Table of Contents Author Guidelines Submit a Manuscript
Neural Plasticity
Volume 2018, Article ID 9234105, 10 pages
https://doi.org/10.1155/2018/9234105
Review Article

Exercise Intervention Associated with Cognitive Improvement in Alzheimer’s Disease

Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China

Correspondence should be addressed to Ran Ji Cui; nc.ude.ulj@ijnariuc

Received 6 November 2017; Accepted 16 January 2018; Published 11 March 2018

Academic Editor: Weina Liu

Copyright © 2018 Meng Ying Cui et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. L. Murphy, J. Xu, and K. D. Kochanek, “Deaths: final data for 2010,” National Vital Statistics Report, vol. 61, no. 4, pp. 1–117, 2013. View at Google Scholar
  2. M. Wortmann, “Dementia: a global health priority - highlights from an ADI and World Health Organization report,” Alzheimer’s Research & Therapy, vol. 4, no. 5, p. 40, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. A. M. Kirova, R. B. Bays, and S. Lagalwar, “Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer’s disease,” BioMed Research International, vol. 2015, Article ID 748212, 9 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  4. S. D. Skaper, L. Facci, M. Zusso, and P. Giusti, “Synaptic plasticity, dementia and Alzheimer disease,” CNS & Neurological Disorders Drug Targets, vol. 16, no. 3, pp. 220–233, 2017. View at Publisher · View at Google Scholar · View at Scopus
  5. S. G. Di Santo, F. Prinelli, F. Adorni, C. Caltagirone, and M. Musicco, “A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer’s disease,” Journal of Alzheimer’s Disease, vol. 35, no. 2, pp. 349–361, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. J. S. Lin, E. O’Connor, R. C. Rossom, L. A. Perdue, and E. Eckstrom, “Screening for cognitive impairment in older adults: a systematic review for the U.S. Preventive Services Task Force,” Annals of Internal Medicine, vol. 159, no. 9, pp. 601–612, 2013. View at Publisher · View at Google Scholar
  7. L. S. Nagamatsu, T. C. Handy, C. L. Hsu, M. Voss, and T. Liu-Ambrose, “Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment,” Archives of Internal Medicine, vol. 172, no. 8, pp. 666–668, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. H. Guiney, S. J. Lucas, J. D. Cotter, and L. Machado, “Evidence cerebral blood-flow regulation mediates exercise-cognition links in healthy young adults,” Neuropsychology, vol. 29, no. 1, pp. 1–9, 2015. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Schrag, C. Mueller, M. Zabel et al., “Oxidative stress in blood in Alzheimer’s disease and mild cognitive impairment: a meta-analysis,” Neurobiology of Disease, vol. 59, pp. 100–110, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. P. A. Adlard, V. M. Perreau, V. Pop, and C. W. Cotman, “Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease,” The Journal of Neuroscience, vol. 25, no. 17, pp. 4217–4221, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. O. Lazarov, J. Robinson, Y. P. Tang et al., “Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice,” Cell, vol. 120, no. 5, pp. 701–713, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. P. G. MacRae, W. W. Spirduso, T. J. Walters, R. P. Farrar, and R. E. Wilcox, “Endurance training effects on striatal D2 dopamine receptor binding and striatal dopamine metabolites in presenescent older rats,” Psychopharmacology, vol. 92, no. 2, pp. 236–240, 1987. View at Publisher · View at Google Scholar · View at Scopus
  13. M. P. Mattson, S. Maudsley, and B. Martin, “A neural signaling triumvirate that influences ageing and age-related disease: insulin/IGF-1, BDNF and serotonin,” Ageing Research Reviews, vol. 3, no. 4, pp. 445–464, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. J. C. Smith, K. A. Nielson, P. Antuono et al., “Semantic memory functional MRI and cognitive function after exercise intervention in mild cognitive impairment,” Journal of Alzheimer’s Disease, vol. 37, no. 1, pp. 197–215, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Anderson-Hanley, P. J. Arciero, A. M. Brickman et al., “Exergaming and older adult cognition: a cluster randomized clinical trial,” American Journal of Preventive Medicine, vol. 42, no. 2, pp. 109–119, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. G. G. de Assis and K. M. de Almondes, “Exercise-dependent BDNF as a modulatory factor for the executive processing of individuals in course of cognitive decline. A systematic review,” Frontiers in Psychology, vol. 8, p. 584, 2017. View at Publisher · View at Google Scholar · View at Scopus
  17. S. B. Hindin and E. M. Zelinski, “Extended practice and aerobic exercise interventions benefit untrained cognitive outcomes in older adults: a meta-analysis,” Journal of the American Geriatrics Society, vol. 60, no. 1, pp. 136–141, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. G. W. Rebok, K. Ball, L. T. Guey et al., “Ten-year effects of the advanced cognitive training for independent and vital elderly cognitive training trial on cognition and everyday functioning in older adults,” Journal of the American Geriatrics Society, vol. 62, no. 1, pp. 16–24, 2014. View at Publisher · View at Google Scholar · View at Scopus
  19. M. J. Graff, M. J. Vernooij-Dassen, M. Thijssen, J. Dekker, W. H. Hoefnagels, and M. G. Rikkert, “Community based occupational therapy for patients with dementia and their care givers: randomised controlled trial,” BMJ, vol. 333, no. 7580, p. 1196, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. A. M. Owen, A. Hampshire, J. A. Grahn et al., “Putting brain training to the test,” Nature, vol. 465, no. 7299, pp. 775–778, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. T. L. Harrison, Z. Shipstead, K. L. Hicks, D. Z. Hambrick, T. S. Redick, and R. W. Engle, “Working memory training may increase working memory capacity but not fluid intelligence,” Psychological Science, vol. 24, no. 12, pp. 2409–2419, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. T. Epperly, M. A. Dunay, and J. L. Boice, “Alzheimer disease: pharmacologic and nonpharmacologic therapies for cognitive and functional symptoms,” American Family Physician, vol. 95, no. 12, pp. 771–778, 2017. View at Google Scholar
  23. S. L. Willis, S. L. Tennstedt, M. Marsiske et al., “Long-term effects of cognitive training on everyday functional outcomes in older adults,” JAMA, vol. 296, no. 23, pp. 2805–2814, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. L. Clare and R. T. Woods, “Cognitive rehabilitation and cognitive training for early-stage Alzheimer’s disease and vascular dementia,” Cochrane Database of Systematic Reviews, no. 4, article CD003260, 2003. View at Publisher · View at Google Scholar
  25. C. Basak, W. R. Boot, M. W. Voss, and A. F. Kramer, “Can training in a real-time strategy video game attenuate cognitive decline in older adults,” Psychology and Aging, vol. 23, no. 4, pp. 765–777, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Ballesteros, A. Prieto, J. Mayas et al., “Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial,” Frontiers in Aging Neuroscience, vol. 6, p. 277, 2014. View at Publisher · View at Google Scholar · View at Scopus
  27. L. E. Middleton, D. E. Barnes, L. Y. Lui, and K. Yaffe, “Physical activity over the life course and its association with cognitive performance and impairment in old age,” Journal of the American Geriatrics Society, vol. 58, no. 7, pp. 1322–1326, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Guiney and L. Machado, “Benefits of regular aerobic exercise for executive functioning in healthy populations,” Psychonomic Bulletin & Review, vol. 20, no. 1, pp. 73–86, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. K. I. Erickson, R. S. Prakash, M. W. Voss et al., “Aerobic fitness is associated with hippocampal volume in elderly humans,” Hippocampus, vol. 19, no. 10, pp. 1030–1039, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. D. E. Barnes, T. Blackwell, K. L. Stone, S. E. Goldman, T. Hillier, and K. Yaffe, “Cognition in older women: the importance of daytime movement,” Journal of the American Geriatrics Society, vol. 56, no. 9, pp. 1658–1664, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. B. M. Brown, J. J. Peiffer, H. R. Sohrabi et al., “Intense physical activity is associated with cognitive performance in the elderly,” Translational Psychiatry, vol. 2, no. 11, article e191, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. F. Sofi, D. Valecchi, D. Bacci et al., “Physical activity and risk of cognitive decline: a meta-analysis of prospective studies,” Journal of Internal Medicine, vol. 269, no. 1, pp. 107–117, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. T. Liu-Ambrose, L. S. Nagamatsu, P. Graf, B. L. Beattie, M. C. Ashe, and T. C. Handy, “Resistance training and executive functions: a 12-month randomized controlled trial,” Archives of Internal Medicine, vol. 170, no. 2, pp. 170–178, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. R. C. Cassilhas, V. A. Viana, V. Grassmann et al., “The impact of resistance exercise on the cognitive function of the elderly,” Medicine & Science in Sports & Exercise, vol. 39, no. 8, pp. 1401–1407, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. Y. K. Chang, Y. H. Nien, C. L. Tsai, and J. L. Etnier, “Physical activity and cognition in older adults: the potential of Tai Chi Chuan,” Journal of Aging and Physical Activity, vol. 18, no. 4, pp. 451–472, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. P. M. Wayne, B. J. Gow, M. D. Costa et al., “Complexity-based measures inform effects of Tai Chi training on standing postural control: cross-sectional and randomized trial studies,” PLoS One, vol. 9, no. 12, article e114731, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. A. K. Brown, T. Liu-Ambrose, R. Tate, and S. R. Lord, “The effect of group-based exercise on cognitive performance and mood in seniors residing in intermediate care and self-care retirement facilities: a randomised controlled trial,” British Journal of Sports Medicine, vol. 43, no. 8, pp. 608–614, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Liu-Ambrose, M. G. Donaldson, Y. Ahamed et al., “Otago home-based strength and balance retraining improves executive functioning in older fallers: a randomized controlled trial,” Journal of the American Geriatrics Society, vol. 56, no. 10, pp. 1821–1830, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. S. A. Neeper, F. Gómez-Pinilla, J. Choi, and C. Cotman, “Exercise and brain neurotrophins,” Nature, vol. 373, no. 6510, p. 109, 1995. View at Publisher · View at Google Scholar · View at Scopus
  40. N. F. Johnson, C. Kim, J. L. Clasey, A. Bailey, and B. T. Gold, “Cardiorespiratory fitness is positively correlated with cerebral white matter integrity in healthy seniors,” NeuroImage, vol. 59, no. 2, pp. 1514–1523, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. Q. Tian, E. M. Simonsick, K. I. Erickson et al., “Cardiorespiratory fitness and brain diffusion tensor imaging in adults over 80 years of age,” Brain Research, vol. 1588, pp. 63–72, 2014. View at Publisher · View at Google Scholar · View at Scopus
  42. S. E. Borst, D. V. De Hoyos, L. Garzarella et al., “Effects of resistance training on insulin-like growth factor-I and IGF binding proteins,” Medicine and Science in Sports and Exercise, vol. 33, no. 4, pp. 648–653, 2001. View at Publisher · View at Google Scholar
  43. K. R. Vincent, R. W. Braith, T. Bottiglieri, H. K. Vincent, and D. T. Lowenthal, “Homocysteine and lipoprotein levels following resistance training in older adults,” Preventive Cardiology, vol. 6, no. 4, pp. 197–203, 2003. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Snowden, L. Steinman, K. Mochan et al., “Effect of exercise on cognitive performance in community-dwelling older adults: review of intervention trials and recommendations for public health practice and research,” Journal of the American Geriatrics Society, vol. 59, no. 4, pp. 704–716, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. M. E. Kelly, D. Loughrey, B. A. Lawlor, I. H. Robertson, C. Walsh, and S. Brennan, “The impact of exercise on the cognitive functioning of healthy older adults: a systematic review and meta-analysis,” Ageing Research Reviews, vol. 16, pp. 12–31, 2014. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Colcombe and A. F. Kramer, “Fitness effects on the cognitive function of older adults: a meta-analytic study,” Psychological Science, vol. 14, no. 2, pp. 125–130, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. W. D. Oswald, T. Gunzelmann, R. Rupprecht, and B. Hagen, “Differential effects of single versus combined cognitive and physical training with older adults: the SimA study in a 5-year perspective,” European Journal of Ageing, vol. 3, no. 4, pp. 179–192, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. P. Maillot, A. Perrot, and A. Hartley, “Effects of interactive physical-activity video-game training on physical and cognitive function in older adults,” Psychology and Aging, vol. 27, no. 3, pp. 589–600, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. P. D. Bamidis, P. Fissler, S. G. Papageorgiou et al., “Gains in cognition through combined cognitive and physical training: the role of training dosage and severity of neurocognitive disorder,” Frontiers in Aging Neuroscience, vol. 7, p. 152, 2015. View at Publisher · View at Google Scholar · View at Scopus
  50. F. G. Coelho, L. P. Andrade, R. V. Pedroso et al., “Multimodal exercise intervention improves frontal cognitive functions and gait in Alzheimer’s disease: a controlled trial,” Geriatrics & Gerontology International, vol. 13, no. 1, pp. 198–203, 2013. View at Publisher · View at Google Scholar · View at Scopus
  51. C. K. Barha, J. C. Davis, R. S. Falck, L. S. Nagamatsu, and T. Liu-Ambrose, “Sex differences in exercise efficacy to improve cognition: a systematic review and meta-analysis of randomized controlled trials in older humans,” Frontiers in Neuroendocrinology, vol. 46, pp. 71–85, 2017. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Anderson-Hanley, M. Maloney, N. Barcelos, K. Striegnitz, and A. Kramer, “Neuropsychological benefits of neuro-exergaming for older adults: a pilot study of an interactive physical and cognitive exercise system (iPACES),” Journal of Aging and Physical Activity, vol. 25, no. 1, pp. 73–83, 2017. View at Publisher · View at Google Scholar · View at Scopus
  53. K. Linde and D. Alfermann, “Single versus combined cognitive and physical activity effects on fluid cognitive abilities of healthy older adults: a 4-month randomized controlled trial with follow-up,” Journal of Aging and Physical Activity, vol. 22, no. 3, pp. 302–313, 2014. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Rahe, A. Petrelli, S. Kaesberg, G. R. Fink, J. Kessler, and E. Kalbe, “Effects of cognitive training with additional physical activity compared to pure cognitive training in healthy older adults,” Clinical Interventions in Aging, vol. 10, pp. 297–310, 2015. View at Publisher · View at Google Scholar · View at Scopus
  55. D. E. Barnes, W. Santos-Modesitt, G. Poelke et al., “The Mental Activity and eXercise (MAX) trial: a randomized controlled trial to enhance cognitive function in older adults,” JAMA Internal Medicine, vol. 173, no. 9, pp. 797–804, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. L. D. Baker, L. L. Frank, K. Foster-Schubert et al., “Effects of aerobic exercise on mild cognitive impairment: a controlled trial,” Archives of Neurology, vol. 67, no. 1, pp. 71–79, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. P. J. Smith, J. A. Blumenthal, B. M. Hoffman et al., “Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials,” Psychosomatic Medicine, vol. 72, no. 3, pp. 239–252, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. A. C. Pereira, D. E. Huddleston, A. M. Brickman et al., “An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 13, pp. 5638–5643, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. K. C. O’Leary, M. B. Pontifex, M. R. Scudder, M. L. Brown, and C. H. Hillman, “The effects of single bouts of aerobic exercise, exergaming, and videogame play on cognitive control,” Clinical Neurophysiology, vol. 122, no. 8, pp. 1518–1525, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. M. Roig, K. Skriver, J. Lundbye-Jensen, B. Kiens, and J. B. Nielsen, “A single bout of exercise improves motor memory,” PLoS One, vol. 7, no. 9, article e44594, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. M. A. Statton, M. Encarnacion, P. Celnik, and A. J. Bastian, “A single bout of moderate aerobic exercise improves motor skill acquisition,” PLoS One, vol. 10, no. 10, article e0141393, 2015. View at Publisher · View at Google Scholar · View at Scopus
  62. C. S. Mang, N. J. Snow, K. L. Campbell, C. J. Ross, and L. A. Boyd, “A single bout of high-intensity aerobic exercise facilitates response to paired associative stimulation and promotes sequence-specific implicit motor learning,” Journal of Applied Physiology, vol. 117, no. 11, pp. 1325–1336, 2014. View at Publisher · View at Google Scholar · View at Scopus
  63. A. E. Smith, M. R. Goldsworthy, T. Garside, F. M. Wood, and M. C. Ridding, “The influence of a single bout of aerobic exercise on short-interval intracortical excitability,” Experimental Brain Research, vol. 232, no. 6, pp. 1875–1882, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. T. Lulic, J. El-Sayes, H. J. Fassett, and A. J. Nelson, “Physical activity levels determine exercise-induced changes in brain excitability,” PLoS One, vol. 12, no. 3, article e0173672, 2017. View at Publisher · View at Google Scholar · View at Scopus
  65. P. T. Katzmarzyk, I. Janssen, and C. I. Ardern, “Physical inactivity, excess adiposity and premature mortality,” Obesity Reviews, vol. 4, no. 4, pp. 257–290, 2003. View at Publisher · View at Google Scholar · View at Scopus
  66. H. Naci and J. P. Ioannidis, “Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study,” British Journal of Sports Medicine, vol. 49, no. 21, pp. 1414–1422, 2015. View at Publisher · View at Google Scholar
  67. C. Andrade and R. Radhakrishnan, “The prevention and treatment of cognitive decline and dementia: an overview of recent research on experimental treatments,” Indian Journal of Psychiatry, vol. 51, no. 1, pp. 12–25, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. A. Ströhle, D. K. Schmidt, F. Schultz et al., “Drug and exercise treatment of Alzheimer disease and mild cognitive impairment: a systematic review and meta-analysis of effects on cognition in randomized controlled trials,” The American Journal of Geriatric Psychiatry, vol. 23, no. 12, pp. 1234–1249, 2015. View at Publisher · View at Google Scholar · View at Scopus
  69. M. S. Albert, S. T. DeKosky, D. Dickson et al., “The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease,” Alzheimer’s & Dementia, vol. 7, no. 3, pp. 270–279, 2011. View at Publisher · View at Google Scholar · View at Scopus
  70. C. Jonker, M. I. Geerlings, and B. Schmand, “Are memory complaints predictive for dementia? A review of clinical and population-based studies,” International Journal of Geriatric Psychiatry, vol. 15, no. 11, pp. 983–991, 2000. View at Publisher · View at Google Scholar
  71. J. Attems and K. A. Jellinger, “Olfactory tau pathology in Alzheimer disease and mild cognitive impairment,” Clinical Neuropathology, vol. 25, no. 6, pp. 265–271, 2006. View at Google Scholar
  72. R. C. Petersen, “Mild cognitive impairment: transition between aging and Alzheimer’s disease,” Neurología, vol. 15, no. 3, pp. 93–101, 2000. View at Google Scholar
  73. A. Muscari, C. Giannoni, L. Pierpaoli et al., “Chronic endurance exercise training prevents aging-related cognitive decline in healthy older adults: a randomized controlled trial,” International Journal of Geriatric Psychiatry, vol. 25, no. 10, pp. 1055–1064, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. R. C. Petersen, R. G. Thomas, M. Grundman et al., “Vitamin E and donepezil for the treatment of mild cognitive impairment,” The New England Journal of Medicine, vol. 352, no. 23, pp. 2379–2388, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. L. L. Law, F. Barnett, M. K. Yau, and M. A. Gray, “Effects of functional tasks exercise on older adults with cognitive impairment at risk of Alzheimer’s disease: a randomised controlled trial,” Age and Ageing, vol. 43, no. 6, pp. 813–820, 2014. View at Publisher · View at Google Scholar · View at Scopus
  76. N. T. Hill, L. Mowszowski, S. L. Naismith, V. L. Chadwick, M. Valenzuela, and A. Lampit, “Computerized cognitive training in older adults with mild cognitive impairment or dementia: a systematic review and meta-analysis,” The American Journal of Psychiatry, vol. 174, no. 4, pp. 329–340, 2017. View at Publisher · View at Google Scholar · View at Scopus
  77. E. Galante, G. Venturini, and C. Fiaccadori, “Computer-based cognitive intervention for dementia: preliminary results of a randomized clinical trial,” Giornale italiano di medicina del lavoro ed ergonomia, vol. 29, Supplement B, no. 3, pp. B26–B32, 2007. View at Google Scholar
  78. A. Kurz, C. Pohl, M. Ramsenthaler, and C. Sorg, “Cognitive rehabilitation in patients with mild cognitive impairment,” International Journal of Geriatric Psychiatry, vol. 24, no. 2, pp. 163–168, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. C. Courtney, D. Farrell, R. Gray et al., “Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial,” Lancet, vol. 363, no. 9427, pp. 2105–2115, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. G. K. Wilcock, “Memantine for the treatment of dementia,” The Lancet Neurology, vol. 2, no. 8, pp. 503–505, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. K. H. Pitkälä, M. M. Pöysti, M. L. Laakkonen et al., “Effects of the Finnish Alzheimer disease exercise trial (FINALEX): a randomized controlled trial,” JAMA Internal Medicine, vol. 173, no. 10, pp. 894–901, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Olazarán, B. Reisberg, L. Clare et al., “Nonpharmacological therapies in Alzheimer’s disease: a systematic review of efficacy,” Dementia and Geriatric Cognitive Disorders, vol. 30, no. 2, pp. 161–178, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. Y. Rolland, F. Pillard, A. Klapouszczak et al., “Exercise program for nursing home residents with Alzheimer’s disease: a 1-year randomized, controlled trial,” Journal of the American Geriatrics Society, vol. 55, no. 2, pp. 158–165, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. C. M. Nascimento, C. V. Teixeira, L. T. Gobbi, S. Gobbi, and F. Stella, “A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer’s disease,” Brazilian Journal of Physical Therapy, vol. 16, no. 3, pp. 197–204, 2012. View at Publisher · View at Google Scholar · View at Scopus
  85. F. G. Coelho, F. Stella, L. P. de Andrade et al., “Gait and risk of falls associated with frontal cognitive functions at different stages of Alzheimer’s disease,” Aging, Neuropsychology and Cognition, vol. 19, no. 5, pp. 644–656, 2012. View at Publisher · View at Google Scholar · View at Scopus
  86. L. P. de Andrade, L. T. Gobbi, F. G. Coelho, G. Christofoletti, J. L. Costa, and F. Stella, “Benefits of multimodal exercise intervention for postural control and frontal cognitive functions in individuals with Alzheimer’s disease: a controlled trial,” Journal of the American Geriatrics Society, vol. 61, no. 11, pp. 1919–1926, 2013. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Poynter, J. Kwan, A. A. Sayer, and M. Vassallo, “Does cognitive impairment affect rehabilitation outcome,” Journal of the American Geriatrics Society, vol. 59, no. 11, pp. 2108–2111, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. L. Teri, L. E. Gibbons, S. M. McCurry et al., “Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial,” JAMA, vol. 290, no. 15, pp. 2015–2022, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. D. B. FitzGerald, G. P. Crucian, J. B. Mielke et al., “Effects of donepezil on verbal memory after semantic processing in healthy older adults,” Cognitive and Behavioral Neurology, vol. 21, no. 2, pp. 57–64, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. S. Ferris, L. Schneider, M. Farmer, G. Kay, and T. Crook, “A double-blind, placebo-controlled trial of memantine in age-associated memory impairment (memantine in AAMI),” International Journal of Geriatric Psychiatry, vol. 22, no. 5, pp. 448–455, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. O. P. Almeida, N. T. Lautenschlager, S. Vasikaran, P. Leedman, A. Gelavis, and L. Flicker, “A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: effect on mood, cognition and quality of life,” Neurobiology of Aging, vol. 27, no. 1, pp. 141–149, 2006. View at Publisher · View at Google Scholar · View at Scopus
  92. M. M. Cherrier, A. M. Matsumoto, J. K. Amory et al., “The role of aromatization in testosterone supplementation: effects on cognition in older men,” Neurology, vol. 64, no. 2, pp. 290–296, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. P. R. Solomon, F. Adams, A. Silver, J. Zimmer, and R. DeVeaux, “Ginkgo for memory enhancement: a randomized controlled trial,” JAMA, vol. 288, no. 7, pp. 835–840, 2002. View at Publisher · View at Google Scholar
  94. J. H. Kang, N. Cook, J. Manson, J. E. Buring, and F. Grodstein, “A randomized trial of vitamin E supplementation and cognitive function in women,” Archives of Internal Medicine, vol. 166, no. 22, pp. 2462–2468, 2006. View at Publisher · View at Google Scholar · View at Scopus
  95. A. S. Berry, T. P. Zanto, W. C. Clapp et al., “The influence of perceptual training on working memory in older adults,” PLoS One, vol. 5, no. 7, article e11537, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. G. E. Smith, P. Housen, K. Yaffe et al., “A cognitive training program based on principles of brain plasticity: results from the Improvement in Memory with Plasticity-based Adaptive Cognitive Training (IMPACT) study,” Journal of the American Geriatrics Society, vol. 57, no. 4, pp. 594–603, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. L. D. Baker, L. L. Frank, K. Foster-Schubert et al., “Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer’s disease,” Journal of Alzheimer’s disease: JAD, vol. 22, no. 2, pp. 569–579, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. K. Ball, D. B. Berch, K. F. Helmers et al., “Effects of cognitive training interventions with older adults: a randomized controlled trial,” JAMA, vol. 288, no. 18, pp. 2271–2281, 2002. View at Publisher · View at Google Scholar · View at Scopus
  99. N. Berardi, C. Braschi, S. Capsoni, A. Cattaneo, and L. Maffei, “Environmental enrichment delays the onset of memory deficits and reduces neuropathological hallmarks in a mouse model of Alzheimer-like neurodegeneration,” Journal of Alzheimer’s Disease, vol. 11, no. 3, pp. 359–370, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. G. W. Arendash, M. F. Garcia, D. A. Costa, J. R. Cracchiolo, I. M. Wefes, and H. Potter, “Environmental enrichment improves cognition in aged Alzheimer’s transgenic mice despite stable β-amyloid deposition,” Neuroreport, vol. 15, no. 11, pp. 1751–1754, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. S. A. Wolf, G. Kronenberg, K. Lehmann et al., “Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer’s disease,” Biological Psychiatry, vol. 60, no. 12, pp. 1314–1323, 2006. View at Publisher · View at Google Scholar · View at Scopus
  102. K. Y. Liang, M. A. Mintun, A. M. Fagan et al., “Exercise and Alzheimer’s disease biomarkers in cognitively normal older adults,” Annals of Neurology, vol. 68, no. 3, pp. 311–318, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. A. M. Fagan, D. Head, A. R. Shah et al., “Decreased cerebrospinal fluid Abeta(42) correlates with brain atrophy in cognitively normal elderly,” Annals of Neurology, vol. 65, no. 2, pp. 176–183, 2009. View at Publisher · View at Google Scholar · View at Scopus
  104. C. M. Gidicsin, J. E. Maye, J. J. Locascio et al., “Cognitive activity relates to cognitive performance but not to Alzheimer disease biomarkers,” Neurology, vol. 85, no. 1, pp. 48–55, 2015. View at Publisher · View at Google Scholar · View at Scopus
  105. Z. Radak, S. Kumagai, A. W. Taylor, H. Naito, and S. Goto, “Effects of exercise on brain function: role of free radicals,” Applied Physiology, Nutrition, and Metabolism, vol. 32, no. 5, pp. 942–946, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. N. C. Berchtold, G. Chinn, M. Chou, J. P. Kesslak, and C. W. Cotman, “Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus,” Neuroscience, vol. 133, no. 3, pp. 853–861, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. Y. H. Ding, J. Li, W. X. Yao, J. A. Rafols, J. C. Clark, and Y. Ding, “Exercise preconditioning upregulates cerebral integrins and enhances cerebrovascular integrity in ischemic rats,” Acta Neuropathologica, vol. 112, no. 1, pp. 74–84, 2006. View at Publisher · View at Google Scholar · View at Scopus
  108. F. Sardi, L. Fassina, L. Venturini et al., “Alzheimer’s disease, autoimmunity and inflammation. The good, the bad and the ugly,” Autoimmunity Reviews, vol. 11, no. 2, pp. 149–153, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. E. Blotnick and L. Anglister, “Exercise modulates synaptic acetylcholinesterase at neuromuscular junctions,” Neuroscience, vol. 319, pp. 221–232, 2016. View at Publisher · View at Google Scholar · View at Scopus
  110. N. C. Berchtold, J. P. Kesslak, and C. W. Cotman, “Hippocampal brain-derived neurotrophic factor gene regulation by exercise and the medial septum,” Journal of Neuroscience Research, vol. 68, no. 5, pp. 511–521, 2002. View at Publisher · View at Google Scholar · View at Scopus