The Mediating Effect of Different Exercise Programs on the Immune Profile of Frail Older Women with Cognitive Impairment

Author(s): Guilherme E. Furtado*, Matheus U. Chupel, Lucielle G. Minuzzi, Luís Rama, Juan C. Colado, Eef Hogervorst, José P. Ferreira, Ana M. Teixeira*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 9 , 2020

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Background: Frail individuals experience an accelerated immunosenescence, and exercise has been identified as a therapy to promote a better inflammatory environment.

Objective: To analyze the effects of 28-weeks of two different exercise protocols on the functional fitness and immune profiles of institutionalized pre-frail and frail women with mild cognitive impairment.

Methods: Participants residing in care homes (n=60, 81±7.84 years old) were randomized into three groups: a chair elastic band muscle-strength exercise (CSE, n=21; 81±4.79), a chair multimodal exercise (CME, n=20; 80±8.19), and a control non-exercise (CGne, n=19; 80±10.01). Both CME and CSE groups performed progressive circuit-training exercise sessions. The controls did not change their usual lifestyle. The Fried protocol and the Mini-Mental State Examination questionnaire were used to identify the frail subgroups and the participants with mild cognitive impairment. Data for anti and pro-inflammatory markers and physical fitness were analyzed pre and post-interventions.

Results: After the intervention, a significant effect of time and time by group for sIgA and time by group for IL- 10 levels were found (p > 0.05). Within-group analysis showed a significant moderate decrease in the TNF-α to IL-10 ratio for the CME group and an increase in the controls (p > 0.05) and a slight reduction in the IL-6 and IL- 1β concentrations. The controls showed a negative trend towards a decrease in physical fitness and a trend for increased levels in the pro-inflammatory markers IL-6 and IL-1β.

Conclusion: The evidence regarding the use of systematic and moderate long-term exercise as therapy for promoting a better balance between pro- and anti-inflammatory environments and a decrease in the inflammatory index for the CME group were the most promising results from this study.

Keywords: Frail older adults, muscle-strength, multimodal, exercise, cytokines, inflammation, upper respiratory tract infector.

Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet 2013; 381: 752-62.
Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56: M146-56.
Robertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment--a review of the evidence and causal mechanisms. Ageing Res Rev 2013; 12: 840-51.
Kelaiditi E, Cesari M, Canevelli M, et al. Cognitive frailty: rational and definition from an (I.A.N.A./I.A.G.G.) international consensus group. J Nutr Health Aging 2013; 17(9): 726-34.
[] [PMID: 24154642]
Panza F, Solfrizzi V, Barulli MR, et al. Cognitive frailty: a systematic review of epidemiological and neurobiological evidence of an age-related clinical condition. Rejuvenation Res 2015; 18: 389-412.
Cesari M, Landi F, Vellas B, Bernabei R, Marzetti E. Sarcopenia and physical frailty: two sides of the same coin. Front Aging Neurosci 2014; 6: 192.
Dorner TE, Lackinger C, Haider S, et al. Nutritional intervention and physical training in malnourished frail community-dwelling elderly persons carried out by trained lay “buddies”: study protocol of a randomized controlled trial. BMC Public Health 2013; 13: 1232.
Jensen CS, Hasselbalch SG, Waldemar G, Simonsen AH. biochemical markers of physical exercise on mild cognitive impairment and dementia: systematic review and perspectives. Front Neurol 2015; 6: 187.
[] [PMID: 26379621]
Minciullo PL, Catalano A, Mandraffino G, et al. Inflammaging and anti-inflammaging. Arch Immunol Ther Exp (Warsz) 2016; 64(2): 111-26.
[] [PMID: 26658771]
Papacosta E, Nassis GP. Saliva as a tool for monitoring steroid, peptide and immune markers in sport and exercise science. J Sci Med Sport 2011; 14: 424-34.
Walsh NP, Oliver SJ. Exercise, immune function and respiratory infection: An update on the influence of training and environmental stress. Immunol Cell Biol 2016; 94: 132-9.
Liberman K, Forti LN, Beyer I, Bautmans I. The effects of exercise on muscle strength, body composition, physical functioning and the inflammatory profile of older adults: a systematic review. Curr Opin Clin Nutr Metab Care 2017; 20(1): 30-53.
[] [PMID: 27755209]
Phillips C, Baktir MA, Srivatsan M, Salehi A. Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front Cell Neurosci 2014; 8: 170.
Lu Y, Tze Ying Tan CT, Nyunt MSZ, et al. Inflammatory and immune markers associated with physical frailty syndrome: findings from Singapore longitudinal aging studies. Oncotarget 2016; 7: 28783-95.
Kohut ML, Senchina DS. Reversing age-associated immunosenescence via exercise. Exerc Immunol Rev 2004; 10: 6-41.
Theou O, Stathokostas L, Roland KP, et al. The effectiveness of exercise interventions for the management of frailty: a systematic review. J Aging Res 2011; 2011: 569194
Minuzzi LG, Chupel MU, Rama L, et al. Lifelong exercise practice and immunosenescence: Master athletes cytokine response to acute exercise. Cytokine 2019; 115: 1-7.
Su L, Hao QK, Liu S, Dong BR. Monocytes related inflammatory biomarkers are associated with frailty syndrome. Int J Gerontol 2017; 11: 225-9.
Chupel MU, Direito F, Furtado GE, et al. Strength training decreases inflammation and increases cognition and physical fitness in older women with cognitive impairment. Front Physiol 2017; 8: 377.
Teixeira AM, Ferreira JP, Hogervorst E, et al. Study protocol on hormonal mediation of exercise on cognition, stress and immunity (PRO-HMECSI): effects of different exercise programmes in institutionalized elders. Front Public Health 2016; 4: 133.
[] [PMID: 27446898]
Braga R. Ética na publicação de trabalhos científicos. Rev Port Geral Fam 2013; 29: 354-6.
Petrini C. Helsinki 50 years on. Clin Ter 2014; 165: 179-81.
de Labra C, Guimaraes-Pinheiro C, Maseda A, Lorenzo T, Millán-Calenti JC. Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials. BMC Geriatr 2015; 15: 154.
Picorelli AMA, Pereira LSM, Pereira DS, Felício D, Sherrington C. Adherence to exercise programs for older people is influenced by program characteristics and personal factors: a systematic review. J Physiother 2014; 60: 151-6.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-98.
Mungas D. In-office mental status testing: a practical guide. Geriatrics 1991; 46: 54-8, 63-6.
Salimetrics UK. . Salimetrics: saliva collection, saliva EIA kits, saliva testing, & salivary bioscience research. Salivary Analyts. 2017. Available at:
Woolley T. Comparison between the horiba microsemi point-of-care C-reactive protein and full blood cell analyzer and the horiba pentra 120 and roche cobas 6000. Point Car J Near-Patient Testing Technol 2014; 13: 66-9.
Rikli R, Jones C. Senior Fitness Test Manual Champaing. Human Kinetics Publishers. 2nd ed. 2013; pp. 1-200.
Guigoz Y. The Mini Nutritional Assessment (MNA) review of the literature - what does it tell us? J Nutr Health 2006; 10(6): 466-85.
de Luis DA, López Mongil R, González Sagrado M, López Trigo JA, Mora PF, Castrodeza Sanz J. Evaluation of the mini-nutritional assessment short-form (MNA-SF) among institutionalized older patients in Spain. Nutr Hosp 2011; 26: 1350-4.
Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol 1994; 47: 1245-51.
Viera AJ, Hinderliter AL. Validation of the HEM-780REL with easy wrap cuff for self-measurement of blood pressure according to the European Society of Hypertension International Protocol. Blood Press Monit 2007; 12: 335-8.
Santos M, Almeida A. Polimedicação no idoso. Revista de Enfermagem Refrencia 2010; 2: 149-62.
Lohman T. Roche, A Martorell R Anthropometric Standardization Reference Manual Champaign(IL)Title. Champaign, IL: Human Kinetics Books 1991.
Lohman TG, Roche AF, Martorell R. Anthropometric standardization reference manual. 1988; Vol. 24.
Guderian B, Johnson A, Mathiowetz V. Impact of exercise frequency on hand strength of the elderly. Phys Occup Ther Geriatr 2013; 31: 268-79.
Picorelli AMA, Pereira DS, Felício DC, et al. Adherence of older women with strength training and aerobic exercise. Clin Interv Aging 2014; 9: 323-31.
Robertson RJ, Goss FL, Rutkowski J, et al. Concurrent validation of the OMNI perceived exertion scale for resistance exercise. Med Sci Sports Exerc 2003; 35: 333-41.
Batterham AM, Hopkins WG. Making meaningful inferences about magnitudes. Int J Sports Physiol Perform 2006; 1: 50-7.
Senchina DS, Kohut ML. Immunological outcomes of exercise in older adults. Clin Interv Aging 2007; 2(1): 3-16.
Compté N, Zouaoui Boudjeltia K, Vanhaeverbeek M, et al. Frailty in old age is associated with decreased interleukin-12/23 production in response to toll-like receptor ligation. PLoS One 2013; 8(6): e65325
Allgrove JE, Gomes E, Hough J, Gleeson M. Effects of exercise intensity on salivary antimicrobial proteins and markers of stress in active men. J Sports Sci 2008; 26(6): 653-61.
Shibuya T, Kaburagi T, Nagai R, Oshiro S. The effects of moderate exercise on secretory IgA production in mice depends on dietary carbohydrate intake. J Clin Biochem Nutr 2015; 57: 44-9.
Silva RP. Da , Natali AJ, et al. Salivary immunoglobulin A (s-lgA) and exercise: relevance of its control in athletes and methodological implications. Revista Brasileira de Medicina do Esporte 2009; 15: 459-66.
Akimoto T, Kumai Y, Akama T, et al. Effects of 12 months of exercise training on salivary secretory IgA levels in elderly subjects. Br J Sports Med 2003; 37: 76-9.
Martins RA, Cunha MR, Neves AP, Martins M, Teixeira-Veríssimo M, Teixeira AM. Effects of aerobic conditioning on salivary IgA and plasma IgA, IgG and IgM in older men and women. Int J Sports Med 2009; 30: 906-12.
Neves S da C, Lima RM, Simões HG, Marques MC, Reis VM, de Oliveira RJ. Resistance exercise sessions do not provoke acute immunosuppression in older women. J Strength Cond Res 2009; 23: 259-65.
Soysal P, Stubbs B, Lucato P, et al. Inflammation and frailty in the elderly: A systematic review and meta-analysis. Ageing Res Rev 2016; 31: 1-8.
Brinkley TE, Leng X, Miller ME, et al. Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci 2009; 64: 455-61.
Hubbard RE, O’Mahony MS, Savva GM, Calver BL, Woodhouse KW. Inflammation and frailty measures in older people. J Cell Mol Med 2009; 13: 3103-9.
Nicklas BJ, Brinkley TE. Exercise training as a treatment for chronic inflammation in the elderly. Exerc Sport Sci Rev 2009; 37: 165-70.
Lambert CP, Wright NR, Finck BN, Villareal DT. Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons. J Appl Physiol 2008; 105: 473-8.
Chupel MU, Direito F, Furtado GE, et al. Strength training decreases inflammation and increases cognition and physical fitness in older women with cognitive impairment. Front Physiol 2017; 8: 1-377.
Kumari R, Kumar S, Ahmad MK, et al. TNF-α/IL-10 ratio: An independent predictor for coronary artery disease in North Indian population. Diabetes Metab Syndr 2018; 12(3): 221-5.
Giannopoulou I, Fernhall B, Carhart R, et al. Effects of diet and/or exercise on the adipocytokine and inflammatory cytokine levels of postmenopausal women with type 2 diabetes. Metabolism 2005; 54: 866-75.
Vijayaraghava A. Radhika K. Alteration of interferon gamma (IFN-gamma) in human plasma with graded physical activity. J Clin Diagn Res 2014; 8(6): BC05-7.
Woods JA, Wilund KR, Martin SA, Kistler BM. Exercise, inflammation and aging. Aging Dis 2012; 3(1): 130-40.
Teixeira AM. Martins R a, Neves AP, Coelho-Silva MJ, Veríssimo MT. The effect of aerobic versus strength-based training on high-sensitivity C-reactive protein in older adults. Eur J Appl Physiol 2010; 10: 161-9.
Beavers KM, Hsu FC, Isom S, et al. Long-term physical activity and inflammatory biomarkers in older adults. Med Sci Sports Exerc 2010; 42: 2189-96.
Baker MK, Atlantis E, Fiatarone Singh MA. Multi-modal exercise programs for older adults. Age Ageing 2007; 36: 375-81.
Antunes HKM, Santos RF, Cassilhas R, Santos RVT. Bueno OF a, Mello MT De Exercício físico e função cognitiva: uma revisão. Revista Brasileira de Medicina do Esporte 2006; 12: 108-14.
Lopez P, Pinto RS, Radaelli R, et al. Benefits of resistance training in physically frail elderly: a systematic review. Aging Clin Exp Res 2017; 30(8): 1-11.
José A, Dal Corso S. Inpatient rehabilitation improves functional capacity, peripheral muscle strength and quality of life in patients with community-acquired pneumonia: a randomised trial. J Physiother 2016; 62(2): 96-102.
Andersen LL, Andersen CH, Mortensen OS, Poulsen OM, Bjørnlund IBT, Zebis MK. Muscle activation and perceived loading during rehabilitation exercises: comparison of dumbbells and elastic resistance. Phys Ther 2010; 90(4): 538-49.
[] [PMID: 20133444]
Gage JR, Fonarow G, Hamilton M, Widawski M, Martínez-Maza O, Vredevoe DL. Beta blocker and angiotensin-converting enzyme inhibitor therapy is associated with decreased Th1/Th2 cytokine ratios and inflammatory cytokine production in patients with chronic heart failure. Neuroimmunomodulation 2004; 11(3): 173-80.
Mikus CR, Boyle LJ, Borengasser SJ, et al. Simvastatin impairs exercise training adaptations. J Am Coll Cardiol 2013; 62(8): 709-14.

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Year: 2020
Published on: 22 April, 2020
Page: [906 - 915]
Pages: 10
DOI: 10.2174/1381612826666200203123258
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