follow them post-discharge using SeND Home using a 3:1 randomization. We will determine feasibility by measuring the ability to recruit and enroll the target number of patients, maintain 90% enrollment over a three-month period, and adherence rates to the study protocol. We will test acceptability by interviewing patients and stakeholders. We determine fidelity by measuring the proportion of inventions delivered according to the study protocol. Aim 2: Establish a plausible range of nutrition related outcomes for patients participating in SeND Home. Aim 3: Identify key barriers to nutrition delivery for older adult trauma patients in the hospital and discharge setting.
 
6. Project Title: Individual and dyadic factors associated with older dialysis patients’ physical resilience
  Leader: Nicole DePasquale, PhD, MSPH
  Aim 1. Explore and describe individual (patient and care partner) and dyadic factors influential for patients’ physical resilience. Each member of the care dyad will separately complete semi-structured, qualitative interviews to allow for an in-depth exploration of experience, feelings, perceptions, attitudes, and behaviors regarding patients’ physical resilience, or ability to maintain, regain, or optimize physical function, following dialysis initiation and factors influencing it. Aim 2. Identify dyadic care types associated with different degrees of physical resilience. Each member of the care dyad will separately complete a survey containing measures that complement interview questions in Aim 1. Quantitative survey data obtained from Aim 2 will facilitate examination of similarities and differences in care dyads’ qualitative accounts. These patterns will enable identification of dyadic care types, or groups of care dyads distinguished by contributing factors to and demonstrated levels of physical resilience.
 
7. Project Title: Development of a Risk Assessment Tool to Enhance Physical Resilience in Older Adults following Orthopedic Surgery for Acute Injury: A Feasibility and Acceptability Pilot Study
  Leader: Laura Pietrosimone, PhD and Trevor Lentz, PhD
  Aim 1: Determine the feasibility and acceptability of remotely measuring multidimensional psychological distress, social needs, mobility, and physical function following surgery for lower extremity fracture in older adults. We will conduct a pilot observational cohort study of older adults (?65 years-old) undergoing surgery for ankle fracture (n=15) at Duke Health. Subaim 1a will establish the feasibility of recruitment and retention of older adults in a study that uses remote assessment methods post-surgery. Subaim 1b will assess the feasibility and responsiveness of remotely administered patient-reported measures not commonly used older adults including psychological measures (grit scale, OSPRO Yellow Flag Assessment Tool, SPARE psychological screening tools, STarT MSK tool) and social needs screening (HealthLeads screening tool). Subaim 1c will determine the feasibility and acceptability of remote mobility monitoring and functional assessments (e.g., TUG, gait speed) to establish functional recovery. Pilot data will inform the suitability of using these methods and measures in a future fully-powered cohort study.
 
8. Project Title: The role of pericytes in postoperative neurocognitive disorder during aging
  Leader: Ting Yang, MD, PhD
  The central hypothesis is that pericytes are a key cellular target in protecting the BBB integrity and ensuring neurologic sequalae from systemic inflammatory injury in the aging brain. The Objective is to identify the role and the molecular mechanisms for preserving pericytes function following a predictable stressor (i.e. surgery) thus enhancing brain resilience to long-term cognitive decline during aging. Aim 1: Determine the role of pericyte loss in transitioning from acute to long-lasting cognitive decline during aging. Aim 2: Identify the impacts of aging related pericytes transcriptomic changes on BBB function.
 
DEVELOPMENT PROJECTS (3 Development Projects Listed)
1. Project Title: Cellular senescence burden as a molecular indicator of resilience
  Leader: Virginia Kraus, MD PHD
  Core(s): Molecular Measures Core (MMC)
 

Stress elicits the Senescence Associated Secretory Phenotype (SASP) and the upregulation of lysosomal hydrolases. These cellular senescence responses have recently been discovered to be physiological tissue repair and remodeling responses. The complex systems of tissue repair and remodeling comprise the molecular foundation for resilience. We established the model system and markers in the classic @I38 human fibroblast cell line. These recent exciting insights define a beneficial role in tissue repair for SASP, the increased expression and secretion of a suite of inflammatory cytokines, growth factors, and proteases. When senescence reverts from an acute and transient state, such as in wound healing, to a chronic state with accumulation of senescent cells, the well-known phenomena of aging, including loss of reserve and resilience, are observed. In fact, the SASP is very similar to the inflammatory and coagulation markers associated with frailty and mortality in the elderly. Clearance of senescent cells in mouse models reduces expression of SASP factors in tissue and delays aging. The Specific Aims of this project are: Aim 1) To develop a panel of molecular markers indicative of senescent cell burden based on markers associated with SASP, soluble lysosomal exoglycosidases able to be detected in serum that might be a marker of a senescence process, and microRNAs we identified, through Duke OAIC pilot funding, as associated in elders with high function and longevity; and Aim 2) To evaluate the expression and interdependence of these factors in an in vitro model system followed by analyses of these factors in the CALERIE cohort and in future collaborations with other Duke OAIC projects. We hypothesize that methods that are senomorphic (change senescence) promote resilience.
 
2. Project Title: Testing the resilience of the latent class trajectory model when the conditions of the model are not met
  Leader: Carl Pieper, DrPH and Jane Pendergast, PhD
  Core(s): Analysis (AC)
  The objective of this project is to examine factors which impact the validity of discovering and defining latent classes of change under two types estimation models: commonly latent class trajectory model and Generalized mixed models. Both models are in wide use in assessing latent classes of trajectories, but make different underlying assumptions about the data structure. Initially, in the analysis of a panel data set, we observed that the 2 model types gave different results. We were surprised by the magnitude of the differences and research implications of these initial findings. In a deeper dive into the causes of the differences we observed, we learned that mis-specification of the error structure of the replicate observations led to incorrect definition of the number of classes contained in the data. The mis-classification occurred even in the presence of small correlations (0.1). These findings have implications for the validity of the findings derived under statistical packages used in the field. We demonstrated this both in simulations, where external factors could be controlled, and in real data. Using simulation, we plan to extend these investigations into other analytic issues commonly observed in longitudinal investigations change.
 
3. Project Title: Developing Resiliency Related Health Data Science Capacity
  Leader: Juliessa Pavon, Katherine Hall
  Core(s):
  The goal of this DP is to (Aim 1) develop and build resiliency related health data science capacity in our OAIC, and (Aim 2) grow geriatric and resilience-focused research capacity within the larger Duke community. (Aim 1): This work is directed at two vulnerable, high-risk patient populations in which we intend to identify physical and psychosocial stressors as a potential target for intervention, to identify a resilience phenotype, and to work with key stakeholder providers to translate findings to practice. The DP is housed in the HMC because of Dr. Pavon’s HMC role, but represents an inter-core (HMC and AC) collaboration with Duke’s Center for Actionable Health Data Science (Duke Forge). Methods. We will link Duke geospatial data with EHR clinical data to identify patterns of potentially modifiable clinical factors that may be most characteristic of patients recovering from hip fracture or congestive heart failure who exhibit resilience (days out of hospital, that approximates time spent in good health between hospitalizations) within/across geographic areas identified as disadvantaged. DP methods will be guided and developed by HMC Core faculty Pavon and Dupre, AC Core faculty, and Dr. Ricardo Henao (Forge’s Principal Data Scientist) in collaboration with Forge’s expert informaticists, biostatisticians, and electrical and computer engineers. Forge teams are renowned for signal processing, pattern recognition, machine learning, and predictive modeling of complex biological and clinical data. This project will employ machine learning techniques, e.g., relevance vector machines, to develop descriptive and probabilistic models. Methods (Aim 2): We will use the synergy of our OAIC to grow and develop resilience focused capacity within the OAIC and larger Duke community. AC faculty and Forge will provide the quantitative expertise and use machine learning and other advanced analytic techniques to develop descriptive and predictive models (Data to Knowledge) which will subsequently be shared with OAIC scholars and clinicians (Knowledge to Practice) for dissemination and development of promising data-driven interventions. The proposed DP will build an infrastructure and system-wide relationship that will serve investigators and clinical practice in the years to come and further one of Dr. Pavon’s career goals as a Geriatrics Health Informatics Scientist.
 
RESEARCH (10 Projects Listed)
1. Project Title: PHYSICAL RESILIENCE PREDICTION IN ADVANCED RENAL DISEASE
  Leader(s): BOWLING, CHRISTOPHER BARRETT
    DURHAM VA MEDICAL CENTER
    VA I01HX002704 / ( 2019 - 2023 )
  Core(s):
  ABSTRACTBackground: Older Veterans with advanced chronic kidney disease (CKD) face complex decisions to initiateor forgo dialysis in the context of uncertainty about their future health and physical function. Making thesedecisions is complicated by the course of advanced CKD which is characterized by frequent health events thatfurther worsen function. Decisions support tools are needed that are specific to the clinical course of advancedCKD and predict outcomes that matter most to these patients, such as physical function. Characterizing howpatients bounce back from health events, such as illnesses or injuries that result in emergency department(ED) visits or hospitalizations may be key to predicting future functional status. This approach draws from thenovel geriatric concept of physical resilience, defined as one s ability to resist or recover from functional declinefollowing a health stressor. Objectives: To help older Veterans make informed decisions about kidneydisease treatment by better characterizing physical resilience and identifying patient factors associated withphysical resilience to develop a prediction tool for physical resilience in advanced CKD. This addresses theHSR&D priority of Patient-Centered Care domain. To do this, we propose Physical REsilience Prediction inAdvanced REnal Disease (PREPARED), a prospective cohort study of older Veterans with advanced CKD withthe following Aims:1. To characterize physical function trajectories before and after an acute health stressor in order to define physical resilience among older Veterans with advanced CKD.2. To identify associations between patient characteristics and physical resilience trajectory and potential candidate variables for prediction model development.3. To develop a prediction tool for physical resilience (where this quantity has been defined in Aim 1).4. To determine the association of physical resilience with short-term mortality.Methods: We will conduct a longitudinal cohort study of 800 Veterans = 70 years old, with an estimatedglomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 (excluding dialysis or transplant), and 90-day probabilityof hospitalization = 50% (based on the Care Assessment Needs [CAN] score). Telephone assessments willinclude brief validated measures of function every 8 weeks, and within 14 days following a stressor for up to 6calls. In Aim 1, we will characterize physical resilience, first by identifying latent classes of physical resiliencetrajectories using general growth mixture modeling. Next, among the subset from the physical resilience latenttrajectory class we will fit a piecewise linear mixed effects model to quantify resilience. In Aim 2, we willdetermine how the physical function trajectory is moderated by person-level health and psychosocial factorsand organ system-level physiologic factors. This information will be used to identify potential candidatevariables for our prediction model in Aim 3. The purpose of Aim 4 is to determine the prognostic importance ofphysical resilience by examining the relationship between experiencing a stressor and physical resilience with6-month mortality. Impact: The proposed study addresses the most pressing clinical dilemma in this complexcondition that disproportionately affects older Veterans. Data on physical resilience from the proposed studywill be used to develop a practical tool to address a vital question that CKD patients, their families, andproviders face when making treatment decisions. Limiting uncertainty about future health by predictingresilience will support individualized and patient-centered decision-making for kidney disease. Next steps: Wewill develop a clinical trial to test the use of our physical resilience prediction tool and work with our local andnational operations partners (Durham VA Renal Service, Office of Geriatrics and Extended Care, Renal FieldAdvisory Committee) to implement physical resilience assessment into care for these patients.
 
2. Project Title: EXPLORING THE EFFECTS OF EXERCISE TRAINING ON PTSD SYMPTOMS AND PHYSICAL HEALTH IN OLDER VETERANS WITH PTSD
  Leader(s): HALL, KATHERINE SHEPARD
    DURHAM VA MEDICAL CENTER
    VA I01RX003120 / ( 2020 - 2024 )
  Core(s):
  Posttraumatic stress disorder (PTSD) is prevalent among military Veterans, and affects over 30% of older, Vietnam-era Veterans. These servicemembers have endured nearly 40 years with these symptoms, and as a result, have significantly poorer health, higher rates of chronic disease and obesity, and an excess mortality rate 3 times higher than the general population. Clearly PTSD is more than just a psychological disorder. There is evidence to suggest that the pathway from PTSD to poor health is mediated by behavioral risk factors, such as exercise. Structured exercise is a highly effective, pluripotent strategy for the prevention, treatment, and management of chronic physical and psychological health conditions in older adults. To date, only a few pilot studies of exercise and PTSD have been published, and all suffer a major limitation: a singular focus on outcomes above the neck. These studies do not report the impact of exercise on physical health- and mobility-related outcomes that contribute to long-term impairment and disability in Veterans with PTSD. There have been no studies of exercise and PTSD done in older adults, representing a significant research gap. This research examines a wellness-based approach to promoting health in older Veterans with PTSD, targeting exercise, a major modifiable risk factor. The objective of this study is to compare the impact of a supervised exercise program on PTSD symptoms and related health outcomes versus a healthy aging attention control group (HA-ATC). This study will be a randomized controlled trial of a 6-month, supervised exercise program among 188 Veterans 60 years of age with PTSD at the Durham VAHCS. Participants will be randomly assigned to Supervised Exercise or HA-ATC. The exercise arm will include 3 weekly exercise sessions, each one lasting approximately 60 minutes, led by an exercise specialist. The HA-ATC will receive a health education program and materials modeled on the 10 KeysTM to Healthy Aging curriculum and the National Council on Agings Aging Mastery Program. The HA-ATC will include an 8-week face-to-face group program followed by 4 monthly sessions, the latter of which will be further supplemented with mailed informational packets, email newsletters, webinars, and group video telehealth sessions. Participants in the Exercise intervention arm will receive an individualized exercise prescription based on the individual s exercise history, current exercise capacity, personal preferences, and current health status. This will be a multicomponent program that includes a selection of 8 to 12 strengthening, balance, and flexibility exercises targeting the major muscle groups as well as primary joints. Participants will also be instructed in endurance exercise, including treadmill walking or recumbent bicycle. The exercise protocol will consist of a 5-10 minute warm-up, followed by a series of progressive aerobic and strengthening exercises, and will end with a 5 minute cool-down. The primary outcome for this study will be PTSD symptoms assessed with the CAPS-5. Physical function, another outcome of primary interest will be measured objectively with a Physical Performance Battery. This test battery assesses aspects of daily function including balance (single leg stance), gait speed (4 meter walk), and chair stands (# in 30 seconds). Aerobic endurance, the investigators primary functional outcome, will be assessed with the 6-minute walk test (6MWT). Secondary outcomes include depression, sleep, and cognitive function. Outcomes will be assessed at baseline, 3 months, and 6 months. Assessments will be repeated 12 weeks post-intervention (9 months) to examine whether any observed exercise intervention effects are maintained. Mixed linear models will be used to compare outcomes for the two study arms.
 
3. Project Title: DEPRESCRIBING CENTRAL NERVOUS SYSTEM MEDICATIONS IN HOSPITALIZED OLDER ADULTS
  Leader(s): PAVON, JULIESSA M
    DUKE UNIVERSITY
    NIH K23AG058788 / ( 2019 - 2024 )
  Core(s):
  This K23 Career Development Award in Aging focuses on the development of Dr. Juliessa Pavon, a hospital-based geriatrician, and on reducing central nervous system (CNS) medication use in hospitalized older adults.Dr. Pavon s long-term goal is to improve the resilience of older adults against the acute stressors ofhospitalization. She has built her research program on investigating hazards of hospitalization, and a majorthreat is high-risk medication exposure. Sub-optimal CNS medication use during hospitalization is a keymodifiable risk factor for poor health outcomes; common classes include opioids, anxiolytics, anti-depressants,antipsychotics, and hypnotics. Our preliminary data suggests that nearly 40% of hospitalized older adults areexposed to anxiolytics and 60% to opioids during their hospital stay. De-prescribing is a systematic process oftapering or reducing medications. Interventions to facilitate de-prescribing that target specific medicationclasses, like CNS medications, or specific populations, like those with existing cognitive impairment, have notbeen well-studied in the inpatient setting. This gap represents a key opportunity to reduce potentiallyinappropriate CNS medications and their debilitating side effects in vulnerable patients--in line with the NationalInstitute of Aging s priorities to improve medication use in older adults. Dr. Pavon s K23 award proposes todevelop and pilot test a de-prescribing intervention that is informed by a theoretical model of behavioralchange. Aim 1 results will inform the epidemiology of the problem and identify target populations forrecruitment. Aim 2 will use qualitative methods to examine barriers and facilitators of hospital de-prescribing.Results will inform the intervention delivery strategies best suited to facilitate CNS medication de-prescribing ina well-tolerated, feasible manner. Aim 3 will develop and pilot test a multi-component hospital-based de-prescribing intervention that uses health informatics for content delivery, and provider behavior change andpatient activation strategies. This work will advance understanding of 1) which patients and CNS medicationclasses to target for de-prescribing interventions, 2) whether there are unique barriers to de-prescribing in thehospital setting, and 3) the optimal delivery strategy for safely de-prescribing. During this K23 grant period, Dr.Pavon will also complete additional training in Markov modeling statistical techniques, interventiondevelopment, health informatics, and leadership. Dr. Pavon s mentor team will provide scientific support withexpertise in aging, pharmacology, hospital medicine, and research methodology. This career developmentplan will give Dr. Pavon the skills in conducting intervention development studies within the hospital setting.This training and resulting data will establish Dr. Pavon as a strong candidate for an R01 intervention designedto facilitate de-prescribing of CNS medications for the nearly 1 in 2 older adults that will experience exposure toa CNS medication during hospitalization.
 
4. Project Title: METABOLOMIC & RADIOGRAPHIC MARKERS OF FRACTURE RISK AMONG OLDER ADULTS WITH DIABETES
  Leader(s): LEE, RICHARD H.
    DUKE UNIVERSITY
    NIH K23AG058797 / ( 2018 - 2023 )
  Core(s):
  ABSTRACTAmong its medical complications, type 2 diabetes mellitus in older adults is associated with atwo-fold increase in the risk of hip and other low-trauma bone fractures. Paradoxically, thisincreased risk occurs despite a higher average bone mineral density. This increased fracturerisk is likely multifactorial, stemming from metabolic dysfunction that results in both increasedfalls risk and decreased bone strength. However, fracture risk stratification currently is limitedlargely to bone density testing and clinical risk tools that do not perform adequately for adultswith diabetes. Because bone is both a metabolic and structural tissue, metabolomics andbiomechanical analyses would be particularly useful for developing and assessing newmeasures of fracture risk. The objective of this application is to develop and evaluateradiographic and laboratory biomarkers of fracture risk among older adults with diabetes,utilizing biomechanical and translational measures. The proposed research has the followingaims: 1) Determine the association between metabolomic profiles and incident clinical fractureamong older adults with diabetes; 2) Compare geometric and biomechanical measures at thefemoral neck and intertrochanteric region among older adults with diabetes, with and without hipfracture. This application builds upon the prior published work and clinical expertise of thePrinciple Investigator, Dr. Richard Lee, and provides him additional research skills to assist withhis career development goal of understanding the interaction of chronic medical conditions onthe bone health of older adults, focusing on diabetes. Dr. Lee is a dual-trained Geriatrician andEndocrinologist with expertise in metabolic bone disease. The primary training goals of thisproposal include the following: 1) Develop laboratory and analytical skills in translational sciencethat will be used in the development and evaluation of clinical biomarkers, including omicstechnologies; 2) Acquire principles and skills in biomechanical engineering and materialsscience to integrate with clinical and epidemiological analyses. By integrating biomechanicalengineering and metabolomics approaches with epidemiologic research to identify new markersof fracture risk, this application addresses a significant source of morbidity and mortality amongan increasing proportion of older adults.
 
5. Project Title: DEPRESCRIBING FOR OLDER DIALYSIS PATIENTS
  Leader(s): HALL, RASHEEDA K
    DUKE UNIVERSITY
    NIH K76AG059930 / ( 2018 - 2023 )
  Core(s):
  ABSTRACTThis is a Beeson Emerging Leaders in Aging career development award (K76) for Dr. Rasheeda Hall, MD,MBA, MHS. Dr. Hall is a nephrologist who conducts aging research at Duke University, and her long-term goalis to become a leader in geriatric nephrology and develop effective interventions targeting geriatric conditionsin older dialysis patients. Compared to older adults without kidney disease, older dialysis patients are morelikely develop severe cognitive impairment, experience more falls, and have more frequent hospitalizations.These adverse outcomes are also known to be associated with potentially inappropriate medications, and olderdialysis patients are highly susceptible to adverse effects of potentially inappropriate medications because ofaltered medication clearance due to absent kidney function and common occurrences of hypotension and mini-strokes. Given this susceptibility, reduction of potentially inappropriate medications is a logical goal forimproving quality of care for these vulnerable patients. The objective of Dr. Hall s proposed research is todevelop an evidence-based strategy to reduce inappropriate prescribing in older dialysis patients. Theresearch aims are to: 1) identify the prevalence of specific potentially inappropriate medications and the extentto which there is an association with hospitalization risk in prevalent older dialysis patients, 2) identify elementsof a deprescribing intervention that are acceptable to nephrologists, primary care providers, and patients, and3) determine the feasibility of a deprescribing intervention tailored for older dialysis patients. This work willprovide evidence to support a definitive clinical trial of deprescribing in dialysis units. Effective deprescribinginterventions have the potential to reduce hospitalizations and ameliorate geriatric syndromes in dialysispatients which is consistent with NIA s mission. Complementary to this research, this career developmentaward will solidify Dr. Hall s transition to research independence through coursework and mentoring to: a) fillknowledge gaps in directing a team of statisticians, interpretation of pharmacoepidemiologic data, advancedmethods in handling bias in observational data, timely qualitative analyses, execution of a pilot study, andclinical trial design; b) enhance her leadership skills; and c) successfully compete for a R01. Duke University isthe ideal environment for Dr. Hall to pursue this research career development because of the strong agingresearch expertise housed in its Center for Aging and affiliated Pepper Center, as well as, rich resourcesavailable through Duke s Clinical and Translational Institute.
 
6. Project Title: EPIGENETIC MECHANISMS PROMOTING LONGEVITY
  Leader(s): KRAUS, VIRGINIA
    DUKE UNIVERSITY
    NIH R01AG054840 / ( 2018 - 2023 )
  Core(s):
  AbstractCirculating small regulatory RNAs (sRNAs) are short non-coding RNAs (typically ~19-25nt in size). They mediatea broad spectrum of biological processes through regulation of gene expression. Our experimental evidenceindicates that serum levels of miRNAs (one form of sRNA) change considerably, the vast majority increasingwith age. The ability of circulating sRNAs to travel among tissues enables them to transmit signals and regulatea broad spectrum of biological functions. sRNAs exist in a variety of RNase-insensitive ribonucleoprotein or lipidcomplexes, or are encapsulated inside different types of extracellular vesicles. Consequently, in contrast tomessenger RNA, sRNAs are protected from extracellular RNases and are measurable and stable in samplesstored for decades. Despite numerous recent developments, we are far from understanding the role of sRNAsin aging. An understanding of their role in aging mammals, and in humans in particular, is still very limited dueto the increased complexity and longer life-spans of mammals compared with invertebrates. This projectleverages existing human sample resources from three completed NIH-funded studies (EPESE, STRRIDE andCALERIE), to discover and validate longevity-associated miRNAs in humans. Our preliminary analysis of 175circulating microRNA--in the NIA-funded Duke Established Populations for Epidemiologic Studies of the Elderly(Duke EPESE) community-based cohort of elders--identified 32 differentially expressed circulating miRNAs(p<0.05) associated with longevity; in all cases, their concentrations at baseline were higher in long-termsurvivors (>10 years) compared with age, sex and race matched but short-term survivors (<2 years); a subsetof these miRNAs predicted longevity independent of age, gender, race and functional status. The Duke EPESEcohort was aged 71 and older at the time of blood sampling and now has 25 years of longitudinal mortality data(through 2016) with which to address key questions about sRNAs and longevity in humans. sRNA discoveriesin Duke EPESE will be validated in plasma and muscle samples from completed human clinical trials of relevanceto longevity that investigated the health-promoting effects of exercise (STRRIDE cohort) and caloric restriction(CALERIE cohort). A human three-dimensional muscle tissue organ system will be used to understand theirmechanisms of action (with and without simulated exercise and caloric restriction), by testing sRNA mimics andinhibitors. Our preliminary analyses of 7 of our top longevity-related miRNA in this model system demonstratedproduction and secretion of all of them by muscle and statistically significantly increased secretion of two of themwith simulated muscle exercise. Together our approach will permit us to determine if sRNAs associated withlongevity are favorably modulated in tissue and blood in humans by exercise and/or caloric restriction, and ifthey appear to mediate any of the observed health benefits of these interventions. The totality of the data(generated in vivo and in vitro), will be systematically examined to identify pathways of sRNA action in humansand profiles of sRNA that could serve as biomarkers to predict longevity status.
 
7. Project Title: GENOMIC ANALYSIS OF THE CALERIE TRIAL TO GENERATE NEW KNOWLEDGE FOR GEROSCIENCE
  Leader(s): BELSKY, DANIEL WALKER
    COLUMBIA UNIVERSITY HEALTH SCIENCES
    NIH R01AG061378 / ( 2019 - 2024 )
  Core(s):
  SUMMARYThe graying global population makes interventions to extend healthy lifespan (healthspan) a public heathpriority. Therapies targeting basic biological processes of aging show proof-of-concept in animals: early-to-midlife intervention can delay disease onset and prolong healthspan. But translating these geroprotectivetherapies to humans faces the barrier that human clinical trials of midlife geroprotective therapy wouldrequire decades of follow-up to measure healthspan extension. An alternative is a short-term acceleratedgeroprotector trial that tests if geroprotective intervention can slow the rate of biological aging. Biologicalaging is the gradual and progressive decline in system integrity that occurs with advancing chronologicalage. This process is thought to be the root cause of increases in morbidity and disability in later life. Newresearch shows that biological aging can be measured in humans and that measures of biological agingpredict human healthspan. Geroprotective therapies that target basic biological processes of aging arehypothesized to slow the rate of biological aging. But this has not been tested. Our study will test if the best-established geroprotective intervention in animals, long-term caloric restriction, slows the rate of biologicalaging in midlife humans, who are still young enough for age-related disease to be delayed or prevented.We will conduct new assays of stored biospecimens from the National Institute on Aging's recently-completed CALERIE Trial, which randomized 220 non-obese adults to 25% caloric restriction (CR, N=145)or ad libitum normal diet (AL, N=75) for a period of 2 years. We have already shown that CR slows aging-related deterioration in organ-system integrity. Now, we propose to extend this test to genomic measures ofbiological aging. We will assay whole-genome DNA methylation (using Illumina chips) and gene expression(using RNA sequencing) from blood samples collected at CALERIE baseline, and at 12-, and 24-monthfollow-ups. We will use this 3-time-point repeated-measures multi-omics dataset to test (i) Does CR slowsthe rate of biological aging as measured from DNA methylation (ii) Does CR cause changes to geneexpression in the pathways known to mediate healthspan-extending effects of CR in animals, e.g. themTOR pathway (iii) Do changes to DNA methylation and gene expression mediate effects of CR on organsystem functioning We will share the multi-omics data we generate with the CALERIE Biorepository,making the resource freely available to all interested researchers. The proposed project will generate newknowledge about effects of caloric restriction on biological aging in humans and test proof of concept for anaccelerated geroprotector trial design that can speed translation of new age-delaying therapies fromanimals to humans. Open data sharing through the CALERIE Biorepository will enable research beyond thescope of this project to improve understanding of caloric restriction and advance the field of geroscience.
 
8. Project Title: FUNCTIONAL LIMITATIONS AND DISABILITY AMONG MIDDLE-AGED ADULTS
  Leader(s): BOWLING, CHRISTOPHER BARRETT
    DUKE UNIVERSITY
    NIH R01AG062502 / ( 2020 - 2023 )
  Core(s):
  Project summary/Abstract The burden of functional limitations (restrictions in basic physical actions) and disability (problems with daily activities and life participation) may be more common in middle-aged US adults than previously recognized. However, studies of middle-age populations have not typically included functional assessments. The Coronary Artery Risk Development in Young Adults (CARDIA) study provides a unique opportunity to study functional status in a diverse, aging cohort. The Year 35 in-person exam is scheduled for 2020 and 2021, at which time, participants will be 53 to 65 years old. We propose a CARDIA ancillary study to obtain measures of function by self-report and physical performance to be paired with the existing data collected from early adulthood through middle age to address the following aims: 1. To quantify the burden of functional limitations and disability in middle age and assess the degree to which this can be attributed to the accumulation of chronic conditions, 2. To assess domains of functional limitations and disability captured by physical performance versus self-report, 3. To identify health-related risk factors in early adulthood for functional limitations and disability in middle-age, 4. To identify health-related, socioeconomic, and psychosocial factors that contribute to between- and within- race differences in functional limitations and disability among middle-aged adults. We will add measures of physical performance (fast and usual gait speed, single leg balance, timed chair stands, 6-minute walk test, and grip strength) to the CARDIA Year 35 exam (projected N=3,270; 1,563 black, 1,707 white). Also, self- reported functional limitations (Patient-Reported Outcomes Measurement Information System [PROMIS] Physical Function Short Form 20a) and disability measures (basic and instrumental activities of daily living) will be added to the Year 35 exam and annual telephone calls (1 call prior to and 2 after the Year 35 exam). As studies of younger populations have not often included functional assessments, the conceptualization, measurement approaches, risk factors, and implications of functional limitations and disability are poorly understood. Filling this knowledge gap by adding appropriate functional measures to an ongoing population based cohort, that represents the next wave of aging black and white adults will lead to new approaches to prevent functional decline and improve population health.
 
9. Project Title: MECHANOTRANSDUCTION IN MENISCUS HEALTH AND REPAIR
  Leader(s): MCNULTY, AMY L
    DUKE UNIVERSITY
    NIH R01AR073221 / ( 2019 - 2023 )
  Core(s):
  ABSTRACT.Meniscal injuries are a significant clinical problem as each year 850,000 meniscal surgeries are performed in theUnited States and nearly twice as many worldwide. Meniscal tears in the avascular inner zone of the tissue donot heal well with suturing or conservative treatments and can ultimately lead to the development of osteoarthritis(OA). Therefore, new strategies are needed to enhance endogenous meniscus repair and tissue regeneration.The menisci play a critical biomechanical role in the knee, providing load support, joint stability, and congruity.Meniscus tissue is maintained through a balance of anabolic and catabolic activities of meniscus cells. Thesecellular activities are controlled not only by biochemical factors in the joint but also by physical factors associatedwith joint loading. Mechanobiology, which is the influence of mechanical factors on the biologic response of cells,is important in converting physical signals into metabolic and inflammatory responses in meniscus. However,the mechanisms by which mechanical signals are transduced in meniscus cells have yet to be identified. Ouroverall goal is to identify critical meniscus mechanotransduction pathways and modulate thesepathways to promote meniscus repair and prevent OA development.Our work has shown that transient receptor potential vanilloid 4 (TRPV4) is a critical component in cartilagemechanotransduction and metabolism. The activation of TRPV4 can block IL-1 induced catabolic responses andalso increases cell migration and proliferation, which are important processes to enhance tissue repair. Whilewe have found that TRPV4 is expressed in the meniscus, the function of this mediator in meniscus health anddisease is currently unknown. In this proposal, we will determine how mechanotransduction occurs throughTRPV4 in meniscus and identify modulators of this pathway that will be used to enhance tissue repair and preventOA development. We hypothesize that mechanotransduction by TRPV4 plays a key role in meniscus metabolismand can be modulated to enhance meniscus repair and prevent the development of OA. In this proposal, we willdetermine the effects of mechanical stimulation on TRPV4-mediated metabolism in healthy meniscus cells.Next, we will elucidate alterations in TRPV4-mediated mechanotransduction pathways in meniscus pathology.Finally, we will enhance integrative meniscus repair and prevent the development of OA by modulation ofmechanotransduction pathways. In this proposal, we will identify the key signaling pathways downstream ofTRPV4 that may function as novel drug targets to 1) treat patients with immobilized joints to simulate exerciseand maintain joint health; 2) enhance meniscus tissue regeneration using tissue engineering strategies; and 3)enhance meniscus repair and prevent the development of OA. Novel therapeutic targets identified in thisproposal can subsequently be developed into drugs to enhance meniscus repair and prevent the developmentof OA.
 
10. Project Title: PRAGMATIC EVALUATION OF EVENTS AND BENEFITS OF LIPID-LOWERING IN OLDER ADULTS (PREVENTABLE)
  Leader(s): ALEXANDER, KAREN P; AMBROSIUS, WALTER T ; HERNANDEZ, ADRIAN ; WILLIAMSON, JEFF DOUGLAS ;
    DUKE UNIVERSITY
    NIH U19AG065188 / ( 2019 - 2026 )
  Core(s):
  There is an urgent need for evidence to guide clinical care of older adults due to demographic shifts, includinglonger life expectancy and a recent doubling of the older adult population. Statins reduce recurrent CVD eventsand prevent initial events in patients younger than 75 years. However, clinical research has often excludedpersons older than 75 years due to a higher prevalence of comorbidity and frailty so little to no evidence isavailable to guide care in this population. For older adults living longer, the promise of preventing cognitiveimpairment is as compelling as preventing a CVD event, but some evidence suggests statins maycontribute to memory difficulty or muscle symptoms. There is equipoise regarding the usefulness of statinsfor primary CVD, dementia, and disability prevention in adults older than 75 years, especially in the settingof multiple chronic conditions, advanced age, or frailty. Evidence to improve cognitive and functionaloutcomes in older populations with diverse race/ethnicity and health status will require new clinical trialapproaches with sustainable methodology and infrastructure. We propose PREVENTABLE (PRagmaticEValuation of evENTs And Benefits of Lipid-lowering in oldEr adults), the first statin trial with a non-CVDprimary outcome survival free of dementia or persisting disability. Using a placebo-controlled pragmaticclinical trial (PCT) design across PCORnet and VA network, the trial will be under the leadership of Dr. KarenAlexander at DCRI, Dr. Jeff Williamson at WFSM, Dr. Adrian Hernandez at DCRI, and Dr. Walter Ambrosius atWFSM. This team has established experience and track-record of accomplishment in the design and conductof PCTs, trial expertise in ascertaining cognitive and disability outcomes in older adults, and is supported by arobust administrative infrastructure for coordinating these shared responsibilities for success. The overarchinggoal of PREVENTABLE is to generate knowledge about the role of statins in older adults, a population in whichrisk/benefit for primary prevention has been under studied. The hypothesis is that a large trial conducted in anolder adult population will demonstrate the benefit of statins for reducing dementia, disability, and CV events.We further hypothesize that extensive genomic, biochemical and imaging ancillary studies will offer uniqueinsights into these key outcomes. PREVENTABLE has the following specific aims: AIM 1: Determine the roleof a moderate-intensity statin in preventing dementia and prolonging disability-free survival in patients 75 yearsand older without clinically evident coronary heart disease, including those with frailty, impaired physicalfunction, mild cognitive impairment, polypharmacy, and multi-morbidity. AIM 2: Determine the role of moderate-intensity statin in preventing hospitalization for myocardial infarction/acute coronary syndrome, stroke, heartfailure, revascularization or cardiovascular-related death, and preventing either mild cognitive impairment ordementia. AIM 3: Test the safety and tolerability of statins in older adults and collect 17,000 bio-specimens toadvance precision health.
 
PUBLICATIONS
2023
  1. Remotely Supervised Weight Loss and Exercise Training to Improve Rheumatoid Arthritis Cardiovascular Risk: Rationale and Design of the Supervised Weight Loss Plus Exercise Training-Rheumatoid Arthritis Trial.
    Andonian B, Ross LM, Zidek AM, Fos LB, Piner LW, Johnson JL, Belski KB, Counts JD, Pieper CF, Siegler IC, Bales CW, Porter Starr KN, Kraus WE, Huffman KM
    ACR Open Rheumatol, 2023 May, 5(5): 252-263
    https://doi.org/10.1002/acr2.11536 | PMID: 36992545 | PMCID: PMC10184018
    Citations: 112 | AltScore: NA
  2. Which types of stress are associated with accelerated biological aging? Comparing perceived stress, stressful life events, childhood adversity, and posttraumatic stress disorder.
    Bourassa KJ, Caspi A, Brennan GM, Hall KS, Harrington H, Houts R, Kimbrel NA, Poulton R, Ramrakha S, Taylor GA, Moffitt TE
    Psychosom Med, 2023 Apr 6
    https://doi.org/10.1097/PSY.0000000000001197 | PMID: 37053097
    Citations: | AltScore: 16.85
  3. Elevated C-Reactive Protein and Subsequent Patient-Reported Cognitive Problems in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study.
    Carroll JE, Nakamura ZM, Small BJ, Zhou X, Cohen HJ, Ahles TA, Ahn J, Bethea TN, Extermann M, Graham D, Isaacs C, Jim HSL, Jacobsen PB, McDonald BC, Patel SK, Rentscher K, Root J, Saykin AJ, Tometich DB, Van Dyk K, Zhai W, Breen EC, Mandelblatt JS
    J Clin Oncol, 2023 Jan 10, 41(2): 295-306
    https://doi.org/10.1200/JCO.22.00406 | PMID: 36179271 | PMCID: PMC9839283
    Citations: 80 | AltScore: 247.762
  4. Association of Dipeptidylpeptidase 4 (CD26) With Chondrocyte Senescence and Radiographic Progression in Knee Osteoarthritis.
    Chen YH, Zhang X, Chou CH, Hsueh MF, Attarian D, Li YJ, Kraus VB
    Arthritis Rheumatol, 2023 Jan 27
    https://doi.org/10.1002/art.42455 | PMID: 36704903
    Citations: | AltScore: NA
  5. RELATIONSHIP BETWEEN REPRODUCTIVE AND BONE BIOMARKERS AND OSTEOARTHRITIS IN ZOO ASIAN (ELEPHAS MAXIMUS) AND AFRICAN (LOXODONTA AFRICANA) ELEPHANTS.
    Chusyd DE, Brown JL, Golzarri-Arroyo L, Dickinson SL, Kraus VB, Siegal-Willott J, Griffin TM, Huebner JL, Edwards KL, Allison DB, Austad SN
    J Zoo Wildl Med, 2023 Jan, 53(4): 801-810
    https://doi.org/10.1638/2021-0080 | PMID: 36640083 | PMCID: PMC10150656
    Citations: 26 | AltScore: NA
  6. CERAD (Consortium to Establish a Registry for Alzheimer's Disease) Neuropsychology Assessment Battery: 35 Years and Counting.
    Fillenbaum GG, Mohs R
    J Alzheimers Dis, 2023, 93(1): 1-27
    https://doi.org/10.3233/JAD-230026 | PMID: 36938738 | PMCID: PMC10175144
    Citations: 214 | AltScore: 7
  7. SARS-CoV-2 Antibody Prevalence among Industrial Livestock Operation Workers and Nearby Community Residents, North Carolina, 2021 to 2022.
    Gigot C, Pisanic N, Kruczynski K, Gregory Rivera M, Spicer K, Kurowski KM, Randad P, Koehler K, Clarke WA, Holmes P, Hall DJ Jr, Hall DJ, Heaney CD
    mSphere, 2023 Feb 21, 8(1): e0052222
    https://doi.org/10.1128/msphere.00522-22 | PMID: 36656002 | PMCID: PMC9942583
    Citations: 54 | AltScore: NA
  8. Biomarkers and longitudinal changes in lumbar spine degeneration and low back pain: the Johnston County Osteoarthritis Project.
    Goode AP, Cleveland RJ, Kraus VB, Taylor KA, George SZ, Schwartz TA, Renner J, Huebner JL, Jordan JM, Golightly YM
    Osteoarthritis Cartilage, 2023 Jun, 31(6): 809-818
    https://doi.org/10.1016/j.joca.2023.02.005 | PMID: 36804589 | PMCID: PMC10200763
    Citations: 47 | AltScore: 7.1
  9. Branched-chain a-keto acids and glutamate/glutamine: Biomarkers of insulin resistance in childhood obesity.
    Gumus Balikcioglu P, Jachthuber Trub C, Balikcioglu M, Ilkayeva O, White PJ, Muehlbauer M, Bain JR, Armstrong S, Freemark M
    Endocrinol Diabetes Metab, 2023 Jan, 6(1): e388
    https://doi.org/10.1002/edm2.388 | PMID: 36415168 | PMCID: PMC9836245
    Citations: 64 | AltScore: NA
  10. Using Movement Disorder Society Unified Parkinson's Disease Rating Scale Parts 2 and 3 Simultaneously: Combining the Patient Voice with Clinician Ratings.
    Guo Y, Goetz CG, Stebbins GT, Mestre TA, Luo S
    Mov Disord, 2023 Jan 9, 38(3): 453-463
    https://doi.org/10.1002/mds.29308 | PMID: 36621935 | PMCID: PMC10033355
    Citations: 35 | AltScore: 0.5
  11. Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan.
    Hemmersbach-Miller M, Balevic SJ, Winokur PL, Landersdorfer CB, Gu K, Chan AW, Cohen-Wolkowiez M, Conrad T, An G, Kirkpatrick CMJ, Swamy GK, Walter EB, Schmader KE
    Clin Pharmacokinet, 2023 Jan 12, 62(1): 127-139
    https://doi.org/10.1007/s40262-022-01198-z | PMID: 36633812 | PMCID: PMC9969806
    Citations: 43 | AltScore: 1
  12. Inflammation and Clinical Decline After Adjuvant Chemotherapy in Older Adults With Breast Cancer: Results From the Hurria Older Patients Prospective Study.
    Ji J, Sun CL, Cohen HJ, Synold T, Muss H, Sedrak MS
    J Clin Oncol, 2023 Jan 10, 41(2): 307-315
    https://doi.org/10.1200/JCO.22.01217 | PMID: 36126235 | PMCID: PMC9839275
    Citations: 59 | AltScore: 62.086
  13. Chondroprotection of leptin deficiency demystified?
    Kraus VB, Nelson AE, Huang Z
    Osteoarthritis Cartilage, 2023 Jan, 31(1): 18-20
    https://doi.org/10.1016/j.joca.2022.10.006 | PMID: 36244625 | PMCID: PMC9772286
    Citations: 17 | AltScore: 4.2
  14. Metabolic factors associated with incident fracture among older adults with type 2 diabetes mellitus: a nested case-control study.
    Lee RH, Bain J, Muehlbauer M, Ilkayeva O, Pieper C, Wixted D, Col?n-Emeric C
    Osteoporos Int, 2023 Apr 26
    https://doi.org/10.1007/s00198-023-06763-1 | PMID: 37100949
    Citations: | AltScore: NA
  15. Novel Genetic Variants in TP37, PIK3R1, CALM1, and PLCG2 of the Neurotrophin Signaling Pathway Are Associated with the Progression from Mild Cognitive Impairment to Alzheimer's Disease.
    Li H, Liu H, Lutz MW, Luo S, Alzheimer?s Disease Neuroimaging Initiative
    J Alzheimers Dis, 2023, 91(3): 977-987
    https://doi.org/10.3233/JAD-220680 | PMID: 36530083 | PMCID: PMC9905310
    Citations: 50 | AltScore: 1
  16. Comparison of Postoperative Outcomes of Laparoscopic vs Open Inguinal Hernia Repair.
    Meier J, Stevens A, Berger M, Makris KI, Bramos A, Reisch J, Cullum CM, Lee SC, Sugg Skinner C, Zeh H, Brown CJ, Balentine CJ
    JAMA Surg, 2023 Feb 1, 158(2): 172-180
    https://doi.org/10.1001/jamasurg.2022.6616 | PMID: 36542394 | PMCID: PMC9857280
    Citations: 18 | AltScore: 40.8
  17. Mitigation behavior prior to COVID-19 vaccination availability is associated with COVID-19 infection and time to vaccination.
    Neighbors CE, Sloane R, Pieper CF, Wixted D, Woods CW, Newby LK
    PLoS One, 2023, 18(3): e0283381
    https://doi.org/10.1371/journal.pone.0283381 | PMID: 36961840 | PMCID: PMC10038251
    Citations: 41 | AltScore: NA
  18. Physical activity and relationship to physical function, quality of life, and cognitive function in older patients with acute decompensated heart failure.
    Nelson MB, Shiroma EJ, Kitzman DW, Duncan PW, Reeves GR, Whellan DJ, Mentz RJ, Chen H, Pastva AM
    Am Heart J, 2023 Feb, 256: 85-94
    https://doi.org/10.1016/j.ahj.2022.11.002 | PMID: 36372251 | PMCID: PMC9840656
    Citations: 54 | AltScore: 21.3
  19. Frailty and Effects of a Multidomain Physical Rehabilitation Intervention Among Older Patients Hospitalized for Acute Heart Failure: A Secondary Analysis of a Randomized Clinical Trial.
    Pandey A, Kitzman DW, Nelson MB, Pastva AM, Duncan P, Whellan DJ, Mentz RJ, Chen H, Upadhya B, Reeves GR
    JAMA Cardiol, 2023 Feb 1, 8(2): 167-176
    https://doi.org/10.1001/jamacardio.2022.4903 | PMID: 36598761 | PMCID: PMC9857661
    Citations: 35 | AltScore: 88.7
  20. Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.
    Parker DC, Kraus WE, Whitson HE, Kraus VB, Smith PJ, Cohen HJ, Pieper CF, Faldowski RA, Hall KS, Huebner JL, Ilkayeva OR, Bain JR, Newby LK, Huffman KM
    J Alzheimers Dis, 2023, 91(3): 1141-1150
    https://doi.org/10.3233/JAD-220906 | PMID: 36565121 | PMCID: PMC10074831
    Citations: 29 | AltScore: 6.6
  21. Machine learning functional impairment classification with electronic health record data.
    Pavon JM, Previll L, Woo M, Henao R, Solomon M, Rogers U, Olson A, Fischer J, Leo C, Fillenbaum G, Hoenig H, Casarett D
    J Am Geriatr Soc, 2023 May 17
    https://doi.org/10.1111/jgs.18383 | PMID: 37195174
    Citations: | AltScore: 1.25
  22. A Novel Movement-Evoked Pain Provocation Test for Older Adults With Persistent Low Back Pain: Safety, Feasibility, and Associations With Self-reported Physical Function and Usual Gait Speed.
    Simon CB, Hicks GE, Pieper CF, Byers Kraus V, Keefe FJ, Col?n-Emeric C
    Clin J Pain, 2023 Apr 1, 39(4): 166-174
    https://doi.org/10.1097/AJP.0000000000001101 | PMID: 36943160 | PMCID: PMC10034602
    Citations: 60 | AltScore: NA
  23. Cognitive-motor dual-task interference in adults with sickle cell disease.
    Subramaniam AP, Oyedeji CI, Parikh JS, Feld JA, Strouse JJ
    Gait Posture, 2023 May, 102: 164-170
    https://doi.org/10.1016/j.gaitpost.2023.03.009 | PMID: 37023564
    Citations: | AltScore: NA
  24. Recommendations for using the 5Ts Framework to support research inclusion across the lifespan.
    Thomas J, Eckstrom E, Lam WKK, Sullivan S, Bentley-Edwards K, Gierisch JM, Bowling CB
    J Am Geriatr Soc, 2023 Apr 10
    https://doi.org/10.1111/jgs.18359 | PMID: 37036034
    Citations: | AltScore: NA
  25. An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.
    Yan R, Cigliola V, Oonk KA, Petrover Z, DeLuca S, Wolfson DW, Vekstein A, Mendiola MA, Devlin G, Bishawi M, Gemberling MP, Sinha T, Sargent MA, York AJ, Shakked A, DeBenedittis P, Wendell DC, Ou J, Kang J, Goldman JA, Baht GS, Karra R, Williams AR, Bowles DE, Asokan A, Tzahor E, Gersbach CA, Molkentin JD, Bursac N, Black BL, Poss KD
    Cell Stem Cell, 2023 Jan 5, 30(1): 96-111.e6
    https://doi.org/10.1016/j.stem.2022.11.012 | PMID: 36516837 | PMCID: PMC9830588
    Citations: 73 | AltScore: 263.26
  26. Development and Validation of a Lifespan Prediction Model in Chinese Adults Aged 65?Years or Older.
    Zhou J, Chen C, Wang J, Liu S, Li X, Wei Y, Ye L, Ye J, Kraus VB, Lv Y, Shi X
    J Am Med Dir Assoc, 2023 Mar 22
    pii: S1525-8610(23)00135-4. https://doi.org/10.1016/j.jamda.2023.02.016 | PMID: 36965505
    Citations: | AltScore: NA
  27. Summing MDS-UPDRS Parts 1 + 2 (Non-motor and Motor Experience of Daily Living): The Patient's Voice.
    Zou H, Goetz CG, Stebbins GT, Schrag A, Mestre TA, Luo S
    Mov Disord, 2023 Apr 23
    https://doi.org/10.1002/mds.29417 | PMID: 37087725
    Citations: | AltScore: NA
  28. Multivariate functional mixed model with MRI data: An?application to Alzheimer's disease.
    Zou H, Xiao L, Zeng D, Luo S, Alzheimer's Disease Neuroimaging Initiative
    Stat Med, 2023 May 10, 42(10): 1492-1511
    https://doi.org/10.1002/sim.9683 | PMID: 36805635 | PMCID: PMC10133011
    Citations: 56 | AltScore: 9.5
 
2022
  1. Clin-Star corner: What's new at the interface of geriatrics, infectious diseases, and antimicrobial stewardship.
    Advani SD, Schmader KE, Mody L
    J Am Geriatr Soc, 2022 Aug, 70(8): 2214-2218
    https://doi.org/10.1111/jgs.17907 | PMID: 35704918 | PMCID: PMC9378540
    Citations: 16 | AltScore: 26.34
  2. Tibiofemoral knee osteoarthritis progresses symmetrically by knee compartment in the GOGO cohort.
    Alexander LC Jr, Huebner JL, Cicconetti G, Jordan JM, Renner JB, Doherty M, Wilson AG, Hochberg MC, Loeser R, Kraus VB
    Osteoarthr Cartil Open, 2022 Sep, 4(3):
    pii: 100288. https://doi.org/10.1016/j.ocarto.2022.100288 | PMID: 36081777 | PMCID: PMC9451142
    Citations: 15 | AltScore: NA
  3. Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers.
    Bay-Jensen AC, Mobasheri A, Thudium CS, Kraus VB, Karsdal MA
    Curr Opin Rheumatol, 2022 Jan 1, 34(1): 54-60
    https://doi.org/10.1097/BOR.0000000000000845 | PMID: 34652292 | PMCID: PMC8635261
    Citations: 53 | AltScore: NA
  4. Implementation of a telehealth videoconference to improve hospital-to-skilled nursing care transitions: Preliminary data.
    Bellantoni J, Clark E, Wilson J, Pendergast J, Pavon JM, White HK, Malone D, Knechtle W, Jolly Graham A
    J Am Geriatr Soc, 2022 Mar 25, 70(6): 1828-1837
    https://doi.org/10.1111/jgs.17751 | PMID: 35332931
    Citations: | AltScore: 9.2
  5. Postoperative changes in cognition and cerebrospinal fluid neurodegenerative disease biomarkers.
    Berger M, Browndyke JN, Cooter Wright M, Nobuhara C, Reese M, Acker L, Bullock WM, Colin BJ, Devinney MJ, Moretti EW, Moul JW, Ohlendorf B, Laskowitz DT, Waligorska T, Shaw LM, Whitson HE, Cohen HJ, Mathew JP, MADCO-PC Investigators.
    Ann Clin Transl Neurol, 2022 Feb 1, 9(2): 155-170
    https://doi.org/10.1002/acn3.51499 | PMID: 35104057 | PMCID: PMC8862419
    Citations: 75 | AltScore: 34.2
  6. Developing a Real-Time Electroencephalogram-Guided Anesthesia-Management Curriculum for Educating Residents: A Single-Center Randomized Controlled Trial.
    Berger M, Eleswarpu SS, Cooter Wright M, Ray AM, Wingfield SA, Heflin MT, Bengali S, Udani AD
    Anesth Analg, 2022 Jan 1, 134(1): 159-170
    https://doi.org/10.1213/ANE.0000000000005677 | PMID: 34709008 | PMCID: PMC8678191
    Citations: 40 | AltScore: 18.3
  7. Associations between longitudinal changes in sleep disturbance and depressive and anxiety symptoms during the COVID-19 virus pandemic among older women with and without breast cancer in the thinking and living with breast cancer study.
    Bethea TN, Zhai W, Zhou X, Ahles TA, Ahn J, Cohen HJ, Dilawari AA, Graham DMA, Jim HSL, McDonald BC, Nakamura ZM, Patel SK, Rentscher KE, Root J, Saykin AJ, Small BJ, Van Dyk KM, Mandelblatt JS, Carroll JE
    Cancer Med, 2022 Mar 22, 11(17): 3352-3363
    https://doi.org/10.1002/cam4.4682 | PMID: 35315588 | PMCID: PMC9110906
    Citations: 52 | AltScore: 15.5
  8. Reserve and resilience in CKD: concept introduction and baseline results from the Physical REsilience Prediction in Advanced REnal Disease (PREPARED) study.
    Bowling CB, Olsen MK, Berkowitz TSZ, Smith B, Floyd B, Majette N, Miles AL, Crowley SD, Wang V, Maciejewski ML, Whitson HE
    BMC Nephrol, 2022 Dec 31, 23(1): 418
    https://doi.org/10.1186/s12882-022-03033-w | PMID: 36585609 | PMCID: PMC9803898
    Citations: 30 | AltScore: 0.5
  9. Preoperative dysphagia risk in community-dwelling adults aged =50 years: Prevalence and risk factors.
    Canick J, Campbell JC, Cohen SM, Jones HN, Leiman DA, Raman S, Porter Starr KN
    Nutr Clin Pract, 2022 Jul 5, 38(1): 157-166
    https://doi.org/10.1002/ncp.10889 | PMID: 35788985 | PMCID: PMC10026185
    Citations: 55 | AltScore: 1
  10. Hevin/Sparcl1 drives pathological pain through spinal cord astrocyte and NMDA receptor signaling.
    Chen G, Xu J, Luo H, Luo X, Singh SK, Ramirez JJ, James ML, Mathew JP, Berger M, Eroglu C, Ji RR
    JCI Insight, 2022 Dec 8, 7(23):
    https://doi.org/10.1172/jci.insight.161028 | PMID: 36256481 | PMCID: PMC9746899
    Citations: 46 | AltScore: NA
  11. CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.
    Chen YH, Zhang X, Ko KY, Hsueh MF, Kraus VB
    Oxid Med Cell Longev, 2022, 2022: 5503575
    https://doi.org/10.1155/2022/5503575 | PMID: 35251476 | PMCID: PMC8890863
    Citations: 50 | AltScore: 1
  12. Economic Outcomes of Rehabilitation Therapy in Older Patients With Acute Heart Failure in the REHAB-HF Trial: A Secondary Analysis of a Randomized Clinical Trial.
    Chew DS, Li Y, Zeitouni M, Whellan DJ, Kitzman D, Mentz RJ, Duncan P, Pastva AM, Reeves GR, Nelson MB, Chen H, Reed SD
    JAMA Cardiol, 2022 Feb 1, 7(2): 140-148
    https://doi.org/10.1001/jamacardio.2021.4836 | PMID: 34817542 | PMCID: PMC8613698
    Citations: 34 | AltScore: 33
  13. A Processed Electroencephalogram-Based Brain Anesthetic Resistance Index Is Associated With Postoperative Delirium in Older Adults: A Dual Center Study.
    Cooter Wright M, Bunning T, Eleswarpu SS, Heflin MT, McDonald SR, Lagoo-Deenadalayan S, Whitson HE, Martinez-Camblor P, Deiner SG, Berger M
    Anesth Analg, 2022 Jan 1, 134(1): 149-158
    https://doi.org/10.1213/ANE.0000000000005660 | PMID: 34252066 | PMCID: PMC8678136
    Citations: 46 | AltScore: 7.2
  14. \I know that my role is going to change\: a mixed-methods study of the relationship between amyloid-? PET scan results and caregiver burden.
    Couch E, Belanger E, Gadbois EA, DePasquale N, Zhang W, Wetle T
    Aging Clin Exp Res, 2022 Dec 9, 35(2): 387-397
    https://doi.org/10.1007/s40520-022-02314-6 | PMID: 36484946 | PMCID: PMC9735001
    Citations: 23 | AltScore: 2.85
  15. The potential link between obstructive sleep apnea and postoperative neurocognitive disorders: current knowledge and possible mechanisms.
    Devinney MJ, VanDusen KW, Kfouri JM, Avasarala P, Spector AR, Mathew JP, Berger M
    Can J Anaesth, 2022 Oct, 69(10): 1272-1287
    https://doi.org/10.1007/s12630-022-02302-4 | PMID: 35982354 | PMCID: PMC9924301
    Citations: 108 | AltScore: 17.55
  16. A Multidimensional Bioinformatic Platform for the Study of Human Response to Surgery.
    Eckhoff AM, Connor AA, Thacker JKM, Blazer DG, Moore HG, Scheri RP, Lagoo-Deenadayalan SA, Harpole DH, Seymour KA, Purves JT, Ravindra KV, Southerland KW, Rocke DJ, Gilner JB, Parker DC, Bain JR, Muehlbauer MJ, Ilkayeva OR, Corcoran DL, Modliszewski JL, Devos N, Foster MW, Moseley MA, Dressman HK, Chan C, Huebner JL, Chasse S, Stempora L, Aschenbrenner ME, Joshi MB, Hollister B, Henao R, Barfield RT, Ellison MA, Bailey S, Woody S, Huang ES, Kirk A, Hwang ES
    Ann Surg, 2022 Mar 3, 275(6): 1094-1102
    https://doi.org/10.1097/SLA.0000000000005429 | PMID: 35258509
    Citations: | AltScore: 7.5
  17. It Is as It Was: MDS-UPDRS Part III Scores Cannot Be Combined with Other Parts to Give a Valid Sum.
    Goetz CG, Choi D, Guo Y, Stebbins GT, Mestre TA, Luo S
    Mov Disord, 2022 Dec 8, 38(2): 342-347
    https://doi.org/10.1002/mds.29279 | PMID: 36480107 | PMCID: PMC9974855
    Citations: 22 | AltScore: 6
  18. Biomarker clusters differentiate phenotypes of lumbar spine degeneration and low back pain: The Johnston County Osteoarthritis Project.
    Goode AP, Hu D, George SZ, Schwartz TA, Kraus VB, Huebner JL, Cleveland RJ, Taylor KA, Jordan JM, Golightly YM
    Osteoarthr Cartil Open, 2022 Sep, 4(3):
    pii: 100270. https://doi.org/10.1016/j.ocarto.2022.100270 | PMID: 35991624 | PMCID: PMC9387345
    Citations: 43 | AltScore: 6.05
  19. The role of Meteorin-like in skeletal development and bone fracture healing.
    Huang R, Balu AR, Molitoris KH, White JP, Robling AG, Ayturk UM, Baht GS
    J Orthop Res, 2022 Jan 25, 40(11): 2510-2521
    https://doi.org/10.1002/jor.25286 | PMID: 35076116 | PMCID: PMC9309188
    Citations: 49 | AltScore: NA
  20. Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.
    Huang ZY, Luo ZY, Cai YR, Chou CH, Yao ML, Pei FX, Kraus VB, Zhou ZK
    Osteoarthritis Cartilage, 2022 Mar, 30(3): 475-480
    https://doi.org/10.1016/j.joca.2021.12.007 | PMID: 34971754 | PMCID: PMC10097426
    Citations: 19 | AltScore: 2.85
  21. The association of accelerated epigenetic age with all-cause mortality in cardiac catheterization patients as mediated by vascular and cardiometabolic outcomes.
    Jiang R, Hauser ER, Kwee LC, Shah SH, Regan JA, Huebner JL, Kraus VB, Kraus WE, Ward-Caviness CK
    Clin Epigenetics, 2022 Dec 3, 14(1): 165
    https://doi.org/10.1186/s13148-022-01380-x | PMID: 36461124 | PMCID: PMC9719253
    Citations: 34 | AltScore: NA
  22. Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults.
    Kraus VB, Ma S, Tourani R, Fillenbaum GG, Burchett BM, Parker DC, Kraus WE, Connelly MA, Otvos JD, Cohen HJ, Orenduff MC, Pieper CF, Zhang X, Aliferis CF
    EBioMedicine, 2022 Nov, 85: 104292
    https://doi.org/10.1016/j.ebiom.2022.104292 | PMID: 36182774 | PMCID: PMC9526168
    Citations: 34 | AltScore: 220.218
  23. Geriatric Assessment Reveals Actionable Impairments in Hematopoietic Stem Cell Transplantation Candidates Age 18 to 80 Years.
    Lew MV, Ren Y, Lowder YP, Siamakpour-Reihani S, Ramalingam S, Romero KM, Thompson JC, Bohannon LM, McIntyre J, Tang H, Van Opstal J, Johnson E, Cohen HJ, Bartlett DB, Pastva AM, Morey M, Hall KS, Smith P, Peters KB, Somers TJ, Kelleher S, Smith SK, Wischmeyer PE, Lin PH, Wood WA, Thorpe G, Minor K, Wiggins K, Hennig T, Helms T, Welch R, Matthews B, Liu J, Burleson J, Aberant T, Engemann AK, Henshall B, Darby M, Proch C, Dellascio M, Pittman A, Suminguit J, Choi T, Gasparetto C, Long GD, Lopez RD, Sarantopoulos S, Horwitz ME, Chao NJ, Sung AD
    Transplant Cell Ther, 2022 Aug, 28(8): 498.e1-498.e9
    https://doi.org/10.1016/j.jtct.2022.05.018 | PMID: 35595226 | PMCID: PMC10042624
    Citations: 45 | AltScore: NA
  24. Deep learning for the dynamic prediction of multivariate longitudinal and survival data.
    Lin J, Luo S
    Stat Med, 2022 Mar 28, 41(15): 2894-2907
    https://doi.org/10.1002/sim.9392 | PMID: 35347750 | PMCID: PMC9232978
    Citations: 32 | AltScore: NA
  25. Genetic Association Between Epigenetic Aging-Acceleration and the Progression of Mild Cognitive Impairment to Alzheimer's Disease.
    Liu H, Lutz M, Luo S, Alzheimer?s Disease Neuroimaging Initiative
    J Gerontol A Biol Sci Med Sci, 2022 Sep 1, 77(9): 1734-1742
    https://doi.org/10.1093/gerona/glac138 | PMID: 35797594 | PMCID: PMC9434458
    Citations: 59 | AltScore: 13.25
  26. Resolving Missing Data from the Movement Disorder Society Unified Parkinson's Disease Rating Scale: Implications for Telemedicine.
    Luo S, Goetz CG, Choi D, Aggarwal S, Mestre TA, Stebbins GT
    Mov Disord, 2022 Jun 18, 37(8): 1749-1755
    https://doi.org/10.1002/mds.29129 | PMID: 35716143 | PMCID: PMC9391277
    Citations: 24 | AltScore: 1.25
  27. Dissecting the Domains of Parkinson's Disease: Insights from Longitudinal Item Response Theory Modeling.
    Luo S, Zou H, Stebbins GT, Schwarzschild MA, Macklin EA, Chan J, Oakes D, Simuni T, Goetz CG, Parkinson Study Group SURE-PD3 Investigators.
    Mov Disord, 2022 Jul 16, 37(9): 1904-1914
    https://doi.org/10.1002/mds.29154 | PMID: 35841312 | PMCID: PMC9897939
    Citations: 29 | AltScore: 3
  28. Aging reduces liver resiliency by dysregulating Hedgehog signaling.
    Maeso-D?az R, Dalton GD, Oh S, Du K, Tang L, Chen T, Dutta RK, Hartman JH, Meyer JN, Diehl AM
    Aging Cell, 2022 Jan 4, 21(2): e13530
    https://doi.org/10.1111/acel.13530 | PMID: 34984806 | PMCID: PMC8844109
    Citations: 43 | AltScore: 2.5
  29. Physical Rehabilitation in Older Patients Hospitalized with Acute Heart Failure and Diabetes: Insights from REHAB-HF.
    Murray EM, Whellan DJ, Chen H, Bertoni AG, Duncan P, Pastva AM, Kitzman DW, Mentz RJ
    Am J Med, 2022 Jan, 135(1): 82-90
    https://doi.org/10.1016/j.amjmed.2021.08.001 | PMID: 34516959 | PMCID: PMC8688185
    Citations: 41 | AltScore: 7.85
  30. Intervention Adherence in REHAB-HF: Predictors and Relationship With Physical Function, Quality of Life, and Clinical Events.
    Nelson MB, Gilbert ON, Duncan PW, Kitzman DW, Reeves GR, Whellan DJ, Mentz RJ, Chen H, Hewston LA, Taylor KM, Pastva AM
    J Am Heart Assoc, 2022 Jun 7, 11(11): e024246
    https://doi.org/10.1161/JAHA.121.024246 | PMID: 35656973 | PMCID: PMC9238741
    Citations: 29 | AltScore: 2
  31. The Sickle Cell Disease Functional Assessment (SCD-FA) tool: a feasibility pilot study.
    Oyedeji CI, Hall K, Luciano A, Morey MC, Strouse JJ
    Pilot Feasibility Stud, 2022 Mar 4, 8(1): 53
    https://doi.org/10.1186/s40814-022-01005-3 | PMID: 35246265 | PMCID: PMC8895638
    Citations: 58 | AltScore: 9.35
  32. \Death is as Much Part of Life as Living\: Attitudes and Experiences Preparing for Death from Older Adults with Sickle Cell Disease.
    Oyedeji CI, Strouse JJ, Masese R, Gray N, Oyesanya TO
    Omega (Westport), 2022 Jul 20 302228221116513
    https://doi.org/10.1177/00302228221116513 | PMID: 35857485 | PMCID: PMC10082645
    Citations: 37 | AltScore: 8.45
  33. Obesity Status and Physical Rehabilitation in Older Patients Hospitalized With Acute HF: Insights From REHAB-HF.
    Peters AE, Kitzman DW, Chen H, Nelson MB, Pastva AM, Duncan PW, Reeves GR, Upadhya B, Whellan DJ, Mentz RJ
    JACC Heart Fail, 2022 Dec, 10(12): 918-927
    https://doi.org/10.1016/j.jchf.2022.07.008 | PMID: 36164731
    Citations: | AltScore: 22.95
  34. Partnering to cope with pain: A pilot study of a caregiver-assisted pain coping skills intervention for patients with cognitive impairment and dementia.
    Porter LS, Weiner DK, Ramos K, Barnes DE, Schmader KE, Gwyther L, Ritchie CS, Keefe FJ
    Palliat Support Care, 2022 Dec, 20(6): 785-793
    https://doi.org/10.1017/S1478951521001747 | PMID: 36942584 | PMCID: PMC10032330
    Citations: 34 | AltScore: 1.5
  35. Epigenome-wide Association Study Analysis of Calorie Restriction in Humans, CALERIETM Trial Analysis.
    Ramaker ME, Corcoran DL, Apsley AT, Kobor MS, Kraus VB, Kraus WE, Lin DTS, Orenduff MC, Pieper CF, Waziry R, Huffman KM, Belsky DW
    J Gerontol A Biol Sci Med Sci, 2022 Dec 29, 77(12): 2395-2401
    https://doi.org/10.1093/gerona/glac168 | PMID: 35965483 | PMCID: PMC9799188
    Citations: 50 | AltScore: 22.8
  36. Association of markers of tumor aggressivity and cognition in women with breast cancer before adjuvant treatment: The Thinking and Living with Cancer Study.
    Root JC, Zhou X, Ahn J, Small BJ, Zhai W, Bethea T, Carroll JE, Cohen HJ, Dilawari A, Extermann M, Graham D, Isaacs C, Jacobsen PB, Jim H, McDonald BC, Nakamura ZM, Patel SK, Rentscher K, Saykin AJ, Van Dyk K, Mandelblatt JS, Ahles TA
    Breast Cancer Res Treat, 2022 May 19, 194(2): 413-422
    https://doi.org/10.1007/s10549-022-06623-2 | PMID: 35587324 | PMCID: PMC9392482
    Citations: 44 | AltScore: 1.25
  37. Evaluating immune response and metabolic related biomarkers pre-allogenic hematopoietic stem cell transplant in acute myeloid leukemia.
    Siamakpour-Reihani S, Cao F, Lyu J, Ren Y, Nixon AB, Xie J, Bush AT, Starr MD, Bain JR, Muehlbauer MJ, Ilkayeva O, Byers Kraus V, Huebner JL, Chao NJ, Sung AD
    PLoS One, 2022, 17(6): e0268963
    https://doi.org/10.1371/journal.pone.0268963 | PMID: 35700185 | PMCID: PMC9197059
    Citations: 74 | AltScore: 11.5
  38. Change in four measures of physical function among older adults during lung cancer treatment: A mixed methods cohort study.
    Singhal S, Walter LC, Smith AK, Loh KP, Cohen HJ, Zeng S, Shi Y, Boscardin WJ, Presley CJ, Williams GR, Magnuson A, Mohile SG, Wong ML
    J Geriatr Oncol, 2022 Sep 1, 14(2): 101366
    pii: S1879-4068(22)00206-5. https://doi.org/10.1016/j.jgo.2022.08.015 | PMID: 36058839 | PMCID: PMC9974579
    Citations: 58 | AltScore: 9.95
  39. Home-Based Hematopoietic Cell Transplantation in the United States.
    Sung AD, Giri VK, Tang H, Nichols KR, Lew MV, Bohannon L, Ren Y, Jung SH, Dalton T, Bush A, Van Opstal J, Artica A, Messina J, Shelby R, Frith J, Lassiter M, Burleson J, Leonard K, Potter AS, Choi T, Gasparetto CJ, Horwitz ME, Long GD, Lopez RD, Sarantopoulos S, Chao NJ
    Transplant Cell Ther, 2022 Jan 20, 28(4): 207.e1-207.e8
    pii: S2666-6367(22)00034-3. https://doi.org/10.1016/j.jtct.2022.01.015 | PMID: 35066211 | PMCID: PMC8977260
    Citations: 41 | AltScore: NA
  40. Financial incentives to increase stool collection rates for microbiome studies in adult bone marrow transplant patients.
    Thompson JC, Ren Y, Romero K, Lew M, Bush AT, Messina JA, Jung SH, Siamakpour-Reihani S, Miller J, Jenq RR, Peled JU, van den Brink MRM, Chao NJ, Shrime MG, Sung AD
    PLoS One, 2022, 17(5): e0267974
    https://doi.org/10.1371/journal.pone.0267974 | PMID: 35507633 | PMCID: PMC9067695
    Citations: 21 | AltScore: 16.83
  41. Associating persistent self-reported cognitive decline with neurocognitive decline in older breast cancer survivors using machine learning: The Thinking and Living with Cancer study.
    Van Dyk K, Ahn J, Zhou X, Zhai W, Ahles TA, Bethea TN, Carroll JE, Cohen HJ, Dilawari AA, Graham D, Jacobsen PB, Jim H, McDonald BC, Nakamura ZM, Patel SK, Rentscher KE, Saykin AJ, Small BJ, Mandelblatt JS, Root JC
    J Geriatr Oncol, 2022 Nov, 13(8): 1132-1140
    https://doi.org/10.1016/j.jgo.2022.08.005 | PMID: 36030173 | PMCID: PMC10016202
    Citations: 62 | AltScore: 5.35
  42. Differential microRNA profiles of intramuscular and secreted extracellular vesicles in human tissue-engineered muscle.
    Vann CG, Zhang X, Khodabukus A, Orenduff MC, Chen YH, Corcoran DL, Truskey GA, Bursac N, Kraus VB
    Front Physiol, 2022, 13: 937899
    https://doi.org/10.3389/fphys.2022.937899 | PMID: 36091396 | PMCID: PMC9452896
    Citations: 109 | AltScore: NA
  43. Comparison of a Blood Self-Collection System with Routine Phlebotomy for SARS-CoV-2 Antibody Testing.
    Wixted D, Neighbors CE, Pieper CF, Wu A, Kingsbury C, Register H, Petzold E, Newby LK, Woods CW
    Diagnostics (Basel), 2022 Jul 31, 12(8):
    https://doi.org/10.3390/diagnostics12081857 | PMID: 36010206 | PMCID: PMC9406345
    Citations: 39 | AltScore: NA
  44. Impact of a Novel Training Approach on Hemodynamic and Vascular Profiles in Older Adults.
    Woessner MN, Welsch MA, VanBruggen MD, Johannsen NM, Credeur DP, Pieper CF, Sloane R, Earnest CP, Ortiz De Zevallos Munoz J, Church TS, Ravussin E, Kraus WE, Allen JD
    J Aging Phys Act, 2022 Apr 1, 30(2): 196-203
    https://doi.org/10.1123/japa.2020-0509 | PMID: 34348230 | PMCID: PMC9182940
    Citations: 35 | AltScore: 2.85
  45. Severity of functional impairments by race and sex in older patients hospitalized with acute decompensated heart failure.
    Ye F, Nelson MB, Bertoni AG, Ditzenberger GL, Duncan P, Mentz RJ, Reeves G, Whellan D, Chen H, Upadhya B, Kitzman DW, Pastva AM
    J Am Geriatr Soc, 2022 Dec, 70(12): 3447-3457
    https://doi.org/10.1111/jgs.18006 | PMID: 36527410 | PMCID: PMC9759671
    Citations: 52 | AltScore: 1.5
  46. Rejuvenation of neutrophils and their extracellular vesicles is associated with enhanced aged fracture healing.
    Zhang X, Baht GS, Huang R, Chen YH, Molitoris KH, Miller SE, Kraus VB
    Aging Cell, 2022 Jun 3, 21(7): e13651
    https://doi.org/10.1111/acel.13651 | PMID: 35657721 | PMCID: PMC9282841
    Citations: 45 | AltScore: 3.35
  47. Glucosamine use, smoking and risk of incident chronic obstructive pulmonary disease: a large prospective cohort study.
    Zhang XR, Zhang PD, Li ZH, Yang P, Wang XM, Liu HM, Liang F, Wang JD, Sun Y, Shen D, Chen PL, Zhong WF, Huang QM, Liu D, Wang ZH, Kraus VB, Mao C
    Br J Nutr, 2022 Aug 28, 128(4): 721-732
    https://doi.org/10.1017/S000711452100372X | PMID: 34526168 | PMCID: PMC9892851
    Citations: 59 | AltScore: 8.2
  48. Albumin-Corrected Fructosamine Predicts All-Cause and Non-CVD Mortality Among the Very Elderly Aged 80 Years or Older Without Diabetes.
    Zhou J, Lv Y, Zhao F, Wei Y, Gao X, Chen C, Lu F, Liu Y, Li C, Wang J, Zhang X, Gu H, Yin Z, Cao Z, Kraus VB, Mao C, Shi X
    J Gerontol A Biol Sci Med Sci, 2022 Aug 12, 77(8): 1673-1682
    https://doi.org/10.1093/gerona/glab339 | PMID: 34758092 | PMCID: PMC9373969
    Citations: 41 | AltScore: 1.25
  49. Geriatric Preoperative Optimization: A Review.
    Zietlow KE, Wong S, Heflin MT, McDonald SR, Sickeler R, Devinney M, Blitz J, Lagoo-Deenadayalan S, Berger M
    Am J Med, 2022 Jan, 135(1): 39-48
    https://doi.org/10.1016/j.amjmed.2021.07.028 | PMID: 34416164 | PMCID: PMC8688225
    Citations: 73 | AltScore: 104.75
  50. Application of longitudinal item response theory models to modeling Parkinson's disease progression.
    Zou H, Aggarwal V, Stebbins GT, M?ller MLTM, Cedarbaum JM, Pedata A, Stephenson D, Simuni T, Luo S
    CPT Pharmacometrics Syst Pharmacol, 2022 Oct, 11(10): 1382-1392
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EXTERNAL ADVISORY BOARD MEMBERS

Karen Bandeen Roche
John Hopkins University
Serving since 2010 (13 years)

George Kuchel MD
University of Connecticut, Geriatrics and Gerontology
Serving since 2016 (7 years)

Neil Alexander, MD
University of Michigan
Serving since 2016 (7 years)

RECOGNITION AND AWARDS (2022-2023)
Harvey J. Cohen, MD (2022)
  • Inaugural winner of Duke Department of Medicine Career Achievement Award
Heather Whitson, MD, MHS (2022)
  • Outstanding Committee Service Award, Research Committee, American Geriatrics Society
James R. Bain, PhD (2022)
  • Visiting Professor in the Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington
Kenneth Schmader, MD (2022)
  • Appointed to CDC ACIP Work Group on Respiratory Syncytial Virus vaccines

MINORITY RESEARCH

General Brief Description of Minority Activities:

Determinants of maintenance and recovery of function in a representative older community-resident biracial sample

Gerda Fillenbaum, PhD, co-investigator, Katherine Hall, PhD, Carl Pieper, DPh, Heather Whitson, MD, MHS, Cathleen Colón-Emeric, MD, MHS, Core leaders

Focus on decline in performance of activities of daily living (ADL) has not been matched by studies of recovery of function. Advised by a broad conceptual model of physical resilience, we ascertain characteristics that identify (1) maintenance, (2) decline, and (3) recovery of personal self-maintenance activities over six years in an older (age 65-105 years), community representative sample (n = 3187; African American: 54%, White: 45%). All were participants in the Duke Established Populations for Epidemiologic Studies of the Elderly, and were unimpaired at baseline.

Over six years, ~75% remained unimpaired, of whom 30% were unimpaired when they dropped out or died. Of ~25% who became impaired, just over half recovered. Analyses, which took into account demographic characteristics, health conditions, health service use, social services provided and received, neighborhood safety, and survival status, indicated that those who became impaired were in poorer health, were younger, and more likely to be African American. Characteristics of recovery included younger age, not hospitalized in the previous year, and increased social support.

Our analyses indicate that maintenance of health status facilitated continued unimpaired basic activities of daily living. While decline was associated with poorer health, younger age, and being African American, recovery was also associated with younger age, and in addition social support, and no further deterioration in health as measured here.

Following decline in functioning, increased effort is needed to improve health and avoid further decline, and effort that takes into account not only physical but also personal social conditions.

 

Fillenbaum GG, Sloane R, Burchett BM, Hall K, Pieper CF, Whitson HE, Colón-Emeric CS.  Determinants of maintenance and recovery of function in a representative older community- resident biracial sample. J Am Med Dir Assoc. 2020 Feb 6:S1525-8610(19)30891-6. doi: 10.1016/j.jamda.2019.12.021. Online ahead of print. PMID: 32037299 NIHMS 1569426   https://doi.org/10.1016/j.jamda.2019.12.021

Minority Trainee(s):
  • Charity Oyedeji, MD, PESC Scholar, Assistant Professor of Medicine (Hematology)
    Dr. Charity Oyedeji's research focuses on implementing a geriatric assessment into clinical assessments of older adults with sickle cell disease. Due to advances in care and access, patients with sickle cell disease (SCD) are living longer than they have in previous generations. SCD is recognized as a condition that mimics accelerated aging, but little is known about aging with SCD. In particular, SCD patients face frequent health stressors including hypoxia, pain crises, and frequent hospitalizations, but little is known about how aging with SCD affects one’s resilience to these stressors. The objective of this study is to test the feasibility and safety of focused geriatric assessment and provocative tests that measure physiological reserve in SCD patients over age 50 and to determine the feasibility of a protocol to assess resilience to the stressor of hospitalization in older SCD patients. In addition, biomarkers of inflammation, coagulation, and longevity will be compared in 20 older (age 50-70) people with SCD and 20 younger (age 18-49) people with SCD. Thus far, the study has demonstrated that focused geriatric assessment, including provocative performance measures was safe and well-tolerated by older SCD patients. 50% of the older participants experienced a hospitalization within 12 months of a baseline assessment, indicating the feasibility of a future study to prospectively measure resilience after hospitalization by following a cohort of well-characterized participants for 2 years. Measures of physiological reserve in older SCD patients, on average, were consistent with normative measures from healthy seniors 20-30 years older. In 2020, Dr. Oyedeji used these findings to support a successful application for funding from the American Society of Hematology. She was also the recipient of 3 outstanding abstract awards at national meetings, and the recipient of the 2019 Duke Maddox Award for Aging Research. In 2021, Dr. Oyedeji received a Duke REACH Equity Career Development Award, an invitation to present at the American Society of Hematology Annual Meeting in December, and submitted a manuscript to the ASH Education Program.
  • Gentzon Hall, MD, PhD, Assistant Professor of Medicine (Nephrology)
    Dr. Hall is an Assistant Professor of Medicine (Nephrology) whose lab utilizes sophisticated genetic studies to better understand contributors to glomerulosclerosis (AAGS), a common cause of chronic kidney disease (CKD) in older adults. His ultimate goal is to identify targets for pharmacological intervention that will protect kidney function, especially in populations at highest risk for AAGS. Progressive loss of glomerular visceral epithelial cells (i.e. podocytes) with age is thought to be the principal driver of AAGS. Based on his own previous findings, Dr. Hall hypothesizes that impaired IL-15/IL-15R axis signaling reduces podocyte resiliency to proapototic stimuli, increasing risk of AAGS across the lifespan. In Aim 1 of his pilot study, he utilizes immortalized human podocyte lines to quantify podocyte apoptosis in gene knockdown and controls after exposure to two well-validated proapototic stimuli. In Aim 2, he will utilize targeted gene deletion in zebrafish embryos to understand the role of the IL-15 signaling in vivo. A validated surrogate model for albuminuria in humans will be used to detect and quantify proteinuria in knockdown IL-15 and IL-15R zebrafish compared to controls. If these experiments confirm the role ofIL-15 signaling in podocyte survival and function after nephrotoxic stressors, it will justify future research to develop IL-15 signaling agents to enhance kidney resilience and protect against AAGS.
  • Katherine Ramos, PhD, Assistant Professor of Medicine, Psychiatry and Behavioral Sciences
    Dr. Ramos' research focuses on developing and implementing behavioral interventions for older adults to enhance both their psychological and physical well-being in the context of medical complexity and/ or metastatic cancer. Despite the availability of interventions to improve functioning and quality of life in older adults by targeting their behaviors and mental health, there is a scarcity of research that focuses exclusively on older adults living with serious, life-limiting illness such as late-stage lung cancer. The objective of the Roybal study was to provide 8-12 sessions of Self-System Therapy (an evidenced-based psychotherapy treatment for depression) adapted and implemented for older adults over 65 years of age with Stage III or Stage IV lung cancer. The intervention primarily focuses on teaching older adults how to integrate promotion-focused and prevention-focused goal setting to improve self-regulation and increase behaviors that promote mental health and physical well-being. The study was recently completed with a sample of 12 focus group members, 5 user testers, 5 advisory members, and 30 participants enrolled in the pilot. Analyses are underway. An extension of this work has been recently funding by the NIA Research Centers Collaborative Network (RCCN) via Wake Forest School of Medicine. This study is currently underway with a focus on piloting measures targeting physical and psychological resilience(including accelerometry data collection) as older adults with late-stage lung cancer participate in the Self-System Therapy for Lung Cancer Intervention. Study completion is anticipated by March 2022. Thus far, from this work Dr. Ramos has presented her findings in national and international conferences, these include the: Association for Behavioral and Cognitive Therapies (ABCT), the American Psychological Association (APA), and the International Society for Psychotherapy Research in Heidelberg, Germany. A special issue paper abstract has been submitted for a full manuscript submission and an NIH R21 grant submission is currently underway to test the initial efficacy of the intervention in a larger randomized control trial.
  • Nicole DePasquale, PhD, Assistant Professor, Dept. of Medicine
    Nicole DePasquale's research addresses questions about health, well-being, and multiple role management in the context of middle and late adulthood, with the ultimate aim of informing intervention efforts. She addresses these questions through two lines of research that utilize quantitative and qualitative methodology. One line examines the ways in which patients with chronic kidney disease and their family care partners work together to self-manage the disease and the impact dyadic self-management has on their health both as individuals and as a unit. The second line examines the work/nonwork interface of long-term care employees with family caregiving roles, or double- and triple-duty caregivers. Recent research includes patient-family discussions about living-donor kidney transplantation, decisional conflict regarding kidney failure treatment modalities, and the work and nonwork benefits of family-supportive supervisor behavior among double- and triple-duty caregiving men. Dr. DePasquale has self-identified as an Individual from a disadvantaged background, as defined by the Notice of NIH’s Interest in Diversity (NOT-OD-20-031) released in 2019 regarding Underrepresented Populations in the U.S. Biomedical, Clinical, Behavioral and Social Sciences Research Enterprise. Dr. DePasquale's OAIC funded research project titled, “Individual and dyadic factors associated with older dialysis patients’ physical resilience” currently does not intentionally seek to examine minority groups or racial differences, but the nature of her work does heavily focus on African Americans given that they are disproportionately burdened with chronic kidney disease/renal failure. This pilot project serves as an add-on component to the Shared Kidney Care Study and expands the parent study’s existing strengths by adding a new and unique focus on physical resilience. It will examine how kidney failure dyads work together (or not) to maintain, regain, or optimize older patients’ physical function amid dialysis initiation and its negative downstream effects for patients and family care partners alike.

Minority Grant(s):