Resistance Training Does not have an Effect on Cognition or Related Serum Biomarkers in Nonagenarians: A Randomized Controlled Trial

J. R. Ruiz; F. Gil-Bea; N. Bustamante-Ara; G. Rodríguez-Romo; C. Fiuza-Luces; J. A. Serra-Rexach; A. Cedazo-Minguez; A. Lucia

doi:10.1055/s-0034-1375693

International Journal of Sports Medicine, Table of Contents

Int J Sports Med 2015; 36(01): 54-60
DOI: 10.1055/s-0034-1375693

Training & Testing

Resistance Training Does not have an Effect on Cognition or Related Serum Biomarkers in Nonagenarians: A Randomized Controlled Trial

J. R. Ruiz

¹PROmoting FITness and Health through physical activity research group (PROFITH), Department of Physical Education and Sport, University of Granada, Granada, Spain

,

F. Gil-Bea

²Department of Cellular and Molecular Neuropharmacology, Center for Applied Medical Research, Pamplona, Spain

,

N. Bustamante-Ara

³Biomedicine, Universidad Europea de Madrid, Madrid, Spain

,

G. Rodríguez-Romo

⁴INEF, Universidad Politécnica, Madrid, Spain

,

C. Fiuza-Luces

³Biomedicine, Universidad Europea de Madrid, Madrid, Spain

,

J. A. Serra-Rexach

⁵Geriatry, Hospital General Universitario Gregorio Marañón, Madrid, Spain

,

A. Cedazo-Minguez

⁶Karolinska Institutet, KI-Alzheimer’s Disease Research Center, Huddinge, Sweden

,

A. Lucia

⁷Physiology, Universidad Europea De Madrid, Madrid, Spain

› Author Affiliations

Abstract

The aim of this randomized controlled trial was to determine the effects of 8-week exercise-intervention on cognition and related serum biochemical markers in nonagenarians. We also studied the effects of a 4-week training cessation (‘detraining’) period on our study variables. Participants were randomly allocated to a standard-care (control) or intervention (exercise) group [n=20 (16 women)/group]. The intervention focused on supervised, light-to-moderate-intensity aerobic and resistance exercises (mainly leg press), and included 3 weekly sessions. Cognitive status was determined by the mini-mental state examination and geriatric depression scale. We analysed proteins with reported relation with mechanisms behind cognition changes such as serum levels of angiotensin converting enzyme, amyloid-precursor protein, epidermal growth factor, brain-derived neural factor and tumor necrosis factor. No significant change (P>0.05) in any of the variables studied was found following the exercise intervention compared with the standard-care group. Similarly, no significant changes (P>0.05) were observed following the detraining period compared with the standard-care group. Overall changes after the exercise intervention in serum biomarkers were not associated with changes in functional capacity and cognitive measures. An 8-week exercise intervention focusing on resistance exercises neither benefits cognitive function nor affects the levels of the serum proteins analysed in nonagenarians.

Key words

physical activity - cognitive decline - cognitive function - mini-mental state examination - elderly

Full Text

References

References
1 ACSM . American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc 2009; 41: 687-708
2 Adams V, Linke A, Breuckmann F, Leineweber K, Erbs S, Krankel N, Brocker-Preuss M, Woitek F, Erbel R, Heusch G, Hambrecht R, Schuler G, Mohlenkamp S. Circulating progenitor cells decrease immediately after marathon race in advanced-age marathon runners. Eur J Cardiovasc Prev Rehabil 2008; 15: 602-607
3 Akinyemi RO, Mukaetova-Ladinska EB, Attems J, Ihara M, Kalaria RN. Vascular risk factors and neurodegeneration in ageing related dementias: Alzheimer’s disease and vascular dementia. Curr Alzheimer Res 2013; 10: 642-653
4 Angevaren M, Aufdemkampe G, Verhaar HJ, Aleman A, Vanhees L. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev 2008; CD005381
5 Bjorkqvist M, Ohlsson M, Minthon L, Hansson O. Evaluation of a previously suggested plasma biomarker panel to identify Alzheimer’s disease. PLoS One 2012; 7: e29868
6 Cassilhas RC, Viana VA, Grassmann V, Santos RT, Santos RF, Tufik S, Mello MT. The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exerc 2007; 39: 1401-1407
7 Castellano V, White LJ. Serum brain-derived neurotrophic factor response to aerobic exercise in multiple sclerosis. J Neurol Sci 2008; 269: 85-91
8 Cedazo-Minguez A, Winblad B. Biomarkers for Alzheimer’s disease and other forms of dementia: clinical needs, limitations and future aspects. Exp Gerontol 2010; 45: 5-14
9 Chasseigneaux S, Allinquant B. Functions of Abeta, sAPPalpha and sAPPbeta: similarities and differences. J Neurochem 2012; 120 (Suppl. 01) 99-108
10 Chen-Plotkin AS, Hu WT, Siderowf A, Weintraub D, Goldmann Gross R, Hurtig HI, Xie SX, Arnold SE, Grossman M, Clark CM, Shaw LM, McCluskey L, Elman L, Van Deerlin VM, Lee VM, Soares H, Trojanowski JQ. Plasma epidermal growth factor levels predict cognitive decline in Parkinson disease. Ann Neurol 2011; 69: 655-663
11 Coelho FG, Gobbi S, Andreatto CA, Corazza DI, Pedroso RV, Santos-Galduroz RF. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr 2013; 56: 10-15
12 Coelho FM, Pereira DS, Lustosa LP, Silva JP, Dias JM, Dias RC, Queiroz BZ, Teixeira AL, Teixeira MM, Pereira LS. Physical therapy intervention (PTI) increases plasma brain-derived neurotrophic factor (BDNF) levels in non-frail and pre-frail elderly women. Arch Gerontol Geriatr 2012; 54: 415-420
13 Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 2003; 14: 125-130
14 Correia PR, Pansani A, Machado F, Andrade M, Silva AC, Scorza FA, Cavalheiro EA, Arida RM. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels. Clinics (Sao Paulo) 2010; 65: 1123-1126
15 Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002; 25: 295-301
16 de Salles BF, Simao R, Fleck SJ, Dias I, Kraemer-Aguiar LG, Bouskela E. Effects of resistance training on cytokines. Int J Sports Med 2010; 31: 441-450
17 Denkinger MD, Nikolaus T, Denkinger C, Lukas A. Physical activity for the prevention of cognitive decline: current evidence from observational and controlled studies. Z Gerontol Geriatr 2012; 45: 11-16
18 Direk N, Koudstaal PJ, Hofman A, Ikram MA, Hoogendijk WJ, Tiemeier H. Cerebral hemodynamics and incident depression: the Rotterdam Study. Biol Psychiatry 2012; 72: 318-323
19 Direk N, Schrijvers EM, de Bruijn RF, Mirza S, Hofman A, Ikram MA, Tiemeier H. Plasma amyloid beta, depression, and dementia in community-dwelling elderly. J Psychiatr Res 2013; 47: 479-485
20 Etnier JL, Nowell PM, Landers DM, Sibley BA. A meta-regression to examine the relationship between aerobic fitness and cognitive performance. Brain Res Rev 2006; 52: 119-130
21 Fatouros I, Chatzinikolaou A, Paltoglou G, Petridou A, Avloniti A, Jamurtas A, Goussetis E, Mitrakou A, Mougios V, Lazaropoulou C, Margeli A, Papassotiriou I, Mastorakos G. Acute resistance exercise results in catecholaminergic rather than hypothalamic-pituitary-adrenal axis stimulation during exercise in young men. Stress 2010; 13: 461-468
22 Foster PP, Rosenblatt KP, Kuljis RO. Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer’s disease. Front Neurol 2011; 2: 28
23 Goekint M, De Pauw K, Roelands B, Njemini R, Bautmans I, Mets T, Meeusen R. Strength training does not influence serum brain-derived neurotrophic factor. Eur J Appl Physiol 2010; 110: 285-293
24 Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol 2002; 88: 2187-2195
25 Gonzalo-Ruiz A, Gonzalez I, Sanz-Anquela JM. Effects of beta-amyloid protein on serotoninergic, noradrenergic, and cholinergic markers in neurons of the pontomesencephalic tegmentum in the rat. J Chem Neuroanat 2003; 26: 153-169
26 Hamer M, Chida Y. Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol Med 2009; 39: 3-11
27 Harriss DJ, Atkinson G. Ethical standards in sport and exercise science research: 2014 update. Int J Sports Med 2013; 34: 1025-1028
28 Heyn PC, Johnson KE, Kramer AF. Endurance and strength training outcomes on cognitively impaired and cognitively intact older adults: a meta-analysis. J Nutr Health Aging 2008; 12: 401-409
29 Higashi Y, Yoshizumi M. Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients. Pharmacol Ther 2004; 102: 87-96
30 Huang T, Larsen KT, Ried-Larsen M, Moller NC, Andersen LB. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans: A review. Scand J Med Sci Sports 2013;
31 Kimura K, Obuchi S, Arai T, Nagasawa H, Shiba Y, Watanabe S, Kojima M. The influence of short-term strength training on health-related quality of life and executive cognitive function. J Physiol Anthropol 2010; 29: 95-101
32 Kitazume S, Yoshihisa A, Yamaki T, Oikawa M, Tachida Y, Ogawa K, Imamaki R, Hagiwara Y, Kinoshita N, Takeishi Y, Furukawa K, Tomita N, Arai H, Iwata N, Saido T, Yamamoto N, Taniguchi N. Soluble amyloid precursor protein 770 is released from inflamed endothelial cells and activated platelets: a novel biomarker for acute coronary syndrome. J Biol Chem 2012; 287: 40817-40825
33 Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR, Chason J, Vakil E, Bardell L, Boileau RA, Colcombe A. Ageing, fitness and neurocognitive function. Nature 1999; 400: 418-419
34 Lachman ME, Neupert SD, Bertrand R, Jette AM. The effects of strength training on memory in older adults. J Aging Phys Act 2006; 14: 59-73
35 Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, Greenop KR, Almeida OP. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 2008; 300: 1027-1037
36 Levinger I, Goodman C, Matthews V, Hare DL, Jerums G, Garnham A, Selig S. BDNF, metabolic risk factors, and resistance training in middle-aged individuals. Med Sci Sports Exerc 2008; 40: 535-541
37 Li NC, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 2010; 340: b5465
38 Liu-Ambrose T, Nagamatsu LS, Graf P, Beattie BL, Ashe MC, Handy TC. Resistance training and executive functions: a 12-month randomized controlled trial. Arch Intern Med 2010; 170: 170-178
39 Loffler J, Huber G. Beta-amyloid precursor protein isoforms in various rat brain regions and during brain development. J Neurochem 1992; 59: 1316-1324
40 Lucia A, Ruiz JR. Exercise is beneficial for patients with Alzheimer’s disease: a call for action. Br J Sports Med 2011; 45: 468-469
41 Macaluso F, Myburgh KH. Current evidence that exercise can increase the number of adult stem cells. J Muscle Res Cell Motil 2012; 33: 187-198
42 Paganelli R, Di Iorio A, Patricelli L, Ripani F, Sparvieri E, Faricelli R, Iarlori C, Porreca E, Di Gioacchino M, Abate G. Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer’s disease patients. Exp Gerontol 2002; 37: 257-263
43 Park KM, Bowers WJ. Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction. Cell Signal 2010; 22: 977-983
44 Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev 2008; 88: 1379-1406
45 Perrig-Chiello P, Perrig WJ, Ehrsam R, Staehelin HB, Krings F. The effects of resistance training on well-being and memory in elderly volunteers. Age Ageing 1998; 27: 469-475
46 Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 2009; 94: 1062-1069
47 Ray S, Britschgi M, Herbert C, Takeda-Uchimura Y, Boxer A, Blennow K, Friedman LF, Galasko DR, Jutel M, Karydas A, Kaye JA, Leszek J, Miller BL, Minthon L, Quinn JF, Rabinovici GD, Robinson WH, Sabbagh MN, So YT, Sparks DL, Tabaton M, Tinklenberg J, Yesavage JA, Tibshirani R, Wyss-Coray T. Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat Med 2007; 13: 1359-1362
48 Roy S, Rauk A. Alzheimer’s disease and the ‘ABSENT’ hypothesis: mechanism for amyloid beta endothelial and neuronal toxicity. Med Hypotheses 2005; 65: 123-137
49 Rubio-Perez JM, Morillas-Ruiz JM. A review: inflammatory process in Alzheimer’s disease, role of cytokines. Scient World J 2012; 2012: 756357.
50 Schiffer T, Schulte S, Hollmann W, Bloch W, Struder HK.. Effects of strength and endurance training on brain-derived neurotrophic factor and insulin-like growth factor 1 in humans. Horm Metab Res 2009; 41: 250-254
51 Schulz KH, Gold SM, Witte J, Bartsch K, Lang UE, Hellweg R, Reer R, Braumann KM, Heesen C. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci 2004; 225: 11-18
52 Seifert T, Brassard P, Wissenberg M, Rasmussen P, Nordby P, Stallknecht B, Adser H, Jakobsen AH, Pilegaard H, Nielsen HB, Secher NH.. Endurance training enhances BDNF release from the human brain. Am J Physiol 2010; 298: R372-R377
53 Selkoe DJ, Podlisny MB, Joachim CL, Vickers EA, Lee G, Fritz LC, Oltersdorf T. Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci USA 1988; 85: 7341-7345
54 Serra-Rexach JA, Ruiz JR, Bustamante-Ara N, Villaran MH, Gil PG, Sanz Ibanez MJ, Sanz NB, Santamaria VO, Sanz NG, Prada AB, Gallardo C, Romo GR, Lucia A. Health enhancing strength training in nonagenarians (STRONG): rationale, design and methods. BMC Public Health 2009; 9: 152
55 Singh M, Meyer EM, Simpkins JW. The effect of ovariectomy and estradiol replacement on brain-derived neurotrophic factor messenger ribonucleic acid expression in cortical and hippocampal brain regions of female Sprague-Dawley rats. Endocrinology 1995; 136: 2320-2324
56 Smith PJ, Blumenthal JA, Hoffman BM, Cooper H, Strauman TA, Welsh-Bohmer K, Browndyke JN, Sherwood A. Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosom Med 2010; 72: 239-252
57 Suijo K, Inoue S, Ohya Y, Odagiri Y, Takamiya T, Ishibashi H, Itoh M, Fujieda Y, Shimomitsu T. Resistance exercise enhances cognitive function in mouse. Int J Sports Med 2013; 34: 368-375
58 Tsutsumi T, Don BM, Zaichkowsky LD, Delizonna LL. Physical fitness and psychological benefits of strength training in community dwelling older adults. Appl Human Sci 1997; 16: 257-266
59 van Uffelen JG, Chinapaw MJ, van Mechelen W, Hopman-Rock M. Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial. Br J Sports Med 2008; 42: 344-351
60 Yang YH, Liu CK. Angiotensin-converting enzyme gene in Alzheimer’s disease. Tohoku J Exp Med 2008; 215: 295-298
61 Yarrow JF, White LJ, McCoy SC, Borst SE. Training augments resistance exercise induced elevation of circulating brain derived neurotrophic factor (BDNF). Neurosci Lett 2010; 479: 161-165
62 Zoladz JA, Pilc A. The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies. J Physiol Pharmacol 2010; 61: 533-541
63 Zoladz JA, Pilc A, Majerczak J, Grandys M, Zapart-Bukowska J, Duda K. Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. J Physiol Pharmacol 2008; 59 (Suppl. 07) 119-132