Physical Activity in Preventing Alzheimer’s Disease and Cognitive Decline: A Narrative Review

Abstract

A large body of epidemiological and experimental data exploring the relationship between physical activity (PA) and Alzheimer’s disease (AD) are now available. Despite observational evidence supporting a role for PA in delaying the onset of AD, randomised controlled trials have reported mixed findings, likely due to the heterogeneity in study cohorts, outcome measures, and the adopted PA intervention. The primary objective of this narrative review is to evaluate the extant evidence on the relationship between PA, cognitive decline and AD in older populations. The interaction between PA and the putative mechanisms underlying AD progression, including genetic factors and amyloid-β levels will be explored. In this context, particular attention will be given to studies assessing PA in the early clinical and preclinical, asymptomatic stages of AD. Based on current evidence, clinical considerations for implementation of exercise-based interventions are discussed, along with limitations of previous research and directions for future studies.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Wimo A, Guerchet M, Ali GC, Wu YT, Prina AM, Winblad B, et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement. 2017;13(1):1–7.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9(1):63–75.

    PubMed  Article  Google Scholar 

  3. 3.

    Wortmann M. Dementia: a global health priority-highlights from an ADI and World Health Organization report. Alzheimers Res Ther. 2012;4(5):40.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Graham WV, Bonito-Oliva A, Sakmar TP. Update on Alzheimer’s disease therapy and prevention strategies. Annu Rev Med. 2017;68:413–30.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012;148(6):1204–22.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Salthouse TA. When does age-related cognitive decline begin? Neurobiol Aging. 2009;30(4):507–14.

    PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–9.

    PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Epelbaum S, Genthon R, Cavedo E, Habert MO, Lamari F, Gagliardi G, et al. Preclinical Alzheimer’s disease: a systematic review of the cohorts underlying the concept. Alzheimers Dement. 2017;13(4):454–67.

    PubMed  Article  Google Scholar 

  9. 9.

    Jessen F, Wolfsgruber S, Wiese B, Bickel H, Mösch E, Kaduszkiewicz H, et al. AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimers Dement. 2014;10(1):76–83.

    PubMed  Article  Google Scholar 

  10. 10.

    Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, 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. Alzheimers Dement. 2011;7(3):270–9.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Mitchell AJ, Beaumont H, Ferguson D, Yadegarfar M, Stubbs B. Risk of dementia and mild cognitive impairment in older people with subjective memory complaints: meta-analysis. Acta Psychiatr Scand. 2014;130(6):439–51.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Sperling RA, Jack CR, Aisen PS. Testing the right target and right drug at the right stage. Sci Transl Med. 2011;3(111):111cm33.

    PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Haan MN, Wallace R. Can dementia be prevented? Brain aging in a population-based context. Annu Rev Public Health. 2004;25:1–24.

    PubMed  Article  Google Scholar 

  14. 14.

    Jessen F, Amariglio RE, Van Boxtel M, Breteler M, Ceccaldi M, Chételat G, et al. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimers Dement. 2014;10(6):844–52.

    PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–92.

    PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Herrup K. The case for rejecting the amyloid cascade hypothesis. Nat Neurosci. 2015;18(6):794–9.

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Vinters HV. Emerging concepts in Alzheimer’s disease. Annu Rev Pathol. 2015;10:291–319.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Sala Frigerio C, De Strooper B. Alzheimer’s disease mechanisms and emerging roads to novel therapeutics. Annu Rev Neurosci. 2016;39:57–79.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Karran E, Hardy J. A critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease. Ann Neurol. 2014;76(2):185–205.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Jonker C, Geerlings MI, Schmand B. Are memory complaints predictive for dementia? A review of clinical and population-based studies. Int J Geriatr Psychiatry. 2000;15(11):983–91.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Larrabee GJ, Crook TH. Estimated prevalence of age-associated memory impairment derived from standardized tests of memory function. Int Psychogeriatr. 1994;6(01):95–104.

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Crumley JJ, Stetler CA, Horhota M. Examining the relationship between subjective and objective memory performance in older adults: a meta-analysis. Psychol Aging. 2014;29(2):250–63.

    PubMed  Article  Google Scholar 

  23. 23.

    van der Flier WM, van Buchem MA, Weverling-Rijnsburger AWE, Mutsaers ER, Bollen ELEM, Admiraal-Behloul F, et al. Memory complaints in patients with normal cognition are associated with smaller hippocampal volumes. J Neurol. 2004;251(6):671–5.

    PubMed  Article  Google Scholar 

  24. 24.

    Mendonça MD, Alves L, Bugalho P. From subjective cognitive complaints to dementia who is at risk? A systematic review. Am J Alzheimers Dis Other Demen. 2015;31(2):105–14.

    Article  Google Scholar 

  25. 25.

    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(9):1027–37.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Shah T, Verdile G, Sohrabi H, Campbell A, Putland E, Cheetham C, et al. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly. Transl Psychiatry. 2014;4(12):e487.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255–63.

    PubMed  Article  Google Scholar 

  28. 28.

    Öhman H, Savikko N, Strandberg TE, Pitkälä KH. Effect of physical exercise on cognitive performance in older adults with mild cognitive impairment or dementia: a systematic review. Dement Geriatr Cogn Disord. 2014;38(5–6):347–65.

    PubMed  Article  Google Scholar 

  29. 29.

    Forbes D, Forbes SC, Blake CM, Thiessen EJ, Forbes S. Exercise programs for people with dementia. Cochrane Libr. 2015.doi:10.1002/14651858

  30. 30.

    Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med. 2003;163(13):1524–8.

    PubMed  Article  Google Scholar 

  31. 31.

    Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kåreholt I, Winblad B, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol. 2005;62(10):1556–60.

    PubMed  Article  Google Scholar 

  32. 32.

    Yaffe K, Weston AL, Blackwell T, Krueger KA. The metabolic syndrome and development of cognitive impairment among older women. Arch Neurol. 2009;66(3):324–8.

    PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Beydoun MA, Beydoun H, Wang Y. Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obes Rev. 2008;9(3):204–18.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiatry. 2010;67(6):505–12.

    PubMed  Article  Google Scholar 

  35. 35.

    Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol. 2011;10(9):819–28.

    PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Fontbonne A, Berr C, Ducimetière P, Alpérovitch A. Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects results of the epidemiology of vascular aging study. Diabetes care. 2001;24(2):366–70.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Munshi M, Grande L, Hayes M, Ayres D, Suhl E, Capelson R, et al. Cognitive dysfunction is associated with poor diabetes control in older adults. Diabetes Care. 2006;29(8):1794–9.

    PubMed  PubMed Central  Article  Google Scholar 

  38. 38.

    Grodstein F, Chen J, Wilson RS, Manson JE. Type 2 diabetes and cognitive function in community-dwelling elderly women. Diabetes Care. 2001;24(6):1060–5.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K. Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med. 2004;164(12):1327–33.

    PubMed  Article  Google Scholar 

  40. 40.

    Ryan CM, Freed MI, Rood JA, Cobitz AR, Waterhouse BR, Strachan MW. Improving metabolic control leads to better working memory in adults with type 2 diabetes. Diabetes Care. 2006;29(2):345–51.

    PubMed  Article  Google Scholar 

  41. 41.

    Cukierman T, Gerstein H, Williamson J. Cognitive decline and dementia in diabetes: systematic overview of prospective observational studies. Diabetologia. 2005;48(12):2460–9.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Kalil GZ, Haynes WG. Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications. Hypertens Res. 2012;35(1):4–16.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Wilmot EG, Edwardson CL, Achana FA, Davies MJ, Gorely T, Gray LJ, et al. Sedentary time in adults and the association with diabetes, cardiovascular disease and death: systematic review and meta-analysis. Diabetologia. 2012;55(1):2895–905.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    de Bruijn RF, Ikram MA. Cardiovascular risk factors and future risk of Alzheimer’s disease. BMC Med. 2014;12(1):130–9.

    PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Goldberg I, Auriel E, Russell D, Korczyn A. Microembolism, silent brain infarcts and dementia. J Neurol Sci. 2012;322(1):250–3.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Thorp AA, Owen N, Neuhaus M, Dunstan DW. Sedentary behaviors and subsequent health outcomes in adults: a systematic review of longitudinal studies, 1996–2011. Am J Prev Med. 2011;41(2):207–15.

    PubMed  Article  Google Scholar 

  47. 47.

    Grøntved A, Hu FB. Television viewing and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a meta-analysis. JAMA. 2011;305(23):2448–55.

    PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Manson JE, Skerrett PJ, Greenland P, VanItallie TB. The escalating pandemics of obesity and sedentary lifestyle. A call to action for clinicians. Arch Intern Med. 2004;164(3):249–58.

    PubMed  Article  Google Scholar 

  49. 49.

    Hu FB. Sedentary lifestyle and risk of obesity and type 2 diabetes. Lipids. 2003;38(2):103–8.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Mayer-Davis EJ, Costacou T. Obesity and sedentary lifestyle: modifiable risk factors for prevention of type 2 diabetes. Curr Diab Rep. 2001;1(2):170–6.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer’s disease: an analysis of population-based data. Lancet Neurol. 2014;13(8):788–94.

    PubMed  Article  Google Scholar 

  52. 52.

    Bellou V, Belbasis L, Tzoulaki I, Middleton LT, Ioannidis JP, Evangelou E. Systematic evaluation of the associations between environmental risk factors and dementia: an umbrella review of systematic reviews and meta-analyses. Alzheimers Dement. 2016;13(4):406–18.

    PubMed  Article  Google Scholar 

  53. 53.

    Etgen T, Sander D, Huntgeburth U, Poppert H, Förstl H, Bickel H. Physical activity and incident cognitive impairment in elderly persons: the INVADE study. Arch Intern Med. 2010;170(2):186–93.

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Middleton LE, Barnes DE, Lui LY, Yaffe K. Physical activity over the life course and its association with cognitive performance and impairment in old age. J Am Geriatr Soc. 2010;58(7):1322–6.

    PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Sofi F, Valecchi D, Bacci D, Abbate R, Gensini G, Casini A, et al. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med. 2011;269(1):107–17.

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    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(3):498–504.

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Hamer M, Chida Y. Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol Med. 2009;39(01):3–11.

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Buchman A, Boyle P, Yu L, Shah R, Wilson R, Bennett D. Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology. 2012;78(17):1323–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Focht BC, Sanders WM, Brubaker PH, Rejeski WJ. Initial validation of the CSA activity monitor during rehabilitative exercise among older adults with chronic disease. J Aging Phys Activ. 2003;11(3):293–304.

    Article  Google Scholar 

  60. 60.

    Boon H, Frisard M, Brown C, Jazwinski SM, Delany J, Ravussin E. Validation of accelerometers to assess physical activity in elderly subjects. Obes Res. 2003;11:8.

    Google Scholar 

  61. 61.

    Baranowski T. Validity and reliability of self report measures of physical-activity: an information-processing perspective. Res Q Exerc Sport. 1988;59(4):314–27.

    Article  Google Scholar 

  62. 62.

    Fratiglioni L, Paillard-Borg S, Winblad B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol. 2004;3(6):343–53.

    PubMed  Article  Google Scholar 

  63. 63.

    Sturman MT, Morris MC, de Leon CFM, Bienias JL, Wilson RS, Evans DA. Physical activity, cognitive activity, and cognitive decline in a biracial community population. Arch Neurol. 2005;62(11):1750–4.

    PubMed  Article  Google Scholar 

  64. 64.

    Wang H-X, Karp A, Winblad B, Fratiglioni L. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen project. Am J Epidemiol. 2002;155(12):1081–7.

    PubMed  Article  Google Scholar 

  65. 65.

    Niti M, Yap K-B, Kua E-H, Tan C-H, Ng T-P. Physical, social and productive leisure activities, cognitive decline and interaction with APOE-ε4 genotype in Chinese older adults. Int Psychogeriatr. 2008;20(2):237–51.

    PubMed  Article  Google Scholar 

  66. 66.

    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(7):639–51.

    PubMed  Article  Google Scholar 

  67. 67.

    Van de Winckel A, Feys H, De Weerdt W, Dom R. Cognitive and behavioural effects of music-based exercises in patients with dementia. Clin Rehabil. 2004;18(3):253–60.

    PubMed  Article  Google Scholar 

  68. 68.

    Arcoverde C, Deslandes A, Moraes H, Almeida C, Araujo NBd, Vasques PE, et al. Treadmill training as an augmentation treatment for Alzheimer? s disease: a pilot randomized controlled study. Arq Neuropsiquiatr. 2014;72(3):190–6.

    PubMed  Article  Google Scholar 

  69. 69.

    Venturelli M, Scarsini R, Schena F. Six-month walking program changes cognitive and ADL performance in patients with Alzheimer. Am J Alzheimers Dis Other Demen. 2011;26(5):381–8.

    PubMed  Article  Google Scholar 

  70. 70.

    van Belle G, Uhlmann RF, Hughes JP, Larson EB. Reliability of estimates of changes in mental status test performance in senile dementia of the Alzheimer type. J Clin Epidemiol. 1990;43(6):589–95.

    PubMed  Article  Google Scholar 

  71. 71.

    Eggermont L, Swaab D, Hol E, Scherder E. Walking the line: a randomised trial on the effects of a short term walking programme on cognition in dementia. J Neurol Neurosurg Psychiatry. 2009;80(7):802–4.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Bossers WJ, van der Woude LH, Boersma F, Hortobágyi T, Scherder EJ, van Heuvelen MJ. A 9-week aerobic and strength training program improves cognitive and motor function in patients with dementia: a randomized, controlled trial. Am J Geriatr Psychiatry. 2015;23(11):1106–16.

    PubMed  Article  Google Scholar 

  73. 73.

    Groot C, Hooghiemstra A, Raijmakers P, van Berckel B, Scheltens P, Scherder E, et al. The effect of physical activity on cognitive function in patients with dementia: a meta-analysis of randomized control trials. Ageing Res Rev. 2016;25:13–23.

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Steinberg M, Leoutsakos JMS, Podewils LJ, Lyketsos C. Evaluation of a home-based exercise program in the treatment of Alzheimer’s disease: the Maximizing Independence in Dementia (MIND) study. Int J Geriatr Psychiatry. 2009;24(7):680–5.

    PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Miu D, Szeto S, Mak Y. A randomised controlled trial on the effect of exercise on physical, cognitive and affective function in dementia subjects. Asian J Gerontol Geriatr. 2008;3:8–16.

    Google Scholar 

  76. 76.

    Kemoun G, Thibaud M, Roumagne N, Carette P, Albinet C, Toussaint L, et al. Effects of a physical training programme on cognitive function and walking efficiency in elderly persons with dementia. Dement Geriatr Cogn Disord. 2010;29(2):109–14.

    PubMed  Article  Google Scholar 

  77. 77.

    Kwak Y-S, Um S-Y, Son T-G, Kim D-J. Effect of regular exercise on senile dementia patients. Int J Sports Med. 2008;29(6):471–4.

    PubMed  Article  Google Scholar 

  78. 78.

    Rockwood K, Middleton L. Physical activity and the maintenance of cognitive function. Alzheimers Dement. 2007;3(2):S38–44.

    PubMed  Article  Google Scholar 

  79. 79.

    Semba RD, Moghekar AR, Hu J, Sun K, Turner R, Ferrucci L, et al. Klotho in the cerebrospinal fluid of adults with and without Alzheimer’s disease. Neurosci Lett. 2014;558:37–40.

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Papassotiropoulos A, Stephan DA, Huentelman MJ, Hoerndli FJ, Craig DW, Pearson JV, et al. Common Kibra alleles are associated with human memory performance. Science. 2006;314(5798):475–8.

    CAS  PubMed  Article  Google Scholar 

  81. 81.

    Milnik A, Heck A, Vogler C, Heinze HJ, de Quervain DJF, Papassotiropoulos A. Association of KIBRA with episodic and working memory: a meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2012;159(8):958–69.

    CAS  Article  Google Scholar 

  82. 82.

    Shardell M, Semba RD, Rosano C, Kalyani RR, Bandinelli S, Chia CW, et al. Plasma klotho and cognitive decline in older adults: findings from the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2015;71(5):677–82.

    PubMed  PubMed Central  Article  Google Scholar 

  83. 83.

    Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer disease meta analysis consortium. JAMA. 1997;278(16):1349–56.

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Yu J-T, Tan L, Hardy J. Apolipoprotein E in Alzheimer’s disease: an update. Annu Rev Neurosci. 2014;37:79–100.

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Liu C-C, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106–18.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. 86.

    Purnell C, Gao S, Callahan CM, Hendrie HC. Cardiovascular risk factors and incident Alzheimer disease: A systematic review of the literature. Alzheimer Dis Assoc Disord. 2009;23(1):1–10.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. 87.

    Song Y, Stampfer MJ, Liu S. Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med. 2004;141(2):137–47.

    PubMed  Article  Google Scholar 

  88. 88.

    Grimmer T, Tholen S, Yousefi BH, Alexopoulos P, Förschler A, Förstl H, et al. Progression of cerebral amyloid load is associated with the apolipoprotein E ε4 genotype in Alzheimer’s disease. Biol Psychiatry. 2010;68(10):879–84.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  89. 89.

    Dik MG, Jonker C, Comijs HC, Bouter LM, Twisk JWR, Van Kamp GJ, et al. Memory complaints and APOE-ε4 accelerate cognitive decline in cognitively normal elderly. Neurology. 2001;57(12):2217–22.

    CAS  PubMed  Article  Google Scholar 

  90. 90.

    Mosconi L, De Santi S, Brys M, Tsui WH, Pirraglia E, Glodzik-Sobanska L, et al. Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints. Biol Psychiatry. 2008;63(6):609–18.

    CAS  PubMed  Article  Google Scholar 

  91. 91.

    Schindowski K, Belarbi K, Buee L. Neurotrophic factors in Alzheimer’s disease: role of axonal transport. Genes Brain Behav. 2008;7(s1):43–56.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  92. 92.

    Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller LD. From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem. 2002;9(5):224–37.

    PubMed  PubMed Central  Article  Google Scholar 

  93. 93.

    Fumagalli F, Racagni G, Riva M. The expanding role of BDNF: a therapeutic target for Alzheimer’s disease? Pharmacogenom J. 2006;6(1):8–15.

    CAS  Article  Google Scholar 

  94. 94.

    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(5):695–702.

    CAS  PubMed  Article  Google Scholar 

  95. 95.

    Yu H, Zhang Z, Shi Y, Bai F, Xie C, Qian Y, et al. Association study of the decreased serum BDNF concentrations in amnestic mild cognitive impairment and the Val66Met polymorphism in Chinese Han. J Clin Psychiatry. 2008;69(7):1104–11.

    CAS  PubMed  Article  Google Scholar 

  96. 96.

    Holsinger RD, 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(2):347–54.

    CAS  PubMed  Article  Google Scholar 

  97. 97.

    Yasutake C, Kuroda K, Yanagawa T, Okamura T, Yoneda H. Serum BDNF, TNF-α and IL-1β levels in dementia patients. Eur Arch Psychiatry Clin Neurosci. 2006;256(7):402–6.

    PubMed  Article  Google Scholar 

  98. 98.

    Peng S, Wuu J, Mufson EJ, Fahnestock M. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem. 2005;93(6):1412–21.

    CAS  PubMed  Article  Google Scholar 

  99. 99.

    Shimada H, Makizako H, Yoshida D, Tsutsumimoto K, Anan Y, Uemura K, et al. A large, cross-sectional observational study of serum BDNF, cognitive function, and mild cognitive impairment in the elderly. Front Aging Neurosci. 2014;6:69.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  100. 100.

    Poduslo JF, Curran GL. Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res Mol Brain Res. 1996;36(2):280–6.

    CAS  PubMed  Article  Google Scholar 

  101. 101.

    Small BJ, Rosnick CB, Fratiglioni L, Bäckman L. Apolipoprotein E and cognitive performance: a meta-analysis. Psychol Aging. 2004;19(4):592–600.

    PubMed  Article  Google Scholar 

  102. 102.

    Schuit AJ, Feskens EJ, Launer LJ, Kromhout DAAN. Physical activity and cognitive decline, the role of the apolipoprotein e4 allele. Med Sci Sports Exerc. 2001;33(5):772–7.

    CAS  PubMed  Article  Google Scholar 

  103. 103.

    Etnier JL, Caselli RJ, Reiman EM, Alexander GE, Sibley BA, Tessier D, et al. Cognitive performance in older women relative to ApoE-e4 genotype and aerobic fitness. Med Sci Sports Exerc. 2007;39(1):199–207.

    CAS  PubMed  Article  Google Scholar 

  104. 104.

    Smith JC, Nielson KA, Woodard JL, Seidenberg M, Rao SM. Physical activity and brain function in older adults at increased risk for Alzheimer’s disease. Brain Sci. 2013;3(1):54–83.

    PubMed  PubMed Central  Article  Google Scholar 

  105. 105.

    Rovio S, Kåreholt I, Helkala E-L, 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(11):705–11.

    PubMed  Article  Google Scholar 

  106. 106.

    Correia PR, Scorza FA, da Silva SG, Pansani A, Toscano-Silva M, de Almeida AC, et al. Increased basal plasma brain-derived neurotrophic factor levels in sprint runners. Neurosci Bull. 2011;27(5):325–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  107. 107.

    Zoladz J, Pilc A, Majerczak J, Grandys M, Zapart-Bukowska J, Duda K. Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. J Physiol Pharmacol. 2008;59(Suppl 7):119–32.

    PubMed  Google Scholar 

  108. 108.

    Chan KL, Tong KY, Yip SP. Relationship of serum brain-derived neurotrophic factor (BDNF) and health-related lifestyle in healthy human subjects. Neurosci Lett. 2008;447(2):124–8.

    CAS  PubMed  Article  Google Scholar 

  109. 109.

    Jung SH, Kim J, Davis JM, Blair SN, Cho H-C. Association among basal serum BDNF, cardiorespiratory fitness and cardiovascular disease risk factors in untrained healthy Korean men. Eur J Appl Physiol. 2011;111(2):303–11.

    CAS  PubMed  Article  Google Scholar 

  110. 110.

    Nofuji Y, Suwa M, Moriyama Y, Nakano H, Ichimiya A, Nishichi R, et al. Decreased serum brain-derived neurotrophic factor in trained men. Neurosci Lett. 2008;437(1):29–32.

    CAS  PubMed  Article  Google Scholar 

  111. 111.

    Winker R, Lukas I, Perkmann T, Haslacher H, Ponocny E, Lehrner J, et al. Cognitive function in elderly marathon runners: cross-sectional data from the marathon trial (APSOEM). Wien Klin Wochenschr. 2010;122(23–24):704–16.

    CAS  PubMed  Article  Google Scholar 

  112. 112.

    Huang T, Larsen K, Ried-Larsen M, Møller N, Andersen LB. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans: a review. Scand J Med Sci Sports. 2014;24(1):1–10.

    PubMed  Article  Google Scholar 

  113. 113.

    Begliuomini S, Lenzi E, Ninni F, Casarosa E, Merlini S, Pluchino N, et al. Plasma brain-derived neurotrophic factor daily variations in men: correlation with cortisol circadian rhythm. J Endocrinol. 2008;197(2):429–35.

    CAS  PubMed  Article  Google Scholar 

  114. 114.

    Pluchino N, Cubeddu A, Begliuomini S, Merlini S, Giannini A, Bucci F, et al. Daily variation of brain-derived neurotrophic factor and cortisol in women with normal menstrual cycles, undergoing oral contraception and in postmenopause. Hum Reprod. 2009;24(9):2303–9.

    CAS  PubMed  Article  Google Scholar 

  115. 115.

    Griffin ÉW, Mullally S, Foley C, Warmington SA, O’Mara SM, Kelly ÁM. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males. Physiol Behav. 2011;104(5):934–41.

    CAS  PubMed  Article  Google Scholar 

  116. 116.

    Ruscheweyh R, Willemer C, Krüger K, Duning T, Warnecke T, Sommer J, et al. Physical activity and memory functions: an interventional study. Neurobiol Aging. 2011;32(7):1304–19.

    CAS  PubMed  Article  Google Scholar 

  117. 117.

    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. 2010;67(1):71–9.

    PubMed  PubMed Central  Article  Google Scholar 

  118. 118.

    Ferris LT, Williams JS, Shen C-L. The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc. 2007;39(4):728–34.

    CAS  PubMed  Article  Google Scholar 

  119. 119.

    Goekint M, Heyman E, Roelands B, Njemini R, Bautmans I, Mets T, et al. No influence of noradrenaline manipulation on acute exercise-induced increase of brain-derived neurotrophic factor. Med Sci Sports Exerc. 2008;40(11):1990–6.

    CAS  PubMed  Article  Google Scholar 

  120. 120.

    Gustafsson G, Lira CM, Johansson J, Wisén A, Wohlfart B, Ekman R, et al. The acute response of plasma brain-derived neurotrophic factor as a result of exercise in major depressive disorder. Psychiatry Res. 2009;169(3):244–8.

    CAS  PubMed  Article  Google Scholar 

  121. 121.

    Vega SR, Strüder HK, Wahrmann BV, Schmidt A, Bloch W, Hollmann W. Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans. Brain Res. 2006;1121(1):59–65.

    Article  CAS  Google Scholar 

  122. 122.

    Vega SR, Abel T, Lindschulten R, Hollmann W, Bloch W, Strüder H. Impact of exercise on neuroplasticity-related proteins in spinal cord injured humans. Neurosci. 2008;153(4):1064–70.

    Article  CAS  Google Scholar 

  123. 123.

    Tang SW, Chu E, Hui T, Helmeste D, Law C. Influence of exercise on serum brain-derived neurotrophic factor concentrations in healthy human subjects. Neurosci Lett. 2008;431(1):62–5.

    CAS  PubMed  Article  Google Scholar 

  124. 124.

    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(10):1062–9.

    CAS  PubMed  Article  Google Scholar 

  125. 125.

    Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity: exercise-induced response of peripheral brain-derived neurotrophic factor. Sports Med. 2010;40(9):765–801.

    PubMed  Article  Google Scholar 

  126. 126.

    Coelho F, Pereira D, Lustosa L, Silva J, Dias J, Dias R, et al. Physical therapy intervention (PTI) increases plasma brain-derived neurotrophic factor (BDNF) levels in non-frail and pre-frail elderly women. Arch Gerontol Geriatr. 2012;54(3):415–20.

    CAS  PubMed  Article  Google Scholar 

  127. 127.

    Yarrow JF, White LJ, McCoy SC, Borst SE. Training augments resistance exercise induced elevation of circulating brain derived neurotrophic factor (BDNF). Neurosci Lett. 2010;479(2):161–5.

    CAS  PubMed  Article  Google Scholar 

  128. 128.

    Correia PR, Pansani A, Machado F, Andrade M, Silva AC, Scorza FA, et al. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels. Clinics. 2010;65(11):1123–6.

    PubMed  PubMed Central  Article  Google Scholar 

  129. 129.

    Schiffer T, Schulte S, Hollmann W, Bloch W, Strüder H. Effects of strength and endurance training on brain-derived neurotrophic factor and insulin-like growth factor 1 in humans. Horm Metab Res. 2009;41(03):250–4.

    CAS  PubMed  Article  Google Scholar 

  130. 130.

    Levinger I, Goodman C, Matthews V, Hare DL, Jerums G, Garnham A, et al. BDNF, metabolic risk factors, and resistance training in middle-aged individuals. Med Sci Sports Exerc. 2008;40(3):535–41.

    PubMed  Article  Google Scholar 

  131. 131.

    Katoh-Semba R, Wakako R, Komori T, Shigemi H, Miyazaki N, Ito H, et al. Age-related changes in BDNF protein levels in human serum: differences between autism cases and normal controls. Int J Dev Neurosci. 2007;25(6):367–72.

    CAS  PubMed  Article  Google Scholar 

  132. 132.

    Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12(4):357–67.

    CAS  PubMed  Article  Google Scholar 

  133. 133.

    Vellas B, Aisen PS, Sampaio C, Carrillo M, Scheltens P, Scherrer B, et al. Prevention trials in Alzheimer’s disease: an EU-US task force report. Prog Neurobiol. 2011;95(4):594–600.

    PubMed  Article  Google Scholar 

  134. 134.

    Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack CR, Jagust W, et al. Ways toward an early diagnosis in Alzheimer’s disease: the Alzheimer’s disease neuroimaging initiative (ADNI). Alzheimers Dement. 2005;1(1):55–66.

    PubMed  PubMed Central  Article  Google Scholar 

  135. 135.

    Patwardhan MB, McCrory DC, Matchar DB, Samsa GP, Rutschmann OT. Alzheimer disease: operating characteristics of PET—a meta-analysis. Radiol. 2004;231(1):73–80.

    Article  Google Scholar 

  136. 136.

    Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306–19.

    CAS  PubMed  Article  Google Scholar 

  137. 137.

    Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31(8):1275–83.

    PubMed  Article  Google Scholar 

  138. 138.

    Nordberg A, Carter SF, Rinne J, Drzezga A, Brooks DJ, Vandenberghe R, et al. A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2013;40(1):104–14.

    CAS  PubMed  Article  Google Scholar 

  139. 139.

    Rowe CC, Bourgeat P, Ellis KA, Brown B, Lim YY, Mulligan R, et al. Predicting Alzheimer disease with β-amyloid imaging: results from the Australian imaging, biomarkers, and lifestyle study of ageing. Ann Neurol. 2013;74(6):905–13.

    CAS  PubMed  Article  Google Scholar 

  140. 140.

    Mosconi L, Berti V, Glodzik L, Pupi A, De Santi S, de Leon MJ. Pre-clinical detection of Alzheimer’s disease using FDG-PET, with or without amyloid imaging. J Alzheimers Dis. 2010;20(3):843–54.

    PubMed  PubMed Central  Article  Google Scholar 

  141. 141.

    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(3):311–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  142. 142.

    Brown B, Peiffer J, Taddei K, Lui J, Laws S, Gupta VB, et al. Physical activity and amyloid-β plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle study of ageing. Mol Psychiatry. 2013;18(8):875–81.

    CAS  PubMed  Article  Google Scholar 

  143. 143.

    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(5):636–43.

    PubMed  PubMed Central  Article  Google Scholar 

  144. 144.

    Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Update on hypothetical model of Alzheimer’s disease biomarkers. Lancet Neurol. 2013;12(2):207–16.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  145. 145.

    Ibanez V, Pietrini P, Alexander G, Furey M, Teichberg D, Rajapakse J, et al. Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer’s disease. Neurology. 1998;50(6):1585–93.

    CAS  PubMed  Article  Google Scholar 

  146. 146.

    Deeny SP, Winchester J, Nichol K, Roth SM, Wu JC, Dick M, et al. Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ɛ4 carriers. Alzheimers Dement. 2012;8(4):352–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  147. 147.

    Rolland Y, van Kan GA, Vellas B. Physical activity and Alzheimer’s disease: from prevention to therapeutic perspectives. J Am Med Dir Assoc. 2008;9(6):390–405.

    PubMed  Article  Google Scholar 

  148. 148.

    Warren JM, Ekelund U, Besson H, Mezzani A, Geladas N, Vanhees L. Assessment of physical activity—a review of methodologies with reference to epidemiological research: a report of the exercise physiology section of the European Association of Cardiovascular Prevention and Rehabilitation. Eur J Cardiovasc Prev Rehabil. 2010;17(2):127–39.

    PubMed  Article  Google Scholar 

  149. 149.

    Zaccai J. How to assess epidemiological studies. Postgrad Med J. 2004;80(941):140–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  150. 150.

    Aadahl M, Kjær M, Jørgensen T. Perceived exertion of physical activity: negative association with self-rated fitness. Scand J Public Health. 2007;35(4):403–9.

    PubMed  Article  Google Scholar 

  151. 151.

    Lindsay J, Laurin D, Verreault R, Hébert R, Helliwell B, Hill GB, et al. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002;156(5):445–53.

    PubMed  Article  Google Scholar 

  152. 152.

    Prakash RS, Voss MW, Erickson KI, Kramer AF. Physical activity and cognitive vitality. Annu Rev Psychol. 2015;66:769–97.

    PubMed  Article  Google Scholar 

  153. 153.

    van Uffelen JG, Paw MJCA, Hopman-Rock M, van Mechelen W. The effects of exercise on cognition in older adults with and without cognitive decline: a systematic review. Clin J Sport Med. 2008;18(6):486–500.

    PubMed  Article  Google Scholar 

  154. 154.

    Prince SA, Adamo KB, Hamel ME, Hardt J, Gorber SC, Tremblay M. A comparison of direct versus self-report measures for assessing physical activity in adults: a systematic review. Int J Behav Nutr Phys Act. 2008;5(1):56.

    PubMed  PubMed Central  Article  Google Scholar 

  155. 155.

    Rolland Y, Pillard F, Klapouszczak A, Reynish E, Thomas D, Andrieu S, et al. Exercise program for nursing home residents with Alzheimer’s disease: a 1-year randomized, controlled trial. J Am Geriatr Soc. 2007;55(2):158–65.

    PubMed  Article  Google Scholar 

  156. 156.

    Larson EB. Physical activity for older adults at risk for Alzheimer disease. JAMA. 2008;300(9):1077–9.

    CAS  PubMed  Article  Google Scholar 

  157. 157.

    Vellas B, Andrieu S, Sampaio C, Coley N, Wilcock G. Endpoints for trials in Alzheimer’s disease: a European task force consensus. Lancet Neurol. 2008;7(5):436–50.

    CAS  PubMed  Article  Google Scholar 

  158. 158.

    Vellas B, Andrieu S, Sampaio C, Wilcock G. Disease-modifying trials in Alzheimer’s disease: a European task force consensus. Lancet Neurol. 2007;6(1):56–62.

    PubMed  Article  Google Scholar 

  159. 159.

    McGlone J, Gupta S, Humphrey D, Oppenheimer S, Mirsen T, Evans DR. Screening for early dementia using memory complaints from patients and relatives. Arch Neurol. 1990;47(11):1189–93.

    CAS  PubMed  Article  Google Scholar 

  160. 160.

    Tierney MC, Szalai JP, Snow WG, Fisher RH. The prediction of Alzheimer disease: the role of patient and informant perceptions of cognitive deficits. Arch Neurol. 1996;53(5):423–7.

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Timothy J. Fairchild.

Ethics declarations

Funding

Stefano Brini was on a PhD scholarship from Murdoch University during the completion of this review.

Conflicts of interest

Ralph N. Martinsis is the founder and Chief Scientific Officer of the biotech company, Alzhyme. Hamid R. Sohrabi has received, and continues to receive, remuneration from activities with Takeda Pharmaceuticals. Stefano Brini, Jeremiah J. Peiffer, Mira Karrasch, Heikki Hämäläinen and Timothy J. Fairchild declare that they have no conflicts of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Brini, S., Sohrabi, H.R., Peiffer, J.J. et al. Physical Activity in Preventing Alzheimer’s Disease and Cognitive Decline: A Narrative Review. Sports Med 48, 29–44 (2018). https://doi.org/10.1007/s40279-017-0787-y

Download citation