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Vascular hippocampal plasticity after aerobic exercise in older adults

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Abstract

Aerobic exercise in young adults can induce vascular plasticity in the hippocampus, a critical region for recall and recognition memory. In a mechanistic proof-of-concept intervention over 3 months, we investigated whether healthy older adults (60–77 years) also show such plasticity. Regional cerebral blood flow (rCBF) and volume (rCBV) were measured with gadolinium-based perfusion imaging (3 Tesla magnetic resonance image (MRI)). Hippocampal volumes were assessed by high-resolution 7 Tesla MRI. Fitness improvement correlated with changes in hippocampal perfusion and hippocampal head volume. Perfusion tended to increase in younger, but to decrease in older individuals. The changes in fitness, hippocampal perfusion and volume were positively related to changes in recognition memory and early recall for complex spatial objects. Path analyses indicated that fitness-related changes in complex object recognition were modulated by hippocampal perfusion. These findings indicate a preserved capacity of the aging human hippocampus for functionally relevant vascular plasticity, which decreases with progressing age.

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References

  1. 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.

    CAS  Article  Google Scholar 

  2. 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  Google Scholar 

  3. 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  Google Scholar 

  4. Tulving E . Memory and consciousness. Canadian Psychology 1985; 26: 1–12.

    Article  Google Scholar 

  5. Grady C . The cognitive neuroscience of ageing. Nat Rev Neurosci 2012; 13: 491–505.

    CAS  Article  Google Scholar 

  6. Voss MW, Vivar C, Kramer AF, van Praag H . Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn Sci 2013; 17: 525–544.

    Article  Google Scholar 

  7. Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA 2007; 104: 5638–5643.

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  9. Sahay A, Scobie KN, Hill AS, O'Carroll CM, Kheirbek MA, Burghardt NS et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 2011; 472: 466–470.

    CAS  Article  Google Scholar 

  10. Dery N, Pilgrim M, Gibala M, Gillen J, Wojtowicz JM, Macqueen G et al. Adult hippocampal neurogenesis reduces memory interference in humans: opposing effects of aerobic exercise and depression. Front Neurosci 2013; 7: 66.

    Article  Google Scholar 

  11. Vivar C, van Praag H . Functional circuits of new neurons in the dentate gyrus. Front Neural Circuits 2013; 7: 15.

    Article  Google Scholar 

  12. Vivar C, Potter MC, Choi J, Lee JY, Stringer TP, Callaway EM et al. Monosynaptic inputs to new neurons in the dentate gyrus. Nat Commun 2012; 3: 1107.

    Article  Google Scholar 

  13. Burke SN, Ryan L, Barnes CA . Characterizing cognitive aging of recognition memory and related processes in animal models and in humans. Front Aging Neurosci 2012; 4: 15.

    Article  Google Scholar 

  14. Eichenbaum H, Yonelinas AP, Ranganath C . The medial temporal lobe and recognition memory. Annu Rev Neurosci 2007; 30: 123–152.

    CAS  Article  Google Scholar 

  15. Baxter MG, Murray EA . Impairments in visual discrimination learning and recognition memory produced by neurotoxic lesions of rhinal cortex in rhesus monkeys. Eur J Neurosci 2001; 13: 1228–1238.

    CAS  Article  Google Scholar 

  16. Bussey TJ, Saksida LM, Murray EA . Impairments in visual discrimination after perirhinal cortex lesions: testing 'declarative' vs. 'perceptual-mnemonic' views of perirhinal cortex function. Eur J Neurosci 2003; 17: 649–660.

    Article  Google Scholar 

  17. Bartko SJ, Winters BD, Cowell RA, Saksida LM, Bussey TJ . Perceptual functions of perirhinal cortex in rats: zero-delay object recognition and simultaneous oddity discriminations. J Neurosci 2007; 27: 2548–2559.

    CAS  Article  Google Scholar 

  18. Burke SN, Wallace JL, Hartzell AL, Nematollahi S, Plange K, Barnes CA . Age-associated deficits in pattern separation functions of the perirhinal cortex: a cross-species consensus. Behav Neurosci 2011; 125: 836–847.

    Article  Google Scholar 

  19. Eichenbaum H, Sauvage M, Fortin N, Komorowski R, Lipton P . Towards a functional organization of episodic memory in the medial temporal lobe. Neurosci Biobehav Rev 2012; 36: 1597–1608.

    Article  Google Scholar 

  20. 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  Article  Google Scholar 

  21. Burdette JH, Laurienti PJ, Espeland MA, Morgan A, Telesford Q, Vechlekar CD et al. Using network science to evaluate exercise-associated brain changes in older adults. Front Aging Neurosci 2010; 2: 23.

    PubMed  PubMed Central  Google Scholar 

  22. Bakker A, Kirwan CB, Miller M, Stark CE . Pattern separation in the human hippocampal CA3 and dentate gyrus. Science 2008; 319: 1640–1642.

    CAS  Article  Google Scholar 

  23. Comijs HC, Gerritsen L, Penninx BW, Bremmer MA, Deeg DJ, Geerlings MI . The association between serum cortisol and cognitive decline in older persons. Am J Geriatr Psychiatry 2010; 18: 42–50.

    Article  Google Scholar 

  24. Mezzani A, Corra U, Bosimini E, Giordano A, Giannuzzi P . Contribution of peak respiratory exchange ratio to peak VO2 prognostic reliability in patients with chronic heart failure and severely reduced exercise capacity. Am Heart J 2003; 145: 1102–1107.

    Article  Google Scholar 

  25. Noonan V, Dean E . Submaximal exercise testing: clinical application and interpretation. Phys Ther 2000; 80: 782–807.

    CAS  PubMed  Google Scholar 

  26. Karvonen MJ, Kentala E, Mustala O . The effects of training on heart rate; a longitudinal study. Ann Med Exp Biol Fenn 1957; 35: 307–315.

    CAS  PubMed  Google Scholar 

  27. Borg E, Kaijser L . A comparison between three rating scales for perceived exertion and two different work tests. Scand J Med Sci Sports 2006; 16: 57–69.

    CAS  Article  Google Scholar 

  28. Jacobson E . Progressive relaxation. 2nd edn. Chicago: University of Chicago Press, 1938. p494.

    Google Scholar 

  29. Folstein MF, Robins LN, Helzer JE . The Mini-Mental State Examination. Arch Gen Psychiatry 1983; 40: 812.

    CAS  Article  Google Scholar 

  30. Beck AT, Steer RA, Beck GK B . Depression Inventory. 2nd edn. Manual San Antonio: The Psychological Corporation, 1996.

    Google Scholar 

  31. Helmstaedter C, Durwen HF . [The Verbal Learning and Retention Test. A useful and differentiated tool in evaluating verbal memory performance]. Schweiz Arch Neurol Psychiatr 1990; 141: 21–30.

    CAS  PubMed  Google Scholar 

  32. Rey A . L'examen psychologique dans les cas d'encephalopathie traumatique. Archives de Psychologie 1941; 28: 286–340.

    Google Scholar 

  33. Strauss E, Sherman EMS, Spreen O . A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary. 3rd New York: Oxford University Press, 2006).

    Google Scholar 

  34. Wechsler DA . Wechsler Adult Intelligence Scale. 3rd edn. San Antonio, TX: The Psychological Corporation, 1997.

    Google Scholar 

  35. Lehrl S . Mehrfachwahl-Wortschatz-Intelligenztest: MWT-B. Balingen: Spitta, 2005.

    Google Scholar 

  36. Hubley AM . Using the Rey-Osterrieth and modified Taylor complex figures with older adults: a preliminary examination of accuracy score comparability. Arch Clin Neuropsychol 2010; 25: 197–203.

    Article  Google Scholar 

  37. Casarotti A, Papagno C, Zarino B . Modified Taylor Complex Figure: Normative data from 290 adults. J Neuropsychol 2013; 8: 186–198.

    Article  Google Scholar 

  38. Streitburger DP, Moller HE, Tittgemeyer M, Hund-Georgiadis M, Schroeter ML, Mueller K . Investigating structural brain changes of dehydration using voxel-based morphometry. PloS One 2012; 7: e44195.

    Article  Google Scholar 

  39. Kempton MJ, Ettinger U, Foster R, Williams SC, Calvert GA, Hampshire A et al. Dehydration affects brain structure and function in healthy adolescents. Hum Brain Mapp 2011; 32: 71–79.

    Article  Google Scholar 

  40. Meng X-lR, Robert R, Donald B . Comparing correlated correlation coefficients. Psychological Bulletin 1992; 111: 172–175.

    Article  Google Scholar 

  41. Bandettini PA, Wong EC . Magnetic resonance imaging of human brain function. Principles, practicalities, and possibilities. Neurosurg Clin N Am 1997; 8: 345–371.

    CAS  Article  Google Scholar 

  42. Hu LT, Bentler PM . Cutoff criteria for fit indexes in covariance structure analysis: conventional criteria versus new alternatives. Structural Equation Modeling 1999; 6: 1–55.

    Article  Google Scholar 

  43. Stark SM, Yassa MA, Lacy JW, Stark CE . A task to assess behavioral pattern separation (BPS) in humans: Data from healthy aging and mild cognitive impairment. Neuropsychologia 2013; 51: 2442–2449.

    Article  Google Scholar 

  44. Licht T, Goshen I, Avital A, Kreisel T, Zubedat S, Eavri R et al. Reversible modulations of neuronal plasticity by VEGF. Proc Natl Acad Sci USA 2011; 108: 5081–5086.

    CAS  Article  Google Scholar 

  45. Makanya AN, Hlushchuk R, Djonov VG . Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling. Angiogenesis 2009; 12: 113–123.

    CAS  Article  Google Scholar 

  46. van Praag H, Shubert T, Zhao C, Gage FH . Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 2005; 25: 8680–8685.

    CAS  Article  Google Scholar 

  47. Jack CR Jr, Wiste HJ, Vemuri P, Weigand SD, Senjem ML, Zeng G et al. Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease. Brain 2010; 133: 3336–3348.

    Article  Google Scholar 

  48. Bomfim TR, Forny-Germano L, Sathler LB, Brito-Moreira J, Houzel JC, Decker H et al. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated Abeta oligomers. J Clin Invest 2012; 122: 1339–1353.

    CAS  Article  Google Scholar 

  49. Ekstrand J, Hellsten J, Tingstrom A . Environmental enrichment, exercise and corticosterone affect endothelial cell proliferation in adult rat hippocampus and prefrontal cortex. Neurosci Lett 2008; 442: 203–207.

    CAS  Article  Google Scholar 

  50. Raichlen DA, Alexander GE . Exercise, APOE genotype, and the evolution of the human lifespan. Trends Neurosci 2014; 37: 247–255.

    CAS  Article  Google Scholar 

  51. Thomas AG, Dennis A, Bandettini PA, Johansen-Berg H . The effects of aerobic activity on brain structure. Front Psychol 2012; 3: 86.

    Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  53. Trejo JL, Piriz J, Llorens-Martin MV, Fernandez AM, Bolos M, LeRoith D et al. Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects. Mol Psychiatry 2007; 12: 1118–1128.

    CAS  Article  Google Scholar 

  54. Correia SC, Perry G, Castellani R, Moreira PI . Is exercise-in-a-bottle likely to proffer new insights into Alzheimer's disease? J Neurochem 2013; 127: 4–6.

    CAS  Article  Google Scholar 

  55. Gerritsen L, Comijs HC, Deeg DJ, Penninx BW, Geerlings MI . Salivary cortisol, APOE-epsilon4 allele and cognitive decline in a prospective study of older persons. Neurobiol Aging 2011; 32: 1615–1625.

    CAS  Article  Google Scholar 

  56. Duzel E, Bunzeck N, Guitart-Masip M, Duzel S . Novelty-related motivation of anticipation and exploration by dopamine (NOMAD): implications for healthy aging. Neurosci Biobehav Rev 2010; 34: 660–669.

    Article  Google Scholar 

  57. Lovden M, Schaefer S, Noack H, Bodammer NC, Kuhn S, Heinze HJ et al. Spatial navigation training protects the hippocampus against age-related changes during early and late adulthood. Neurobiol Aging 2012; 33: 620 e629–620, e622.

    Article  Google Scholar 

  58. Curlik DM 2nd, Maeng LY, Agarwal PR, Shors TJ . Physical skill training increases the number of surviving new cells in the adult hippocampus. PloS One 2013; 8: e55850.

    CAS  Article  Google Scholar 

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Acknowledgements

We thank the German Center for Neurodegenerative Diseases and the Otto-von-Guericke University (IKND) for funding this study and the Leibniz Institute for Neurobiology for providing access to their 7 Tesla MR scanner. Furthermore, we thank Urte Schneider for recruitment and neuropsychological testing and Anica Weber for subfield segmentation. We also thank Hartmut Schütze for editing the figures. LB was supported by grants from the Swedish Research Council, the Swedish Research Council for Health, Working Life, and Welfare, Swedish Brain Power, an Alexander von Humboldt Research Award, and a donation from the af Jochnick Foundation.

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Correspondence to E Düzel.

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Maass, A., Düzel, S., Goerke, M. et al. Vascular hippocampal plasticity after aerobic exercise in older adults. Mol Psychiatry 20, 585–593 (2015). https://doi.org/10.1038/mp.2014.114

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