Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 6, Issue 1 , Pages 1-10.e1 , January 2010

Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial

  • Philip Scheltens

      Affiliations

    • Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands
    • Corresponding Author InformationCorresponding author. Tel.: 31-20-444-0742; Fax: 31-20-444-0715.
    • ,
  • Patrick J.G.H. Kamphuis

      Affiliations

    • Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands
    • ,
  • Frans R.J. Verhey

      Affiliations

    • Alzheimer Centre Limburg, Maastricht University Medical Centre, The Netherlands
    • ,
  • Marcel G.M. Olde Rikkert

      Affiliations

    • Alzheimer Centre Nijmegen, Radboud University Medical Centre Nijmegen, The Netherlands
    • ,
  • Richard J. Wurtman

      Affiliations

    • Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
    • ,
  • David Wilkinson

      Affiliations

    • Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, United Kingdom
    • ,
  • Jos W.R. Twisk

      Affiliations

    • Department of Health Sciences, VU University Medical Center, Amsterdam, The Netherlands
    • ,
  • Alexander Kurz

      Affiliations

    • Department of Psychiatry, Klinikum Rechts der Isar, Technische Universität München, Germany

References 

  1. Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002;298:789–791
  2. Terry RD. Alzheimer's disease and the aging brain. J Geriatr Psychiatry Neurol. 2006;19:125–128
  3. Wurtman RJ, Ulus IH, Cansev M, Watkins CJ, Wang L, Marzloff G. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006;1088:83–92
  4. Cansev M, Wurtman RJ, Sakamoto T, Ulus IH. Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses. Alzheimers Dement. 2008;4:153S–168S
  5. Cansev M, Wurtman RJ. Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils. Neuroscience. 2007;148:421–431
  6. Sakamoto T, Cansev M, Wurtman RJ. Oral supplementation with docosahexaenoic acid and uridine-5'-monophosphate increases dendritic spine density in adult gerbil hippocampus. Brain Res. 2007;1182:50–59
  7. Arellano JI, Espinosa A, Fairen A, Yuste R, DeFelipe J. Non-synaptic dendritic spines in neocortex. Neuroscience. 2007;145:464–469
  8. Toni N, Teng EM, Bushong EA, Aimone JB, Zhao C, Consiglio A, et al. Synapse formation on neurons born in the adult hippocampus. Nat Neurosci. 2007;10:727–734
  9. Hering H, Sheng M. Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci. 2001;2:880–888
  10. Holguin S, Martinez J, Chow C, Wurtman R. Dietary uridine enhances the improvement in learning and memory produced by administering DHA to gerbils. FASEB J. 2008;22:3938–3946
  11. De Bruin NM, Kiliaan AJ, De Wilde MC, Broersen LM. Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats. Neurobiol Learn Mem. 2003;80:63–79
  12. US Food and Drug Administration. Frequently Asked Questions About Medical Foods. College Park, MD: FDA, Center for Food Safety and Applied Nutrition, US Department of Health and Human Services; 2007;
  13. Wechsler D. Wechsler Memory Scale-Revised Manual. San Diego, CA: Psychological Corp; 1987;
  14. Petersen RC. Normal aging, mild cognitive impairment, and early Alzheimer's disease. Neurologist. 1995;1:326–344
  15. Hodges JR, Patterson K. Is semantic memory consistently impaired early in the course of Alzheimer's disease? Neuroanatomical and diagnostic implications. Neuropsychologia. 1995;33:441–459
  16. Mohs RC, Knopman D, Petersen RC, Ferris SH, Ernesto C, Grundman M, et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(Suppl. 2):S13–S21
  17. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984;34:939–944
  18. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–198
  19. Hachinski VC, Lassen NA, Marshall J. Multi-infarct dementia. A cause of mental deterioration in the elderly. Lancet. 1974;2:207–210
  20. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17:37–49
  21. Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves verbal memory in aging. Arch Neurol. 1996;53:441–448
  22. Schneider LS, Olin JT, Doody RS, Clark CM, Morris JC, Reisberg B, et al. Validity and reliability of the Alzheimer's Disease Cooperative study–Clinical global impression of change. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11:S22–S32
  23. Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48:S10–S16
  24. Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11:S33–S39
  25. Logsdon RG, Gibbons LE, McCurry SM, Teri L. Quality of life in Alzheimer's disease: patient and caregiver reports. J Ment Health Aging. 1999;5:21–32
  26. Alvarez XA, Mouzo R, Pichel V, Perez P, Laredo M, Fernandez-Novoa L, et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients: effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol. 1999;21:633–644
  27. Burns A, Yeates A, Akintade L, Del Valle M, Zhang RY, Schwam EM, et al. Defining treatment response to donepezil in Alzheimer's disease: responder analysis of patient-level data from randomized, placebo-controlled studies. Drugs Aging. 2008;25:707–714
  28. Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine. Int J Geriatr Psychiatry. 2001;16:609–614
  29. Boston PF, Bennett A, Horrobin DF, Bennett CN. Ethyl-EPA in Alzheimer's disease: a pilot study. Prostaglandins Leukot Essent Fatty Acids. 2004;71:341–346
  30. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006;63:1402–1408
  31. Broersen LM, De Wilde MC, Leenders I, Kuipers AA, Anwijk NV, Kamphuis PJ, et al. Reduced beta-amyloid plaque burden and neurodegeneration in APP/PS1 transgenic mice following multi-nutrient dietary intervention. In: Society for Neuroscience; 2007; San Diego, CA.
  32. van der Beek EM, Kamphuis PJ. The potential role of nutritional components in the management of Alzheimer's disease. Eur J Pharmacol. 2008;585:197–207
  33. de Wilde MC, Leenders I, Kuipers AAM, van Wijk N, Kamphuis PJ, Broersen LM. Combined nutrient incubation improves receptor function stimulation over single nutrient incubation in pheochromocytoma cells. Presented at: International Conference on Alzheimer's Disease; 2008; Chicago, IL.
  34. Vellas B, Andrieu S, Sampaio C, Wilcock G. Disease-modifying trials in Alzheimer's disease: a European task force consensus. Lancet Neurol. 2007;6:56–62
  35. Schneider LS, Sano M. Current Alzheimer‘s disease clinical trials: methods and placebo outcomes. Alzheimers Dement. 2009;5:388–397

 Potential conflicts of interest: P. Scheltens is employed by VU University Medical Center, Amsterdam. The Alzheimer Center VU University Medical Center receives unrestricted funding from Danone Research. He is a member of the Nutricia Advisory Board; P.J.G.H. Kamphuis is an employee of Danone Research; F.R.J. Verhey is employed by the Department of Psychiatry and Neuropsychology of the Maastricht University Medical Centre. He is a member of the Nutricia Advisory Board; M.G.M. Olde Rikkert is employed by the Geriatric Department of the Radboud University Medical Centre Nijmegen. He is a member of the Nutricia Advisory Board; R.J. Wurtman is employed by The Massachusetts Institute of Technology, which owns patents on uridine, omega-3 fatty acids, and choline to treat brain diseases by enhancing synapses. He is consultant to the Danone Company and advises on research related to such uses; D. Wilkinson has no conflicts of interest to declare; J.W.R. Twisk has no conflicts of interest to declare; A. Kurz has no conflicts of interest to declare.

 Contributors: Investigators: P. Scheltens, M.G.M. Olde Rikkert, F. Verhey, P. Dautzenberg, R.J. van Marum, L. Boelaarts, J.P.J. Slaets, D.C.M. Verheijen, S. Stevens, A. Weverling, E. Sanders, A. Kurz, H. Gertz, V. Holthoff, J. Schröder, H. Jahn, R. Horn, M. Ribbat, G. Reifschneider, K. Oehler, R. Schellenberg, K. Steinwachs, R. Vandenberghe, P.P. de Deyn, N. de Klippel, M. Petrovic, Ph. Bourgeois, Ph. PPMGA Tack, D. Wilkinson, T.K. Malstrom; Steering committee: M.J. van der Mooren (Chairman), P. Scheltens, P.J.G.H. Kamphuis; Independent data monitoring committee: I.G. McKeith, K. Rockwood, J.H. Koeman, J.W.R. Twisk.

PII: S1552-5260(09)02329-2

doi: 10.1016/j.jalz.2009.10.003

Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Volume 6, Issue 1 , Pages 1-10.e1 , January 2010

Article Tools

* Image Usage & Resolution