Andrea Trombetti, MD; Mélany Hars, PhD; Fang-Chi Hsu, PhD; Kieran F. Reid, PhD; Timothy S. Church, MD, PhD; Thomas M. Gill, MD; Abby C. King, PhD; Christine K. Liu, MD; Todd M. Manini, PhD; Mary M. McDermott, MD; Anne B. Newman, MD; W. Jack Rejeski, PhD; Jack M. Guralnik, MD, PhD; Marco Pahor, MD; Roger A. Fielding, PhD; for the LIFE Study Investigators *
Note: The authors had full access to all the study data, take responsibility for the accuracy or integrity of the analysis, and had authority over manuscript preparation and the decision to submit the manuscript for publication. All authors approved the manuscript and agree to adhere to all terms outlined in Annals of Internal Medicine information for authors including terms for copyright.
Disclaimer: The content of this article is solely the responsibility of the authors and does not necessarily represent the official view of the U.S. Department of Agriculture.
Grant Support: The LIFE study was funded by cooperative agreement UO1AG22376 from the NIH and National Institute on Aging (NIA) and supplement 3U01AG022376-05A2S from the National Heart, Lung, and Blood Institute (NHLBI), and was sponsored in part by the Intramural Research Program. The research is partially supported by the Claude D. Pepper Older Americans Independence Centers at the University of Florida (1 P30 AG028740), Wake Forest University (1 P30 AG21332), Tufts University (1P30AG031679), University of Pittsburgh (P30 AG024827), and Yale University (P30AG021342), and is supported by the NIH/National Center for Research Resources Clinical and Translational Science Award program at Stanford University (UL1 RR025744), University of Florida (U54RR025208), and Yale University (UL1 TR000142). Tufts University is also supported by the Boston Rehabilitation Outcomes Center (1R24HD065688-01A1). The following LIFE investigators also are partially supported: Dr. Gill (Yale University) is the recipient of an Academic Leadership Award (K07AG3587) from the NIA. Dr. Fielding (Tufts University) is partially supported by the U.S. Department of Agriculture under agreement 58-1950-4-003.
Disclosures: Dr. McDermott reports grants from the NHLBI during the conduct of the study, and donations of study medication from ReserveAge, grants from Novartis and the Patient-Centered Outcomes Research Institute, and donations of study intervention from Hershey's, outside the submitted work. Dr. Fielding reports grants from the NIH (NIA) during the conduct of the study and grants, personal fees, and equity stock options from Axcella Health; equity stock options from InsideTracker; grants and personal fees from Biophytis, Astellas, and Nestlé; and personal fees from Cytokinetics, Amazentis, and GlaxoSmithKline, outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2011.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Available at www.thelifestudy.org/public/index.cfm. Statistical code and data set: Available to approved persons through agreement with the LIFE study steering committee (e-mail, Roger.Fielding@tufts.edu).
Requests for Single Reprints: Andrea Trombetti, MD, Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva 14, Switzerland; e-mail, Andrea.Trombetti@hcuge.ch.
Current Author Addresses: Drs. Trombetti and Hars: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva 14, Switzerland.
Dr. Hsu: Department of Biostatistical Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157.
Drs. Reid and Fielding: Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111.
Dr. Church: 6400 Perkins Road, Baton Rouge, LA 75080.
Dr. Gill: Yale School of Medicine, Adler Geriatric Center, 874 Howard Avenue, New Haven, CT 06510.
Dr. King: Stanford University School of Medicine, 259 Campus Drive, HRP Redwood Building, Room T221, Stanford, CA 94305.
Dr. Liu: Boston University School of Medicine, 88 East Newton Street, Robinson 2, Boston, MA 02118.
Dr. Manini: Institute on Aging, Department of Aging and Geriatric Research, P.O. Box 112610, Gainesville, FL 32611.
Dr. McDermott: Department of Medicine and Preventive Medicine, Northwestern University, Feinberg School of Medicine, Galter Room 18-200, 675 North Saint Clair, Chicago, IL 60611.
Dr. Newman: Graduate School of Public Health, University of Pittsburgh, A527 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261.
Dr. Rejeski: Department of Health and Exercise Science, Box 7868, Wake Forest University, Winston-Salem, NC 27109.
Dr. Guralnik: University of Maryland School of Medicine, Department of Epidemiology and Public Health, Division of Gerontology, 660 West Redwood Street, Room 204, Baltimore, MD 21201.
Dr. Pahor: Department of Aging and Geriatric Research, College of Medicine, University of Florida, 2004 Mowry Road, Gainesville, FL 32611.
Author Contributions: Conception and design: A. Trombetti, M. Hars, F.-C. Hsu, K.F. Reid, T.S. Church, T.M. Gill, A.C. King, C.K. Liu, T.M. Manini, M.M. McDermott, A.B. Newman, W.J. Rejeski, J.M. Guralnik, M. Pahor, R.A. Fielding.
Analysis and interpretation of the data: A. Trombetti, M. Hars, F.-C. Hsu, K.F. Reid, T.S. Church, T.M. Gill, A.C. King, C.K. Liu, T.M. Manini, M.M. McDermott, A.B. Newman, W.J. Rejeski, J.M. Guralnik, M. Pahor, R.A. Fielding.
Drafting of the article: A. Trombetti, M. Hars, K.F. Reid, R.A. Fielding.
Critical revision of the article for important intellectual content: A. Trombetti, M. Hars, F.-C. Hsu, K.F. Reid, T.S. Church, T.M. Gill, A.C. King, C.K. Liu, T.M. Manini, M.M. McDermott, A.B. Newman, W.J. Rejeski, J.M. Guralnik, M. Pahor, R.A. Fielding.
Final approval of the article: A. Trombetti, M. Hars, F.-C. Hsu, K.F. Reid, T.S. Church, T.M. Gill, A.C. King, C.K. Liu, T.M. Manini, M.M. McDermott, A.B. Newman, W.J. Rejeski, J.M. Guralnik, M. Pahor, R.A. Fielding.
Provision of study materials or patients: K.F. Reid, T.S. Church, T.M. Gill, A.C. King, C.K. Liu, T.M. Manini, M.M. McDermott, A.B. Newman, W.J. Rejeski, J.M. Guralnik, M. Pahor, R.A. Fielding.
Statistical expertise: F.-C. Hsu.
Administrative, technical, or logistic support: K.F. Reid, T.S. Church, T.M. Gill, A.C. King, C.K. Liu, T.M. Manini, M.M. McDermott, A.B. Newman, W.J. Rejeski, J.M. Guralnik, M. Pahor, R.A. Fielding.
Collection and assembly of data: A. Trombetti, M. Hars, F.-C. Hsu, K.F. Reid, R.A. Fielding.
Limited evidence suggests that physical activity may prevent frailty and associated negative outcomes in older adults. Definitive data from large long-term randomized trials are lacking.
To determine whether a long-term, structured, moderate-intensity physical activity program is associated with a lower risk for frailty and whether frailty status alters the effect of physical activity on the reduction in major mobility disability (MMD) risk.
Multicenter, single-blind, randomized trial.
8 centers in the United States.
1635 community-dwelling adults, aged 70 to 89 years, with functional limitations.
A structured, moderate-intensity physical activity program incorporating aerobic, resistance, and flexibility activities or a health education program consisting of workshops and stretching exercises.
Frailty, as defined by the SOF (Study of Osteoporotic Fractures) index, at baseline and 6, 12, and 24 months, and MMD, defined as the inability to walk 400 m, for up to 3.5 years.
Over 24 months of follow-up, the risk for frailty (n = 1623) was not statistically significantly different in the physical activity versus the health education group (adjusted prevalence difference, −0.021 [95% CI, −0.049 to 0.007]). Among the 3 criteria of the SOF index, the physical activity intervention was associated with improvement in the inability to rise from a chair (adjusted prevalence difference, −0.050 [CI, −0.081 to −0.020]). Baseline frailty status did not modify the effect of physical activity on reducing incident MMD (P for interaction = 0.91).
Frailty status was neither an entry criterion nor a randomization stratum.
A structured, moderate-intensity physical activity program was not associated with a reduced risk for frailty over 2 years among sedentary, community-dwelling older adults. The beneficial effect of physical activity on the incidence of MMD did not differ between frail and nonfrail participants.
National Institute on Aging, National Institutes of Health.
Trombetti A, Hars M, Hsu F, Reid KF, Church TS, Gill TM, et al. Effect of Physical Activity on Frailty: Secondary Analysis of a Randomized Controlled Trial. Ann Intern Med. 2018;168:309–316. doi: 10.7326/M16-2011
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Published: Ann Intern Med. 2018;168(5):309-316.
Published at www.annals.org on 9 January 2018
Endocrine and Metabolism, Geriatric Medicine, Metabolic Bone Disorders, Prevention/Screening.
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