Exercise Strategies to Counteract Brain Aging Effects

  • Dominika Szalewska
  • Marek Radkowski
  • Urszula Demkow
  • Pawel J. WinklewskiEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1020)


Stimulating structural and functional adaptation that improves cognitive performance in specific tasks is the major objective of therapeutic exercise training. In this review we briefly summarize central physiological mechanisms activated by exercise. We further discuss the influence of different kinds of exercise on cognitive improvement. In particular, the effects on cognitive function of aerobic endurance, resistance and respiratory exercise, and combinations thereof are presented. The accumulating evidence reinforces the position that regular aerobic, and possibly also resistance training, offers a powerful tool to cope with biologic aging of central nervous system functions. Nevertheless, the potential magnitude of cognition improvement or restrain of age-related cognition deterioration and the quantity of physical activity required to induce meaningful responses remain to be clarified.


Brain aging Exercise Central noradrenergic system Cognition Hypothalamic-pituitary-adrenal axis Respiratory exercise 


Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.


  1. Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403–450CrossRefPubMedGoogle Scholar
  2. Aston-Jones G, Waterhouse B (2016) Locus coeruleus: from global projection system to adaptive regulation of behavior. Brain Res 1645:75–78CrossRefPubMedPubMedCentralGoogle Scholar
  3. Aston-Jones G, Rajkowski J, Ivanova S, Usher M, Cohen J (1998) Neuromodulation and cognitive performance: recent studies of noradrenergic locus coeruleus neurons in behaving monkeys. Adv Pharmacol 42:755–759CrossRefPubMedGoogle Scholar
  4. Atzori M, Cuevas-Olguin R, Esquivel-Rendon E, Garcia-Oscos F, Salgado-Delgado RC, Saderi N, Miranda-Morales M, Treviño M, Pineda JC, Salgado H (2016) Locus coeruleus norepinephrine release: a central regulator of CNS spatio-temporal activation? Front Synaptic Neurosci 8:25CrossRefPubMedPubMedCentralGoogle Scholar
  5. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Cholerton BA, Plymate SR, Fishel MA, Watson GS, Duncan GE, Mehta PD, Craft S (2010a) Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer’s disease. J Alzheimers Dis 22:569–579CrossRefPubMedPubMedCentralGoogle Scholar
  6. Baker LD, Frank L, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Plymate SR, Fishel MA, Watson GS, Cholerton BA, Duncan GE, Mehta PD, Craft S (2010b) Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol 67:71–79PubMedPubMedCentralGoogle Scholar
  7. Benveniste EN, Huneycutt BS, Shrikant P, Ballestas ME (1995) Second messenger systems in the regulation of cytokines and adhesion molecules in the central nervous system. Brain Behav Immun 9:304–314CrossRefPubMedGoogle Scholar
  8. Berthoud HR, Neuhuber WL (2000) Functional and chemical anatomy of the afferent vagal system. Auton Neurosci 85:1–17CrossRefPubMedGoogle Scholar
  9. Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors 22:123–131CrossRefPubMedPubMedCentralGoogle Scholar
  10. Bossers WJ, van der Woude LH, Boersma F, Hortobágyi T, Scherder EJ, van Heuvelen MJ (2015) A 9-week aerobic and strength training program improves cognitive and motor function in patients with dementia: a randomized, controlled trial. Am J Geriatr Psychiatry 23:1106–1611CrossRefPubMedGoogle Scholar
  11. Braun D, Madrigal JL, Feinstein DL (2014) Noradrenergic regulation of glial activation: molecular mechanisms and therapeutic implications. Curr Neuropharmacol 12:342–352CrossRefPubMedPubMedCentralGoogle Scholar
  12. Buchman AS, Boyle PA, Yu L, Shah RC, Wilson RS, Bennett DA (2012) Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology 78(17):1323–1329CrossRefPubMedPubMedCentralGoogle Scholar
  13. Burghardt PR, Pasumarthi RK, Wilson MA, Fadel J (2006) Alterations in fear conditioning and amygdalar activation following chronic wheel running in rats. Pharmacol Biochem Behav 84:306–312CrossRefPubMedGoogle Scholar
  14. Burley CV, Bailey DM, Marley CJ, Lucas SJ (2016) Brain train to combat brain drain; focus on exercise strategies that optimise neuroprotection. Exp Physiol. doi: 10.1113/EP085672 PubMedGoogle Scholar
  15. Campbell A (2004) Inflammation, neurodegenerative diseases, and environmental exposures. Ann N Y Acad Sci 1035:117–132CrossRefPubMedGoogle Scholar
  16. Campeau S, Nyhuis TJ, Sasse SK, Kryskow EM, Herlihy L, Masini CV, Babb JA, Greenwood BN, Fleshner M, Day HE (2010) Hypothalamic pituitary adrenal axis responses to low-intensity stressors are reduced after voluntary wheel running in rats. J Neuroendocrinol 22:872–888PubMedPubMedCentralGoogle Scholar
  17. Chandler DJ (2016) Evidence for a specialized role of the locus coeruleus noradrenergic system in cortical circuitries and behavioral operations. Brain Res 1641:197–206CrossRefPubMedGoogle Scholar
  18. Chapman SN, Aslan S, Spence JS, Defina LF, Keebler MW, Didehbani N, Lu H (2013) Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging. Front Aging Neurosci 5:1–9CrossRefGoogle Scholar
  19. Chapman SN, Aslan S, Spence JS, Keebler MW, DeFina LF, Didehbani N, Perez AM, Lu H, D’Esposito M (2016) Distinct brain and behavioral benefits from cognitive vs. physical training: a randomized trial in aging adults. Front Aging Neurosci 10:1–15Google Scholar
  20. Chiba T, Doba N (1976) Catecholaminergic axo-axonic synapses in the nucleus of the tractus solitarius (pars commissuralis) of the cat: possible relation to presynaptic regulation of baroreceptor reflexes. Brain Res 102:255–665CrossRefPubMedGoogle Scholar
  21. Chiba T, Kato M (1978) Synaptic structures and quantification of catecholaminergic axons in the nucleus tractus solitarius of the rat: possible modulatory roles of catecholamines in baroreceptor reflexes. Brain Res 151:323–338CrossRefPubMedGoogle Scholar
  22. Clarkson PM (1978) The relationship of age and level of physical activity with the fractionated components of patellar reflex time. J Gerontol 3:650CrossRefGoogle Scholar
  23. Cooper CJ (1973) Anatomical and physiological mechanisms of arousal, with special reference to the effects of exercise. Ergonomics 16:601–609CrossRefPubMedGoogle Scholar
  24. Costa VD, Rudebeck PH (2016) More than meets the eye: the relationship between pupil size and locus coeruleus activity. Neuron 89:8–10CrossRefPubMedPubMedCentralGoogle Scholar
  25. Fallah N, Hsu CL, Bolandzadeh N, Davis J, Beattie BL, Graf P, Liu-Ambrose TA (2013) Multi-state model of cognitive dynamics in relation to resistance training: the contribution of baseline function. Ann Epidemiol 23:463–468CrossRefPubMedPubMedCentralGoogle Scholar
  26. Feinstein DL, Kalinin S, Braun D (2016) Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system. J Neurochem. doi: 10.1111/jnc.13447 PubMedCentralGoogle Scholar
  27. Ferreira L, Tanaka K, Santos-Galduróz RF, Galduróz JC (2015) Respiratory training as a strategy to prevent cognitive decline in aging: a randomized controlled trial. Clin Interv Aging 10:593–603PubMedPubMedCentralGoogle Scholar
  28. Forbes SC, Forbes D, Forbes S, Blake CM, Chong LY, Thiessen EJ, Little JP, Rutjes AWS (2015) Exercise interventions for preventing dementia or delaying cognitive decline in people with mild cognitive impairment (Protocol). Cochrane Database Syst Rev 5, art. no CD011706Google Scholar
  29. Frohman EM, Vayuvegula B, Gupta S, van den Noort S (1998) Norepinephrine inhibits gamma-interferon-induced major histocompatibility class II (Ia) antigen expression on cultured astrocytes via beta-2-adrenergic signal transduction mechanisms. Proc Natl Acad Sci U S A 85:1292–1296CrossRefGoogle Scholar
  30. Griffin WS, Sheng JG, Royston MC, Gentleman SM, McKenzie JE, Graham DI, Roberts GQ, Mark RE (1998) Glial-neuronal interactions in Alzheimer’s disease: the potential role of a ‘cytokine cycle’ in disease progression. Brain Pathol 8:65–72CrossRefPubMedGoogle Scholar
  31. Hetier E, Ayala J, Bousseau A, Prochiantz A (1991) Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells. Exp Brain Res 86:407–413CrossRefPubMedGoogle Scholar
  32. Ho RT, Cheung JK, Chan WC, Cheung IK, Lam LC (2015) A 3-arm randomized controlled trial on the effects of dance movement intervention and exercises on elderly with early dementia. BMC Geriatr 15:1CrossRefGoogle Scholar
  33. Jackson PA, Pialoux V, Corbett D, Drogos L, Erickson KI, Eskes GA, Poulin MJ (2016) Promoting brain health through exercise and diet in older adults: a physiological perspective. J Physiol 594:4485–4498CrossRefPubMedPubMedCentralGoogle Scholar
  34. Joels M, Pu Z, Wiegert O, Oitzl MS, Krugers HJ (2006) Learning under stress: how does it work? Trends Cogn Sci 10:152–158CrossRefPubMedGoogle Scholar
  35. Joshi S, Li Y, Kalwani RM, Gold JI (2016) Relationships between pupil diameter and neuronal activity in the locus coeruleus, colliculi, and cingulate cortex. Neuron 89:221–234CrossRefPubMedGoogle Scholar
  36. Juric DM, Loncar D, Carman-Krzan M (2008) Noradrenergic stimulation of BDNF synthesis in astrocytes: mediation via alpha1- and beta1/beta2-adrenergic receptors. Neurochem Int 52:297–306CrossRefPubMedGoogle Scholar
  37. Kemoun G, Thibaud M, Roumagne N, Carette P, Albinet C, Toussaint L, Paccalin M, Dugué B (2010) Effects of a physical training programme on cognitive function wand walking efficiency in elderly persons with dementia. Dement Geriatr Cogn Disord 29:109–114CrossRefPubMedGoogle Scholar
  38. Kennedy G, Hardman RJ, Macpherson H, Scholey AB, Pipingas A (2016) How does exercise reduce the rate of age-associated cognitive decline? A review of potential mechanisms. J Alzheimers 55(1):1–18Google Scholar
  39. Makizako H, Doi T, Shimada H, Yoshida D, Tsutsumimoto K, Uemura K, Suzuki T (2012) Does a multicomponent exercise program improve dual-task performance in amnestic mild cognitive impairment? A randomized controlled trial. Aging Clin Exp Res 24:640–646PubMedGoogle Scholar
  40. Martinez-Velilla N, Casas-Herrero A, Zambom-Ferraresi F, Suarez N, Alonso-Renedo J, Contin KC, de Astesau ML, Echeverria NF, Lazaro MG, Izquierdo M (2015) Functional and cognitive impairment prevention through early physical activity for geriatric hospitalized patients: study protocol for a randomized controlled trial. BMC Geriatr 15:112CrossRefPubMedPubMedCentralGoogle Scholar
  41. McArdle WD (2001) Exercise physiology: energy, nutrition and human performance. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
  42. McGaugh JL, Cahill L, Roozendaal B (1996) Involvement of the amygdala in memory storage: interaction with other brain systems. Proc Natl Acad Sci U S A 93:13508–13514CrossRefPubMedPubMedCentralGoogle Scholar
  43. McMorris T (2016) Developing the catecholamines hypothesis for the acute exercise-cognition interaction in humans: lessons from animal studies. Physiol Behav 165:291–299CrossRefPubMedGoogle Scholar
  44. Miyashita T, Williams CL (2006) Epinephrine administration increases neural impulses propagated along the vagus nerve: role of peripheral beta-adrenergic receptors. Neurobiol Learn Mem 85:116–124CrossRefPubMedGoogle Scholar
  45. Moor T, Mundorff L, Bohringer A, Philippsen C, Langewitz W, Reino ST, Schachinger H (2005) Evidence that baroreflex feedback influences long-termincidental visual memory in men. Neurobiol Learn Mem 84:168–174CrossRefPubMedGoogle Scholar
  46. Mravec B (2006) Possible involvement of the vagus nerve in monitoring plasma catecholamine levels. Neurobiol Learn Mem 86:353–355CrossRefPubMedGoogle Scholar
  47. Muscari A, Giannoni C, Pierpaoli L, Berzigotti A, Maietta P, Foschi E, Ravaioli C, Poggiopollini G, Bianchi G, Magalotti D, Tentoni C, Zoli M (2010) Chronic endurance exercise training prevents aging-related cognitive decline in healthy older adults: a randomized controlled trial. Int J Geriatr Psychiatry 25:1055–1064CrossRefPubMedGoogle Scholar
  48. O’Donnell J, Zeppenfeld D, McConnell E, Pena S, Nedergaard M (2012) Norepinephrine: a neuromodulator that boosts the function of multiple cell types to optimize CNS performance. Neurochem Res 37:2496–2512CrossRefPubMedPubMedCentralGoogle Scholar
  49. Rajkowski J, Kubiak P, Aston-Jones G (1994) Locus coeruleus activity in monkey: phasic and tonic changes are associated with altered vigilance. Brain Res Bull 35:607–616CrossRefPubMedGoogle Scholar
  50. Ransohoff RM (2016) How neuroinflammation contributes to neurodegeneration. Science 353:777–783CrossRefPubMedGoogle Scholar
  51. Rhodes JS, Garland T Jr, Gammie SC (2003) Patterns of brain activity associated with variation in voluntary wheel-running behavior. Behav Neurosci 117:1243–1256CrossRefPubMedGoogle Scholar
  52. Roozendaal B, McEwen BS, Chattarji S (2009) Stress, memory and the amygdala. Nat Rev Neurosci 10:423–433CrossRefPubMedGoogle Scholar
  53. Samuels ER, Szabadi E (2008a) Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part I: principles of functional organisation. Curr Neuropharmacol 6:235–253CrossRefPubMedPubMedCentralGoogle Scholar
  54. Samuels ER, Szabadi E (2008b) Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans. Curr Neuropharmacol 6:254–285CrossRefPubMedPubMedCentralGoogle Scholar
  55. Sandi C, Pinelo-Nava MT (2007) Stress and memory: behavioral effects and neurobiological mechanisms. Neural Plast 2007:78970CrossRefPubMedPubMedCentralGoogle Scholar
  56. Singh MAF, Gates N, Saigal N, Wilson GC, Meiklejohn J, Brodaty H, Wen W, Baune BT, Suo C, Baker MK, Foroughi N, Wang Y, Sachdey PS, Valenzuela M, The Study of Mental and Resistance Training (SMART) (2014) Study – resistance training and/or cognitive training in mild cognitive impairment: a randomized, double-blind, double-sham controlled trial. JAMDA 15:873–880PubMedGoogle Scholar
  57. Stranahan AM, Lee K, Mattson MP (2008) Central mechanisms of HPA axis regulation by voluntary exercise. Neruomol Med 10:118–127CrossRefGoogle Scholar
  58. ten Brinke LF, Bolandzadeh N, Nagamatsu LS, Hsu CL, Davis JC, Miran-Khan K, Liu-Ambrose T (2015) Aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: a 6-month randomized controlled trial. Br J Sports Med 49:248–254CrossRefPubMedGoogle Scholar
  59. Usher M, Cohen JD, Servan-Schreiber D, Rajkowski J, Aston-Jones G (1999) The role of locus coeruleus in the regulation of cognitive performance. Science 283:549–554CrossRefPubMedGoogle Scholar
  60. Van Boxtel MPJ, Paas FG, Houx PJ, Adam JJ, Teeken JC, Jolles J (1997) Aerobic capacity and cognitive performance in a cross-sectional aging study. Med Sci Sports Exerc 29:1357CrossRefPubMedGoogle Scholar
  61. Varma VR, Chuang Y, Harris GC, Tan EJ, Carlson MC (2015) Low-intensity daily walking activity is associated with hippocampal volume in older adults. Hippocampus 25:605–615CrossRefPubMedGoogle Scholar
  62. Venturelli M, Scarsini R, Schena F (2011) Six-month walking program changes cognitive and ADL performance in patients with Alzheimer. Am J Alzheimers Dis Other Demen 26:381–389CrossRefPubMedGoogle Scholar
  63. Winchester J, Dick MB, Gillen D, Reed B, Miller B, Tinklenberg J, Mungas D, Chui H, Galasko D, Hewett L, Cotman CW (2013) Walking stabilizes cognitive functioning in Alzheimer’s disease across one year. Arch Gerontol Geriatr 56:96–103CrossRefPubMedGoogle Scholar
  64. Winklewski PJ, Radkowski M, Wszedybyl-Winklewska M, Demkow U (2015) Brain inflammation and hypertension: the chicken or the egg? J Neuroinflammation 12:85CrossRefPubMedPubMedCentralGoogle Scholar
  65. Winklewski PJ, Radkowski M, Demkow U (2016) Neuroinflammatory mechanisms of hypertension: potential therapeutic implications. Curr Opin Nephrol Hypertens 25:410–416CrossRefPubMedGoogle Scholar
  66. Wolf OT, Atsak P, de Quervain DJ, Roozendaal B, Wingenfeld K (2016) Stress and memory: a selective review on recent developments in the understanding of stress hormone effects on memory and their clinical relevance. J Neuroendocrinol. doi: 10.1111/jne.12353 PubMedGoogle Scholar
  67. Zafra F, Lindholm D, Castren E, Hartikka J, Thoenen H (1992) Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes. J Neurosci 12:4793–4799PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Dominika Szalewska
    • 1
  • Marek Radkowski
    • 2
  • Urszula Demkow
    • 3
  • Pawel J. Winklewski
    • 4
    • 5
    Email author
  1. 1.Rehabilitation Medicine, Medical University of GdanskGdanskPoland
  2. 2.Department of Immunopathology of Infectious and Parasitic DiseasesMedical University of WarsawWarsawPoland
  3. 3.Department of Laboratory Diagnostics and Clinical Immunology of Developmental AgeMedical University of WarsawWarsawPoland
  4. 4.Department of Human PhysiologyMedical University of GdanskGdanskPoland
  5. 5.Department of Clinical SciencesInstitute of Health Sciences, Pomeranian University of SlupskSlupskPoland

Personalised recommendations