Born to move: a review on the impact of physical exercise on brain health and the evidence from human controlled trials

Vorkapic, Camila; Leal, Silvânia; Alves, Heloisa; Douglas, Michael; Britto, André; Dantas, Estélio Henrique Martin

doi:10.1590/0004-282X-ANP-2020-0166

Camila Vorkapic Correspondence: Camila Vorkapic; E-mail: camilavorkapic@gmail.com.

Universidade Tiradentes, Departamento de Medicina, Laboratório de Biociências da Cinética Humana, Aracaju SE, Brazil.

http://orcid.org/0000-0002-0809-3964

Silvânia Leal

Universidade Federal do Estado do Rio de Janeiro, Laboratório de Biociências da Cinética Humana, Rio de Janeiro RJ, Brazil.

http://orcid.org/0000-0003-0473-7205

Heloisa Alves

University of Massachusetts, Department of Psychology, Dartmouth MA, United States.

http://orcid.org/0000-0002-6102-7616

Michael Douglas

Universidade Tiradentes, Departamento de Medicina, Laboratório de Biociências da Cinética Humana, Aracaju SE, Brazil.

http://orcid.org/0000-0003-2564-1464

André Britto

Universidade Estácio, Departamento de Psicologia, Aracaju SE, Brazil.

http://orcid.org/0000-0002-0106-7210

Estélio Henrique Martin Dantas

Universidade Tiradentes, Departamento de Medicina, Laboratório de Biociências da Cinética Humana, Aracaju SE, Brazil.

http://orcid.org/0000-0003-0981-8020

Correspondence: Camila Vorkapic; E-mail: camilavorkapic@gmail.com.

Conflict of interest: There is no conflict of interest to declare.

Authors’ contributions: CFV: designed and implemented the study, designed the data extraction, carried out data analysis and wrote the manuscript with support from SL, HA and AB. EHMD: helped with data extraction and literature search. EHMD and MD gave support in the interpretation of the data. All authors read and approved the final version.

Study	Selection bias	Study design	Confounders	Blinding	Data collection methods	Withdrawals and drop-outs	Intervention integrity	Analyses	Overall rating Strong: no weak ratings, Moderate: one weak rating, Weak: two or more weak ratings
Nagamatsu et al., 2016³⁴34. Nagamatsu LS, Weinstein AM, Erickson KI, Fanning J, Awick EA, Kramer AF, et al. Exercise mode moderates the relationship between mobility and basal ganglia volume in healthy older adults. J Am Geriatr Soc. 2016 Jan;64(1):102-8. https://doi.org/10.1111/jgs.13882 https://doi.org/10.1111/jgs.13882...	1	1	3	3	1	3	1	1	WEAK
Neimann et al., 2014³⁵35. Niemann C, Godde B, Staudinger UM, Voelcker-Rehage C. Exercise-induced changes in basal ganglia volume and cognition in older adults. Neuroscience. 2014 Dec;281:147-63. https://doi.org/10.1016/j.neuroscience.2014.09.033 https://doi.org/10.1016/j.neuroscience.2...	1	1	3	3	1	3	1	1	WEAK
Best et al., 2015 ²⁶26. 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 Nov;21(10):745-56. https://doi.org/10.1017/S1355617715000673 https://doi.org/10.1017/S135561771500067...	1	1	1	3	1	3	1	1	WEAK
Nocera et al., 2016³⁶36. Nocera J, Crosson B, Mammino K, McGregor KM. Changes in Cortical Activation Patterns in Language Areas following an Aerobic Exercise Intervention in Older Adults. Neural Plast. 2017;2017:6340302. https://doi.org/10.1155/2017/6340302 https://doi.org/10.1155/2017/6340302...	1	1	3	3	1	3	1	1	WEAK
Demiracka et al., 2015²⁷27. Demirakca T, Cardinale V, Dehn S, Ruf M, Ende G. The exercising brain: changes in functional connectivity induced by an integrated multimodal cognitive and whole-body coordination training. Neural Plast. 2015 Dec;2016:8240894. https://doi.org/10.1155/2016/8240894 https://doi.org/10.1155/2016/8240894...	1	1	2	3	1	3	1	1	WEAK
Suwabe et al., 2018³⁸38. Suwabe K, Byun K, Hyodo K, Reagh ZM, Roberts JM, Matsushita A, et al. Rapid stimulation of human dentate gyrus function with acute mild exercise. Proc Proc Natl Acad Sci U S A. 2018 Oct;115(41):10487-92. https://doi.org/10.1073/pnas.1805668115 https://doi.org/10.1073/pnas.1805668115...	1	1	2	3	1	3	1	1	WEAK
Oliveira et al., 2019³⁷37. Oliveira AB, Ribeiro RT, Mello MT, Tufik S, Peres M. Anandamide Is related to clinical and cardiorespiratory benefits of aerobic exercise training in migraine patients: a randomized controlled clinical trial. Cannabis Cannabinoid Res. 2019 Dec;4(4):275-284. https://doi.org/10.1089/can.2018.0057 https://doi.org/10.1089/can.2018.0057...	1	1	2	3	1	3	1	1	WEAK
Church et al., 2016¹⁰10. Church DD, Hoffman JR, Mangine GT, Jajtner AR, Townsend JR, Beyer KS, et al. Comparison of high-intensity vs. high-volume resistance training on the BDNF response to exercise. J Appl Physiol (1985). 2016 Jul;121(1):123-8. https://doi.org/10.1152/japplphysiol.00233.2016 https://doi.org/10.1152/japplphysiol.002...	1	1	2	3	1	3	1	1	WEAK
Hriv et al., 2017²⁹29. 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 Jul;93:29-35. https://doi.org/10.1016/j.exger.2017.03.019 https://doi.org/10.1016/j.exger.2017.03....	1	1	2	3	1	3	1	1	WEAK
Gregoire et al., 2019²⁸28. Grégoire CA, Berryman N, St-Onge F, Vu T, Bosquet L, Arbour N, et al. Gross motor skills training leads to increased brain-derived neurotrophic factor levels in healthy older adults: a pilot study. Front Physiol. 2019 Apr;10:410. https://doi.org/10.3389/fphys.2019.00410 https://doi.org/10.3389/fphys.2019.00410...	1	1	2	3	1	3	1	1	WEAK
Kim J et al., 2018³⁰30. Kim JH, Kim DY. Aquarobic exercises improve the serum blood irisin and brain-derived neurotrophic factor levels in elderly women. Exp Gerontol. 2018 Apr;104:60-5. https://doi.org/10.1016/j.exger.2018.01.024 https://doi.org/10.1016/j.exger.2018.01....	1	1	2	3	1	3	1	1	WEAK
Marston et al., 2019³³33. Marston KJ, Peiffer JJ, Rainey-Smith SR, Gordon N, Teo SY, Laws SM, et al. Resistance training enhances delayed memory in healthy middle-aged and older adults: A randomised controlled trial. J Sci Med Sport. 2019 Nov;22(11):1226-31. https://doi.org/10.1016/j.jsams.2019.06.013 https://doi.org/10.1016/j.jsams.2019.06....	1	1	2	3	1	3	1	1	WEAK
Vaughan et al., 2014¹¹11. 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 Sep;43(5):623-9. https://doi.org/10.1093/ageing/afu010 https://doi.org/10.1093/ageing/afu010...	1	1	2	1	1	3	1	1	WEAK
Forti et al., 2015⁶6. Forti LN, Van Roie E, Njemini R, Coudyzer W, Beyer I, Delecluse C, 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 Oct;70:144-9. https://doi.org/10.1016/j.exger.2015.08.004 https://doi.org/10.1016/j.exger.2015.08....	1	1	2	1	1	3	1	1	WEAK
Magon et al., 2016³²32. Magon S, Donath L, Gaetano L, Thoeni A, Radue EW, Faude O, et al. Striatal functional connectivity changes following specific balance training in elderly people: MRI results of a randomized controlled pilot study. Gait Posture. 2016 Sep;49:334-9. https://doi.org/10.1016/j.gaitpost.2016.07.016 https://doi.org/10.1016/j.gaitpost.2016....	1	1	3	3	1	1	1	1	WEAK
Maddock et al., 2016⁹9. Maddock RJ, Casazza GA, Fernandez DH, Maddock MI. Acute modulation of cortical glutamate and GABA content by physical activity. J Neurosci. 2016 Feb;36(8):2449-57. https://doi.org/10.1523/JNEUROSCI.3455-15.2016 https://doi.org/10.1523/JNEUROSCI.3455-1...	1	1	2	3	1	1	1	1	MODERATE
Matura et al., 2017³¹31. Matura S, Fleckenstein J, Deichmann R, Engeroff T, Füzéki E, Hattingen E, 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 Jul;7(7):e1172. https://doi.org/10.1038/tp.2017.135 https://doi.org/10.1038/tp.2017.135...	1	1	3	1	1	3	1	1	WEAK
Zschucke et al., 2014⁴¹41. Zschucke E, Renneberg B, Dimeo F, Wüstenberg T, Ströhle A. The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback. Psychoneuroendocrinology. 2015 Jan;51:414-25. https://doi.org/10.1016/j.psyneuen.2014.10.019 https://doi.org/10.1016/j.psyneuen.2014....	1	1	3	3	1	3	1	1	WEAK
Tamura et al., 2014³⁹39. Tamura M, Nemoto K, Kawaguchi A, Kato M, Arai T, Kakuma T, et al. Long-term mild-intensity exercise regimen preserves prefrontal cortical volume against aging. Int J Geriatr Psychiatry. 2015 Jul;30(7):686-94. https://doi.org/10.1002/gps.4205 https://doi.org/10.1002/gps.4205...	1	1	1	3	1	3	1	1	WEAK
Wagner et al., 2017¹²12. Wagner G, Herbsleb M, de la Cruz F, Schumann A, Brünner F, Schachtzabel C, et al. Hippocampal structure, metabolism, and inflammatory response after a 6-week intense aerobic exercise in healthy young adults: a controlled trial. J Cereb Blood Flow Metab. 2015 Oct;35(10):1570-8. https://doi.org/10.1038/jcbfm.2015.125 https://doi.org/10.1038/jcbfm.2015.125...	1	1	2	1	1	3	1	1	WEAK
Varma et al., 2015¹⁴14. Varma VR, Chuang YF, Harris GC, Tan EJ, Carlson MC. Low-intensity daily walking activity is associated with hippocampal volume in older adults. Hippocampus. 2015 May;25(5):605-15. https://doi.org/10.1002/hipo.22397 https://doi.org/10.1002/hipo.22397...	1	1	2	1	1	1	1	1	MODERATE
Rosano et al., 2017⁴⁰40. Rosano C, Guralnik J, Pahor M, Glynn NW, Newman AB, Ibrahim TS, et al. Hippocampal Response to a 24-Month Physical Activity Intervention in Sedentary Older Adults. Am J Geriatr Psychiatry. 2017 Mar;25(3):209-17. https://doi.org/10.1016/j.jagp.2016.11.007 https://doi.org/10.1016/j.jagp.2016.11.0...	1	1	2	3	1	1	1	1	MODERATE
Kleemeyer et al., 2015¹³13. Kleemeyer MM, Kühn S, Prindle J, Bodammer NC, Brechtel L, Garthe A, et al. Changes in fitness are associated with changes in hippocampal microstructure and hippocampal volume among older adults. Neuroimage. 2016 May;131:155-61. https://doi.org/10.1016/j.neuroimage.2015.11.026 https://doi.org/10.1016/j.neuroimage.201...	1	1	2	3	1	1	1	1	MODERATE
Kim L et al., 2017¹⁷17. Kim YS, Shin SK, Hong SB, Kim HJ. The effects of strength exercise on hippocampus volume and functional fitness of older women. Exp Gerontol. 2017 Oct;97:22-8. https://doi.org/10.1016/j.exger.2017.07.007 https://doi.org/10.1016/j.exger.2017.07....	1	1	2	3	1	1	1	1	MODERATE

Study	Sample	Intervention	Control condition	Intensity of intervention	Volume and frequency	Duration	Variables of interest	Outcomes
Best et al., 2015 (S1)²⁶26. 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 Nov;21(10):745-56. https://doi.org/10.1017/S1355617715000673 https://doi.org/10.1017/S135561771500067...	n=155	Resistance training	Balance and toning exercises	High	60 min 3x/week	52 weeks	Brain volume, mood and cognition.	1. Resistance training improves memory, reduces cortical white matter atrophy and increases peak muscle power executive function, compared with balance-and-toning. 2. These effects persisted at 2-year follow-up, relative to balance-and-toning.
Church et al., 2016 (S2)¹⁰10. Church DD, Hoffman JR, Mangine GT, Jajtner AR, Townsend JR, Beyer KS, et al. Comparison of high-intensity vs. high-volume resistance training on the BDNF response to exercise. J Appl Physiol (1985). 2016 Jul;121(1):123-8. https://doi.org/10.1152/japplphysiol.00233.2016 https://doi.org/10.1152/japplphysiol.002...	n=20	High-intensity low-volume (HI)	Low-intensity high-volume (HV)	Moderate to high	Duration not informed 4x/week	8 weeks	Plasma BDNF	1. BDNF response is significantly elevated after both high-intensity and high-volume training protocols.
Demirakca et al., 2016 (S3)³⁷37. Oliveira AB, Ribeiro RT, Mello MT, Tufik S, Peres M. Anandamide Is related to clinical and cardiorespiratory benefits of aerobic exercise training in migraine patients: a randomized controlled clinical trial. Cannabis Cannabinoid Res. 2019 Dec;4(4):275-284. https://doi.org/10.1089/can.2018.0057 https://doi.org/10.1089/can.2018.0057...	n=21	Coordination exercises + cognitive training	Rest	n/a	60 min, 1x/week	13 weeks	Functional connectivity (rs-fMRI)	1. Significant connectivity alterations occurred between the visual cortex and parts of the superior parietal area (BA7). Premotor area and cingulate gyrus were also affected.
Forti et al., 2015 (S4⁶6. Forti LN, Van Roie E, Njemini R, Coudyzer W, Beyer I, Delecluse C, 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 Oct;70:144-9. https://doi.org/10.1016/j.exger.2015.08.004 https://doi.org/10.1016/j.exger.2015.08....	n=56	High and low resistance training	Mixed low resistance training	Low and high	Duration not informed 3x/week	12 weeks	Plasma BDNF	1. Only the mixed-low-resistance training program (high number of repetitions at a sufficiently high external resistance) was able to increase circulating BDNF in older male participants. 2. Training to volitional fatigue might be necessary to obtain optimal results.
Gregoire et al., 2019 (S5)²⁸28. Grégoire CA, Berryman N, St-Onge F, Vu T, Bosquet L, Arbour N, et al. Gross motor skills training leads to increased brain-derived neurotrophic factor levels in healthy older adults: a pilot study. Front Physiol. 2019 Apr;10:410. https://doi.org/10.3389/fphys.2019.00410 https://doi.org/10.3389/fphys.2019.00410...	n=34	Lower body strength + aerobic training (LBS-A) and upper body strength + aerobic training (UBS-A)	Gross motor activities (GMA).	Not informed	60 min, 3x/week	8 weeks	Plasma BDNF and cognition	1. All interventions resulted in improved cognitive functions but the GMA intervention induced a larger increase in plasma BDNF concentration (cognition improvement could occur without concomitant detectable changes in BDNF). 2. No correlation was observed between changes in BDNF concentrations and cognitive performances.
Hvid et al., 2017 (S6)²⁹29. 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 Jul;93:29-35. https://doi.org/10.1016/j.exger.2017.03.019 https://doi.org/10.1016/j.exger.2017.03....	n=47	Progressive high-intensity power training	No intervention	Moderate to high	Approx. 45 min, 2x/week	12 weeks	Serum BDNF (mature and total)	1. Baseline systemic levels of serum mBDNF and tBDNF were not affected by exercise training.
Kim L et al., 2017 (S7)¹⁷17. Kim YS, Shin SK, Hong SB, Kim HJ. The effects of strength exercise on hippocampus volume and functional fitness of older women. Exp Gerontol. 2017 Oct;97:22-8. https://doi.org/10.1016/j.exger.2017.07.007 https://doi.org/10.1016/j.exger.2017.07....	n=21	Strength training	No intervention	Moderate	50-60 min, 3x/week	24 weeks	Hippocampus volume	1. Hippocampus volume was significantly increased in the strength exercise group, but decreased in the control group.
Kim J et al., 2018 (S8)³⁰30. Kim JH, Kim DY. Aquarobic exercises improve the serum blood irisin and brain-derived neurotrophic factor levels in elderly women. Exp Gerontol. 2018 Apr;104:60-5. https://doi.org/10.1016/j.exger.2018.01.024 https://doi.org/10.1016/j.exger.2018.01....	n=26	Aquarobic exercise program	Not informed	Moderate	60 min, 2x/week	12 weeks	Plasma BDNF and irisin	1. Significantly higher serum irisin and BDNF levels in the exercise group than in the control group were found. 2. Serum irisin and BDNF levels were significantly higher 30 min after the first exercise session and 30 min after the last exercise session.
Kleemeyer et al., 2015 (S9)¹³13. Kleemeyer MM, Kühn S, Prindle J, Bodammer NC, Brechtel L, Garthe A, et al. Changes in fitness are associated with changes in hippocampal microstructure and hippocampal volume among older adults. Neuroimage. 2016 May;131:155-61. https://doi.org/10.1016/j.neuroimage.2015.11.026 https://doi.org/10.1016/j.neuroimage.201...	n=52	High-intensity aerobic exercise	Low-intensity aerobic exercise	Low-vigorous	25-55 min, 2-3x/week	6 months	Hippocampus volume and microstructure	1. More positive changes in fitness were associated with more positive changes in tissue density and more positive changes in tissue density were associated with more positive changes in volume. 2. Fitness-related changes in hippocampus volume may be brought about by changes in tissue density.
Maddock et al., 2016 (S10)⁹9. Maddock RJ, Casazza GA, Fernandez DH, Maddock MI. Acute modulation of cortical glutamate and GABA content by physical activity. J Neurosci. 2016 Feb;36(8):2449-57. https://doi.org/10.1523/JNEUROSCI.3455-15.2016 https://doi.org/10.1523/JNEUROSCI.3455-1...	n=38	Aerobic exercise	Rest	Vigorous	30 min	Acute	Cortical glutamate and GABA levels (MRS)	1. Results showed that glutamate and GABA signals increased significantly in the visual cortex following exercise. In addition, there was an increase in glutamate following exercise in the anterior cingulate cortex. 2. The results are consistent with an exercise-induced expansion of the cortical pools of glutamate and GABA.
Matura et al., 2017 (S11)³¹31. Matura S, Fleckenstein J, Deichmann R, Engeroff T, Füzéki E, Hattingen E, 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 Jul;7(7):e1172. https://doi.org/10.1038/tp.2017.135 https://doi.org/10.1038/tp.2017.135...	n=53	Aerobic exercise	Waiting list	Moderate	30 min, 3x/week	12 weeks	Brain metabolism, gray matter (GM) volume and cognition.	1. Cerebral choline concentrations remained stable in the exercise group, while increasing in the control group. 2. No effect of training was seen on cerebral N-acetyl aspartate or BDNF levels and no changes in cortical GM volume in response to aerobic exercise. 3. Stable choline concentrations in the intervention group might indicate a neuroprotective effect of aerobic exercise.
Magon et al., 2016 (S12)³²32. Magon S, Donath L, Gaetano L, Thoeni A, Radue EW, Faude O, et al. Striatal functional connectivity changes following specific balance training in elderly people: MRI results of a randomized controlled pilot study. Gait Posture. 2016 Sep;49:334-9. https://doi.org/10.1016/j.gaitpost.2016.07.016 https://doi.org/10.1016/j.gaitpost.2016....	n=28	Slackline training	Educational Sessions	n/a	90 min, 3x/week	6 weeks	Functional connectivity (MRI)	1. MRI analysis did not reveal morphological or functional connectivity differences before or after the training between the intervention and control groups. 2. However, subsequent analysis in subjects with improved slackline performance showed a decrease of connectivity between the striatum and other brain areas during the training period, which means an increased efficiency of the striatal network.
Marston et al., 2019 (S13)³³33. Marston KJ, Peiffer JJ, Rainey-Smith SR, Gordon N, Teo SY, Laws SM, et al. Resistance training enhances delayed memory in healthy middle-aged and older adults: A randomised controlled trial. J Sci Med Sport. 2019 Nov;22(11):1226-31. https://doi.org/10.1016/j.jsams.2019.06.013 https://doi.org/10.1016/j.jsams.2019.06....	n=45	High-load resistance training and moderate-load resistance training	No intervention	Moderate to high	Duration not informed 2x/week	12 weeks	Peripheral growth factors and homocysteine	1. High-load or moderate-load resistance training twice per week for 12 weeks has no effect on peripheral growth factors or homocysteine in healthy late middle-aged adults.
Nagamatsu et al., 2016 (S14)³⁴34. Nagamatsu LS, Weinstein AM, Erickson KI, Fanning J, Awick EA, Kramer AF, et al. Exercise mode moderates the relationship between mobility and basal ganglia volume in healthy older adults. J Am Geriatr Soc. 2016 Jan;64(1):102-8. https://doi.org/10.1111/jgs.13882 https://doi.org/10.1111/jgs.13882...	n=101	Aerobic exercise	Toning exercises	Moderate	40 min, 1x/week	12 months	Mobility and basal ganglion volume	1. In both groups, no differences were observed in the putamen volume regardless of change in mobility. 2. However, those who declined in mobility levels significantly decreased in left putamen volume.
Neimann et al., 2014 (S15)³⁵35. Niemann C, Godde B, Staudinger UM, Voelcker-Rehage C. Exercise-induced changes in basal ganglia volume and cognition in older adults. Neuroscience. 2014 Dec;281:147-63. https://doi.org/10.1016/j.neuroscience.2014.09.033 https://doi.org/10.1016/j.neuroscience.2...	n=92	Aerobic exercise and coordination training	Stretching and relaxation	Moderate	45-60 min, 3x/week	12 months	Basa ganglion volume	1. Motor fitness but not cardiovascular fitness was positively related with the volume of the putamen and the globus pallidus. 2. Coordination training increased caudate and globus pallidus volume.
Nocera et al., 2017 (S16)³⁶36. Nocera J, Crosson B, Mammino K, McGregor KM. Changes in Cortical Activation Patterns in Language Areas following an Aerobic Exercise Intervention in Older Adults. Neural Plast. 2017;2017:6340302. https://doi.org/10.1155/2017/6340302 https://doi.org/10.1155/2017/6340302...	n=32	Aerobic exercise	Balance exercises	Moderate to vigorous	20-45 min, 3x/week	12 weeks	Brain activity during cognitive tasks	1. Cognition (verbal fluency) was improved in the aerobic exercise group, compared with controls. 2. fMRI comparisons of IFG (inferior frontal gyrus) activity showed lower activity in the right IFG following the intervention in the aerobic group, compared with controls.
Oliveira et al., 2019 (S17)³⁷37. Oliveira AB, Ribeiro RT, Mello MT, Tufik S, Peres M. Anandamide Is related to clinical and cardiorespiratory benefits of aerobic exercise training in migraine patients: a randomized controlled clinical trial. Cannabis Cannabinoid Res. 2019 Dec;4(4):275-284. https://doi.org/10.1089/can.2018.0057 https://doi.org/10.1089/can.2018.0057...	n=34	Aerobic exercise	Waiting list	Moderate	40 min, 3x/week	12 weeks	Plasma anandamide (AEA), mood and body weight	1. Regular moderate aerobic exercise reduces plasma AEA levels. 2. This reduction was associated with weight loss and improved mood, in particular, reduced anger.
Suwabe et al., 2018 (S18)³⁸38. Suwabe K, Byun K, Hyodo K, Reagh ZM, Roberts JM, Matsushita A, et al. Rapid stimulation of human dentate gyrus function with acute mild exercise. Proc Proc Natl Acad Sci U S A. 2018 Oct;115(41):10487-92. https://doi.org/10.1073/pnas.1805668115 https://doi.org/10.1073/pnas.1805668115...	n=36	Aerobic exercise	Rest	Low	10 min	Acute	Functional connectivity during cognitive task	1. A single 10-min bout of exercise increased functional connectivity between hippocampus DG/CA3 and cortical regions. 2. The magnitude of the enhanced functional connectivity predicted the extent of memory improvement.
Tamura et al., 2014 (S19)³⁹39. Tamura M, Nemoto K, Kawaguchi A, Kato M, Arai T, Kakuma T, et al. Long-term mild-intensity exercise regimen preserves prefrontal cortical volume against aging. Int J Geriatr Psychiatry. 2015 Jul;30(7):686-94. https://doi.org/10.1002/gps.4205 https://doi.org/10.1002/gps.4205...	n=110	Calisthenics	Not informed	Moderate	10 min/day, everyday	2 years	Brain volume and cognition	1. The exercise group showed significant improvements in attentional shift. 2. Neuroimaging analysis revealed the significant preservation of bilateral prefrontal volume in the exercise group. 3. The longitudinal changes in attentional shift and memory were positively correlated with the prefrontal volumetric changes.
Rosano et al., 2017 (S20)⁴⁰40. Rosano C, Guralnik J, Pahor M, Glynn NW, Newman AB, Ibrahim TS, et al. Hippocampal Response to a 24-Month Physical Activity Intervention in Sedentary Older Adults. Am J Geriatr Psychiatry. 2017 Mar;25(3):209-17. https://doi.org/10.1016/j.jagp.2016.11.007 https://doi.org/10.1016/j.jagp.2016.11.0...	n=27	Aerobic exercise	Health education	Moderate	Not reported	2 years	Hippocampus volume	1. Increased volume of the left hippocampus, left cornu ammonis and right hippocampus in the intervention group.
Varma et al 2015 (S21)¹⁴14. Varma VR, Chuang YF, Harris GC, Tan EJ, Carlson MC. Low-intensity daily walking activity is associated with hippocampal volume in older adults. Hippocampus. 2015 May;25(5):605-15. https://doi.org/10.1002/hipo.22397 https://doi.org/10.1002/hipo.22397...	n=92	Aerobic exercise (walking)	Not informed	Low to vigorous	10,000 steps/day threshold (pedometer)	Not informed	Hippocampus volume	1. A greater amount, duration, and frequency of total daily walking activity were each associated with larger hippocampus volume among older women, but not men. 2. These relationships were specific to hippocampus volume, compared to the thalamus, used as a control brain region, and remained significant for low-intensity walking activity, independent of moderate to vigorous-intensity activity and self-reported exercise
Vaughan et al., 2014 (S22)¹¹11. 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 Sep;43(5):623-9. https://doi.org/10.1093/ageing/afu010 https://doi.org/10.1093/ageing/afu010...	n=49	Multimodal exercise program (cardiovascular, strength and motor fitness)	Waiting list	Not reported	60 min, 2x/week	16 weeks	BDNF and cognition	1. The exercise program resulted in neurocognitive and physical performance improvements and increased levels of plasma BDNF, in older women, compared with controls. 2. Increases in BDNF levels imply neurogenesis may be a component of the mechanism underpinning the cognitive improvements associated with exercise.
Wagner et al., 2015 (S23)¹²12. Wagner G, Herbsleb M, de la Cruz F, Schumann A, Brünner F, Schachtzabel C, et al. Hippocampal structure, metabolism, and inflammatory response after a 6-week intense aerobic exercise in healthy young adults: a controlled trial. J Cereb Blood Flow Metab. 2015 Oct;35(10):1570-8. https://doi.org/10.1038/jcbfm.2015.125 https://doi.org/10.1038/jcbfm.2015.125...	n=34	Aerobic exercise	Not informed	Moderate	60 min, 3x/week	6 weeks	Hippocampus volume, hippocampus glutamate/ glutamine and NAA (N-acetyl aspartate).	1. A positive correlation between the degree of fitness improvement and increased BDNF levels was found. 2. A volume decrease of about 2% of the hippocampus was negatively correlated with fitness improvement and increased BDNF levels; and positively correlated with increased TNF-α concentrations. 3. A decrease in glutamate-glutamine levels was observed in the right anterior hippocampus in the exercise group only.
Zschucke et al., 2014 (S24)⁴¹41. Zschucke E, Renneberg B, Dimeo F, Wüstenberg T, Ströhle A. The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback. Psychoneuroendocrinology. 2015 Jan;51:414-25. https://doi.org/10.1016/j.psyneuen.2014.10.019 https://doi.org/10.1016/j.psyneuen.2014....	n=40	Aerobic exercise	Light stretching exercises	Moderate	30 min	Acute	Brain activation (fMRI) during stress task (MIST) cortisol and amylase	1. Participants of the aerobic group showed a significantly reduced cortisol response to the MIST, which was inversely related to the previous exercise-induced amylase and cortisol fluctuations. 2. Higher bilateral hippocampus activity and lower prefrontal cortex (PFC) activity was observed in the aerobic group.

[1] Correspondence: Camila Vorkapic; E-mail: camilavorkapic@gmail.com.

Brasil

Brasil

Born to move: a review on the impact of physical exercise on brain health and the evidence from human controlled trials

Nascidos para o movimento: uma revisão sobre o impacto do exercício físico na saúde do cérebro e as evidências de estudos controlados em humanos

Abstract

Background:

Objective:

Methods:

Results:

Conclusions: