Journal of Neural Transmission

, Volume 119, Issue 12, pp 1529–1532 | Cite as

Positive argument for debate in J Neural Transmission: Alzheimer’s disease: are we intervening too late? Yes, by years if not decades

  • Thomas B. Shea
  • Ruth Remington
Dementias - Short communication


The ongoing debate as to whether we are or are not early enough in treatment for Alzheimer’s disease presents distinct vantage points. Points expressed range from stressing the need for early preventive measures to highlighting the failure of “alternative” therapies, and concluding that we are unfortunately doing all that we can at present. Herein, we stress the worth of nutritional intervention, and review why such studies are often inherently compromised. We conclude that considerable education is needed to advance lifestyle modifications early enough to obtain their optimal effect, and instead of positioning “classical” interventions against “alternative” interventions, the combinations of both may impart maximal benefit. The introduction of novel detection methods at the earliest indications of cognitive impairment may provide a window of opportunity for initiation of preventative approaches.


Alzheimer’s disease Mild cognitive impairment Nutrition Therapy Dietary modification Supplements 


  1. Akter K, Lanza EA, Martin SA, Myronyuk N, Rua M, Raffa RB (2011) Diabetes mellitus and Alzheimer’s disease: shared pathology and treatment? Br J Clin Pharmacol 71:365–376PubMedCrossRefGoogle Scholar
  2. Ames D (2011) Negative argument for debate with V. O. Emery for J Neural Transmission: Alzheimer’s disease: are we intervening too late? No we are not. Con J Neural Transm 118:1379–1381CrossRefGoogle Scholar
  3. Andreeva VA, Kesse-Guyot E, Barberger-Gateau P, Fezeu L, Hercberg S, Galan P (2011) Cognitive function after supplementation with B vitamins and long-chain omega-3 fatty acids: ancillary findings from the SU.FOL.OM3 randomized trial. Am J Clin Nutr 94:278–286PubMedCrossRefGoogle Scholar
  4. Ballard C, Khan Z, Clack H, Corbett A (2011) Nonpharmacological treatment of Alzheimer disease. Can J Psychiatry 56:589–595PubMedGoogle Scholar
  5. Bragin V, Chemodanova M, Dzhafarova N, Bragin I, Czerniawski JL, Aliev G (2005) Integrated treatment approach improves cognitive function in demented and clinically depressed patients. Am J Alzheimers Dis Other Demen 20:21–26PubMedCrossRefGoogle Scholar
  6. Chan A, Tchantchou F, Graves V, Rozen R, Shea TB (2008a) Dietary and genetic compromise in folate availability reduces acetylcholine and cognitive performance: critical role of S-adenosylmethionine. J Health Nutr Aging 12:252–261CrossRefGoogle Scholar
  7. Chan A, Paskavitz J, Remington R, Shea TB (2008b) Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer’s disease: a one-year open-label pilot study with a 16-month extension. Am J Alzheimer Dis Other Dement 23:571–585CrossRefGoogle Scholar
  8. Chan A, Tchantchou F, Rogers EJ, Shea TB (2009) Dietary deficiency increases presenilin expression, gamma-secretase activity, and Abeta levels: potentiation by ApoE genotype and alleviation by S-adenosyl methionine. J Neurochem 110:831–836PubMedCrossRefGoogle Scholar
  9. Chan A, Lepore A, Kotoya E, Zemianek J, Remington R, Shea TB (2010) Efficacy of a vitamin/nutriceutical formulation on cognitive speed and recall in adults with no known or suspected dementia. J Nutri Health Aging 14:224–230CrossRefGoogle Scholar
  10. Connelly PJ, Prentice NP, Cousland G, Bonham J (2008) A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer’s disease. Int J Geriatr Psychiatry 23:155–160PubMedCrossRefGoogle Scholar
  11. Cornelli U (2010) Treatment of Alzheimer’s disease with a cholinesterase inhibitor combined with antioxidants. Neurodegener Dis 7:193–202PubMedCrossRefGoogle Scholar
  12. Daviglus ML, Plassman BL, Pirzada A, Bell CC, Bowen PE, Burke JR, Connolly ES Jr, Dunbar-Jacob JM, Granieri EC, McGarry K, Patel D, Trevisan M, Williams JW Jr (2011) Risk factors and preventive interventions for Alzheimer disease: state of the science. Arch Neurol 68:1185–1190PubMedCrossRefGoogle Scholar
  13. de Sousa OL, Amaral TF (2012) Three-week nutritional supplementation effect on long-term nutritional status of patients with mild Alzheimer disease. Alzheimer Dis Assoc Disord 26:119–123Google Scholar
  14. Dhitavat S, Ortiz D, Rogers E, Rivera E, Shea TB (2005) Folate, vitamin E and acetyl-l-carnitine provide synergistic protection against oxidative stress resulting from exposure of human neuroblastoma cells to amyloid beta. Brain Res 1061:114–117PubMedCrossRefGoogle Scholar
  15. Dubois B, Feldman HH, Jacova C, Dekosy ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O’Brien K, Paquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P (2007) Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS—ADRDA criteria. Lancet Neurol 6:734–746PubMedCrossRefGoogle Scholar
  16. Durga J, van Boxtel MP, Schouten EG et al (2007) Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet 369:208–216PubMedCrossRefGoogle Scholar
  17. Ellison M, Thomas J, Patterson A (2004) A critical evaluation of the relationship between serum vitamin B12, folate and total homocysteine with cognitive impairment in the elderly. J Ji Mitr Doetet 17:371–383Google Scholar
  18. Emery VO (2011) Alzheimer disease: are we intervening too late? Pro J Neural Transm 118:1361–1378CrossRefGoogle Scholar
  19. Fuso A, Cavallaro RA, Zampelli A, D’Anselmi F, Piscopo P, Confaloni A, Scarpa S (2007) Gamma-secretase is differentially modulated by alterations of homocysteine cycle in neuroblastoma and glioblastoma cells. J Alzheimer Dis 11:275–290Google Scholar
  20. Fuso A, Nicolia V, Ricceri L, Cavallaro RA, Isopi E, Mangia F, Fiorenza MT, Scarpa S (2012) S-adenosylmethionine reduces the progress of the Alzheimer-like features induced by B-vitamin deficiency in mice. Neurobiol Aging 33:1482e1–1482e16Google Scholar
  21. Kang JH, Cook N, Manson J, Buring JE, Grodstein F (2006) A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med 166:2462–2468PubMedCrossRefGoogle Scholar
  22. Kang JH, Cook N, Manson J, Buring JE, Albert CM, Grodstein F (2008) A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr 88:1602–1610PubMedCrossRefGoogle Scholar
  23. Kroner Z (2009) The relationship between Alzheimer’s disease and diabetes: type 3 diabetes? Altern Med Rev 14:373–379PubMedGoogle Scholar
  24. LaMonte MJ, Blair SN, Church TS (2005) Physical activity and diabetes prevention. J Appl Physiol 99:1205–1213PubMedCrossRefGoogle Scholar
  25. Lee S, Lemere CA, Frost JL, Shea TB (2011) Dietary supplementation with S-adenosyl methionine delayed amyloid-β and tau pathology in 3xTg-AD mice. J Alzheimers Dis 28:423–431Google Scholar
  26. Lopez OL, McDade E, Riverol M, Becker JT (2011) Evolution of the diagnostic criteria for degenerative and cognitive disorders. Curr Opin Neurol 24:532–541PubMedCrossRefGoogle Scholar
  27. Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A (2004) Vitamin B12 and folate depletion in cognition: a review. Neurol India 52:310–318PubMedGoogle Scholar
  28. Morris MC, Tangney CC (2011) A potential design flaw of randomized trials of vitamin supplements. JAMA 305:1348–1349PubMedCrossRefGoogle Scholar
  29. Okosun IS, Davis-Smith M, Seale JP (2012) Awareness of diabetes risks is associated with healthy lifestyle behavior in diabetes free American adults: evidence from a nationally representative sample. Prim Care Diabetes 6:87–94Google Scholar
  30. Panza F, Frisardi V, Capurso C, D’Introno A, Colacicco AM, Vendemiale G, Capurso A, Solfrizzi V (2009) Possible role of S-adenosylmethionine, S-adenosylhomocysteine, and polyunsaturated fatty acids in predementia syndromes and Alzheimer’s disease. J Alzheimers Dis 16:467–470PubMedGoogle Scholar
  31. Planel E, Miyasaka T, Launey T, Chui DH, Tanemura K, Sato S, Murayama O, Ishiguro K, Tatebayashi Y, Takashima A (2004) Alterations in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities: implications for Alzheimer’s disease. J Neurosci 24:2401–2411PubMedCrossRefGoogle Scholar
  32. Qi L, Hu FB, Hu G (2008) Genes, environment, and interactions in prevention of type 2 diabetes: a focus on physical activity and lifestyle changes. Curr Mol Med 8:519–532PubMedCrossRefGoogle Scholar
  33. Remington R, Chan A, Shea TB (2009) Efficacy of a vitamin/nutriceutical formulation for moderate to late-stage Alzheimer’s disease: a placebo-controlled pilot study. Am J Alzheimer Dis Other Dement 24:27–33CrossRefGoogle Scholar
  34. Rivière S, Gillette-Guyonnet S, Voisin T, Reynish E, Andrieu S, Lauque S, Salva A, Frisoni G, Nourhashemi F, Micas M, Vellas B (2001) A nutritional education program could prevent weight loss and slow cognitive decline in Alzheimer’s disease. J Nutr Health Aging 5:295–299PubMedGoogle Scholar
  35. Sebastian RS, Cleveland LE, Goldman JD, Moshfegh AJ (2007) Older adults who use vitamin/mineral supplements differ from nonusers in nutrient intake adequacy and dietary attitudes. J Am Diet Assoc 107:1322–1332PubMedCrossRefGoogle Scholar
  36. Shea TB, Chan A (2008) S-adenosyl methionine: a natural therapeutic agent effective against multiple hallmarks and risk factors associated with Alzheimer’s disease. J Alzheimer Dis 13:67–70Google Scholar
  37. Solfrizzi V, Frisardi V, Seripa D, Logroscino G, Imbimbo BP, D’Onofrio G, Addante F, Sancarlo D, Cascavilla L, Pilotto A, Panza F (2011a) Mediterranean diet in predementia and dementia syndromes. Curr Alzheimer Res 8:520–542PubMedCrossRefGoogle Scholar
  38. Solfrizzi V, Panza F, Frisardi V, Seripa D, Logroscino G, Imbimbo BP, Pilotto A (2011b) Diet and Alzheimer’s disease risk factors or prevention: the current evidence. Expert Rev Neurother 11:677–708PubMedCrossRefGoogle Scholar
  39. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) 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 7:280–292PubMedCrossRefGoogle Scholar
  40. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, Xu XJ, Wands JR, de la Monte SM (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—is this type 3 diabetes? J Alzheimers Dis 7:63–80Google Scholar
  41. Sun Y, Lu CJ, Chien KL, Chen ST, Chen RC (2007) Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer’s disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Clin Ther 29:2204–2214PubMedCrossRefGoogle Scholar
  42. Vellas B, Lauque S, Gillette-Guyonnet S, Andrieu S, Cortes F, Nourhashémi F, Cantet C, Ousset PJ, Grandjean H, REAL.FR Group (2005) Impact of nutritional status on the evolution of Alzheimer’s disease and on response to acetylcholinesterase inhibitor treatment. J Nutr Health Aging 9:75–80PubMedGoogle Scholar
  43. Werder SF (2010) Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatr Dis Treat 6:159–195PubMedCrossRefGoogle Scholar
  44. Wollen KA (2010) 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 Alt. Med Rev 15:226–244Google Scholar
  45. Zawia NH, Lahiri DK, Cardozo-Pelaez (2009) Epigenetics, oxidative stress and Alzheimer’s disease. Free Rad Biol Med 46:1241–1249Google Scholar
  46. Zhu X, Raina AK, Lee HG, Casadesus G, Smith MA, Perry G (2004) Oxidative stress signaling in Alzheimer’s disease. Brain Res 1000:32–39PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Departments of Biological Sciences and Nursing, Center for Cellular Neurobiology and Neurodegeneration ResearchUMass LowellLowellUSA
  2. 2.Framingham State UniversityFraminghamUSA

Personalised recommendations