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Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer’s disease?

Molecular Psychiatry volume 18, pages 864–874 (2013)Cite this article

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Abstract

Western countries are experiencing aging populations and increased longevity; thus, the incidence of dementia and Alzheimer’s disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology; clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes.

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References

  1. NIH. Physical activity and cardiovascular health. NIH Consensus Development Panel on Physical Activity and Cardiovascular Health. JAMA 1996; 276: 241–246.

    Article  Google Scholar 

  2. Powell KE, Thompson PD, Caspersen CJ, Kendrick JS . Physical activity and the incidence of coronary heart disease. Annu Rev Public Health 1987; 8: 253–287.

    Article  CAS  PubMed  Google Scholar 

  3. Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 2003; 107: 3109–3116.

    Article  PubMed  Google Scholar 

  4. World Health Organisation. Chronic disease information sheets: physical activity 2006.

  5. Middleton LE, Mitnitski A, Fallah N, Kirkland SA, Rockwood K . Changes in cognition and mortality in relation to exercise in late life: a population based study. PLoS ONE 2008; 3: e3124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Barnes DE, Blackwell T, Stone KL, Goldman SE, Hillier T, Yaffe K . Cognition in older women: the importance of daytime movement. J Am Geriatr Soc 2008; 56: 1658–1664.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Yaffe K, Barnes D, Nevitt M, Lui LY, Covinsky K . A prospective study of physical activity and cognitive decline in elderly women: women who walk. Arch Intern Med 2001; 161: 1703–1708.

    Article  CAS  PubMed  Google Scholar 

  8. Podewils LJ, Guallar E, Kuller LH, Fried LP, Lopez OL, Carlson M et al. Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study. Am J Epidemiol 2005; 161: 639–651.

    Article  PubMed  Google Scholar 

  9. Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K . Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol 2001; 58: 498–504.

    Article  CAS  PubMed  Google Scholar 

  10. Adlard PA, Perreau VM, Pop V, Cotman CW . Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. J Neurosci 2005; 25: 4217–4221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Um HS, Kang EB, Leem YH, Cho IH, Yang CH, Chae KR et al. Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer’s disease in an NSE/APPsw-transgenic model. Int J Mol Med 2008; 22: 529–539.

    CAS  PubMed  Google Scholar 

  12. Spirduso WW, Clifford P . Replication of age and physical activity effects on reaction and movement time. J Gerontol 1978; 33: 26–30.

    Article  CAS  PubMed  Google Scholar 

  13. Weuve J, Kang JH, Manson JE, Breteler MM, Ware JH, Grodstein F . Physical activity, including walking, and cognitive function in older women. JAMA 2004; 292: 1454–1461.

    Article  CAS  PubMed  Google Scholar 

  14. Fabre C, Chamari K, Mucci P, Masse-Biron J, Prefaut C . Improvement of cognitive function by mental and/or individualized aerobic training in healthy elderly subjects. Int J Sports Med 2002; 23: 415–421.

    Article  CAS  PubMed  Google Scholar 

  15. Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 2008; 300: 1027–1037.

    Article  CAS  PubMed  Google Scholar 

  16. Angevaren M, Vanhees L, Wendel-Vos W, Verhaar HJ, Aufdemkampe G, Aleman A et al. Intensity, but not duration, of physical activities is related to cognitive function. Eur J Cardiovasc Prev Rehabil 2007; 14: 825–830.

    Article  PubMed  Google Scholar 

  17. Geda YE, Roberts RO, Knopman DS, Christianson TJ, Pankratz VS, Ivnik RJ et al. Physical exercise, aging, and mild cognitive impairment: a population-based study. Arch Neurol 67: 80–86.

  18. Shephard RJ . Limits to the measurement of habitual physical activity by questionnaires. Br J Sports Med 2003; 37: 197–206, discussion 206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Aadahl M, Kjaer M, Jorgensen T . Perceived exertion of physical activity: negative association with self-rated fitness. Scand J Public Health 2007; 35: 403–409.

    Article  PubMed  Google Scholar 

  20. Barnes DE, Yaffe K, Satariano WA, Tager IB . A longitudinal study of cardiorespiratory fitness and cognitive function in healthy older adults. J Am Geriatr Soc 2003; 51: 459–465.

    Article  PubMed  Google Scholar 

  21. Middleton LE, Manini TM, Simonsick EM, Harris TB, Barnes DE, Tylavsky F et al. Activity energy expenditure and incident cognitive impairment in older adults. Arch Intern Med 2011; 171: 1251–1257.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med 2006; 144: 73–81.

    Article  PubMed  Google Scholar 

  23. Scarmeas N, Luchsinger JA, Schupf N, Brickman AM, Cosentino S, Tang MX et al. Physical activity, diet, and risk of Alzheimer disease. JAMA 2009; 302: 627–637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Buchman AS, Boyle PA, Yu L, Shah RC, Wilson RS, Bennett DA . Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology 2012; 78: 1323–1329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wilson RS, Bennett DA, Bienias JL, Aggarwal NT, Mendes De Leon CF, Morris MC et al. Cognitive activity and incident AD in a population-based sample of older persons. Neurology 2002; 59: 1910–1914.

    Article  CAS  PubMed  Google Scholar 

  26. Wilson RS, Mendes De Leon CF, Barnes LL, Schneider JA, Bienias JL, Evans DA et al. Participation in cognitively stimulating activities and risk of incident Alzheimer disease. JAMA 2002; 287: 742–748.

    Article  PubMed  Google Scholar 

  27. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol 2009; 67: 71–79.

    Google Scholar 

  28. Williamson JD, Espeland M, Kritchevsky SB, Newman AB, King AC, Pahor M et al. Changes in cognitive function in a randomized trial of physical activity: results of the lifestyle interventions and independence for elders pilot study. J Gerontol A Biol Sci Med Sci 2009; 64: 688–694.

    Article  PubMed  Google Scholar 

  29. Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR et al. Ageing, fitness and neurocognitive function. Nature 1999; 400: 418–419.

    Article  CAS  PubMed  Google Scholar 

  30. Cassilhas RC, Viana VA, Grassmann V, Santos RT, Santos RF, Tufik S et al. The impact of resistance exercise on the cognitive function of the elderly. Med Sci Sports Exerc 2007; 39: 1401–1407.

    Article  PubMed  Google Scholar 

  31. Liu-Ambrose T, Nagamatsu LS, Graf P, Beattie BL, Ashe MC, Handy TC . Resistance training and executive functions: a 12-month randomized controlled trial. Arch Intern Med 2010; 170: 170–178.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Colcombe S, Kramer AF . Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci 2003; 14: 125–130.

    Article  PubMed  Google Scholar 

  33. Liu-Ambrose T, Nagamatsu LS, Voss MW, Khan KM, Handy TC . Resistance training and functional plasticity of the aging brain: a 12-month randomized controlled trial. Neurobiol Aging 2012; 33: 1690–1698.

    Article  PubMed  Google Scholar 

  34. Nagamatsu LS, Handy TC, Hsu CL, Voss M, Liu-Ambrose T . Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment. Arch Intern Med 2012; 172: 666–668.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Paterson DH, Warburton DE . Physical activity and functional limitations in older adults: a systematic review related to Canada's Physical Activity Guidelines. Int J Behav Nutr Phys Act 2010; 7: 38.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A et al. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med 2011; 269: 107–117.

    Article  CAS  PubMed  Google Scholar 

  37. Hamer M, Chida Y . Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol Med 2009; 39: 3–11.

    Article  CAS  PubMed  Google Scholar 

  38. Day DS . Exercise physiologists talk about sex differences. Med Sci Sports Exerc 2008; 40: 646–647.

    Article  PubMed  Google Scholar 

  39. Schuit AJ, Feskens EJ, Launer LJ, Kromhout D . Physical activity and cognitive decline, the role of the apolipoprotein e4 allele. Med Sci Sports Exerc 2001; 33: 772–777.

    Article  CAS  PubMed  Google Scholar 

  40. van Gelder BM, Tijhuis MA, Kalmijn S, Giampaoli S, Nissinen A, Kromhout D . Physical activity in relation to cognitive decline in elderly men: the FINE Study. Neurology 2004; 63: 2316–2321.

    Article  CAS  PubMed  Google Scholar 

  41. Abbott RD, White LR, Ross GW, Masaki KH, Curb JD, Petrovitch H . Walking and dementia in physically capable elderly men. JAMA 2004; 292: 1447–1453.

    Article  CAS  PubMed  Google Scholar 

  42. Ho SC, Woo J, Sham A, Chan SG, Yu AL . A 3-year follow-up study of social, lifestyle and health predictors of cognitive impairment in a Chinese older cohort. Int J Epidemiol 2001; 30: 1389–1396.

    Article  CAS  PubMed  Google Scholar 

  43. Pike CJ, Carroll JC, Rosario ER, Barron AM . Protective actions of sex steroid hormones in Alzheimer's disease. Front Neuroendocrinol 2009; 30: 239–258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Liang KY, Mintun MA, Fagan AM, Goate AM, Bugg JM, Holtzman DM et al. Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Ann Neurol 2010; 68: 311–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A et al. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease. J Alzheimers Dis 2010; 22: 569–579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Brown BM, Peiffer JJ, Taddei K, Lui JK, Laws SM, Gupta VB et al. Physical activity and amyloid-beta plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing. Mol Psychiatry 2012.

  47. Bugg JM, Head D . Exercise moderates age-related atrophy of the medial temporal lobe. Neurobiol Aging 2009; 32: 506–514.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E et al. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci 2003; 58: 176–180.

    Article  PubMed  Google Scholar 

  49. Erickson KI, Prakash RS, Voss MW, Chaddock L, Hu L, Morris KS et al. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus 2009; 19: 1030–1039.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E et al. Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci 2006; 61: 1166–1170.

    Article  PubMed  Google Scholar 

  51. Honea RA, Thomas GP, Harsha A, Anderson HS, Donnelly JE, Brooks WM et al. Cardiorespiratory fitness and preserved medial temporal lobe volume in Alzheimer disease. Alzheimer Dis Assoc Disord 2009; 23: 188–197.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 2011; 108: 3017–3022.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Miller SL, Celone K, DePeau K, Diamond E, Dickerson BC, Rentz D et al. Age-related memory impairment associated with loss of parietal deactivation but preserved hippocampal activation. Proc Natl Acad Sci USA 2008; 105: 2181–2186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Park DC, Reuter-Lorenz P . The adaptive brain: aging and neurocognitive scaffolding. Annu Rev Psychol 2009; 60: 173–196.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Voss MW, Prakash RS, Erickson KI, Basak C, Chaddock L, Kim JS et al. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci 2010; 2: 32.

    PubMed  PubMed Central  Google Scholar 

  56. Holzschneider K, Wolbers T, Roder B, Hotting K . Cardiovascular fitness modulates brain activation associated with spatial learning. Neuroimage 2012; 59: 3003–3014.

    Article  PubMed  Google Scholar 

  57. Erickson KI, Weinstein AM, Sutton BP, Prakash RS, Voss MW, Chaddock L et al. Beyond vascularization: aerobic fitness is associated with N-acetylaspartate and working memory. Brain Behav 2012; 2: 32–41.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Moffett JR, Namboodiri MA, Cangro CB, Neale JH . Immunohistochemical localization of N-acetylaspartate in rat brain. Neuroreport 1991; 2: 131–134.

    Article  CAS  PubMed  Google Scholar 

  59. Adlard PA, Perreau VM, Engesser-Cesar C, Cotman CW . The timecourse of induction of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus following voluntary exercise. Neurosci Lett 2004; 363: 43–48.

    Article  CAS  PubMed  Google Scholar 

  60. Winter B, Breitenstein C, Mooren FC, Voelker K, Fobker M, Lechtermann A et al. High impact running improves learning. Neurobiol Learn Mem 2007; 87: 597–609.

    Article  PubMed  Google Scholar 

  61. Fabrigoule C, Letenneur L, Dartigues JF, Zarrouk M, Commenges D, Barberger-Gateau P . Social and leisure activities and risk of dementia: a prospective longitudinal study. J Am Geriatr Soc 1995; 43: 485–490.

    Article  CAS  PubMed  Google Scholar 

  62. Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E et al. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 2009; 94: 1062–1069.

    Article  CAS  PubMed  Google Scholar 

  63. Neeper SA, Gomez-Pinilla F, Choi J, Cotman C . Exercise and brain neurotrophins. Nature 1995; 373: 109.

    Article  CAS  PubMed  Google Scholar 

  64. Holsinger RM, Schnarr J, Henry P, Castelo VT, Fahnestock M . Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer's disease. Brain Res Mol Brain Res 2000; 76: 347–354.

    Article  CAS  PubMed  Google Scholar 

  65. Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW . BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease. Neuron 1991; 7: 695–702.

    Article  CAS  PubMed  Google Scholar 

  66. Michalski B, Fahnestock M . Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease. Brain Res Mol Brain Res 2003; 111: 148–154.

    Article  CAS  PubMed  Google Scholar 

  67. Berchtold NC, Kesslak JP, Pike CJ, Adlard PA, Cotman CW . Estrogen and exercise interact to regulate brain-derived neurotrophic factor mRNA and protein expression in the hippocampus. Eur J Neurosci 2001; 14: 1992–2002.

    Article  CAS  PubMed  Google Scholar 

  68. Currie J, Ramsbottom R, Ludlow H, Nevill A, Gilder M . Cardio-respiratory fitness, habitual physical activity and serum brain derived neurotrophic factor (BDNF) in men and women. Neurosci Lett 2009; 451: 152–155.

    Article  CAS  PubMed  Google Scholar 

  69. Knaepen K, Goekint M, Heyman EM, Meeusen R . Neuroplasticity—exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sports Med 2010; 40: 765–801.

    Article  PubMed  Google Scholar 

  70. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease–is this type 3 diabetes? J Alzheimers Dis 2005; 7: 63–80.

    Article  CAS  PubMed  Google Scholar 

  71. Trejo JL, Carro E, Nunez A, Torres-Aleman I . Sedentary life impairs self-reparative processes in the brain: the role of serum insulin-like growth factor-I. Rev Neurosci 2002; 13: 365–374.

    Article  CAS  PubMed  Google Scholar 

  72. Torres-Aleman I . Serum growth factors and neuroprotective surveillance: focus on IGF-1. Mol Neurobiol 2000; 21: 153–160.

    Article  CAS  PubMed  Google Scholar 

  73. Aberg MA, Aberg ND, Hedbacker H, Oscarsson J, Eriksson PS . Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 2000; 20: 2896–2903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Trejo JL, Carro E, Torres-Aleman I . Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 2001; 21: 1628–1634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F . Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function. Neuroscience 2006; 140: 823–833.

    Article  CAS  PubMed  Google Scholar 

  76. McCusker RH, McCrea K, Zunich S, Dantzer R, Broussard SR, Johnson RW et al. Insulin-like growth factor-I enhances the biological activity of brain-derived neurotrophic factor on cerebrocortical neurons. J Neuroimmunol 2006; 179: 186–190.

    Article  CAS  PubMed  Google Scholar 

  77. Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D et al. Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci USA 2010; 107: 6058–6063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Martorana A, Mori F, Esposito Z, Kusayanagi H, Monteleone F, Codeca C et al. Dopamine modulates cholinergic cortical excitability in Alzheimer's disease patients. Neuropsychopharmacology 2009; 34: 2323–2328.

    Article  CAS  PubMed  Google Scholar 

  79. Sutoo D, Akiyama K . Regulation of brain function by exercise. Neurobiol Dis 2003; 13: 1–14.

    Article  CAS  PubMed  Google Scholar 

  80. Hattori S, Naoi M, Nishino H . Striatal dopamine turnover during treadmill running in the rat: relation to the speed of running. Brain Res Bull 1994; 35: 41–49.

    Article  CAS  PubMed  Google Scholar 

  81. Sarbadhikari SN, Saha AK . Moderate exercise and chronic stress produce counteractive effects on different areas of the brain by acting through various neurotransmitter receptor subtypes: a hypothesis. Theor Biol Med Model 2006; 3: 33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. van Praag H, Kempermann G, Gage FH . Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999; 2: 266–270.

    Article  CAS  PubMed  Google Scholar 

  83. van Praag H, Christie BR, Sejnowski TJ, Gage FH . Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 1999; 96: 13427–13431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR . Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 2004; 124: 71–79.

    Article  CAS  PubMed  Google Scholar 

  85. Endres M, Gertz K, Lindauer U, Katchanov J, Schultze J, Schrock H et al. Mechanisms of stroke protection by physical activity. Ann Neurol 2003; 54: 582–590.

    Article  PubMed  Google Scholar 

  86. Gertz K, Priller J, Kronenberg G, Fink KB, Winter B, Schrock H et al. Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase-dependent augmentation of neovascularization and cerebral blood flow. Circ Res 2006; 99: 1132–1140.

    Article  CAS  PubMed  Google Scholar 

  87. Jeon CY, Lokken RP, Hu FB, van Dam RM . Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review. Diabetes Care 2007; 30: 744–752.

    Article  PubMed  Google Scholar 

  88. Balkau B, Mhamdi L, Oppert JM, Nolan J, Golay A, Porcellati F et al. Physical activity and insulin sensitivity: the RISC study. Diabetes 2008; 57: 2613–2618.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ford ES, Li C, Zhao G, Pearson WS, Tsai J, Churilla JR . Sedentary behavior, physical activity, and concentrations of insulin among US adults. Metabolism 2010; 59: 1268–1275.

    Article  CAS  PubMed  Google Scholar 

  90. Carro E, Torres-Aleman I . The role of insulin and insulin-like growth factor I in the molecular and cellular mechanisms underlying the pathology of Alzheimer's disease. Eur J Pharmacol 2004; 490: 127–133.

    Article  CAS  PubMed  Google Scholar 

  91. Prasad S, Sung B, Aggarwal BB . Age-associated chronic diseases require age-old medicine: role of chronic inflammation. Prev Med 2012; 54 (Suppl): S29–S37.

    Article  CAS  PubMed  Google Scholar 

  92. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261: 921–923.

    Article  CAS  PubMed  Google Scholar 

  93. Mahley RW, Weisgraber KH, Huang Y . Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc Natl Acad Sci USA 2006; 103: 5644–5651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Obisesan TO, Umar N, Paluvoi N, Gillum RF . Association of leisure-time physical activity with cognition by apolipoprotein-E genotype in persons aged 60 years and over: the National Health and Nutrition Examination Survey (NHANES-III). Clin Interv Aging 2012; 7: 35–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Head D, Bugg JM, Goate AM, Fagan AM, Mintun MA, Benzinger T et al. Exercise engagement as a moderator of the effects of APOE genotype on amyloid deposition. Arch Neurol 2012; 69: 636–643.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Caspersen CJ, Powell KE, Christenson GM . Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 1985; 100: 126–131.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Barnes J, Behrens TK, Benden ME, Biddle S, Bond D, Brassard P et al. Letter to the Editor: standardized use of the terms ‘sedentary’ and ‘sedentary behaviours’. Appl Physiol Nutr Metab 2012; 37: 540–542.

    Article  Google Scholar 

  98. Rovio S, Kareholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease. Lancet Neurol 2005; 4: 705–711.

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr Laura Baker for her review and comments on the manuscript.

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  1. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia

    B M Brown & R N Martins

  2. School of Medical Sciences, Edith Cowan University, Perth, Australia

    B M Brown & R N Martins

  3. The McCusker Alzheimer’s Research Foundation, Perth, Australia

    B M Brown & R N Martins

  4. School of Psychology and Exercise Science, Murdoch University, Perth, Australia

    J J Peiffer

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Brown, B., Peiffer, J. & Martins, R. Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer’s disease?. Mol Psychiatry 18, 864–874 (2013). https://doi.org/10.1038/mp.2012.162

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