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The Role of Vitamin E in Aging and Alzheimer’s Disease

  • Gunter P. EckertEmail author
Chapter
Part of the Nutrition and Health book series (NH)

Abstract

Rising life expectancy is leading to an increasing number of patients with age-related diseases, including neurodegenerative disorders such as Alzheimer’s disease (AD). One of the hallmarks of AD are elevated markers of oxidative damage, as increased concentrations of oxidized nucleic acids, proteins, and lipids have been found in AD brains. Vitamin E is an essential antioxidant micronutrient and plays an important role in protecting cells from oxidative damage, such as the harmful effects of free radicals observed in brain aging and AD. Animal studies showed sufficient evidence to consider a treatment with vitamin E for patients suffering from AD. However, the results of clinical studies on AD patients are conflicting. To date, there is no convincing evidence from meta-analyses on randomized, placebo-controlled trials that vitamin E alone or in combination with other antioxidants prevents the progression or improves cognitive function in people with mild cognitive impairment (MCI) or AD. Additional research is needed to explore the effects of vitamin E treatment on other clinically relevant outcomes, such as quality of life. Furthermore, and in addition to the practical challenges when conducting randomized trials among older people with AD, key issues that need to be carefully considered for further vitamin E therapy trials include dosing, timing, mono- or multimodal therapy, and selection of different vitamers including γ-tocopherol and tocotrienols.

Keywords

Alzheimer’s disease Clinical trials Mild cognitive impairment Reactive species Tocopherols Tocotrienols Vitamin E 

Abbreviations

ADAS-cog

Alzheimer’s Disease Assessment Scale-cognitive subscale

BPT

Brief Praxis Test

BSD

Blessed dementia scale

CDR

Clinical dementia rating

CDT

Clock drawing test

CERAD

Consortium to Establish a Registry in Alzheimer’s Disease

Clox-1

Spontaneous clock drawing task

CS

Cohort study

DMR SOC

The Dementia Questionnaire for Mentally Retarded Persons Sum of Cognitive Scores

DRS

Dementia Rating Scale

DS

Down syndrome

DSM-IV

Diagnostic and Statistical Manual of Mental Disorders-IV diagnosis

GSSG

Oxidized glutathione (glutathione disulfide)

LS

Longitudinal study

MCI

Mild cognitive impairment

MIS

Memory Impairment Screen

MMSE

Mini-Mental State Examination

nc

Not calculated

n.s.

Not specified

OLS

Open-label study

RCT

Randomized clinical trial

SIB

Severe Impairment Battery

TICS-m

Modified Telephone Interview for Cognitive Status

References

  1. 1.
    Abuja PM, Albertini R. Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clin Chim Acta. 2001;306(1–2):1–17.  https://doi.org/10.1016/S0009-8981(01)00393-X.PubMedCrossRefGoogle Scholar
  2. 2.
    Aksenov MY, Aksenova MV, Butterfield DA, Geddes JW, Markesbery WR. Protein oxidation in the brain in Alzheimer’s disease. Neuroscience. 2001;103(2):373–83. https://www.ncbi.nlm.nih.gov/pubmed/11246152?dopt=AbstractPlus PubMedCrossRefGoogle Scholar
  3. 3.
    Amanatkar HR, Papagiannopoulos B, Grossberg GT. Analysis of recent failures of disease modifying therapies in Alzheimer’s disease suggesting a new methodology for future studies. Expert Rev Neurother. 2017;  https://doi.org/10.1080/14737175.2016.1194203.
  4. 4.
    Andreyev AYI, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry-Moscow. 2005;70(2):200–14. https://doi.org/BCM70020246 [pii].PubMedCrossRefGoogle Scholar
  5. 5.
    Association, Alzheimer’s. 2012 Alzheimer’s disease facts and figures. Alzheimers Dement. 2012;8(2):131–68.  https://doi.org/10.1016/j.jalz.2012.02.001.CrossRefGoogle Scholar
  6. 6.
    Barnard ND, Bush AI, Ceccarelli A, Cooper J, de Jager CA, Erickson KI, Fraser G, et al. Dietary and lifestyle guidelines for the prevention of Alzheimer’s disease. Neurobiol Aging. 2014;35(Suppl 2):S74–8.  https://doi.org/10.1016/j.neurobiolaging.2014.03.033.PubMedCrossRefGoogle Scholar
  7. 7.
    Berg C, Trofast C, Bengtsson T. Platelets induce reactive oxygen species-dependent growth of human skin fibroblasts. Eur J Cell Biol. 2003;82(11):565–71.  https://doi.org/10.1078/0171-9335-00344.PubMedCrossRefGoogle Scholar
  8. 8.
    Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, Zonderman AB, Wang Y. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014;14:643.  https://doi.org/10.1186/1471-2458-14-643.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Birringer M, Pfluger P, Kluth D, Landes N, Brigelius-Flohé R. Identities and differences in the metabolism of tocotrienols and tocopherols in HepG2 cells. J Nutr. 2002;132(10):3113–8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12368403 PubMedCrossRefGoogle Scholar
  10. 10.
    Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297(8):842–57.  https://doi.org/10.1001/jama.297.8.842 [pii].
  11. 11.
    Borg J, Chereul E. Differential MRI patterns of brain atrophy in double or single transgenic mice for APP and/or SOD. J Neurosci Res. 2008;86(15):3275–84.  https://doi.org/10.1002/jnr.21778.
  12. 12.
    Brewer GJ. Why vitamin e therapy fails for treatment of Alzheimer’s disease. Lovell MA, editor. J Alzheimers Dis. IOS Press. 2010.  https://doi.org/10.3233/JAD-2010-1238.
  13. 13.
    Chen S-H, Xian-Le B, Jin W-S, Shen L-L, Wang J, Zhuang Z-Q, Zhang T, et al. Altered peripheral profile of blood cells in Alzheimer disease: a hospital-based case-control study. Medicine. 2017;96(21):e6843.  https://doi.org/10.1097/MD.0000000000006843.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Citron M. Alzheimer’s disease: strategies for disease modification. Nat Rev Drug Discov. 2010;9(5):387–98.  https://doi.org/10.1038/nrd2896 [pii].
  15. 15.
    Corbett A, Ballard C. The value of vitamin E as a treatment for Alzheimer’s disease remains unproven despite functional improvement, due to a lack of established effect on cognition or other outcomes from RCTs. Evid Based Med. 2014;19(4):140.  https://doi.org/10.1136/eb-2014-101741.PubMedCrossRefGoogle Scholar
  16. 16.
    Cummings J, Aisen PS, DuBois B, Frolich L, Jack CR Jr, Jones RW, Morris JC, Raskin J, Dowsett SA, Scheltens P. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016;8:39.  https://doi.org/10.1186/s13195-016-0207-9.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Czech C, Monning V, Tienari PJ, Hartmann T, Masters C, Beyreuther K, Forstl H. Apolipoprotein E-epsilon 4 allele and Alzheimer’s disease. Lancet. 1993;342(8882):1309.PubMedGoogle Scholar
  18. 18.
    Drachman DA. The amyloid hypothesis, time to move on: amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimers Dement. 2014;10(3):372–80.  https://doi.org/10.1016/j.jalz.2013.11.003.PubMedCrossRefGoogle Scholar
  19. 19.
    Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, Love S, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease. JAMA. 2014;311(1):33.  https://doi.org/10.1001/jama.2013.282834.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Eckert GP, Hooff GP, Strandjord DM, Igbavboa U, Volmer DA, Müller WE, Gibson Wood W, Muller W, Gibson Wood W. Regulation of the brain isoprenoids farnesyl- and geranylgeranylpyrophosphate is altered in male Alzheimer patients. Neurobiol Dis. 2009;35(2):251–7. http://www.ncbi.nlm.nih.gov/pubmed/19464372 PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Edrey YH, Salmon AB. Revisiting an age-old question regarding oxidative stress. Free Radic Biol Med. 2014;71(June):368–78.  https://doi.org/10.1016/j.freeradbiomed.2014.03.038.PubMedCrossRefGoogle Scholar
  22. 22.
    Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JCM, Breteler MMB. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002;287(24):3223–9. https://www.ncbi.nlm.nih.gov/pubmed/12076218?dopt=AbstractPlus PubMedCrossRefGoogle Scholar
  23. 23.
    Evans DA, Morris MC, Rajan KB. Vitamin E, memantine, and Alzheimer disease. JAMA. 2014;311(1):29.  https://doi.org/10.1001/jama.2013.282835.PubMedCrossRefGoogle Scholar
  24. 24.
    Farina N, Llewellyn D, Isaac MGEKN, Tabet N. Vitamin E for Alzheimer’s dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2017;18(4):CDC002854.  https://doi.org/10.1002/14651858.CD002854.pub5.
  25. 25.
    Fata G, Weber P, Mohajeri M. Effects of vitamin E on cognitive performance during ageing and in Alzheimer’s disease. Nutrients. 2014;6(12):5453–72.  https://doi.org/10.3390/nu6125453.
  26. 26.
    Fillenbaum GG, Kuchibhatla MN, Hanlon JT, Artz MB, Pieper CF, Schmader KE, Dysken MW, Gray SL. Dementia and Alzheimer’s disease in community-dwelling elders taking vitamin C and/or vitamin E. Ann Pharmacother. 2005;39(12):2009–14.  https://doi.org/10.1345/aph.1G280.PubMedCrossRefGoogle Scholar
  27. 27.
    Fotuhi M, Zandi PP, Hayden KM, Khachaturian AS, Szekely CA, Wengreen H, Munger RG, et al. Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the cache county study. Alzheimers Dement. 2008;4(3):223–7.  https://doi.org/10.1016/j.jalz.2008.01.004.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Frank J, Chin XWD, Schrader C, Eckert GP, Rimbach G. Do tocotrienols have potential as neuroprotective dietary factors? Ageing Res Rev. 2012;11(1):163–80.  https://doi.org/10.1016/j.arr.2011.06.006.PubMedCrossRefGoogle Scholar
  29. 29.
    Fukui K, Omoi N-O, Hayasaka T, Shinnkai T, Suzuki S, Abe K, Urano S. Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by vitamin E. Ann N Y Acad Sci. 2002;959(April):275–84. https://www.ncbi.nlm.nih.gov/pubmed/11976202?dopt=AbstractPlus PubMedCrossRefGoogle Scholar
  30. 30.
    Gabsi S, Gouider-Khouja N, Belal S, Fki M, Kefi M, Turki I, Ben Hamida M, Kayden H, Mebazaa R, Hentati F. Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. Eur J Neurol. 2001;8(5):477–81.PubMedCrossRefGoogle Scholar
  31. 31.
    Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol. 2012;69(7):836–41.  https://doi.org/10.1001/archneurol.2012.85.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Gardner RC, Valcour V, Yaffe K. Dementia in the oldest old: a multi-factorial and growing public health issue. Alzheimers Res Ther. 2013;5(4):27.  https://doi.org/10.1186/alzrt181.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Gauthier S. Should we encourage the use of high-dose vitamin E in persons with memory complaints as a preventive strategy against Alzheimer’s disease? J Psychiatry Neurosci. 2000;25(4):394.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Go Y-M, Jones DP. Redox theory of aging: implications for health and disease. Clin Sci. 2017;131(14):1669–88.  https://doi.org/10.1042/CS20160897.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Grodstein F, Chen J, Willett WC. High-dose antioxidant supplements and cognitive function in community-dwelling elderly women. Am J Clin Nutr. 2003;77(4):975–84.  https://doi.org/10.1093/ajcn/77.4.975.PubMedCrossRefGoogle Scholar
  36. 36.
    Guan J-Z, Guan W-P, Maeda T, Makino N. Effect of vitamin E administration on the elevated oxygen stress and the telomeric and subtelomeric status in Alzheimer’s disease. Gerontology. 2012;58(1):62–9.  https://doi.org/10.1159/000327821.PubMedCrossRefGoogle Scholar
  37. 37.
    Guggenheim MA, Ringel SP, Silverman A, Grabert BE, Neville HE. Progressive neuromuscular disease in children with chronic cholestasis and vitamin E deficiency: clinical and muscle biopsy findings and treatment with alpha-tocopherol. Ann N Y Acad Sci. 1982;393:84–95.PubMedCrossRefGoogle Scholar
  38. 38.
    Gugliandolo A, Bramanti P, Mazzon E. Role of vitamin E in the treatment of Alzheimer’s disease: evidence from animal models. Int J Mol Sci. 2017;18:2504.  https://doi.org/10.3390/ijms18122504.PubMedCentralCrossRefGoogle Scholar
  39. 39.
    Guzior N, Wieckowska A, Panek D, Malawska B. Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer’s disease. Curr Med Chem. 2015;22(3):373–404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=25386820 PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Harman D. Aging – a theory based on free-radical and radiation-chemistry. J Gerontol. 1956;11(3):298–300. isi:A1956CHD5000009PubMedCrossRefGoogle Scholar
  41. 41.
    Hayden KM, Welsh-Bohmer KA, Wengreen HJ, Zandi PP, Lyketsos CG, Breitner JCS. Risk of mortality with vitamin E supplements: the Cache County study. Am J Med. 2007;120(2):180–4.  https://doi.org/10.1016/J.AMJMED.2006.03.039.PubMedCrossRefGoogle Scholar
  42. 42.
    Hekimi S, Lapointe J, Wen Y. Taking a ‘good’ look at free radicals in the aging process. Trends Cell Biol. 2011;21(10):569–76.  https://doi.org/10.1016/J.TCB.2011.06.008.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Hensley K, Barnes LL, Christov A, Tangney C, Honer WG, Schneider JA, Bennett DA, Morris MC. Analysis of postmortem ventricular cerebrospinal fluid from patients with and without dementia indicates association of vitamin e with neuritic plaques and specific measures of cognitive performance. J Alzheimers Dis. 2011;24(4):767–74.  https://doi.org/10.3233/JAD-2011-101995.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Hermann DM. Insufficient evidence for vitamin E in Alzheimer’s disease. Alzheimers Dement (N Y). 2016;2(3):199–201.  https://doi.org/10.1016/j.trci.2016.08.003.CrossRefGoogle Scholar
  45. 45.
    Herrup K. The case for rejecting the amyloid cascade hypothesis. Nat Neurosci. 2015;18(6):794–9.  https://doi.org/10.1038/nn.4017.PubMedCrossRefGoogle Scholar
  46. 46.
    Hooff GP, Gibson Wood W, Müller WE, Eckert GP. Isoprenoids, small GTPases and Alzheimer’s disease. Biochim Biophys Acta. 2010;1801:896–905.  https://doi.org/10.1016/j.bbalip.2010.03.014.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Huebbe P, Lodge JK, Rimbach G. Implications of apolipoprotein E genotype on inflammation and vitamin E status. Mol Nutr Food Res. 2010;54(5):623–30.  https://doi.org/10.1002/mnfr.200900398.PubMedCrossRefGoogle Scholar
  48. 48.
    Ihl R, Bunevicius R, Frolich L, Winblad B, Schneider LS, Dubois B, Burns A, Thibaut F, Kasper S, Moller HJ. World federation of societies of biological psychiatry guidelines for the pharmacological treatment of dementias in primary care. Int J Psychiatry Clin Pract. 2015;19(1):2–7.  https://doi.org/10.3109/13651501.2014.961931.PubMedCrossRefGoogle Scholar
  49. 49.
    International, Alzheimer’s Disease. World Alzheimer report 2015. London: Alzheimer’s Disease International (ADI); 2015.Google Scholar
  50. 50.
    Jack CR, Petersen RC, Grundman M, Jin S, Gamst A, Ward CP, Sencakova D, et al. Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI. Neurobiol Aging. 2008;29(9):1285–95.  https://doi.org/10.1016/j.neurobiolaging.2007.03.004.PubMedCrossRefGoogle Scholar
  51. 51.
    Jiménez-Jiménez FJ, de Bustos F, Molina JA, Benito-León J, Tallón-Barranco A, Gasalla T, Ortí-Pareja M, et al. Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer’s disease. J Neural Transm. 1997;104(6–7):703–10.  https://doi.org/10.1007/BF01291887.PubMedCrossRefGoogle Scholar
  52. 52.
    Jolitha AB, Subramanyam MV, Asha Devi S. Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: studies on superoxide dismutase isoenzymes and protein oxidation status. Exp Gerontol. 2006;41(8):753–63.  https://doi.org/10.1016/j.exger.2006.04.007.PubMedCrossRefGoogle Scholar
  53. 53.
    Kang JH, Cook N, Manson JA, Buring JE, Grodstein F. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med. 2015;166(22):2462–8.  https://doi.org/10.1001/archinte.166.22.2462.CrossRefGoogle Scholar
  54. 54.
    Kidd PM. Alzheimer’s disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention. Altern Med Rev. 2008;13(2):85–115. http://www.ncbi.nlm.nih.gov/pubmed/18590347 PubMedGoogle Scholar
  55. 55.
    Kim GH, Kim JE, Rhie SJ, Yoon S. The role of oxidative stress in neurodegenerative diseases. Exp Neurol. 2015;24(4):325–40. http://synapse.koreamed.org/DOIx.php?id=10.5607/en.2015.24.4.325 Google Scholar
  56. 56.
    Klapcinska B, Derejczyk J, Wieczorowska-Tobis K, Sobczak A, Sadowska-Krepa E, Danch A. Antioxidant defense in centenarians (a preliminary study). Acta Biochim Pol. 2000;47(2):281–92.PubMedGoogle Scholar
  57. 57.
    Klosowska A, Cwiklinska A, Kuchta A, Berlinska A, Jankowski M, Wierzba J. Down syndrome, increased risk of dementia and lipid disturbances. Dev Period Med. 2017;21(1):69–73. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emexa&NEWS=N&AN=618458967 PubMedGoogle Scholar
  58. 58.
    Kontush A, Mann U, Arlt S, Ujeyl A, Lührs C, Müller-Thomsen T, Beisiegel U. Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer’s disease. Free Radic Biol Med. 2001;31(3):345–54.  https://doi.org/10.1016/S0891-5849(01)00595-0.PubMedCrossRefGoogle Scholar
  59. 59.
    Kryscio RJ, Abner EL, Caban-Holt A, Lovell M, Goodman P, Darke AK, Yee M, Crowley J, Schmitt FA. Association of antioxidant supplement use and dementia in the prevention of Alzheimer’s disease by vitamin E and selenium trial (PREADViSE). JAMA Neurol. 2017;74(5):567.  https://doi.org/10.1001/jamaneurol.2016.5778.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Lansdall CJ. An effective treatment for Alzheimer’s disease must consider both amyloid and tau. Biosci Horiz. 2014;7(0):hzu002-hzu002.  https://doi.org/10.1093/biohorizons/hzu002.CrossRefGoogle Scholar
  61. 61.
    Liochev SI. Reflections on the theories of aging, of oxidative stress, and of science in general. is it time to abandon the free radical (oxidative stress) theory of aging? Antioxid Redox Signal. 2015;23(3):187–207.  https://doi.org/10.1089/ars.2014.5928.PubMedCrossRefGoogle Scholar
  62. 62.
    Lloret A, Badía M-C, Mora NJ, Pallardó FV, Alonso M-D, Viña J. Vitamin E paradox in Alzheimer’s disease: it does not prevent loss of cognition and may even be detrimental. J Alzheimers Dis. 2009;17(1):143–9.  https://doi.org/10.3233/JAD-2009-1033.PubMedCrossRefGoogle Scholar
  63. 63.
    Lott IT. Down’s syndrome, aging, and Alzheimer’s disease: a clinical review. Ann N Y Acad Sci. 1982;396:15–27.PubMedCrossRefGoogle Scholar
  64. 64.
    Lott IT, Doran E, Nguyen VQ, Tournay A, Head E, Gillen DL. Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation. Am J Med Genet A. 2011;155(8):1939–48.  https://doi.org/10.1002/ajmg.a.34114.
  65. 65.
    Mailloux RJ, Jin X, Willmore WG. Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions. Redox Biol Elsevier. 2014;2(C):123–39.  https://doi.org/10.1016/j.redox.2013.12.011.CrossRefGoogle Scholar
  66. 66.
    Mangialasche F, Kivipelto M, Mecocci P, Rizzuto D, Palmer K, Winblad B, Fratiglioni L. High plasma levels of vitamin E forms and reduced Alzheimer’s disease risk in advanced age. J Alzheimers Dis. 2010;20(4):1029–37.  https://doi.org/10.3233/JAD-2010-091450.PubMedCrossRefGoogle Scholar
  67. 67.
    Mangialasche F, Xu W, Kivipelto M, Costanzi E, Ercolani S, Pigliautile M, Cecchetti R, et al. Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiol Aging. 2012;33(10):2282–90.  https://doi.org/10.1016/j.neurobiolaging.2011.11.019.PubMedCrossRefGoogle Scholar
  68. 68.
    Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD. The role of reactive oxygen species in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease: a mini review. Oxidative Med Cell Longev. 2016;  https://doi.org/10.1155/2016/8590578.
  69. 69.
    Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. 2000;54(6):1265–72. http://www.ncbi.nlm.nih.gov/pubmed/10746596 PubMedCrossRefGoogle Scholar
  70. 70.
    Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056.  https://doi.org/10.1038/nrdp.2015.56.PubMedCrossRefGoogle Scholar
  71. 71.
    Meng J, Lv Z, Qiao X, Li X, Li Y, Zhang Y, Chen C. The decay of redox-stress response capacity is a substantive characteristic of aging: revising the redox theory of aging. Redox Biol. 2017;11(April):365–74.  https://doi.org/10.1016/j.redox.2016.12.026.PubMedCrossRefGoogle Scholar
  72. 72.
    Michaelson DM. APOE epsilon4: the most prevalent yet understudied risk factor for Alzheimer’s disease. Alzheimers Dement. 2014;10(6):861–8.  https://doi.org/10.1016/j.jalz.2014.06.015.PubMedCrossRefGoogle Scholar
  73. 73.
    Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, Wilson RS, Scherr PA. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA. 2002a;287(24):3230–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Morris MC, Evans DA, Bienias JL, Tangney CC, Wilson RS. Vitamin E and cognitive decline in older persons. Arch Neurol. 2002b;59(7):1125–32.PubMedCrossRefGoogle Scholar
  75. 75.
    Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS, Aggarwal NT, Scherr PA. Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr. 2005;81(2):508–14. https://doi.org/81/2/508 [pii].PubMedCrossRefGoogle Scholar
  76. 76.
    Morris MC, Schneider JA, Li H, Tangney CC, Nag S, Bennett DA, Honer WG, Barnes LL. Brain tocopherols related to Alzheimer’s disease neuropathology in humans. Alzheimers Dement. 2014;  https://doi.org/10.1016/j.jalz.2013.12.015.
  77. 77.
    Muller, DPR. 2010. Vitamin E and neurological function. Mol Nutr Food Res.  https://doi.org/10.1002/mnfr.200900460.
  78. 78.
    Musiek ES, Holtzman DM. Three dimensions of the amyloid hypothesis: time, space and ‘Wingmen’. Nat Neurosci. 2015;18(6):800–6.  https://doi.org/10.1038/nn.4018.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Navarro A, Gomez C, Sanchez-Pino MJ, Gonzalez H, Bandez MJ, Boveris AD, Boveris A. Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. Am J Physiol Regul Integr Comp Physiol. 2005;289(5):R1392–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Navarro P, Nicolas TS, Gabaldon JA, Mercader-Ros MT, Calin-Sanchez A, Carbonell-Barrachina AA, Perez-Lopez AJ. Effects of cyclodextrin type on vitamin C, antioxidant activity, and sensory attributes of a mandarin juice enriched with pomegranate and goji berries. J Food Sci. 2011;76(5):S319–24.  https://doi.org/10.1111/j.1750-3841.2011.02176.x.PubMedCrossRefGoogle Scholar
  81. 81.
    O’Brien JT, Holmes C, Jones M, Jones R, Livingston G, McKeith I, Mittler P, et al. Clinical practice with anti-dementia drugs: a revised (third) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol. 2017;31(2):147–68.  https://doi.org/10.1177/0269881116680924.PubMedCrossRefGoogle Scholar
  82. 82.
    Ortega RM, Requejo AM, Lopez-Sobaler AM, Andres P, Navia B, Perea JM, Robles F. Cognitive function in elderly people is influenced by vitamin E status. J Nutr. 2002;132(7):2065–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Ouahchi K, Arita M, Kayden H, Hentati F, Ben Hamida M, Sokol R, Arai H, Inoue K, Mandel JL, Koenig M. Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein. Nat Genet. 1995.  https://doi.org/10.1038/ng0295-141.
  84. 84.
    Pelleieux S, Picard C, Lamarre-Théroux L, Dea D, Leduc V, Tsantrizos YS, Poirier J. Isoprenoids and tau pathology in sporadic Alzheimer’s disease. Neurobiol Aging. 2018;65(May):132–9.  https://doi.org/10.1016/J.NEUROBIOLAGING.2018.01.012.PubMedCrossRefGoogle Scholar
  85. 85.
    Peneau S, Galan P, Jeandel C, Ferry M, Andreeva V, Hercberg S, Kesse-Guyot E. Fruit and vegetable intake and cognitive function in the SU.VI.MAX 2 prospective study. Am J Clin Nutr. 2011;94(5):1295–303.  https://doi.org/10.3945/ajcn.111.014712.PubMedCrossRefGoogle Scholar
  86. 86.
    Perkins AJ, Hendrie HC, Callahan CM, Gao S, Unverzagt FW, Xu Y, Hall KS, Hui SL. Association of antioxidants with memory in a multiethnic elderly sample using the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 1999;150(1):37–44.PubMedCrossRefGoogle Scholar
  87. 87.
    Perry G, Avila J, Kinoshita J, Smith MA, editors. Alzheimer’s disease: a century of scientific and clinical research. Amsterdam: IOS Press; 2006.Google Scholar
  88. 88.
    Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, Galasko D, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379–88.  https://doi.org/10.1056/NEJMoa050151.PubMedCrossRefGoogle Scholar
  89. 89.
    Praticò D. Evidence of oxidative stress in Alzheimer’s disease brain and antioxidant therapy. Ann N Y Acad Sci. 2008;1147(1):70–8.  https://doi.org/10.1196/annals.1427.010.PubMedCrossRefGoogle Scholar
  90. 90.
    Qiu C, Kivipelto M, von Strauss E. Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci. 2009;11(2):111–28. http://www.ncbi.nlm.nih.gov/pubmed/19585947.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362(4):329–44.  https://doi.org/10.1056/NEJMra0909142.PubMedCrossRefGoogle Scholar
  92. 92.
    Reitz C, Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol. 2014;88(4):640–51.  https://doi.org/10.1016/j.bcp.2013.12.024.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Remington R, Bechtel C, Larsen D, Samar A, Doshanjh L, Fishman P, Luo Y, et al. A phase II randomized clinical trial of a nutritional formulation for cognition and mood in Alzheimer’s disease. J Alzheimers Dis. 2015;45(2):395–405.  https://doi.org/10.3233/JAD-142499.PubMedCrossRefGoogle Scholar
  94. 94.
    Remington R, Bechtel C, Larsen D, Samar A, Page R, Morrell C, Shea TB. Maintenance of cognitive performance and mood for individuals with Alzheimer’s disease following consumption of a nutraceutical formulation: a one-year, open-label study. J Alzheimers Dis. 2016;51(4):991–5.  https://doi.org/10.3233/JAD-151098.PubMedCrossRefGoogle Scholar
  95. 95.
    Rinaldi P, Polidori MC, Metastasio A, Mariani E, Mattioli P, Cherubini A, Catani M, Cecchetti R, Senin U, Mecocci P. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging. 2003;24(7):915–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Rosler M, Retz W, Thome J, Riederer P. Free radicals in Alzheimer’s dementia: currently available therapeutic strategies. J Neural TransmSuppl. 1998;54(211–9):211–9.CrossRefGoogle Scholar
  97. 97.
    Rozemuller JM, Eikelenboom P, Stam FC, Beyreuther K, Masters CL. A4 protein in Alzheimer’s disease: primary and secondary cellular events in extracellular amyloid deposition. J Neuropathol Exp Neurol. 1989;48(6):674–91.PubMedCrossRefGoogle Scholar
  98. 98.
    Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s disease cooperative study. N Engl J Med. 1997;336(17):1216–22.  https://doi.org/10.1056/NEJM199704243361704.PubMedCrossRefGoogle Scholar
  99. 99.
    Sano M, Aisen PS, Andrews HF, Tsai WY, Lai F, Dalton AJ. Vitamin E in aging persons with down syndrome: a randomized, placebo-controlled clinical trial. Neurology. 2016;86(22):2071–6.  https://doi.org/10.1212/WNL.0000000000002714.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Saunders AM, Strittmatter WJ, Schmechel D, St George-Hyslop PH, Pericak Vance MA, Joo SH, Rosi BL, et al. Association of apolipoprotein E allele 4 with late-onset falmilial and sporadic Alzheimer’s disease. Neurology. 1993;43:1467–72.PubMedCrossRefGoogle Scholar
  101. 101.
    Schöttker B, Saum K-U, Jansen EHJM, Boffetta P, Trichopoulou A, Holleczek B, Dieffenbach AK, Brenner H. Oxidative stress markers and all-cause mortality at older age: a population-based cohort study. J Gerontol A Biol Sci Med Sci. 2015;70(4):518–24.  https://doi.org/10.1093/gerona/glu111.PubMedCrossRefGoogle Scholar
  102. 102.
    Selkoe DJ, Abraham C, Ihara Y. Alzheimer-disease – insolubility of paired helical filaments (Phf) and the potential role of enzymatic cross-linking. Neurology. 1982;32(4).: A227–A227. isi:A1982NJ70600514.Google Scholar
  103. 103.
    Serbinova E, Kagan V, Han D, Packer L. Free radical recycling and intramembrane mobility in the antioxidant properties of alpha-tocopherol and alpha-tocotrienol. Free Radic Biol Med. 1991;10(5):263–75.PubMedCrossRefGoogle Scholar
  104. 104.
    Shapira Y, Amit R, Rachmilewitz E. Vitamin E deficiency in Werdnig-Hoffmann disease. Ann Neurol. 1981;10(3):266–8.  https://doi.org/10.1002/ana.410100312.PubMedCrossRefGoogle Scholar
  105. 105.
    Slomski A. Clinical trials update: vitamin E and selenium fail to prevent dementia in men. JAMA. 2017;317(20):2054.  https://doi.org/10.1097/00002820-200312001-00004.PubMedCrossRefGoogle Scholar
  106. 106.
    Smith, MA, Zhu X, Tabaton M, Liu G, McKeel DW, Cohen ML, Wang X, et al. Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. Lovell MA, editor. J Alzheimers Dis. 2010;19:353–72.  https://doi.org/10.3233/JAD-2010-1239.
  107. 107.
    Soininen H, Solomon A, Visser PJ, Hendrix SB, Blennow K, Kivipelto M, Hartmann T, et al. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer’s disease (LipiDiDiet): a randomised, double-blind, controlled trial. Lancet Neurol. 2017;16(12):965–75.  https://doi.org/10.1016/S1474-4422(17)30332-0.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Swomley AM, Allan Butterfield D. Oxidative stress in Alzheimer disease and mild cognitive impairment: evidence from human data provided by redox proteomics. Arch Toxicol. 2015;89(10):1669–80.  https://doi.org/10.1007/s00204-015-1556-z.PubMedCrossRefGoogle Scholar
  109. 109.
    Tan CC, Yu JT, Wang HF, Tan MS, Meng XF, Wang C, Jiang T, Zhu XC, Tan L. Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2014;41(2):615–31.  https://doi.org/10.3233/jad-132690.PubMedCrossRefGoogle Scholar
  110. 110.
    Teipel SJ, Hampel H. Neuroanatomy of down syndrome in vivo: a model of preclinical Alzheimer’s disease. Behav Genet. 2006;36(3):405–15.  https://doi.org/10.1007/s10519-006-9047-x.PubMedCrossRefGoogle Scholar
  111. 111.
    Thakurta IG, Chattopadhyay M, Ghosh A, Chakrabarti S. Dietary supplementation with N-acetyl cysteine, α-tocopherol and α-lipoic acid reduces the extent of oxidative stress and proinflammatory state in aged rat brain. Biogerontology. 2012;13(5):479–88.  https://doi.org/10.1007/s10522-012-9392-5.PubMedCrossRefGoogle Scholar
  112. 112.
    Thomas A, Iacono D, Bonanni L, D’Andreamatteo G, Onofrj M. Donepezil, rivastigmine, and vitamin E in Alzheimer disease: a combined P300 event-related potentials/neuropsychologic evaluation over 6 months. Clin Neuropharmacol. 2001;24(1):31–42.PubMedCrossRefGoogle Scholar
  113. 113.
    Torres-Aleman I. Mouse models of Alzheimer’s dementia: current concepts and new trends. Endocrinology. 2008;149(12):5952–7.  https://doi.org/10.1210/en.2008-0905 [pii].
  114. 114.
    Tramutola A, Lanzillotta C, Perluigi M, Allan Butterfield D. Oxidative stress, protein modification and Alzheimer disease. Brain Res Bull. 2017;133(July):88–96.  https://doi.org/10.1016/J.BRAINRESBULL.2016.06.005.PubMedCrossRefGoogle Scholar
  115. 115.
    Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(2):335–44.  https://doi.org/10.1111/j.1469-7793.2003.00335.x.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Usoro OB, Mousa SA. Vitamin E forms in Alzheimer’s disease: a review of controversial and clinical experiences. Crit Rev Food Sci Nutr. 2010;50(5):414–9.  https://doi.org/10.1080/10408390802304222.PubMedCrossRefGoogle Scholar
  117. 117.
    WHO. World report on ageing and health; 2015 September, 1–260. https://www.who.int/ageing/events/world-report-2015-launch/en/.
  118. 118.
    de Wilde MC, Vellas B, Girault E, Yavuz AC, Sijben JW. Lower brain and blood nutrient status in Alzhiemer’s disease: results from meta-analyses. Alzheimers Dement (N Y). 2017;3(3):416–31.  https://doi.org/10.1016/j.trci.2017.06.002.CrossRefGoogle Scholar
  119. 119.
    Wollen KA. Alzheimer’s disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Altern Med Rev. 2010;15(3):223–44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=21155625 PubMedGoogle Scholar
  120. 120.
    Wong RSY, Radhakrishnan AK. Tocotrienol research: past into present. Nutr Rev. 2012;70(9):483–90.  https://doi.org/10.1111/j.1753-4887.2012.00512.x.PubMedCrossRefGoogle Scholar
  121. 121.
    Xia W, Mo H. Potential of tocotrienols in the prevention and therapy of Alzheimer’s disease. J Nutr Biochem. 2016;31(May):1–9.  https://doi.org/10.1016/J.JNUTBIO.2015.10.011.PubMedCrossRefGoogle Scholar
  122. 122.
    Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JAT, Norton MC, Welsh-Bohmer KA, Breitner JCS. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements. Arch Neurol. 2004;61(1):82.  https://doi.org/10.1001/archneur.61.1.82.PubMedCrossRefGoogle Scholar
  123. 123.
    Ziegler-Graham K, Brookmeyer R, Johnson E, Michael Arrighi H. Worldwide variation in the doubling time of Alzheimer’s disease incidence rates. Alzheimers Dement. 2008;4(5):316–23.  https://doi.org/10.1016/j.jalz.2008.05.2479.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Justus-Liebig-University Giessen, Institute of Nutritional SciencesGiessenGermany

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