Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial

Abstract Background Whether physical activity can reduce cognitive frailty—a relatively new “compound” phenotype proposed in 2013—and whether the effect of physical activity differs based on levels of inflammation are unknown. Therefore, this study aimed to evaluate the effect of physical activity o...

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Main Authors: Zuyun Liu, Fang-Chi Hsu, Andrea Trombetti, Abby C. King, Christine K. Liu, Todd M. Manini, Roger A. Fielding, Marco Pahor, Anne B. Newman, Stephen Kritchevsky, Thomas M. Gill, for the LIFE Study investigators
Format: Article
Language:English
Published: BMC 2018-10-01
Series:BMC Medicine
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Online Access:http://link.springer.com/article/10.1186/s12916-018-1174-8
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author Zuyun Liu
Fang-Chi Hsu
Andrea Trombetti
Abby C. King
Christine K. Liu
Todd M. Manini
Roger A. Fielding
Marco Pahor
Anne B. Newman
Stephen Kritchevsky
Thomas M. Gill
for the LIFE Study investigators
author_facet Zuyun Liu
Fang-Chi Hsu
Andrea Trombetti
Abby C. King
Christine K. Liu
Todd M. Manini
Roger A. Fielding
Marco Pahor
Anne B. Newman
Stephen Kritchevsky
Thomas M. Gill
for the LIFE Study investigators
author_sort Zuyun Liu
collection DOAJ
description Abstract Background Whether physical activity can reduce cognitive frailty—a relatively new “compound” phenotype proposed in 2013—and whether the effect of physical activity differs based on levels of inflammation are unknown. Therefore, this study aimed to evaluate the effect of physical activity on cognitive frailty and whether baseline interleukin-6 (IL-6) levels modified this effect. Methods We used data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter, single-blinded randomized trial conducted at eight US field centers between February 2010 and December 2013. The main outcome was cognitive frailty at 24 months, expressed as an ordinal variable based on the six combinations of its two components: frailty (non-frail, pre-frail, and frail) and mild cognitive impairment (yes, no). Frailty and cognition were assessed by the Study of Osteoporotic Fractures (SOF) index and the Modified Mini-Mental State Examination (3MSE) scale, respectively. Plasma IL-6 was measured at baseline. Of the 1635 original randomized sedentary participants (70–89 years), this study included 1298 participants with data on both cognitive frailty and IL-6 assessments at baseline. Results After adjusting for field center, sex, and baseline levels of cognitive frailty, the ordinal logistic regression model revealed that participants in the physical activity group had 21% lower odds (odds ratio, 0.79; 95% confidence interval, 0.64–0.98) of worsening cognitive frailty over 24 months than those in the health education group. The effect of physical activity on cognitive frailty did not differ according to baseline IL-6 levels (P for interaction = 0.919). The results did not change after additional adjustment for IL-6 subgroups and the inverse probability of remaining in the study. Comparable results were observed according to age, sex, ethnicity/race, and short physical performance battery score (P for interaction = 0.835, 0.536, 0.934, and 0.458, respectively). Conclusions A 24-month structured, moderate-intensity physical activity program reduced cognitive frailty compared with a health education program in sedentary older persons, and this beneficial effect did not differ according to baseline levels of inflammatory biomarker IL-6. These findings suggest that the new cognitive frailty construct is modifiable and highlight the potential of targeting cognitive frailty for promoting healthy aging. Trial registration Clinicaltrials.gov, NCT01072500
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spelling doaj.art-c766bf883964400ba811213e529c13482022-12-22T00:53:33ZengBMCBMC Medicine1741-70152018-10-0116111010.1186/s12916-018-1174-8Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trialZuyun Liu0Fang-Chi Hsu1Andrea Trombetti2Abby C. King3Christine K. Liu4Todd M. Manini5Roger A. Fielding6Marco Pahor7Anne B. Newman8Stephen Kritchevsky9Thomas M. Gill10for the LIFE Study investigatorsDepartment of Internal Medicine, Yale School of MedicineDepartment of Biostatistical Sciences, Wake Forest University Health SciencesDivision of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of MedicineDepartment of Health Research and Policy and the Stanford Prevention Research Center, Department of Medicine, Stanford University, School of MedicineNutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityDepartment of Aging and Geriatric Research, University of FloridaNutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityDepartment of Aging and Geriatric Research, University of FloridaDepartment of Epidemiology, Graduate School of Public Health, University of PittsburghSticht Center on Aging, Wake Forest School of MedicineDepartment of Internal Medicine, Yale School of MedicineAbstract Background Whether physical activity can reduce cognitive frailty—a relatively new “compound” phenotype proposed in 2013—and whether the effect of physical activity differs based on levels of inflammation are unknown. Therefore, this study aimed to evaluate the effect of physical activity on cognitive frailty and whether baseline interleukin-6 (IL-6) levels modified this effect. Methods We used data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter, single-blinded randomized trial conducted at eight US field centers between February 2010 and December 2013. The main outcome was cognitive frailty at 24 months, expressed as an ordinal variable based on the six combinations of its two components: frailty (non-frail, pre-frail, and frail) and mild cognitive impairment (yes, no). Frailty and cognition were assessed by the Study of Osteoporotic Fractures (SOF) index and the Modified Mini-Mental State Examination (3MSE) scale, respectively. Plasma IL-6 was measured at baseline. Of the 1635 original randomized sedentary participants (70–89 years), this study included 1298 participants with data on both cognitive frailty and IL-6 assessments at baseline. Results After adjusting for field center, sex, and baseline levels of cognitive frailty, the ordinal logistic regression model revealed that participants in the physical activity group had 21% lower odds (odds ratio, 0.79; 95% confidence interval, 0.64–0.98) of worsening cognitive frailty over 24 months than those in the health education group. The effect of physical activity on cognitive frailty did not differ according to baseline IL-6 levels (P for interaction = 0.919). The results did not change after additional adjustment for IL-6 subgroups and the inverse probability of remaining in the study. Comparable results were observed according to age, sex, ethnicity/race, and short physical performance battery score (P for interaction = 0.835, 0.536, 0.934, and 0.458, respectively). Conclusions A 24-month structured, moderate-intensity physical activity program reduced cognitive frailty compared with a health education program in sedentary older persons, and this beneficial effect did not differ according to baseline levels of inflammatory biomarker IL-6. These findings suggest that the new cognitive frailty construct is modifiable and highlight the potential of targeting cognitive frailty for promoting healthy aging. Trial registration Clinicaltrials.gov, NCT01072500http://link.springer.com/article/10.1186/s12916-018-1174-8Physical activityCognitive frailtyInterleukin-6Older persons
spellingShingle Zuyun Liu
Fang-Chi Hsu
Andrea Trombetti
Abby C. King
Christine K. Liu
Todd M. Manini
Roger A. Fielding
Marco Pahor
Anne B. Newman
Stephen Kritchevsky
Thomas M. Gill
for the LIFE Study investigators
Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial
BMC Medicine
Physical activity
Cognitive frailty
Interleukin-6
Older persons
title Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial
title_full Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial
title_fullStr Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial
title_full_unstemmed Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial
title_short Effect of 24-month physical activity on cognitive frailty and the role of inflammation: the LIFE randomized clinical trial
title_sort effect of 24 month physical activity on cognitive frailty and the role of inflammation the life randomized clinical trial
topic Physical activity
Cognitive frailty
Interleukin-6
Older persons
url http://link.springer.com/article/10.1186/s12916-018-1174-8
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