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Physical Exercise Training Improves Judgment and Problem-Solving and Modulates Serum Biomarkers in Patients with Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is characterized by progressive impairment of memory, with an etiology involving oxidative stress and inflammation. Exercise training is a safe, efficacious, and economic approach to manage neurodegenerative diseases. In AD, the biomarkers of oxidative damage to lipids, proteins, and DNA are elevated. In the present study, we aimed to evaluate whether exercise is effective in patients with AD by assessing the serum biomarkers associated with the redox status, neurotrophin levels, and inflammatory system. This nonrandomized clinical study (n = 15) involved 22 training sessions performed twice a week (60 min/session) in patients diagnosed with AD. The cognitive and self-awareness tests were performed 48 h before and after the physical training session. In patients with AD, physical training significantly improved the judgment and problem-solving domains of the memory score; however, general mental health, memory, orientation, and home/hobby domains were improved slightly, and the neurotrophin levels remained unaltered. Significantly, the markers of protein integrity also increased following exercise. Furthermore, catalase activity and ROS levels decreased, nitrite levels increased, and interleukin-4 level increased following physical training in patients with AD. Although proinflammatory cytokines remained unaltered, the levels of neuron-specific enolase, a marker of neuronal damage, decreased following exercise training in these patients. In conclusion, physical exercise training could be a safe and effective method for blocking the AD progression and improving the antioxidant capacity and anti-inflammatory system, whereas certain assessed biomarkers could be utilized to monitor AD therapy.

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References

  1. Dement A (2016) Alzheimer’s disease facts and figures. Alzheimer’s Dement J Alzheimer’s Assoc 12(4):459–509. https://doi.org/10.1016/j.jalz.2016.03.001

    Article  Google Scholar 

  2. Querfurth H, LaFerla F (2010) Alzheimer’s disease. N Engl J Med 329:10

    Google Scholar 

  3. Fratiglioni L, Qiu C (2009) Prevention of common neurodegenerative disorders in the elderly. Exp Gerontol 44(1–2):46–50

    Article  Google Scholar 

  4. Padurariu M, Ciobica A, Hritcu L, Stoica B, Bild W, Stefanescu C (2010) Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer’s disease. Neurosci Lett 469(1):6–10. https://doi.org/10.1016/j.neulet.2009.11.033

    Article  CAS  PubMed  Google Scholar 

  5. Keller J, Schmitt F, Scheff S, Ding Q, Chen Q, Butterfield D et al (2005) Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 64(7):1152–1156. https://doi.org/10.1212/01.WNL.0000156156.13641.BA

    Article  CAS  PubMed  Google Scholar 

  6. Schrag M, Mueller C, Zabel M, Crofton A, Kirsch W, Ghribi O et al (2013) Oxidative stress in blood in Alzheimer’s disease and mild cognitive impairment: a meta-analysis. Neurobiol Dis 59:100–110. https://doi.org/10.1016/j.nbd.2013.07.005

    Article  CAS  PubMed  Google Scholar 

  7. van der Kleij L, Petersen E, Siebner H, Hendrikse J, Frederiksen K, Sobol N et al (2016) The effect of physical exercise on cerebral blood flow in Alzheimer’s disease: P32004. Eur J Neurol 23:749–750. https://doi.org/10.1016/j.nicl.2018.09.003

    Article  Google Scholar 

  8. Zhu X, Lee H, Casadesus G, Avila J, Drew K, Perry G et al (2005) Oxidative imbalance in Alzheimer’s disease. Mol Neurobiol 31(1–3):205–217. https://doi.org/10.1385/MN:31:1-3:205

    Article  CAS  PubMed  Google Scholar 

  9. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29(3–4):222–230. https://doi.org/10.1016/S0891-5849(00)00317-8

    Article  CAS  PubMed  Google Scholar 

  10. Hajjar I, Hayek SS, Goldstein FC, Martin G, Jones DP, Quyyumi A (2018) Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study. J Neuroinflammation 15(1):1–7. https://doi.org/10.1186/s12974-017-1026-z

    Article  Google Scholar 

  11. Verdile G, Keane KN, Cruzat VF, Medic S, Sabale M, Rowles J, et al (2015) Inflammation and oxidative stress: the molecular connectivity between insulin resistance, obesity, and Alzheimer’s disease. Mediators Inflamm 2015. https://doi.org/10.1155/2015/105828

  12. Kamat PK, Kalani A, Rai S, Swarnkar S, Tota S, Nath C et al (2016) Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer’s disease: understanding the therapeutics strategies. Mol Neurobiol 53(1):648–661. https://doi.org/10.1007/s12035-014-9053-6

    Article  CAS  PubMed  Google Scholar 

  13. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm- Aging Evol Perspect Immunosenescence. Ann NY Acad Sci 908:244–254. https://doi.org/10.1111/j.1749-6632.2000.tb06651.x

    Article  CAS  PubMed  Google Scholar 

  14. Chen W, Zhang X, Huang W (2016) Role of physical exercise in Alzheimer’s disease. Biomed Rep 4(4):403–407. https://doi.org/10.3892/br.2016.607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kennedy G, Hardman RJ, Macpherson H, Scholey AB, Pipingas A (2017) How does exercise reduce the rate of age-associated cognitive decline? A review of potential mechanisms. J Alzheimers Dis 55(1):1–18. https://doi.org/10.3233/JAD-160665

    Article  PubMed  Google Scholar 

  16. Chen Z, Qin X, Zhang X, Liu B, Chen M (2020) Upregulation of IL-4 signaling contributes to aerobic exercise-induced insulin sensitivity. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2020.02.103

  17. Ryan SM, Nolan YM (2016) Neuroinflammation negatively affects adult hippocampal neurogenesis and cognition: can exercise compensate? Neurosci Biobehav Rev 61:121–131. https://doi.org/10.1016/j.neubiorev.2015.12.004

    Article  CAS  PubMed  Google Scholar 

  18. Kramer AF, Erickson KI, Colcombe SJ (2006) Exercise, cognition, and the aging brain. J Appl Physiol 101(4):1237–1242. https://doi.org/10.1152/japplphysiol.00500.2006

    Article  PubMed  Google Scholar 

  19. Teri L, Logsdon RG, McCurry SM (2008) Exercise interventions for dementia and cognitive impairment: the Seattle Protocols. J Nutr Health Aging 12(6):391–394. https://doi.org/10.1007/BF02982672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Christofoletti G, Oliani MM, Gobbi S, Stella F, Bucken Gobbi LT, Renato CP (2008) A controlled clinical trial on the effects of motor intervention on balance and cognition in institutionalized elderly patients with dementia. Clin Rehabil 22(7):618–626. https://doi.org/10.1177/0269215507086239

    Article  PubMed  Google Scholar 

  21. Hoffmann K, Sobol NA, Frederiksen KS, Beyer N, Vogel A, Vestergaard K et al (2016) Moderate-to-high intensity physical exercise in patients with Alzheimer’s disease: a randomized controlled trial. J Alzheimers Dis 50(2):443–453. https://doi.org/10.3233/JAD-150817

    Article  PubMed  Google Scholar 

  22. Cotman CW, Berchtold NC, Christie L-A (2007) Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 30(9):464–472. https://doi.org/10.1016/j.tins.2007.06.011

    Article  CAS  Google Scholar 

  23. Muller AP, Gnoatto J, Moreira JD, Zimmer ER, Haas CB, Lulhier F et al (2011) Exercise increases insulin signaling in the hippocampus: physiological effects and pharmacological impact of intracerebroventricular insulin administration in mice. Hippocampus 21(10):1082–1092. https://doi.org/10.1002/hipo.20822

    Article  CAS  PubMed  Google Scholar 

  24. Muller AP, Zimmer ER, Kalinine E, Haas CB, Oses JP, Martimbianco de Assis A et al (2012) Physical exercise exacerbates memory deficits induced by intracerebroventricular STZ but improves insulin regulation of H 2O 2 production in mice synaptosomes. J Alzheimers Dis 30(4):889–898. https://doi.org/10.3233/JAD-2012-112066

    Article  CAS  PubMed  Google Scholar 

  25. Medhat E, Rashed L, Abdelgwad M, Aboulhoda BE, Khalifa MM, El-Din SS (2020) Exercise enhances the effectiveness of vitamin D therapy in rats with Alzheimer’s disease: emphasis on oxidative stress and inflammation. Metab Brain Dis 35(1):111–120. https://doi.org/10.1007/s11011-019-00504-2

    Article  CAS  PubMed  Google Scholar 

  26. Özbeyli D, Sarı G, Özkan N, Karademir B, Yüksel M, Kaya ÖTÇ et al (2017) Protective effects of different exercise modalities in an Alzheimer’s disease-like model. Behav Brain Res 328:159–177. https://doi.org/10.1016/j.bbr.2017.03.044

    Article  PubMed  Google Scholar 

  27. De la Rosa A, Solana E, Corpas R, Bartrés-Faz D, Pallàs M, Vina J et al (2019) Long-term exercise training improves memory in middle-aged men and modulates peripheral levels of BDNF and Cathepsin B. Sci Rep 9(1):1–11. https://doi.org/10.1038/s41598-019-40040-8

    Article  CAS  Google Scholar 

  28. Bernardo T, Marques-Aleixo I, Beleza J, Oliveira P, Ascensao A, Magalhaes J (2016) Physical exercise and brain mitochondrial fitness: the possible role against Alzheimer’s disease. Brain Pathol 26(5):648–663. https://doi.org/10.1111/bpa.12403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39(1):73–82. https://doi.org/10.1080/01616412.2016.1251711

    Article  CAS  PubMed  Google Scholar 

  30. Isgrò M, Bottoni P, Scatena R (2015) Advances in cancer biomarkers: from biochemistry to clinic for a critical revision. https://doi.org/10.1007/978-94-017-7215-0

  31. Cunha JA (2001) Manual da versão em português das Escalas Beck. São Paulo Casa Psicólogo 256

  32. Brucki S, Nitrini R, Caramelli P, Bertolucci PH, Okamoto IH (2003) Sugestões para o uso do mini-exame do estado mental no Brasil. Arq Neuropsiquiatr 61(3B):777–781. https://doi.org/10.1590/S0004-282X2003000500014

    Article  PubMed  Google Scholar 

  33. Hughes CP, Berg L, Danziger W, Coben LA, Martin RL (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 140(6):566–572. https://doi.org/10.1192/bjp.140.6.566

    Article  CAS  PubMed  Google Scholar 

  34. Morris J (1993) Current vision and scoring rules the clinical dementia rating (CDR). Neurology 43:2412–2414. https://doi.org/10.1212/WNL.43.11.2412-a

    Article  CAS  PubMed  Google Scholar 

  35. Ware Jr JE, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 473–83

  36. Hempel SL, Buettner GR, O’Malley YQ, Wessels DA, Flaherty DM (1999) Dihydrofluorescein diacetate is superior for detecting intracellular oxidants: comparison with 2′, 7′-dichlorodihydrofluorescein diacetate, 5 (and 6)-carboxy-2′, 7′-dichlorodihydrofluorescein diacetate, and dihydrorhodamine 123. Free Radic Biol Med 27(1–2):146–159. https://doi.org/10.1016/S0891-5849(99)00061-1

    Article  CAS  PubMed  Google Scholar 

  37. Chae SY, Lee M, Kim SW, Bae YH (2004) Protection of insulin secreting cells from nitric oxide induced cellular damage by crosslinked hemoglobin. Biomaterials 25(5):843–850. https://doi.org/10.1016/S0142-9612(03)00605-7

    Article  CAS  PubMed  Google Scholar 

  38. Aebi H (1984) [13] Catalase in vitro. In: Methods in enzymology. Elsevier. p. 121–6. https://doi.org/10.1016/S0076-6879(84)05016-3

  39. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz A-G et al (1990) [49] Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478. https://doi.org/10.1016/0076-6879(90)86141-H

    Article  CAS  PubMed  Google Scholar 

  40. Bhatti GK, Reddy AP, Reddy PH, Bhatti JS (2020) Lifestyle modifications and nutritional interventions in aging-associated cognitive decline and Alzheimer’s disease. Front Aging Neurosci 11:369. https://doi.org/10.3389/fnagi.2019.00369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zanco M, Placido J, Marinho V, Ferreira JV, de Oliveira F, Monteiro-Junior R et al (2018) Spatial navigation in the elderly with Alzheimer’s disease: a cross-sectional study. J Alzheimers Dis 66(4):1683–1694. https://doi.org/10.3233/JAD-180819

    Article  PubMed  Google Scholar 

  42. Binder EF, Storandt M, Birge SJ (1999) The relation between psychometric test performance and physical performance in older adults. J Gerontol Ser Biomed Sci Med Sci 54(8):M428–M432. https://doi.org/10.1093/gerona/54.8.M428

    Article  CAS  Google Scholar 

  43. Weller J, Budson A (2018) Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research 7. https://doi.org/10.12688/f1000research.14506.1

  44. Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM et al (2007) An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci 104(13):5638–5643. https://doi.org/10.1073/pnas.0611721104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Strüder H, Weicker H (2001) Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part I. Int J Sports Med 22(07):467–481. https://doi.org/10.1055/s-2001-17605

    Article  PubMed  Google Scholar 

  46. Vilela TC, Muller AP, Damiani AP, Macan TP, da Silva S, Canteiro PB et al (2017) Strength and aerobic exercises improve spatial memory in aging rats through stimulating distinct neuroplasticity mechanisms. Mol Neurobiol 54(10):7928–7937. https://doi.org/10.1007/s12035-016-0272-x

    Article  CAS  PubMed  Google Scholar 

  47. Bortz W 2nd (1981) Catecholamines, dopamine, and endorphin levels during extreme exercise. N Engl J Med 305:466–467

    PubMed  Google Scholar 

  48. Belviranlı M, Okudan N (2019) Voluntary, involuntary and forced exercises almost equally reverse behavioral impairment by regulating hippocampal neurotrophic factors and oxidative stress in experimental Alzheimer’s disease model. Behav Brain Res 364:245–255. https://doi.org/10.1016/j.bbr.2019.02.030

    Article  CAS  PubMed  Google Scholar 

  49. Bhattarai P, Cosacak MI, Mashkaryan V, Demir S, Popova SD, Govindarajan N et al (2020) Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain. PLoS Biol 18(1):e3000585. https://doi.org/10.1371/journal.pbio.3000585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Khan MZ, Zhuang X, He L (2016) GPR40 receptor activation leads to CREB phosphorylation and improves cognitive performance in an Alzheimer’s disease mouse model. Neurobiol Learn Mem 131:46–55. https://doi.org/10.1016/j.nlm.2016.03.006

    Article  CAS  PubMed  Google Scholar 

  51. Nunomura A, Tamaoki T, Motohashi N, Nakamura M, McKeel DW Jr, Tabaton M et al (2012) The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons. J Neuropathol Exp Neurol 71(3):233–241. https://doi.org/10.1097/NEN.0b013e318248e614

    Article  CAS  PubMed  Google Scholar 

  52. Butterfield DA, Halliwell B (2019) Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat Rev Neurosci 20(3):148–160. https://doi.org/10.1038/s41583/-019-0132-6

    Article  CAS  PubMed  Google Scholar 

  53. Torres LL, Quaglio NB, de Souza GT, Garcia RT, Dati LMM, Moreira WL et al (2011) Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 26(1):59–68. https://doi.org/10.3233/JAD-2011-110284

    Article  CAS  PubMed  Google Scholar 

  54. Kaufmann FN, Gazal M, Mondin TC, Cardoso TA, Quevedo LÁ, Souza LD et al (2015) Cognitive psychotherapy treatment decreases peripheral oxidative stress parameters associated with major depression disorder. Biol Psychol 110:175–181. https://doi.org/10.1016/j.biopsycho.2015.08.001

    Article  PubMed  Google Scholar 

  55. Bermejo P, Martín-Aragón S, Benedí J, Susín C, Felici E, Gil P et al (2008) Peripheral levels of glutathione and protein oxidation as markers in the development of Alzheimer’s disease from mild cognitive impairment. Free Radic Res 42(2):162–170. https://doi.org/10.1080/10715760701861373

    Article  CAS  PubMed  Google Scholar 

  56. Hensley K, Hall N, Subramaniam R, Cole P, Harris M, Aksenov M et al (1995) Brain regional correspondence between Alzheimer’s disease histopathology and biomarkers of protein oxidation. J Neurochem 65(5):2146–2156. https://doi.org/10.1046/j.1471-4159.1995.65052146.x

    Article  CAS  PubMed  Google Scholar 

  57. Smith C, Carney JM, Starke-Reed P, Oliver C, Stadtman E, Floyd R et al (1991) Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci 88(23):10540–10543. https://doi.org/10.1073/pnas.88.23.10540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ahmad W, Ijaz B, Shabbiri K, Ahmed F, Rehman S (2017) Oxidative toxicity in diabetes and Alzheimer’s disease: mechanisms behind ROS/RNS generation. J Biomed Sci 24(1):76. https://doi.org/10.1186/s12929-017-0379-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Newsholme P (2010) Homem De Bittencourt Jr PI, O’Hagan C, De Vito G, Murphy C, Krause MS (2010) Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxide. Clin Sci 118(5):341–349. https://doi.org/10.1042/CS20090433

    Article  CAS  Google Scholar 

  60. Mangialasche F, Polidori MC, Monastero R, Ercolani S, Camarda C, Cecchetti R et al (2009) Biomarkers of oxidative and nitrosative damage in Alzheimer’s disease and mild cognitive impairment. Ageing Res Rev 8(4):285–305. https://doi.org/10.1016/j.arr.2009.04.002

    Article  CAS  PubMed  Google Scholar 

  61. Sharma S, Verma S, Kapoor M, Saini A, Nehru B (2016) Alzheimer’s disease like pathology induced six weeks after aggregated amyloid-beta injection in rats: increased oxidative stress and impaired long-term memory with anxiety-like behavior. Neurol Res 38(9):838–850. https://doi.org/10.1080/01616412.2016.1209337

    Article  CAS  PubMed  Google Scholar 

  62. Lundberg JO, Weitzberg E, Gladwin MT (2008) The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 7(2):156–167. https://doi.org/10.1038/nrd2466

    Article  CAS  PubMed  Google Scholar 

  63. Calvert JW (2011) Cardioprotective effects of nitrite during exercise. Cardiovasc Res 89(3):499–506. https://doi.org/10.1093/cvr/cvq307

    Article  CAS  PubMed  Google Scholar 

  64. Ferreira ST, Clarke JR, Bomfim TR, De Felice FG (2014) Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement 10:S76-83. https://doi.org/10.1016/j.jalz.2013.12.010

    Article  PubMed  Google Scholar 

  65. Jiang NM, Cowan M, Moonah SN, Petri WA Jr (2018) The impact of systemic inflammation on neurodevelopment. Trends Mol Med 24(9):794–804. https://doi.org/10.1016/j.molmed.2018.06.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ismail R, Parbo P, Madsen LS, Hansen AK, Hansen KV, Schaldemose JL et al (2020) The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study. J Neuroinflammation 17:1–11. https://doi.org/10.1186/s12974-020-01820-6

    Article  CAS  Google Scholar 

  67. Casella G, Garzetti L, Gatta AT, Finardi A, Maiorino C, Ruffini F et al (2016) IL4 induces IL6-producing M2 macrophages associated to inhibition of neuroinflammation in vitro and in vivo. J Neuroinflammation 13(1):1–10. https://doi.org/10.1186/s12974-016-0596-5

    Article  CAS  Google Scholar 

  68. da Luz Scheffer D, Latini A (2020) Exercise-induced immune system response: anti-inflammatory status on peripheral and central organs. Biochim Biophys Acta BBA-Mol Basis Dis 165823. https://doi.org/10.1016/j.bbadis.2020.165823

  69. Pahk K, Kim EJ, Joung C, Seo HS, Kim S (2020) Exercise training reduces inflammatory metabolic activity of visceral fat assessed by 18F‐FDG PET/CT in obese women. Clin Endocrinol (Oxf). https://doi.org/10.1111/cen.14216

  70. Italiani P, Puxeddu I, Napoletano S, Scala E, Melillo D, Manocchio S et al (2018) Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: new markers of disease progression? J Neuroinflammation 15(1):1–12. https://doi.org/10.1186/s12974-018-1376-1

    Article  CAS  Google Scholar 

  71. Schmidt FM, Mergl R, Stach B, Jahn I, Gertz H-J, Schönknecht P (2014) Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE) in Alzheimer’s disease. Neurosci Lett 570:81–85. https://doi.org/10.1016/j.neulet.2014.04.007

    Article  CAS  PubMed  Google Scholar 

  72. Hoffmann J, Janowitz D, Van der Auwera S, Wittfeld K, Nauck M, Friedrich N et al (2017) Association between serum neuron-specific enolase, age, overweight, and structural MRI patterns in 901 subjects. Transl Psychiatry 7(12):1–9. https://doi.org/10.1038/s41398-017-0035-0

    Article  CAS  Google Scholar 

  73. Chaves ML, Camozzato AL, Ferreira ED, Piazenski I, Kochhann R, Dall’Igna O, et al (2010) Serum levels of S100B and NSE proteins in Alzheimer’s disease patients. J Neuroinflammation 7(1):6. https://doi.org/10.1186/1742-2094-7-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M et al (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet NeuroL 1 de junho de 15(7):673–684. https://doi.org/10.1016/S1474-4422(16)00070-3

    Article  CAS  Google Scholar 

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Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-Instituto Nacional de Neurociência Translacional-INNT #465346/2014–6, Projeto CNPq UNIVERSAL 2018, Fundação de Amparo a Pesquisa do Estado de Santa Catarina (FAPESC)-PPSUS-2016 e Universidade do Extremo Sul Catarinense (UNESC).

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Farias JM: conceptualization, data curation, investigation, methodology, project administration, supervision, writing original manuscript draft. Tramontin NS: investigation, methodology, blood collection, biochemical analyses. Pereira EV: investigation, methodology, physical training, behavioral tasks. Moraes GL: investigation, methodology, physical training, behavioral tasks. Furtado BG: investigation, methodology, physical training, behavioral tasks. Tietbohl LTW: investigation, methodology, blood collection, biochemical analyses. Pereira BC: investigation, methodology, blood collection, biochemical analyses. Simon KU: investigation, methodology, blood collection, biochemical analyses. Muller AP: conceptualization, data curation, investigation, methodology, project administration, supervision, writing original manuscript draft.

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Correspondence to Alexandre Pastoris Muller.

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de Farias, J.M., dos Santos Tramontin, N., Pereira, E.V. et al. Physical Exercise Training Improves Judgment and Problem-Solving and Modulates Serum Biomarkers in Patients with Alzheimer’s Disease. Mol Neurobiol 58, 4217–4225 (2021). https://doi.org/10.1007/s12035-021-02411-z

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