Combined Inflammation and Metabolism Biomarker Indices of Robust and Impaired Physical Function in Older Adults.

Abstract

To determine whether combinations of inflammatory markers are related to physical function.secondary analysis of baseline of three observational studies of community-dwelling older adults MEASUREMENTS: The baseline data from 3 cohorts of older adults with different health and disease status were employed. Twenty markers of inflammation and metabolism were individually assessed for correlation with usual gait speed and were separated into robust and impairment quartiles. For the robustness and impairment indices, individual markers were selected using step-wise regression over bootstrapping iterations, and regression coefficients were estimated for the markers individually and collectively as an additive score.We developed a robustness index involving 6 markers and an impairment index involving 8 markers corresponding positively and negatively with gait speed. Two markers, glycine and tumor necrosis factor receptor 1 (TNFR1), appeared only in the robustness index, and TNFR2; regulated on activation, normal T-cell expressed and secreted; the amino acid factor; and matrix metallopeptidase 3; appeared only in the impairment index.Indices of biomarkers were associated with robust and impaired physical performance but differ, in composition suggesting potential biological differences that may contribute to robustness and impairment.

Department

Description

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Citation

Published Version (Please cite this version)

10.1111/jgs.15393

Publication Info

Zuo, Xintong, Alison Luciano, Carl F Pieper, James R Bain, Virginia B Kraus, William E Kraus, Miriam C Morey, Harvey J Cohen, et al. (2018). Combined Inflammation and Metabolism Biomarker Indices of Robust and Impaired Physical Function in Older Adults. Journal of the American Geriatrics Society. 10.1111/jgs.15393 Retrieved from https://hdl.handle.net/10161/17282.

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Scholars@Duke

Pieper

Carl F. Pieper

Professor of Biostatistics & Bioinformatics

Analytic Interests.

1) Issues in the Design of Medical Experiments: I explore the use of reliability/generalizability models in experimental design. In addition to incorporation of reliability, I study powering longitudinal trials with multiple outcomes and substantial missing data using Mixed models.

2) Issues in the Analysis of Repeated Measures Designs & Longitudinal Data: Use of Hierarchical Linear Models (HLM) or Mixed Models in modeling trajectories of multiple variables over time (e.g., physical and cognitive functioning and Blood Pressure). My current work involves methodologies in simultaneous estimation of trajectories for multiple variables within and between domains, modeling co-occuring change.

Areas of Substantive interest: (1) Experimental design and analysis in gerontology and geriatrics, and psychiatry,
(2) Multivariate repeated measures designs,

Bain

James R. Bain

Professor in Medicine
Kraus

Virginia Byers Kraus

Mary Bernheim Distinguished Professor of Medicine

Virginia Byers Kraus, MD, PhD, is the Mary Bernheim Distinguished Professor of Medicine, Professor of Orthopaedic Surgery, Professor of Pathology and a faculty member of the Duke Molecular Physiology Institute in the Duke University School of Medicine. She is a practicing Rheumatologist with over 30 years’ experience in translational musculoskeletal research focusing on osteoarthritis, the most common of all arthritides. She trained at Brown University (ScB 1979), Duke University (MD 1982, PhD 1993) and the Duke University School of Medicine (Residency in Internal Medicine and Fellowship in Rheumatology). Her career has focused on elucidating osteoarthritis pathogenesis and translational research into the discovery and validation of biomarkers for early osteoarthritis detection, prediction of progression, monitoring of disease status, and facilitation of therapeutic developments. She is co-PI of the Foundation for NIH Biomarkers Consortium Osteoarthritis project. Trained as a molecular biologist and a Rheumatologist, she endeavors to study disease from bedside to bench.

Kraus

William Erle Kraus

Richard and Pat Johnson University Distinguished Professor

My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation.  My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I practice as a preventive cardiologist with a focus on cardiometabolic risk and exercise physiology for older athletes.  My research space has both a basic wet laboratory component and a human integrative physiology one.

One focus of our work is an integrative physiologic examination of exercise effects in human subjects in clinical studies of exercise training in normal individuals, in individuals at risk of disease (such as pre-diabetes and metabolic syndrome; STRRIDE), and in individuals with disease (such as coronary heart disease, congestive heart failure and cancer).

A second focus of my research group is exploration of genetic determinates of disease risk in human subjects.  We conduct studies of early onset cardiovascular disease (GENECARD; CATHGEN), congestive heart failure (HF-ACTION), peripheral arterial disease (AMNESTI), and metabolic syndrome.  We are exploring analytic models of predicting disease risk using established and innovative statistical methodology.

A third focus of my group’s work is to understand the cellular signaling mechanisms underlying the normal adaptive responses of skeletal muscle to physiologic stimuli, such as occur in exercise conditioning, and to understand the abnormal maladaptive responses that occur in response to pathophysiologic stimuli, such as occur in congestive heart failure, aging and prolonged exposure to microgravity.

Recently we have begun to investigate interactions of genes and lifestyle interventions on cardiometabolic outcomes.  We have experience with clinical lifestyle intervention studies, particularly the contributions of genetic variants to interventions responses.  We call this Lifestyle Medicopharmacogenetics.

KEY WORDS:

exercise, skeletal muscle, energy metabolism, cell signaling, gene expression, cell stretch, heart failure, aging, spaceflight, human genetics, early onset cardiovascular disease, lifestyle medicine

Morey

Miriam C. Morey

Professor Emeritus of Medicine

The general focus of Dr. Morey's work is exercise and aging. All of her research examines how physical activity, exercise training, or physical fitness influence the physical functioning and/or pyschosocial quality of life of older adults. She directs a supervised hospital-based program for older adults, which is used to examine longitudinally the effects of exercise training on the musculoskeletal, articular, and cardiorespiratory systems. Furthermore, she has a number of studies that examine how system-wide impairments serve as preclinical indicators of disability and overall decline in the quality of life of older adults. Ongoing studies examine the role of exercise training in attenuation or reversal of functional decline and examination of the effectivenes of different methods of physical activity counseling for home-based exercise.
Dr. Morey's research evolves directly from three sources: (1) primary analyses of clinical trials regarding the impact of exercise on a specific outcome, (2) longitudinal analyses of participants in ongoing clinical exercise programs, and (3) secondary analyses of clinical trials which involve exercise or physical activity.
Although physical activity and exercise are the interventions of interest in all of these studies, the outcomes of interest vary considerably. Within the broad domain of aging, Dr. Morey has examined the impact of exercise on physical performance, well-being, sleep quality, disability, and functional limitations. More recently, Dr. Morey has several studies focusing on the effect of tailored telephone physical activity counseling to improve function in elders. Specific studies are targeted to newly diagnosed cancer survivors, long-term cancer survivors, and frail elders in geriatric and primary care settings.
Dr. Morey's expertise is in the area of exercise physiology and aging. She has specific knowledge in age-related changes in cardiorespiratory functioning, the effects of habitual exercise (longitudinal) on performance, and exercise programming for older adults.


Key Words: Exercise, maximal oxygen uptake, cardiorespiratory fitness, aging, disability,
functional limitations, longitudinal

Cohen

Harvey Jay Cohen

Walter Kempner Distinguished Professor of Medicine, in the School of Medicine

Dr. Cohen's research program includes clinical research relating to aspects of the pathways to functional decline and reilience with aging, geriatric assessment, and cancer and anemia in the elderly.

Pathways to functional decline are being explored through the NIA funded Claude Pepper Older Americans Independence Center, and includes studies of the contributions of age related physiologic change, in particular changes in inflammatory parameters, comorbid diseases and conditions, environment, genetics, and the interactionas among them. Data are derived from several current studies as well as previously collected data sets from the Established Populations for Epidemiologic Studies of the Elderly (EPESE), National Long Term Care Survey, and the Chinese Longevity Study (with Dr. Zeng Yi). Previous work has demonstrated the important contributions of age related inflammation and coagulation activation to functional status. He is Co-PI of the Pepper Center Physical Performance Across the LifeSpan (PALS) study, which is a longitudinal cohort study of community dwelling adults from age 30-90+and includes functional measures and biomarkers on inflammation and metabolism.
 
Geriatric assessment approaches have been studied in a number of randomized and controlled studies and work is now concentrating on the application of Comprehensive Geriatric Assessment tools to the evaluation and treatment of elderly patients with cancer. This is an extension and continuation of a long standing interest in geriatric oncology. Previous studies have elucidated age-related patterns of disease presentation, treatment approaches, clinical trials, survivorship, quality of life, impact of comrobidities and functional outcomes. Dr. Cohen was co-chair, and now member of the Cancer in the Older Adult Committee of the Alliance for Clinical Trials in Oncology (ALLIANCE). A number of active studies and ongoing data bases aree being utilized to address these questions.


Anemia in the older adult is being addressed through an NIA funded U01 consortium (Dr. Cohen Co-PI). the current main study is an observational study followed by a pragmatic treatment trial for anemia in older adults with CHF, in collaboration with the Cardiovascular Research Network (CVRN) of the Health services research network (HSRN) 


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