Exercise for Brain Health: An Investigation into the Underlying Mechanisms Guided by Dose

  • Danylo F. Cabral
  • Jordyn Rice
  • Timothy P. Morris
  • Tatjana Rundek
  • Alvaro Pascual-Leone
  • Joyce Gomes-OsmanEmail author


There is a strong link between the practice of regular physical exercise and maintenance of cognitive brain health. Animal and human studies have shown that exercise exerts positive effects on cognition through a variety of mechanisms, such as changes in brain volume and connectivity, cerebral perfusion, synaptic plasticity, neurogenesis, and regulation of trophic factors. However, much of this data has been conducted in young humans and animals, raising questions regarding the generalizability of these findings to aging adults. Furthermore, it is not clear at which doses these effects might take place, and if effects would differ with varying exercise modes (such as aerobic, resistance training, combinations, or other). The purpose of this review is to summarize the evidence on the effects of exercise interventions on various mechanisms believed to support cognitive improvements: cerebral perfusion, synaptic neuroplasticity, brain volume and connectivity, neurogenesis, and regulation of trophic factors. We synthesized the findings according to exposure to exercise (short- [1 day-16 weeks], medium- [24-40 weeks], and long-term exercise [52 weeks and beyond]) and have limited our discussion of dose effects to studies in aging adults and aged animals (when human data was not available).

Key Words

Physical exercise cognitive brain health exercise dose aging brain older adults physiological mechanisms 



Dr. Gomes-Osman was supported by an Evelyn F. McKnight Pilot Grant. The project described was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number KL2TR002737. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. 1.
    Bureau UC. An aging nation: projected number of children and older adults. Available at: Accessed February 2019.
  2. 2.
    Blazer DG, Yaffe K, Karlawish J. Cognitive aging. JAMA 2015;313:2121.CrossRefPubMedGoogle Scholar
  3. 3.
    DeCarli C, Massaro J, Harvey D, et al. Measures of brain morphology and infarction in the framingham heart study: establishing what is normal. Neurobiol Aging 2005;26:491–510.CrossRefPubMedGoogle Scholar
  4. 4.
    Raz N, Gunning-Dixon F, Head D, et al. Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume. Neurobiol Aging 2004;25:377–396.CrossRefPubMedGoogle Scholar
  5. 5.
    Dong C, Nabizadeh N, Caunca M, et al. Cognitive correlates of white matter lesion load and brain atrophy: the Northern Manhattan Study. Neurology 2015;85:441–449.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Mattson MP, Maudsley S, Martin B. BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 2004;27:589–594.CrossRefPubMedGoogle Scholar
  7. 7.
    Mukherjee J, Christian BT, Dunigan KA, et al. Brain imaging of 18F-fallypride in normal volunteers: blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors. Synapse 2002;46:170–188.CrossRefPubMedGoogle Scholar
  8. 8.
    Nyberg L. Intact frontal memory effect in older age and dementia. Neuron 2004;42:701–2.CrossRefPubMedGoogle Scholar
  9. 9.
    Hsieh H, Boehm J, Sato C, et al. AMPAR removal underlies abeta-induced synaptic depression and dendritic spine loss. Neuron 2006;52:831–843.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lobelo F, Stoutenberg M, Hutber A. The exercise is medicine global health initiative: a 2014 update. Br J Sport Med . 2014;48:1627–1633.CrossRefGoogle Scholar
  11. 11.
    Piercy KL, Troiano RP, Ballard RM, et al. The physical activity guidelines for Americans. JAMA - J Am Med Assoc 2018;320:2020–2028.CrossRefGoogle Scholar
  12. 12.
    Gomes-Osman J, Cabral DF, Morris TP, et al. Exercise for cognitive brain health in aging. Neurol Clin Pract 2018;1–9.Google Scholar
  13. 13.
    Colcombe SJ, Erickson KI, Scalf PE, et al. Aerobic exercise training increases brain volume in aging humans. J Gerontol Ser A Biol Sci Med Sci 2006;61:1166–1170.CrossRefGoogle Scholar
  14. 14.
    Erickson KI, Voss MW, Prakash RS, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci 2011;108:3017–3022.CrossRefPubMedGoogle Scholar
  15. 15.
    Ruscheweyh R, Willemer C, Krüger K, et al. Physical activity and memory functions: an interventional study. Neurobiol Aging 2011;32:1304–1319.CrossRefPubMedGoogle Scholar
  16. 16.
    Weinstein AM, Voss MW, Prakash RS, et al. The association between aerobic fitness and executive function is mediated by prefrontal cortex volume. Brain Behav Immun 2012;26:811–819.CrossRefPubMedGoogle Scholar
  17. 17.
    Maass A, Duzel S, Goerke M, et al. Vascular hippocampal plasticity after aerobic exercise in older adults. Mol Psychiatry 2015;20:585–593.CrossRefPubMedGoogle Scholar
  18. 18.
    Christie BR, Eadie BD, Kannangara TS, Robillard JM, Shin J, Titterness AK. Exercising our brains: how physical activity impacts synaptic plasticity in the dentate gyrus. NeuroMolecular Med 2008 Jun;10:47–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Maass A, Düzel S, Brigadski T, et al. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults. Neuroimage 2016;131:142–154.CrossRefPubMedGoogle Scholar
  20. 20.
    Knaepen K, Goekint M, EM H, Meeusen R. Neuroplasticity—exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sport Med 2010;40:765–801.CrossRefGoogle Scholar
  21. 21.
    Leckie RL, Oberlin LE, Voss MW, et al. BDNF mediates improvements in executive function following a 1-year exercise intervention. Front Hum Neurosci 2014;8:985.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Rasmussen P, Brassard P, Adser H, et al. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 2009;94:1062–1069.CrossRefPubMedGoogle Scholar
  23. 23.
    Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 2007;30:464–472.CrossRefPubMedGoogle Scholar
  24. 24.
    Erickson KI, Hillman CH, Kramer AF. Physical activity, brain, and cognition. Curr Opin Behav Sci 2015;4:27–32.CrossRefGoogle Scholar
  25. 25.
    Chieffi S, Messina G, Villano I, et al. Neuroprotective effects of physical activity: evidence from human and animal studies. Front Neurol 2017;8:1–7.Google Scholar
  26. 26.
    Stimpson NJ, Davison G, Javadi AH. Joggin’ the noggin: towards a physiological understanding of exercise-induced cognitive benefits. Neurosci Biobehav Rev 2018;88:177–86.CrossRefPubMedGoogle Scholar
  27. 27.
    Schneider WJ, McGrew KS. The Cattell-Horn-Carroll model of intellidence. In: DP Flanagan and PL Harrison, editor. Contemporary intellectual assessment theories, tests and issues. 3rd ed New York: Guilford; 2012. p. 99–138.Google Scholar
  28. 28.
    Buijs PC, Krabbe-Hartkamp MJ, Bakker CJ, et al. Effect of age on cerebral blood flow: measurement with ungated two-dimensional phase-contrast MR angiography in 250 adults. Radiology 1998;209:667–674.CrossRefPubMedGoogle Scholar
  29. 29.
    Tarumi T, Ayaz Khan M, Liu J, et al. Cerebral hemodynamics in normal aging: central artery stiffness, wave reflection, and pressure pulsatility. J Cereb Blood Flow Metab 2014;34:971–978.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Moraine JJ, Lamotte M, Berré J, Niset G, Leduc A, Naeije R. Physiology and occupational physiology relationship of middle cerebral artery blood flow velocity to intensity during dynamic exercise in normal subjects. Eur J Appl Physiol 1993;67:35–38.CrossRefGoogle Scholar
  31. 31.
    Fisher JP, Hartwich D, Seifert T, et al. Cerebral perfusion, oxygenation and metabolism during exercise in young and elderly individuals. J Physiol 2013;591:1859–1870.CrossRefPubMedGoogle Scholar
  32. 32.
    Flück D, Braz ID, Keiser S, et al. Age, aerobic fitness, and cerebral perfusion during exercise: role of carbon dioxide. Am J Physiol Circ Physiol 2014;307:515–523.CrossRefGoogle Scholar
  33. 33.
    Murrell CJ, Cotter JD, Thomas KN, Lucas SJE, Williams MJA, Ainslie PN. Cerebral blood flow and cerebrovascular reactivity at rest and during sub-maximal exercise: effect of age and 12-week exercise training. Age (Omaha) 2013;35:905–920.CrossRefGoogle Scholar
  34. 34.
    Chapman SB, Aslan S, Spence JS, et al. Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging. Front Aging Neurosci 2013;5:1–9.CrossRefGoogle Scholar
  35. 35.
    Chapman SB, Aslan S, Spence JS, et al. Distinct brain and behavioral benefits from cognitive vs. physical training: a randomized trial in aging adults. Front Hum Neurosci. 2016;10:1–15.CrossRefGoogle Scholar
  36. 36.
    Burdette JH, Laurienti PJ, Espeland MA, et al. Using network science to evaluate exercise-associated brain changes in older adults. Front Aging Neurosci 2010;2:1–10.Google Scholar
  37. 37.
    Bliss TVP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. 1993.Google Scholar
  38. 38.
    Hölscher C. Synaptic plasticity and learning and memory: LTP and beyond. J Neurosci Res 1999;58:62–75.CrossRefPubMedGoogle Scholar
  39. 39.
    Bliss TVP, Gardner-Medwin AR. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaesthetized rabbit following stimulation of the perforant path. J Physiol 1973;232.Google Scholar
  40. 40.
    Van Praag H. Neurogenesis and exercise: past and future directions. NeuroMolecular Med 2008;10:128–140.CrossRefPubMedGoogle Scholar
  41. 41.
    Christie BR, Swann SE, Fox CJ, et al. Voluntary exercise rescues deficits in spatial memory and long-term potentiation in prenatal ethanol-exposed male rats. Eur J Neurosci 2005;21:1719–1726.CrossRefPubMedGoogle Scholar
  42. 42.
    Zhao G, Liu HL, Zhang H, Tong AXJ. Treadmill exercise enhances synaptic plasticity, but does not alter Î2-amyloid deposition in hippocampi of aged APP/PS1 transgenic mice. Neuroscience 2015;298:357–66.CrossRefPubMedGoogle Scholar
  43. 43.
    Liu H-L, Zhao G, Cai K, Zhao H-H, Shi L-D. Treadmill exercise prevents decline in spatial learning and memory in APP/PS1 transgenic mice through improvement of hippocampal long-term potentiation. Behav Brain Res 2010;218:308–14.CrossRefPubMedGoogle Scholar
  44. 44.
    Dao AT, Zagaar MA, Salim S, Eriksen JL, Alkadhi KA. Regular exercise prevents non-cognitive disturbances in a rat model of Alzheimer’s disease. Int J Neuropsychopharmacol 2014;17:593–602.CrossRefPubMedGoogle Scholar
  45. 45.
    Kumar A, Rani A, Tchigranova O, Lee W, Foster TC. Influence of late-life exposure to environmental enrichment or exercise on hippocampal function and CA1 senescent physiology. Neurobiol Aging. 2012;33:828.e1–828.e17.CrossRefGoogle Scholar
  46. 46.
    O’Callaghan RM, Griffin ÉW, Kelly ÁM. Long-term treadmill exposure protects against age-related neurodegenerative change in the rat hippocampus. Hippocampus 2009;19:1019–1029.CrossRefPubMedGoogle Scholar
  47. 47.
    Raz N, Lindenberger U, Rodrigue KM, et al. Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex . 2005;15:1676–1689.CrossRefPubMedGoogle Scholar
  48. 48.
    Bugg JM, Head D. Exercise moderates age-related atrophy of the medial temporal lobe. Neurobiol Aging . 2011;32:506–514.CrossRefPubMedGoogle Scholar
  49. 49.
    Colcombe SJ, Erickson KI, Raz N, et al. Aerobic fitness reduces brain tissue loss in aging humans. Journals Gerontol Ser A Biol Sci Med Sci . 2003;58:M176–M180.CrossRefGoogle Scholar
  50. 50.
    Carlson MC, Xue QL, Zhou J, Fried LP. Executive decline and dysfunction precedes declines in memory: the Women’s Health and Aging Study II. J Gerontol - Ser A Biol Sci Med Sci 2009;64:110–117.CrossRefGoogle Scholar
  51. 51.
    Matura S, Fleckenstein J, Deichmann R, et al. Effects of aerobic exercise on brain metabolism and grey matter volume in older adults: results of the randomised controlled SMART trial. Transl Psychiatry 2017;7:e1172.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Kleemeyer MM, Kühn S, Prindle J, et al. Changes in fitness are associated with changes in hippocampal microstructure and hippocampal volume among older adults. Neuroimage . 2016;131:155–161.CrossRefPubMedGoogle Scholar
  53. 53.
    Jonasson LS, Nyberg L, Kramer AF, Lundquist A, Riklund K, Boraxbekk C-J. Aerobic exercise intervention, cognitive performance, and brain structure: results from the Physical Influences on Brain in Aging (PHIBRA) study. Front Aging Neurosci. 2017;8:1–15.CrossRefGoogle Scholar
  54. 54.
    Rehfeld K, Lüders A, Hökelmann A, et al. Dance training is superior to repetitive physical exercise in inducing brain plasticity in the elderly. Buchowski MS, editor. PLoS One 2018;13:e0196636.Google Scholar
  55. 55.
    Mortimer JA, Ding D, Borenstein AR, et al. Changes in brain volume and cognition in a randomized trial of exercise and social interaction in a community-based sample of non-demented Chinese elders. J Alzheimers Dis . 2012;30:757–766.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Liu-Ambrose T. Resistance training and executive functions. Arch Intern Med . 2010;170:170.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Enzinger C, Fazekas F, Matthews PM, et al. Risk factors for progression of brain atrophy in aging: six-year follow-up of normal subjects. Neurology 2005;64:1704–1711.CrossRefPubMedGoogle Scholar
  58. 58.
    Fotenos AF, Snyder AZ, Girton LE, Morris JC, Buckner RL. Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD. Neurology . 2005;64:1032–1039.CrossRefPubMedGoogle Scholar
  59. 59.
    Best JR, Chiu BK, Liang Hsu C, Nagamatsu LS, Liu-Ambrose T. Long-term effects of resistance exercise training on cognition and brain volume in older women: results from a randomized controlled trial. J Int Neuropsychol Soc 2015;21:745–756.CrossRefPubMedGoogle Scholar
  60. 60.
    Voss MW, Heo S, Prakash RS, et al. The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: results of a one-year exercise intervention. Hum Brain Mapp 2012;34:2972–2985.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Niemann C, Godde B, Voelcker-Rehage C. Not only cardiovascular, but also coordinative exercise increases hippocampal volume in older adults. Front Aging Neurosci 2014;6:1–24.CrossRefGoogle Scholar
  62. 62.
    Burgess N, Maguire EA, O’Keefe J. The human hippocampus and spatial and episodic memory. Neuron 2002;35:625–641.CrossRefPubMedGoogle Scholar
  63. 63.
    Rosano C, Guralnik J, Pahor M, et al. Hippocampal response to a 24-month physical activity intervention in sedentary older adults. Am J Geriatr Psychiatry 2017;25:209–217.CrossRefPubMedGoogle Scholar
  64. 64.
    Thomas C, Moya L, Avidan G, et al. Reduction in white matter connectivity, revealed by diffusion tensor imaging, may account for age-related changes in face perception. J Cogn Neurosci 2008;20:268–284.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Grady CL, McIntosh AR, Craik FIM. Age-related differences in the functional connectivity of the hippocampus during memory encoding. Hippocampus 2003;13:572–586.CrossRefPubMedGoogle Scholar
  66. 66.
    Dennis NA, Hayes SM, Prince SE, Madden DJ, Huettel SA, Cabeza R. Effects of aging on the neural correlates of successful item and source memory encoding. J Exp Psychol Learn Mem Cogn 2008;34:791–808.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Pudas S, Josefsson M, Rieckmann A, Nyberg L. Longitudinal evidence for increased functional response in frontal cortex for older adults with hippocampal atrophy and memory decline. Cereb Cortex 2017;936–948.Google Scholar
  68. 68.
    Smith JC, Nielson K A, Woodard JL, Seidenberg M, Rao SM. Physical activity and brain function in older adults at increased risk for Alzheimer’s disease. Brain Sci 2013;3:54–83.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Stevens FL, Hurley RA, Taber KH. Anterior cingulate cortex: unique role in cognition and emotion. J Neuropsychiatry Clin Neurosci 2011;23:121–125.CrossRefPubMedGoogle Scholar
  70. 70.
    Colcombe SJ, Kramer AF, Erickson KI, et al. Cardiovascular fitness, cortical plasticity, and aging. Proc Natl Acad Sci 2004;101:3316–3321.CrossRefPubMedGoogle Scholar
  71. 71.
    Voss MW, Prakash RS, Erickson KI, et al. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci 2010;2:1–17.Google Scholar
  72. 72.
    Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network. Ann N Y Acad Sci 2008;1124:1–38.CrossRefPubMedGoogle Scholar
  73. 73.
    Dosenbach NUF, Visscher KM, Palmer ED, et al. A core system for the implementation of task sets. Neuron 2006;50:799–812.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Voelcker-Rehage C, Godde B, Staudinger UM. Cardiovascular and coordination training differentially improve cognitive performance and neural processing in older adults. Front Hum Neurosci 2011;5:1–12.CrossRefGoogle Scholar
  75. 75.
    van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999;2:266–270.CrossRefPubMedGoogle Scholar
  76. 76.
    Pereira AC, Huddleston DE, Brickman AM, et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. PNAS 2007;104.Google Scholar
  77. 77.
    Huang Y-Q, Wu C, He X-F, et al. Effects of voluntary wheel-running types on hippocampal neurogenesis and spatial cognition in middle-aged mice. Front Cell Neurosci 2018;12:1–9.Google Scholar
  78. 78.
    Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, Kempermann G. Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging 2006;27:1505–1513.CrossRefPubMedGoogle Scholar
  79. 79.
    van Praag H. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 2005;25:8680–8685.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Gibbons TE, Pence BD, Petr G, et al. Voluntary wheel running, but not a diet containing (−)-epigallocatechin-3-gallate and β-alanine, improves learning, memory and hippocampal neurogenesis in aged mice. Behav Brain Res . 2014;272:131–140.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Kannangara TS, Lucero MJ, Gil-Mohapel J, et al. Running reduces stress and enhances cell genesis in aged mice. Neurobiol Aging 2011;32:2279–2286.CrossRefPubMedGoogle Scholar
  82. 82.
    Creer DJ, Romberg C, Saksida LM, van Praag H, Bussey TJ. Running enhances spatial pattern separation in mice. Proc Natl Acad Sci 2010;107:2367–2372.CrossRefPubMedGoogle Scholar
  83. 83.
    Blackmore DG, Golmohammadi MG, Large B, Waters MJ, Rietze RL. Exercise increases neural stem cell number in a growth hormone-dependent manner, augmenting the regenerative response in aged mice. Stem Cells 2009;27:2044–2052.CrossRefPubMedGoogle Scholar
  84. 84.
    Itou Y, Nochi R, Kuribayashi H, Saito Y, Hisatsune T. Cholinergic activation of hippocampal neural stem cells in aged dentate gyrus. Hippocampus 2011;21:446–459.CrossRefPubMedGoogle Scholar
  85. 85.
    Jessop P, Toledo-Rodriguez M. Hippocampal TET1 and TET2 expression and DNA hydroxymethylation are affected by physical exercise in aged mice. Front Cell Dev Biol . 2018;6:1–9.CrossRefGoogle Scholar
  86. 86.
    Littlefield AM, Setti SE, Priester C, Kohman RA. Voluntary exercise attenuates LPS-induced reductions in neurogenesis and increases microglia expression of a proneurogenic phenotype in aged mice. J Neuroinflammation 2015;12:1–12.CrossRefGoogle Scholar
  87. 87.
    Kohman RA, DeYoung EK, Bhattacharya TK, Peterson LN, Rhodes JS. Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice. Brain Behav Immun 2012;26:803–810.CrossRefPubMedGoogle Scholar
  88. 88.
    Canas PM, Duarte JMN, Rodrigues RJ, Köfalvi A, Cunha RA. Modification upon aging of the density of presynaptic modulation systems in the hippocampus. Neurobiol Aging 2009;30:1877–1884.CrossRefPubMedGoogle Scholar
  89. 89.
    Nichol K, Deeny SP, Seif J, Camaclang K, Cotman CW. Exercise improves cognition and hippocampal plasticity in APOE ε4 mice. Alz Dement 2009;5:287–294.CrossRefGoogle Scholar
  90. 90.
    Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WT. Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats (paramedian lobule/neural plasticity/exercise). Proc Natl Acad Sci USA 1990;87:5568–5572.CrossRefPubMedGoogle Scholar
  91. 91.
    Boldrini M, Fulmore CA, Tartt AN, et al. Human hippocampal neurogenesis persists throughout Aging Cell Stem Cell 2018;22:589–599.e5.CrossRefPubMedGoogle Scholar
  92. 92.
    Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 2004;20:2580–2590.CrossRefPubMedGoogle Scholar
  93. 93.
    Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F. Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function. Neuroscience 2006;140:823–833.CrossRefPubMedGoogle Scholar
  94. 94.
    Ding Y-H, Li J, Zhou Y, Rafols J, Clark J, Ding Y. Cerebral angiogenesis and expression of angiogenic factors in aging rats after exercise. Curr Neurovasc Res 2006;3:15–23.CrossRefPubMedGoogle Scholar
  95. 95.
    Fabel K, Fabel K, Tam B, et al. VEGF is necessary for exercise-induced adult hippocampal neurogensis. Eur J Neurosci 2003;18:2803–2812.CrossRefPubMedGoogle Scholar
  96. 96.
    Vanzella C, Neves JD, Vizuete AF, et al. Treadmill running prevents age-related memory deficit and alters neurotrophic factors and oxidative damage in the hippocampus of Wistar rats. Behav Brain Res 2017;334:78–85.CrossRefPubMedGoogle Scholar
  97. 97.
    Vilela TC, Muller AP, Damiani AP, et al. Strength and aerobic exercises improve spatial memory in aging rats through stimulating distinct neuroplasticity mechanisms. Mol Neurobiol 2017;54:7928–7937.CrossRefPubMedGoogle Scholar
  98. 98.
    Levinger I, Goodman C, Matthews V, et al. BDNF, metabolic risk factors, and resistance training in middle-aged individuals. Med Sci Sport Exerc 2008;40:535–541.CrossRefGoogle Scholar
  99. 99.
    Coelho FM, Pereira DS, Lustosa LP, et al. 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.CrossRefPubMedGoogle Scholar
  100. 100.
    Ruiz JR, Gil-Bea F, Bustamante-Ara N, et al. Resistance training does not have an effect on cognition or related serum biomarkers in nonagenarians: a randomized controlled trial. Int J Sports Med 2015;36:54–60.PubMedGoogle Scholar
  101. 101.
    Forti LN, Van Roie E, Njemini R, et al. Dose- and gender-specific effects of resistance training on circulating levels of brain derived neurotrophic factor (BDNF) in community-dwelling older adults. Exp Gerontol 2015;70:144–149.CrossRefPubMedGoogle Scholar
  102. 102.
    Forti LN, Njemini R, Beyer I, et al. Strength training reduces circulating interleukin-6 but not brain-derived neurotrophic factor in community-dwelling elderly individuals. Age (Omaha) 2014;36:9704.CrossRefGoogle Scholar
  103. 103.
    Prestes J, da Cunha Nascimento D, Tibana RA, et al. Understanding the individual responsiveness to resistance training periodization. Age (Omaha) 2015;37:55.CrossRefGoogle Scholar
  104. 104.
    Hvid LG, Nielsen MKF, Simonsen C, Andersen M, Caserotti P. Brain-derived neurotrophic factor (BDNF) serum basal levels is not affected by power training in mobility-limited older adults—a randomized controlled trial. Exp Gerontol 2017;93:29–35.CrossRefPubMedGoogle Scholar
  105. 105.
    Kim H, Suzuki T, Kim M, et al. Effects of exercise and milk fat globule membrane (MFGM) supplementation on body composition, physical function, and hematological parameters in community-dwelling frail Japanese women: a randomized double blind, placebo-controlled, follow-up trial. Buchowski M, editor. PLoS One. 2015;10:e0116256.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Vedovelli K, Giacobbo BL, Corrêa MS, Wieck A, Argimon II de L, Bromberg E. Multimodal physical activity increases brain-derived neurotrophic factor levels and improves cognition in institutionalized older women. GeroScience 2017;39:407–417.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Vaughan S, Wallis M, Polit D, Steele M, Shum D, Morris N. The effects of multimodal exercise on cognitive and physical functioning and brain-derived neurotrophic factor in older women: a randomised controlled trial. Age Ageing 2014;43:623–629.CrossRefPubMedGoogle Scholar
  108. 108.
    Baker LD, Frank LL, Foster-Schubert K, et al. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer’s disease. J Alzheimers Dis 2010;22:569–579.CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Voss MW, Erickson KI, Prakash RS, Chaddock L, Kim JS, Alves H, et al. Neurobiological markers of exercise-related brain plasticity in older adults. Brain Behav Immun 2013;28:90–99.CrossRefPubMedGoogle Scholar
  110. 110.
    Lommatzsch M, Virchow JC, Zingler D, et al. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 2004;26:115–123.CrossRefGoogle Scholar
  111. 111.
    Seo D-I, Jun T-W, Park K-S, Chang H, So W-Y, Song W. 12 weeks of combined exercise is better than aerobic exercise for increasing growth hormone in middle-aged women. Int J Sport Nutr Exerc Metab 2010;20:21–26.CrossRefPubMedGoogle Scholar
  112. 112.
    Vale RG, de Oliveira RD, Pernambuco CS, de Meneses YP, Novaes Jda S, Andrade Ade F. Effects of muscle strength and aerobic training on basal serum levels of IGF-1 and cortisol in elderly women Arch Gerontol Geriatr 2009;49:343–7.CrossRefPubMedGoogle Scholar
  113. 113.
    Banitalebi E, Faramarzi M, Bagheri L, Kazemi AR. Comparison of performing 12 weeks’ resistance training before, after and/or in between aerobic exercise on the hormonal status of aged women: a randomized controlled trial. Horm Mol Biol Clin Investig 2018;35:1–10.Google Scholar
  114. 114.
    Ogawa K, Sanada K, MacHida S, Okutsu M, Suzuki K. Resistance exercise training-induced muscle hypertrophy was associated with reduction of inflammatory markers in elderly women. Mediators Inflamm. 2010.Google Scholar
  115. 115.
    Kim H, Suzuki T, Kim M, et al. Effects of exercise and milk fat globule membrane (MFGM) supplementation on body composition, physical function, and hematological parameters in community-dwelling frail Japanese women: a randomized double blind, placebo-controlled, follow-up trial. PLoS One 2015;10:e0116256.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Cassilhas RC, Viana VAR, Grassmann V, et al. The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exerc 2007;39:1401–1407.CrossRefPubMedGoogle Scholar
  117. 117.
    Hofmann M, Schober-Halper B, Oesen S, et al. Effects of elastic band resistance training and nutritional supplementation on muscle quality and circulating muscle growth and degradation factors of institutionalized elderly women: the Vienna Active Ageing Study (VAAS). Eur J Appl Physiol 2016;116:885–897.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Mason C, Xiao L, Duggan C, et al. Effects of dietary weight loss and exercise on insulin-like growth factor-i and insulin-like growth factor-binding protein-3 in postmenopausal women: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 2013;22:1457–1463.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Tsai C-L, Wang C-H, Pan C-Y, Chen F-C. The effects of long-term resistance exercise on the relationship between neurocognitive performance and GH, IGF-1, and homocysteine levels in the elderly. Front Behav Neurosci 2015;9:1–12.Google Scholar
  120. 120.
    Ylikoski R, Ylikoski A, Raininko R, et al. Cardiovascular diseases, health status, brain imaging findings and neuropsychological functioning in neurologically healthy elderly individuals. Arch Gerontol Geriatr 2000;30.Google Scholar
  121. 121.
    Nwankwo T, Sug S, Yoon S, Burt V, Gu Q. Data from the National Health and Nutrition Examination Survey. 2011.Google Scholar
  122. 122.
    CDC. National Diabetes Statistics Report, 2017 Estimates of Diabetes and Its Burden in the United States Background. 2017.Google Scholar
  123. 123.
    Gorelick PB, Furie KL, Iadecola C, et al. Defining optimal brain health in adults: a presidential advisory from the American Heart Association/American Stroke Association. Stroke 2017;48.Google Scholar
  124. 124.
    Bouchard C, An P, Rice T, et al. Familial aggregation of VO (2max) response to exercise training: results from the HERITAGE Family Study. J Appl Physiol. 1999;87:1003–1008.CrossRefPubMedGoogle Scholar
  125. 125.
    Trigiani LJ, Hamel E. An endothelial link between the benefits of physical exercise in dementia. 2017;37:2649–2664.Google Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  1. 1.Department of Physical TherapyUniversity of Miami Miller School of MedicineCoral GablesUSA
  2. 2.Evelyn McKnight Brain InstituteUniversity of Miami Miller School of MedicineMiamiUSA
  3. 3.Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of NeurologyBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  4. 4.Department of NeurologyUniversity of Miami Miller School of MedicineMiamiUSA

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