Advertisement

Forestalling Age-Related Brain Disorders

  • Mark P. MattsonEmail author
Chapter

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are progressive fatal age-related neurodegenerative disorders that place a major burden on patients, their family, and health-care providers. Stroke is also common in the elderly and often results in major long-term disabilities. Because the number of people in the 65–85-year-old age range (the ‘danger zone’ for AD, PD, and stroke) is increasing, and there are no effective treatments, it is critical that approaches for reducing the risk of these diseases be identified and implemented. Evidence is presented that lifestyles incorporating intermittent challenges to the brain and body may forestall AD and PD. Aerobic exercise, dietary challenges (e.g., intermittent fasting and consumption of vegetables and fruits), and intellectual challenges can stimulate neurons in ways that enhance their function and resistance to stress and aging. These challenges can stimulate the production of neurotrophic factors, improve neuronal energy metabolism, and enhance the ability of brain cells to repair damaged DNA and remove damaged proteins and mitochondria. While further research will be required to establish the optimal prescriptions for challenge-based lifestyles, it is clear that the recent increase in unchallenging (sedentary and overindulgent) lifestyles is contributing to the emerging epidemic of age-related neurodegenerative disorders.

Keywords

Adaptive stress responses Alzheimer’s disease Dietary energy intake Neuroplasticity Parkinson’s disease 

Abbreviations

AD

Alzheimer’s disease

AMP

Adenosine monophosphate

ANS

Autonomic nervous system

APP

Amyloid precursor protein

BDNF

Brain-derived neurotrophic factor

CERAD

Consortium to establish a registry for Alzheimer’s disease

CSF

Cerebrospinal fluid

CVD

Cardiovascular disease

HRV

Heart rate variability

HDL

High-density lipoprotein

IER

Intermittent energy restriction

LDL

Low-density lipoprotein

PD

Parkinson’s disease

T2D

Type-2 diabetes

References

  1. 1.
    Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19:181–92.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Mattson MP. Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metab. 2012;16:706–22.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Voss MW, Vivar C, Kramer AF, van Praag H. Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn Sci. 2013;17:525–44.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Barulli D, Stern Y. Efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in cognitive reserve. Trends Cogn Sci. 2013;17:502–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Lee J, Jo DG, Park D, Chung HY, Mattson MP. Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system. Pharmacol Rev. 2014;66:815–68.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, Cedergreen N, et al. Biological stress response terminology: integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol. 2007;222:122–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Rattan SI. Hormesis in aging. Ageing Res Rev. 2008;7:63–78.PubMedCrossRefGoogle Scholar
  8. 8.
    Mattson MP. Evolutionary aspects of human exercise–born to run purposefully. Ageing Res Rev. 2012;11:347–52.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Lee EB, Mattson MP. The neuropathology of obesity: insights from human disease. Acta Neuropathol. 2014;127:3–28.PubMedCrossRefGoogle Scholar
  10. 10.
    Mattson MP, Magnus T. Ageing and neuronal vulnerability. Nat Rev Neurosci. 2006;7:278–94.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    McCarten JR. Clinical evaluation of early cognitive symptoms. Clin Geriatr Med. 2013;29:791–807.PubMedCrossRefGoogle Scholar
  12. 12.
    Mattson MP. Superior pattern processing is the essence of the evolved human brain. Front Neurosci. 2014;8:265.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999;96:13427–31.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, Pearson M, Nassar M, Telljohann R, Maudsley S, Carlson O, John S, Laub DR, Mattson MP. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med. 2007;42:665–74.PubMedCrossRefGoogle Scholar
  15. 15.
    Klempel MC, Kroeger CM, Varady KA. Alternate day fasting (ADF) with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet. Metabolism. 2013;62:137–43.PubMedCrossRefGoogle Scholar
  16. 16.
    Harvie MN, Pegington M, Mattson MP, Frystyk J, Dillon B, Evans G, Cuzick J, Jebb SA, Martin B, Cutler RG, Son TG, Maudsley S, Carlson OD, Egan JM, Flyvbjerg A, Howell A. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond). 2011;35:714–27.CrossRefGoogle Scholar
  17. 17.
    Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, Mattson MP. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiol Dis. 2007;26:212–20.PubMedCrossRefGoogle Scholar
  18. 18.
    Griffioen KJ, Rothman SM, Ladenheim B, Wan R, Vranis N, Hutchison E, Okun E, Cadet JL, Mattson MP. Dietary energy intake modifies brainstem autonomic dysfunction caused by mutant α-synuclein. Neurobiol Aging. 2013;34:928–35.PubMedCrossRefGoogle Scholar
  19. 19.
    Arumugam TV, Phillips TM, Cheng A, Morrell CH, Mattson MP, Wan R. Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol. 2010;67:41–52.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Mattson MP, Allison DB, Fontana L, Harvie M, Longo VD, Malaisse WJ, Mosley M, Notterpek L, Ravussin E, Scheer FAJL, Seyfried T, Varady K, Panda S. Meal frequency and timing in health and disease. Proc Natl Acad Sci U S A. 2014;111:16647–53.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Tolppanen AM, Solomon A, Soininen H, Kivipelto M. Midlife vascular risk factors and Alzheimer’s disease: evidence from epidemiological studies. J Alzheimers Dis. 2012;32:531–40.PubMedGoogle Scholar
  22. 22.
    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;13:788–94.PubMedCrossRefGoogle Scholar
  23. 23.
    Prolla TA, Mattson MP. Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. Trends Neurosci. 2001;24:S21–S31.PubMedCrossRefGoogle Scholar
  24. 24.
    Stranahan AM, Norman ED, Lee K, Cutler RG, Telljohann RS, Egan JM, Mattson MP. Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus. 2008;18:1085–8.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Morrison CD, Pistell PJ, Ingram DK, Johnson WD, Liu Y, Fernandez-Kim SO, White CL, Purpera MN, Uranga RM, Bruce-Keller AJ, Keller JN. High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: implications for decreased Nrf2 signaling. J Neurochem. 2010;114:1581–9.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Cheng A, Wan R, Yang JL, Kamimura N, Son TG, Ouyang X, Luo Y, Okun E, Mattson MP. Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines. Nat Commun. 2012;3:1250.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Yang JL, Lin YT, Chuang PC, Bohr VA, Mattson MP. BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1. Neuromolecular Med. 2014;16:161–74.PubMedCrossRefGoogle Scholar
  28. 28.
    Qiu G, Spangler EL, Wan R, Miller M, Mattson MP, So KF, de Cabo R, Zou S, Ingram DK. Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocorticoids. Neurobiol Aging. 2012;33:2398–410.PubMedCrossRefGoogle Scholar
  29. 29.
    Kashiwaya Y, Bergman C, Lee JH, Wan R, King MT, Mughal MR, Okun E, Clarke K, Mattson MP, Veech RL. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2013;34:1530–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Andrews ZB. The extra-hypothalamic actions of ghrelin on neuronal function. Trends Neurosci. 2011;34:31–40.PubMedCrossRefGoogle Scholar
  31. 31.
    Loprinzi PD, Herod SM, Cardinal BJ, Noakes TD. Physical activity and the brain: a review of this dynamic, bi-directional relationship. Brain Res. 2013;1539:95–104.PubMedCrossRefGoogle Scholar
  32. 32.
    Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc. 2011;86:876–84.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Gregory MA, Gill DP, Petrella RJ. Brain health and exercise in older adults. Curr Sports Med Rep. 2013;12:256–71.PubMedCrossRefGoogle Scholar
  34. 34.
    Etnier J, Labban JD, Piepmeier AT, Davis ME, Henning DA. Effects of an acute bout of exercise on memory in 6th grade children. Pediatr Exerc Sci. 2014;26:250–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Byun K, Hyodo K, Suwabe K, Ochi G, Sakairi Y, Kato M, Dan I, Soya H. Positive effect of acute mild exercise on executive function via arousal-related prefrontal activations: an fNIRS study. Neuroimage. 2014;98:336–45.PubMedCrossRefGoogle Scholar
  36. 36.
    Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011;108:3017–22.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Rhyu IJ, Bytheway JA, Kohler SJ, Lange H, Lee KJ, Boklewski J, McCormick K, Williams NI, Stanton GB, Greenough WT, Cameron JL. Effects of aerobic exercise training on cognitive function and cortical vascularity in monkeys. Neuroscience. 2010;167:1239–48.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Nascimento CM, Pereira JR, Pires de Andrade L, Garuffi M, Ayan C, Kerr DS, Talib LL, Cominetti MR, Stella F. Physical exercise improves peripheral BDNF levels and cognitive functions in elderly mild cognitive impairment individuals with different BDNF Val66Met genotypes. J Alzheimers Dis. 2014. [Epub ahead of print].Google Scholar
  39. 39.
    Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Cholerton BA, Plymate SR, Fishel MA, Watson GS, Duncan GE, Mehta PD, Craft S. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer’s disease. J Alzheimers Dis. 2010;22:569–79.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Erickson KI, Prakash RS, Voss MW, Chaddock L, Hu L, Morris KS, White SM, Wójcicki TR, McAuley E, Kramer AF. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus. 2009;19:1030–9.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Scarmeas N, Luchsinger JA, Brickman AM, Cosentino S, Schupf N, Xin-Tang M, Gu Y, Stern Y. Physical activity and Alzheimer disease course. Am J Geriatr Psychiatry. 2011;19:471–81.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Baker LD, Bayer-Carter JL, Skinner J, Montine TJ, Cholerton BA, Callaghan M, Leverenz JB, Walter BK, Tsai E, Postupna N, Lampe J, Craft S. High-intensity physical activity modulates diet effects on cerebrospinal amyloid-β levels in normal aging and mild cognitive impairment. J Alzheimers Dis. 2012;28:137–46.PubMedPubMedCentralGoogle Scholar
  43. 43.
    van der Kolk NM, King LA. Effects of exercise on mobility in people with Parkinson’s disease. Mov Disord. 2013;28:1587–96.PubMedCrossRefGoogle Scholar
  44. 44.
    Quaney BM, Boyd LA, McDowd JM, Zahner LH, He J, Mayo MS, Macko RF. Aerobic exercise improves cognition and motor function poststroke. Neurorehabil Neural Repair. 2009;23:879–85.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Adlard PA, Perreau VM, Pop V, Cotman CW. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer’s disease. J Neurosci. 2005;25:4217–21.PubMedCrossRefGoogle Scholar
  46. 46.
    García-Mesa Y, López-Ramos JC, Giménez-Llort L, Revilla S, Guerra R, Gruart A, Laferla FM, Cristòfol R, Delgado-García JM, Sanfeliu C. Physical exercise protects against Alzheimer’s disease in 3xTg-AD mice. J Alzheimers Dis. 2011;24:421–54.PubMedGoogle Scholar
  47. 47.
    Maesako M, Uemura K, Kubota M, Kuzuya A, Sasaki K, Asada M, Watanabe K, Hayashida N, Ihara M, Ito H, Shimohama S, Kihara T, Kinoshita A. Environmental enrichment ameliorated high-fat diet-induced Aβ deposition and memory deficit in APP transgenic mice. Neurobiol Aging. 2012;33(5):1011.e11–23.CrossRefGoogle Scholar
  48. 48.
    Nichol KE, Poon WW, Parachikova AI, Cribbs DH, Glabe CG, Cotman CW. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid. J Neuroinflammation. 2008;5:13.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Lau YS, Patki G, Das-Panja K, Le WD, Ahmad SO. Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration. Eur J Neurosci. 2011;33:1264–74.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Tillerson JL, Caudle WM, Reverón ME, Miller GW. Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson’s disease. Neuroscience. 2003;119:899–911.PubMedCrossRefGoogle Scholar
  51. 51.
    Fredriksson A, Stigsdotter IM, Hurtig A, Ewalds-Kvist B, Archer T. Running wheel activity restores MPTP-induced functional deficits. J Neural Transm. 2011;118:407–20.PubMedCrossRefGoogle Scholar
  52. 52.
    Wang Z, Myers KG, Guo Y, Ocampo MA, Pang RD, Jakowec MW, Holschneider DP. Functional reorganization of motor and limbic circuits after exercise training in a rat model of bilateral parkinsonism. PLoS ONE. 2013;8(11):e80058.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Ding Y, Li J, Luan X, Ding YH, Lai Q, Rafols JA, Phillis JW, Clark JC, Diaz FG. Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin. Neuroscience. 2004;124:583–91.PubMedCrossRefGoogle Scholar
  54. 54.
    Ploughman M, Attwood Z, White N, Doré JJ, Corbett D. Endurance exercise facilitates relearning of forelimb motor skill after focal ischemia. Eur J Neurosci. 2007;25:3453–60.PubMedCrossRefGoogle Scholar
  55. 55.
    Gertz K, Priller J, Kronenberg G, Fink KB, Winter B, Schröck H, Ji S, Milosevic M, Harms C, Böhm M, Dirnagl U, Laufs U, Endres M. Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase-dependent augmentation of neovascularization and cerebral blood flow. Circ Res. 2006;99:1132–40.PubMedCrossRefGoogle Scholar
  56. 56.
    Han J, Pollak J, Yang T, Siddiqui MR, Doyle KP, Taravosh-Lahn K, Cekanaviciute E, Han A, Goodman JZ, Jones B, Jing D, Massa SM, Longo FM, Buckwalter MS. Delayed administration of a small molecule tropomyosin-related kinase B ligand promotes recovery after hypoxic-ischemic stroke. Stroke. 2012;43:1918–24.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Caccamo A, Maldonado MA, Bokov AF, Majumder S, Oddo S. CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A. 2010;107:22687–92.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Real CC, Ferreira AF, Chaves-Kirsten GP, Torrão AS, Pires RS, Britto LR. BDNF receptor blockade hinders the beneficial effects of exercise in a rat model of Parkinson’s disease. Neuroscience. 2013;237:118–29.PubMedCrossRefGoogle Scholar
  59. 59.
    Kapogiannis D, Mattson MP. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer’s disease. Lancet Neurol. 2011;10:187–98.PubMedCrossRefGoogle Scholar
  60. 60.
    Reddy PH. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular Med. 2008;10:291–315.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Canugovi C, Misiak M, Ferrarelli LK, Croteau DL, Bohr VA. The role of DNA repair in brain related disease pathology. 2013;12:578–87.Google Scholar
  62. 62.
    Yang JL, Lin YT, Chuang PC, Bohr VA, Mattson MP. BDNF and exercise enhance neuronal DNA repair by stimulating CREB-mediated production of apurinic/apyrimidinic endonuclease 1. Neuromolecular Med. 2014;16:161–74.PubMedCrossRefGoogle Scholar
  63. 63.
    Swain RA, Harris AB, Wiener EC, Dutka MV, Morris HD, Theien BE, Konda S, Engberg K, Lauterbur PC, Greenough WT. Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat. Neuroscience. 2003;117:1037–46.PubMedCrossRefGoogle Scholar
  64. 64.
    Cantwell JD. Cardiovascular aspects of running. Clin Sports Med. 1985;4:627–40.PubMedGoogle Scholar
  65. 65.
    Wan R, Weigand LA, Bateman R, Griffioen K, Mendelowitz D, Mattson MP. Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability. J Neurochem. 2014;129:573–80.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Bennett DA, Arnold SE, Valenzuela MJ, Brayne C, Schneider JA. Cognitive and social lifestyle: links with neuropathology and cognition in late life. Acta Neuropathol. 2014;127:137–50.PubMedCrossRefGoogle Scholar
  67. 67.
    Vemuri P, Lesnick TG, Przybelski SA, Machulda M, Knopman DS, Mielke MM, Roberts RO, Geda YE, Rocca WA, Petersen RC, Jack CR Jr. Association of lifetime intellectual enrichment with cognitive decline in the older population. JAMA Neurol. 2014;71:1017–24.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Riley KP, Snowdon DA, Desrosiers MF, Markesbery WR. Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study. Neurobiol Aging. 2005;26:341–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Stern Y. Cognitive reserve and Alzheimer disease. Alzheimer Dis Assoc Disord. 2006;20:112–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Shpanskaya KS, Choudhury KR, Hostage C Jr, Murphy KR, Petrella JR, Doraiswamy PM, Alzheimer’s Disease Neuroimaging Initiative. Educational attainment and hippocampal atrophy in the Alzheimer’s disease neuroimaging initiative cohort. J Neuroradiol. 2014. pii: S0150-9861(13)00128-4.Google Scholar
  71. 71.
    Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006;7:697–709.PubMedCrossRefGoogle Scholar
  72. 72.
    Freret T, Billard JM, Schumann-Bard P, Dutar P, Dauphin F, Boulouard M, Bouet V. Rescue of cognitive aging by long-lasting environmental enrichment exposure initiated before median lifespan. Neurobiol Aging 2012;33:1005.e1–10.CrossRefGoogle Scholar
  73. 73.
    Herring A, Yasin H, Ambrée O, Sachser N, Paulus W, Keyvani K. Environmental enrichment counteracts Alzheimer’s neurovascular dysfunction in TgCRND8 mice. Brain Pathol. 2008;18:32–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Veeraraghavalu K, Choi SH, Zhang X, Sisodia SS. Endogenous expression of FAD-linked PS1 impairs proliferation, neuronal differentiation and survival of adult hippocampal progenitors. Mol Neurodegener. 2013;8:41.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Maesako M, Uemura K, Kubota M, Kuzuya A, Sasaki K, Asada M, Watanabe K, Hayashida N, Ihara M, Ito H, Shimohama S, Kihara T, Kinoshita A. Environmental enrichment ameliorated high-fat diet-induced Aβ deposition and memory deficit in APP transgenic mice. Neurobiol Aging. 2012;33(5):1011.e11–23.CrossRefGoogle Scholar
  76. 76.
    Cracchiolo JR, Mori T, Nazian SJ, Tan J, Potter H, Arendash GW. Enhanced cognitive activity—over and above social or physical activity—is required to protect Alzheimer’s mice against cognitive impairment, reduce Abeta deposition, and increase synaptic immunoreactivity. Neurobiol Learn Mem. 2007;88:277–94.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Faherty CJ, Raviie Shepherd K, Herasimtschuk A, Smeyne RJ. Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism. Brain Res Mol Brain Res. 2005;134:170–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Jadavji NM, Kolb B, Metz GA. Enriched environment improves motor function in intact and unilateral dopamine-depleted rats. Neuroscience. 2006;140:1127–38.PubMedCrossRefGoogle Scholar
  79. 79.
    Goldberg NR, Fields V, Pflibsen L, Salvatore MF, Meshul CK. Social enrichment attenuates nigrostriatal lesioning and reverses motor impairment in a progressive 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Neurobiol Dis. 2012;45:1051–67.PubMedCrossRefGoogle Scholar
  80. 80.
    Biernaskie J, Corbett D. Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J Neurosci. 2001;21:5272–80.PubMedGoogle Scholar
  81. 81.
    Johansson BB, Belichenko PV. Neuronal plasticity and dendritic spines: effect of environmental enrichment on intact and postischemic rat brain. J Cereb Blood Flow Metab. 2002;22:89–96.PubMedCrossRefGoogle Scholar
  82. 82.
    Donato F, Rompani SB, Caroni P. Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning. Nature. 2013;504:272–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Hu YS, Long N, Pigino G, Brady ST, Lazarov O. Molecular mechanisms of environmental enrichment: impairments in Akt/GSK3β, neurotrophin-3 and CREB signaling. PLoS ONE. 2013;8(5):e64460.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Novkovic T, Mittmann T, Manahan-Vaughan D. BDNF contributes to the facilitation of hippocampal synaptic plasticity and learning enabled by environmental enrichment. Hippocampus. 2014. doi:10.1002/hipo.22342. [Epub ahead of print].Google Scholar
  85. 85.
    Ekstrand J, Hellsten J, Tingström A. Environmental enrichment, exercise and corticosterone affect endothelial cell proliferation in adult rat hippocampus and prefrontal cortex. Neurosci Lett. 2008;442:203–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Frisardi V, Panza F, Seripa D, Imbimbo BP, Vendemiale G, Pilotto A, Solfrizzi V. Nutraceutical properties of Mediterranean diet and cognitive decline: possible underlying mechanisms. J Alzheimers Dis. 2010;22:715–40.PubMedCrossRefGoogle Scholar
  87. 87.
    Gu Y, Scarmeas N. Dietary patterns in Alzheimer’s disease and cognitive aging. Curr Alzheimer Res. 2011;8:510–9.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Kesse-Guyot E, Andreeva VA, Ducros V, Jeandel C, Julia C, Hercberg S, Galan P. Carotenoid-rich dietary patterns during midlife and subsequent cognitive function. Br J Nutr. 2014;111:915–23.PubMedCrossRefGoogle Scholar
  89. 89.
    Beezhold BL, Johnston CS, Daigle DR. Vegetarian diets are associated with healthy mood states: a cross-sectional study in seventh day adventist adults. Nutr J. 2010;9:26. doi:10.1186/1475-2891-9-26.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Beezhold BL, Johnston CS. Restriction of meat, fish, and poultry in omnivores improves mood: a pilot randomized controlled trial. Nutr J. 2012;11:9.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Rendeiro C, Vauzour D, Kean RJ, Butler LT, Rattray M, Spencer JP, Williams CM. Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats. 2012;223:319–30.Google Scholar
  92. 92.
    Cartford MC, Gemma C, Bickford PC. Eighteen-month-old Fischer 344 rats fed a spinach-enriched diet show improved delay classical eyeblink conditioning and reduced expression of tumor necrosis factor alpha (TNFalpha) and TNFbeta in the cerebellum. J Neurosci. 2002;22:5813–6.PubMedGoogle Scholar
  93. 93.
    Poulose SM, Bielinski DF, Shukitt-Hale B. Walnut diet reduces accumulation of polyubiquitinated proteins and inflammation in the brain of aged rats. J Nutr Biochem. 2013;24:912–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Joseph JA, Shukitt-Hale B, Willis LM. Grape juice, berries, and walnuts affect brain aging and behavior. J Nutr. 2009;139:1813 S–7 S.CrossRefGoogle Scholar
  95. 95.
    Fernández-Fernández L, Comes G, Bolea I, Valente T, Ruiz J, Murtra P, Ramirez B, Anglés N, Reguant J, Morelló JR, Boada M, Hidalgo J, Escorihuela RM, Unzeta M. LMN diet, rich in polyphenols and polyunsaturated fatty acids, improves mouse cognitive decline associated with aging and Alzheimer’s disease. Behav Brain Res. 2012;228:261–71.PubMedCrossRefGoogle Scholar
  96. 96.
    Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging. 2001;22:993–1005.PubMedCrossRefGoogle Scholar
  97. 97.
    Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT. Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson’s disease. Free Radic Res. 2005;39:1119–25.PubMedCrossRefGoogle Scholar
  98. 98.
    Dohare P, Garg P, Jain V, Nath C, Ray M. Dose dependence and therapeutic window for the neuroprotective effects of curcumin in thromboembolic model of rat. Behav Brain Res. 2008;193:289–97.PubMedCrossRefGoogle Scholar
  99. 99.
    Wu A, Ying Z, Gomez-Pinilla F. Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition. Exp Neurol. 2006;197:309–17.PubMedCrossRefGoogle Scholar
  100. 100.
    Lee S, Kim J, Seo SG, Choi BR, Han JS, Lee KW, Kim J. Sulforaphane alleviates scopolamine-induced memory impairment in mice. Pharmacol Res. 2014;85:23–32.PubMedCrossRefGoogle Scholar
  101. 101.
    Morroni F, Tarozzi A, Sita G, Bolondi C, Zolezzi Moraga JM, Cantelli-Forti G, Hrelia P. Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson’s disease. Neurotoxicology. 2013;36:63–71.PubMedCrossRefGoogle Scholar
  102. 102.
    Zhao J, Kobori N, Aronowski J, Dash PK. Sulforaphane reduces infarct volume following focal cerebral ischemia in rodents. Neurosci Lett. 2006;393:108–12.PubMedCrossRefGoogle Scholar
  103. 103.
    Dash PK, Zhao J, Orsi SA, Zhang M, Moore AN. Sulforaphane improves cognitive function administered following traumatic brain injury. Neurosci Lett. 2009;460:103–7.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J. 2007;26:3169–79.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Singleton RH, Yan HQ, Fellows-Mayle W, Dixon CE. Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury. J Neurotrauma. 2010;27:1091–9.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993;90:7915–22.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Futuyma DJ, Agrawal AA. Macroevolution and the biological diversity of plants and herbivores. Proc Natl Acad Sci U S A. 2009;106:18054–61.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Isman MB. Botanical insecticides, deterrents, and repellents in modern agriculture and an increasingly regulated world. Annu Rev Entomol. 2006;51:45–66.PubMedCrossRefGoogle Scholar
  109. 109.
    Mattson MP, Cheng A. Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses. Trends Neurosci. 2006;29:632–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Moubarac JC, Martins AP, Claro RM, Levy RB, Cannon G, Monteiro CA. Consumption of ultra-processed foods and likely impact on human health. Evidence from Canada. Public Health Nutr. 2013;16:2240–8.PubMedCrossRefGoogle Scholar
  111. 111.
    Volkow ND, Wang GJ, Tomasi D, Baler RD. The addictive dimensionality of obesity. Biol Psychiatry. 2013;73:811–8.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Harvie M, Wright C, Pegington M, McMullan D, Mitchell E, Martin B, Cutler RG, Evans G, Whiteside S, Maudsley S, Camandola S, Wang R, Carlson OD, Egan JM, Mattson MP, Howell A. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr. 2013;110:1534–47.PubMedCrossRefGoogle Scholar
  113. 113.
    Mosley M, Spencer M. The fast diet. New York: atria books; 2013. p. 208.Google Scholar
  114. 114.
    Hunter R, Dayan AD, Wilson J. Alzheimer’s disease in one monozygotic twin. J Neurol Neurosurg Psychiatry. 1972;35:707–10.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Clare L, Wilson BA, Carter G, Hodges JR. Cognitive rehabilitation as a component of early intervention in Alzheimer’s disease: a single case study. Aging Ment Health. 2010;7:15–21.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Laboratory of NeurosciencesNational Institute on Aging Intramural Research ProgramBaltimoreUSA

Personalised recommendations