, Volume 39, Issue 4, pp 407–417 | Cite as

Multimodal physical activity increases brain-derived neurotrophic factor levels and improves cognition in institutionalized older women

  • Kelem Vedovelli
  • Bruno Lima Giacobbo
  • Márcio Silveira Corrêa
  • Andréa Wieck
  • Irani Iracema de Lima Argimon
  • Elke BrombergEmail author
Original Article


Physical activity has been proposed as a promising intervention to improve cognition and decrease the risk of dementia in older adults. Brain-derived neurotrophic factor (BDNF) appears to mediate, at least partially, these effects of exercise. However, intervention studies of the effects of multimodal exercises on cognition and BDNF levels are scarce and composed by small samples. Thus, the generalization of the conclusions of these studies depends on the reproducibility of the results. In order to contribute to the knowledge on the field, the present study evaluated the effects of a physical activity intervention composed by muscle strengthening and aerobic conditioning on BDNF levels and cognition in older women. Independent and non-demented subjects (≥75 years) were assigned to a 3-month physical activity intervention (n = 22, 60 min exercise sessions three times a week) or to a control condition (n = 10, no exercise). Clinical (anxiety and depression symptoms), neuropsychological (Digit Span, Stroop, Trail Making, and Contextual Memory tests), physical (upper and lower limb strength, aerobic conditioning), and physiological (serum BDNF) parameters were evaluated immediately before, 1 month, and 3 months after starting intervention. Results indicated that controls had stable levels for all measured variables, whereas the intervention group improved on physical fitness, depressive symptoms, cognitive performance, and BDNF levels. Moreover, a linear regression identified an association between aerobic conditioning and BDNF levels. In conclusion, combined muscle strengthening and aerobic conditioning was able to improve cognitive performance and increase BDNF levels. Aerobic conditioning seems to be an important mediator of these outcomes.


BDNF Physical activity Depression symptom Cognitive performance 



E. Bromberg and I.I.L. Argimon are National Counsel of Technological and Scientific Development (CNPq) research fellows. K. Vedovelli has a Research Support Foundation of Rio Grande do Sul (FAPERGS)/Coordination for the Improvement of Higher Education Personnel (CAPES) fellowship, and B.L. Giacobbo, M.S. Corrêa, and A. Wieck have a CAPES fellowship.

Compliance with ethical standards

The study was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and approved by the Research and Ethics Committee of Pontifical Catholic University, Porto Alegre, Brazil. All participants gave their written informed consent.


  1. Archer T, Josefsson T, Lindwall M (2014) Effects of physical exercise on depressive symptoms and biomarkers in depression. CNS Neurol Disord Drug Targets 13(10):1640–1653CrossRefPubMedGoogle Scholar
  2. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A et al (2010a) Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer’s disease. J Alzheimers Dis 22:569–579. doi: 10.3233/jad-2010-100768 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A et al (2010b) Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol 67:71–79. doi: 10.1001/archneurol.2009.307 PubMedPubMedCentralGoogle Scholar
  4. Baltzopoulos V, Brodie DA (1989) Isokinetic dynamometry. Applications and limitations. Sports Med (Auckland, NZ) 8(2):101–116CrossRefGoogle Scholar
  5. Barulli D, Stern Y (2013) Efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in cognitive reserve. Trends Cogn Sci 17(10):502–509. doi: 10.1016/j.tics.2013.08.012 CrossRefPubMedGoogle Scholar
  6. Bean JF, Kiely DK, Leveille SG, Herman S, Huynh C, Fielding R, Frontera W (2002) The 6-minute walk test in mobility-limited elders: what is being measured? J Gerontol A Biol Sci Med Sci 57:M751–M756CrossRefPubMedGoogle Scholar
  7. Beeri MS, Sonnen J (2016) Brain BDNF expression as a biomarker for cognitive reserve against Alzheimer disease progression. Neurology. United States. doi: 10.1212/WNL.0000000000002389
  8. Bekinschtein P, Cammarota M, Izquierdo I, Medina JH (2008) BDNF and memory formation and storage. Neurosci Rev J Bringing Neurobiol Neurol Psychiatr 14(2):147–156. doi: 10.1177/1073858407305850 Google Scholar
  9. Bertolucci PH, Brucki SM, Campacci SR, Juliano Y (1994) The Mini-Mental State Examination in a general population: impact of educational status. Arq Neuropsiquiatr 52(1):1–7CrossRefPubMedGoogle Scholar
  10. Blair SN, Dowda M, Pate RR, Kronenfeld J, Howe HGJ, Parker G et al (1991) Reliability of long-term recall of participation in physical activity by middle-aged men and women. Am J Epidemiol 133(3):266–275CrossRefPubMedGoogle Scholar
  11. Bus BAA, Molendijk ML, Penninx BJWH, Buitelaar JK, Kenis G, Prickaerts J et al (2011) Determinants of serum brain-derived neurotrophic factor. Psychoneuroendocrinology 36(2):228–239. doi: 10.1016/j.psyneuen.2010.07.013 CrossRefPubMedGoogle Scholar
  12. Bus BAA, Tendolkar I, Franke B, de Graaf J, den Heijer M, Buitelaar JK, Oude Voshaar RC (2012) Serum brain-derived neurotrophic factor: determinants and relationship with depressive symptoms in a community population of middle-aged and elderly people. World J Biol Psychiatr Off J World Fed Soc Biol Psychiatr 13(1):39–47. doi: 10.3109/15622975.2010.545187 CrossRefGoogle Scholar
  13. Carlino D, De Vanna M, Tongiorgi E (2013) Is altered BDNF biosynthesis a general feature in patients with cognitive dysfunctions? Neurosci Rev J Bringing Neurobiol Neurol Psychiatr 19(4):345–353. doi: 10.1177/1073858412469444 Google Scholar
  14. Carvalho A, Rea IM, Parimon T, Cusack BJ (2014) Physical activity and cognitive function in individuals over 60 years of age: a systematic review. Clin Interv Aging 9:661–682. doi: 10.2147/CIA.S55520 PubMedPubMedCentralGoogle Scholar
  15. Chan KL, Tong KY, Yip SP (2008) Relationship of serum brain-derived neurotrophic factor (BDNF) and health-related lifestyle in healthy human subjects. Neurosci Lett 447(2–3):124–128. doi: 10.1016/j.neulet.2008.10.013 CrossRefPubMedGoogle Scholar
  16. Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA, Minson CT, Nigg CR, Salem GJ, Skinner JS (2009) American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc 41(7):1510–1530. doi: 10.1249/MSS.0b013e3181a0c95c CrossRefPubMedGoogle Scholar
  17. Coelho FG, Gobbi S, Andreatto CA, Corazza DI, Pedroso RV, Santos-Galduroz RF (2013) Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr 56:10–15. doi: 10.1016/j.archger.2012.06.003 CrossRefPubMedGoogle Scholar
  18. Colcombe S, Kramer AF (2003) Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 14:125–130CrossRefPubMedGoogle Scholar
  19. Correa MS, Vedovelli K, Giacobbo BL, de Souza CEB, Ferrari P, de Lima Argimon II et al (2015) Psychophysiological correlates of cognitive deficits in family caregivers of patients with Alzheimer disease. Neuroscience 286:371–382. doi: 10.1016/j.neuroscience.2014.11.052 CrossRefPubMedGoogle Scholar
  20. Cunha JA (2011) Escalas Beck—manual, 1st edn. Casa do Psicólogo, São PauloGoogle Scholar
  21. Desjardins-Crepeau L, Berryman N, Fraser SA, Vu TTM, Kergoat M-J, Li KZ et al (2016) Effects of combined physical and cognitive training on fitness and neuropsychological outcomes in healthy older adults. Clin Interv Aging 11:1287–1299CrossRefPubMedPubMedCentralGoogle Scholar
  22. Erickson KI, Prakash RS, Voss MW, Chaddock L, Heo S, McLaren M et al (2010) Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume. J Neurosci Off J Soc Neurosci 30(15):5368–5375. doi: 10.1523/JNEUROSCI.6251-09.2010 CrossRefGoogle Scholar
  23. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L et al (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 108(7):3017–3022. doi: 10.1073/pnas.1015950108 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Erickson KI, Miller DL, Roecklein KA (2012) The aging hippocampus: interactions between exercise, depression, and BDNF. Neurosci Rev J Bringing Neurobiol Neurol Psychiatr 18(1):82–97. doi: 10.1177/1073858410397054 Google Scholar
  25. Fleg JL (2002) Can exercise conditioning be effective in older heart failure patients? Heart Fail Rev 7(1):99–103CrossRefPubMedGoogle Scholar
  26. Floel A, Ruscheweyh R, Kruger K, Willemer C, Winter B, Volker K et al (2010) Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link? NeuroImage 49:2756–2763. doi: 10.1016/j.neuroimage.2009.10.043 CrossRefPubMedGoogle Scholar
  27. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMedGoogle Scholar
  28. Gunstad J, Benitez A, Smith J, Glickman E, Spitznagel MB, Alexander T et al (2008) Serum brain-derived neurotrophic factor is associated with cognitive function in healthy older adults. J Geriatr Psychiatry Neurol 21:166–170. doi: 10.1177/0891988708316860 CrossRefPubMedGoogle Scholar
  29. Jaureguizar KV, Vicente-Campos D, Bautista LR, de la Pena CH, Gomez MJA, Rueda MJC, Fernandez Mahillo I (2016) Effect of high-intensity interval versus continuous exercise training on functional capacity and quality of life in patients with coronary artery disease: a randomized clinical trial. J Cardiopulm Rehabil Prev 36(2):96–105. doi: 10.1097/HCR.0000000000000156 CrossRefPubMedGoogle Scholar
  30. Jones CJ, Rikli RE, Beam WC (1999) A 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Res Q Exerc Sport 70:113–119CrossRefPubMedGoogle Scholar
  31. Kern H, Hofer C, Modlin M, Forstner C, Raschka-Hogler D, Mayr W, Stohr H (2002) Denervated muscles in humans: limitations and problems of currently used functional electrical stimulation training protocols. Artif Organs 26(3):216–218CrossRefPubMedGoogle Scholar
  32. Leal G, Bramham CRR, Duarte CBB (2017) BDNF and hippocampal synaptic plasticity. Vitam Horm 104:153–195. doi: 10.1016/bs.vh.2016.10.004 CrossRefPubMedGoogle Scholar
  33. Lee Y, Kim J, Han ES, Chae S, Ryu M, Ahn KH, Park EJ (2015) Changes in physical activity and cognitive decline in older adults living in the community. Age (Dordr) 37(2):20. doi: 10.1007/s11357-015-9759-z CrossRefGoogle Scholar
  34. Lista I, Sorrentino G (2010) Biological mechanisms of physical activity in preventing cognitive decline. Cell Mol Neurobiol 30:493–503. doi: 10.1007/s10571-009-9488-x CrossRefPubMedGoogle Scholar
  35. Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, Virchow JC (2005) The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 26(1):115–123. doi: 10.1016/j.neurobiolaging. 2004.03.002 CrossRefPubMedGoogle Scholar
  36. Lustosa LP, Silva JP, Coelho FM, Pereira DS, Parentoni AN, Pereira LSM (2011) Impact of resistance exercise program on functional capacity and muscular strength of knee extensor in pre-frail community-dwelling older women: a randomized crossover trial. Revista Brasileira de Fisioterapia (Sao Carlos (Sao Paulo, Brazil)) 15(4):318–324CrossRefGoogle Scholar
  37. Martinowich K, Manji H, Lu B (2007) New insights into BDNF function in depression and anxiety. Nat Neurosci 10:1089–1093. doi: 10.1038/nn1971 CrossRefPubMedGoogle Scholar
  38. Nascimento CMC, Pereira JR, de Andrade LP, Garuffi M, Talib LL, Forlenza OV et al (2014) Physical exercise in MCI elderly promotes reduction of pro-inflammatory cytokines and improvements on cognition and BDNF peripheral levels. Curr Alzheimer Res 11(8):799–805CrossRefPubMedGoogle Scholar
  39. Neeper SA, Gomez-Pinilla F, Choi J, Cotman C (1995) Exercise and brain neurotrophins. Nature. England. doi: 10.1038/373109a0
  40. Novkovic T, Mittmann T, Manahan-Vaughan D (2015) BDNF contributes to the facilitation of hippocampal synaptic plasticity and learning enabled by environmental enrichment. Hippocampus 25(1):1–15. doi: 10.1002/hipo.22342 CrossRefPubMedGoogle Scholar
  41. O’Bryant SE, Hobson VL, Hall JR, Barber RC, Zhang S, Johnson L et al, Texas Alzheimer’s Res C (2011) Serum brain-derived neurotrophic factor levels are specifically associated with memory performance among Alzheimer’s disease cases. Dement Geriatr Cogn Disord 31:31–36. doi: 10.1159/000321980
  42. Pahor M, Guralnik JM, Ambrosius WT, Blair S, Bonds DE, Church TS et al (2014) Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA 311(23):2387–2396. doi: 10.1001/jama.2014.5616 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Park H, Poo M (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14(1):7–23. doi: 10.1038/nrn3379 CrossRefPubMedGoogle Scholar
  44. Pereira DS, de Queiroz BZ, Miranda AS, Rocha NP, Felicio DC, Mateo EC et al (2013) Effects of physical exercise on plasma levels of brain-derived neurotrophic factor and depressive symptoms in elderly women—a randomized clinical trial. Arch Phys Med Rehabil 94:1443–1450. doi: 10.1016/j.apmr.2013.03.029 CrossRefPubMedGoogle Scholar
  45. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimer’s Dement J Alzheimer’s Assoc 9(1):63–75.e2. doi: 10.1016/j.jalz.2012.11.007 CrossRefGoogle Scholar
  46. Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E et al (2009) Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 94:1062–1069. doi: 10.1113/expphysiol.2009.048512 CrossRefPubMedGoogle Scholar
  47. Rosas-Vargas H, Martinez-Ezquerro JD, Bienvenu T (2011) Brain-derived neurotrophic factor, food intake regulation, and obesity. Arch Med Res 42(6):482–494. doi: 10.1016/j.arcmed.2011.09.005 CrossRefPubMedGoogle Scholar
  48. Solway S, Brooks D, Lacasse Y, Thomas S (2001) A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest 119:256–270CrossRefPubMedGoogle Scholar
  49. Strait JBJ, Lakatta EEG (2012) Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 8(1):143–164. doi: 10.1016/j.hfc.2011.08.011.Aging-associated CrossRefPubMedPubMedCentralGoogle Scholar
  50. Strath SJ, Swartz AM, Bassett DRJ, O’Brien WL, King GA, Ainsworth BE (2000) Evaluation of heart rate as a method for assessing moderate intensity physical activity. Med Sci Sports Exerc 32(9 Suppl):S465–S470CrossRefPubMedGoogle Scholar
  51. Strauss E, Spreen O, Sherman EMS (2006) A Compendium of Neuropsychological Tests: Administration, Norms, And Commentary. 3rd ed. Oxford University Press, editor, New York, p 1216Google Scholar
  52. Suzuki T, Shimada H, Makizako H, Doi T, Yoshida D, Ito K et al (2013) A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment. PLoS One 8(4):e61483. doi: 10.1371/journal.pone.0061483 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Tadjibaev P, Frolova E, Gurina N, Degryse J, Vaes B (2014) The relationship between physical performance and cardiac function in an elderly Russian cohort. Arch Gerontol Geriatr 59(3):554–561. doi: 10.1016/j.archger.2014.08.003 CrossRefPubMedGoogle Scholar
  54. Tarazona-Santabalbina FJ, Gomez-Cabrera MC, Perez-Ros P, Martinez-Arnau FM, Cabo H, Tsaparas K et al (2016) A multicomponent exercise intervention that reverses frailty and improves cognition, emotion, and social networking in the community-dwelling frail elderly: a randomized clinical trial. J Am Med Dir Assoc 17(5):426–433. doi: 10.1016/j.jamda.2016.01.019 CrossRefPubMedGoogle Scholar
  55. Vaes B, Rezzoug N, Pasquet A, Wallemacq P, Van Pottelbergh G, Mathei C et al (2012) The prevalence of cardiac dysfunction and the correlation with poor functioning among the very elderly. Int J Cardiol 155(1):134–143. doi: 10.1016/j.ijcard.2011.07.024 CrossRefPubMedGoogle Scholar
  56. Van der Bij AK, Laurant MGH, Wensing M (2002) Effectiveness of physical activity interventions for older adults: a review. Am J Prev Med 22(2):120–133CrossRefPubMedGoogle Scholar
  57. Vaughan S, Wallis M, Polit D, Steele M, Shum D, Morris N (2014) The effects of multimodal exercise on cognitive and physical functioning and brain-derived neurotrophic factor in older women: a randomised controlled trial. Age Ageing 43(5):623–629. doi: 10.1093/ageing/afu010 CrossRefPubMedGoogle Scholar
  58. Vaynman S, Ying Z, Gomez-Pinilla F (2004) Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20:2580–2590. doi: 10.1111/j.1460-9568.2004.03720.x CrossRefPubMedGoogle Scholar
  59. Volpi E, Nazemi R, Fujita S (2004) Muscle tissue changes with aging. Curr Opin Clin Nutr Metab Care 7(4):405–410CrossRefPubMedPubMedCentralGoogle Scholar
  60. Ward DD, Summers MJ, Saunders NL, Ritchie K, Summers JJ, Vickers JC (2015) The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function. Transl Psychiatry 5:e590. doi: 10.1038/tp.2015.82 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Watanabe Y, Madarame H, Ogasawara R, Nakazato K, Ishii N (2014) Effect of very low-intensity resistance training with slow movement on muscle size and strength in healthy older adults. Clin Physiol Funct Imaging 34(6):463–470. doi: 10.1111/cpf.12117 CrossRefPubMedGoogle Scholar
  62. Wechsler D (1987) Manual for the Wechsler Memory Scale—revised. The psychological CorporationGoogle Scholar
  63. Wechsler D (1997) WAIS III: Administration and Scoring Manual. Harcourt, editor. San Antonio, TXGoogle Scholar
  64. Wei Z, Liao J, Qi F, Meng Z, Pan S (2015) Evidence for the contribution of BDNF-TrkB signal strength in neurogenesis: an organotypic study. Neurosci Lett 606:48–52. doi: 10.1016/j.neulet.2015.08.032 CrossRefPubMedGoogle Scholar
  65. Wolfson L, Judge J, Whipple R, King M (1995) Strength is a major factor in balance, gait, and the occurrence of falls. J Gerontol A Biol Sci Med Sci 50 Spec No:64–67PubMedGoogle Scholar

Copyright information

© American Aging Association 2017

Authors and Affiliations

  1. 1.Laboratory of Biology and Development of the Nervous System, Faculty of BiosciencesPontifical Catholic University of Rio Grande do SulPorto AlegreBrazil
  2. 2.Graduate Program in Biomedical GerontologyPontifical Catholic University of Rio Grande do SulPorto AlegreBrazil
  3. 3.National Institute for Translational Medicine (INCT-TM)Porto AlegreBrazil
  4. 4.Graduate Program in Cellular and Molecular BiologyPontifical Catholic University of Rio Grande do SulPorto AlegreBrazil
  5. 5.Laboratory of Immunosenescence, Institute of Biomedical ResearchPontifical Catholic University of Rio Grande do SulPorto AlegreBrazil

Personalised recommendations