Aging Clinical and Experimental Research

, Volume 30, Issue 4, pp 395–405 | Cite as

Complex antioxidants in a randomized single-blinded study of memory in seniors

  • William K. Summers
  • Roy L. Martin
  • Yimeng Liu
  • Bernice Peña
  • Gary M. Marsh
Original Article

Abstract

Introduction

Oxidative injury to the brain and aging are theoretical co-causes of Alzheimer’s Disease (AD). Amyloid plaques and tangles are then secondary phenomenon. The preclinical state would then be ‘normal’ elderly.

Methods

A potent complex antioxidant (antiOx) was tested against a popular one-a-day multivitamin (mV) in a randomized single blind design in ‘normal’ senior subjects over 6 months. Memory testing was done at baseline, 1, 3, and 6 months. The generalized estimating equation (GEE) approach was used to compare the change score of NLT100 and 20WR between two groups over time.

Results

Analysis of the antiOx group (30 subjects) demonstrated significant improvement in declarative memory (change score for NLT100 at month 6 = 6.36 p < 0.0001) and working memory (change score for 20WR at month 6 = 3.23, p < 0.0001). A change-score analysis over 6 months suggests possible neurogenesis in the antiOx group. The mV group (33 subjects) had a change score of the NLT100 and 20WR on the sixth month of 2.20 and 0.32 (p = 0.07, 0.35).

Conclusions

A complex antioxidant blend, sold as an over-the-counter (OTC) supplement, can improve memory in elder subjects. Antioxidants may be beneficial in AD and other neurodegerative diseases.

Keywords

Antioxidants Memory improvement Aging Alzheimers Pathophysiology of Alzheimer’s 

Abbreviations

AD

Alzheimer’s disease

BSF

Benign senile forgetfulness

GEE

Generalized estimating equation

MCI

Mild cognitive impairment

MMSE

Mini-mental status examination

NLT100

100 item names-learning paired association test

20WRT

20 word-recall test

OTC

Over-the-counter

Notes

Acknowledgements

Financial support for this research was obtained from Solo Non-Profit Research, Ltd. Interviews of the subjects were conducted at the offices of Alzheimer’s Corporation, 6000 Uptown Blvd, Suite 308, Albuquerque, NM 87110.

Author contributions

All authors significantly contributed to this work. WKS designed and coordinated the study, performed structured interviews, and drafted the manuscript. RLM coordinated the study and performed structured interviews. BP coordinated the blind randomization of subjects and direct communication with subjects about blinded issues. GMM and YL participated in the design of the study and performed statistical analysis of data. All authors read and approved the manuscript.

Compliance with ethical standards

Conflict of interest

GMM, YL, and BP have no conflicts to report. WKS is a stockholder and unpaid officer of Alzheimer’s Corporation. RLM is an employee of Alzheimer’s Corporation.

Ethical approval

The experimental protocol was in compliance with guidelines on human experimentation. The entire study protocol was approved by Ethical and Independent Review Services (Independence, MO 64055).

Informed consent

After explanation of the protocol to a subject, written informed consent was obtained.

References

  1. 1.
    Nunomura A, Perry G, Aliev G, Hiral K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neurophathol Exp Neuro 60:759–767CrossRefGoogle Scholar
  2. 2.
    Summers WK, Martin RL, Cunningham M, DeBoynton VL, Marsh GM (2010) Complex antioxidant blend improves memory in community dwelling seniors. J Alzheimer’s Dis 19:429–439CrossRefGoogle Scholar
  3. 3.
    Zandi PP, Anthony JC, Khachaturian AS, stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KC, Cache County Study Group (2004) Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol 61:82–88CrossRefPubMedGoogle Scholar
  4. 4.
    Petersen RC (2011) Mild Cognitive Impairment. N Engl J Med 364:2227–2234CrossRefPubMedGoogle Scholar
  5. 5.
    Cargin JW, Maruff P, Collie A, Shafig-Antonacci R, Masters C (2007) Decline in verbal memory in non-demented older adults. J Clin Exp Neuropsychol 29:706–718CrossRefPubMedGoogle Scholar
  6. 6.
    Condret-Santi V, Barbeau EJ, Matharan F, Le Goff M, Dartigues JF, Amieva H (2013) Prevalence of word retrieval complaint and prediction of dementia in a population-based study of elderly subjects. Dement Geriatr Cogn Disord 35:313–324CrossRefPubMedGoogle Scholar
  7. 7.
    Kamat CD, Gadal S, Mhatre M, Williamson KS, Pye QN, Hensley K (2008) Antioxidants in central nervous system diseases: preclinical promise and translational challenges. J Alzheimers Dis 15:473–493CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Papandreou MA, Dimakopoulou A, Linardaki ZI, Cordopatis P, Klimis-Zacas D, Margarity M, Lamari FN (2009) Effect of polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity. Behav Brain Res 198:352–358CrossRefPubMedGoogle Scholar
  9. 9.
    Farr SA, Price TO, Banks WA, Ercal N, Morley JE (2012) Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. J Alzheimers Dis 32:447–456PubMedGoogle Scholar
  10. 10.
    Tchantchou F, Xu Y, Wu Y, Christen Y, Lou Y (2007) EGb 761 enhanced adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer’s disease. Faseb J 21:2400–2408CrossRefPubMedGoogle Scholar
  11. 11.
    Dixit S, Harrison FE (2014) The protective role of vitamin C against Alzheimer’s disease. Society for Neuroscience annual meeting (Washington, DC) Poster 528.17Google Scholar
  12. 12.
    Harrison FE (2012) A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer’s disease. J Alzheimers Dis 29:711–726PubMedPubMedCentralGoogle Scholar
  13. 13.
    Summers WK (2011) Current & future treatments of memory complaints and Alzheimer’s disease. Ther Future Med 8:481–504Google Scholar
  14. 14.
    Scheltens P, Kamphuis PJ, Verhey FR, Olde Rikkert MG, Wurtman RJ, Wilkinson D, Twisk JW, Kurz A (2010) Efficacy of a medical food in mild Alzheimer’s disease: a randomized controlled trial. Alzheimers Dement 6:1–10CrossRefPubMedGoogle Scholar
  15. 15.
    Kamphuis PJ, Verhey FR, Olde Rikkert, Twisk JW, Swinkels SH, Scheltens P (2011) Efficacy of a medical food on cognition in Alzheimer’s disease: results from secondary analyses of a randomized, control trial. J Nutr Health Aging 15:720–724CrossRefPubMedGoogle Scholar
  16. 16.
    Scheltens P, Twisk JWR, Blesa R, Scarpini E, von Arnim CA, Bongers A, Harrison J, Swinkels SH, Stam CJ, deWaal H, Wurtman RJ, Wieggers RL, Vellas B, Kamphuis PJ (2012) Efficacy of Souvenaid in mild Alzheimer’s disease: results from a randomized controlled trial. J Alzheimers Dis 31:225–236PubMedGoogle Scholar
  17. 17.
    Thaipisuttikul P, Galvin JE (2012) Use of medical foods and nutritional approaches in the treatment of Alzheimer’s disease. Clin Pract (Lond) 9:199–209CrossRefGoogle Scholar
  18. 18.
    Summers WK (2004) Alzheimer’s disease, oxidative injury, and cytokines. J Alzheimers Dis 6:651–657CrossRefPubMedGoogle Scholar
  19. 19.
    Halliwell B, Gutteridge JMC (2001) Free Radicals in Biology and Medicine, 3rd edn. Oxford University Press, Oxford, pp 105–245Google Scholar
  20. 20.
    Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMedGoogle Scholar
  21. 21.
    Comparator Supplements http://www.MemoryreVITALIZER.com. Accessed 05 Apr 2012
  22. 22.
    Comparator Supplement http://www.centrum.com/centrum-silver-adults-50-plus. Accessed 05 Apr 2012
  23. 23.
    Summers WK, DeBoynton VL, Marsh GM, Majovski LJ (1990) Comparison of seven psychometric instruments used for evaluation of treatment effect in Alzheimer’s disease. Neuroepidemiology 9:193–207CrossRefPubMedGoogle Scholar
  24. 24.
    Lucki I, Rickels K, Giesecke MA, Geller A (1987) Differential effects of the anxiolytic drugs, diazepam and buspirone, on memory function. Br J Clin Pharmacol 23:207–211CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Cargin JW, Maruff P, Collie A., Shafig-Antonaeei R, Masters C (2007) Decline in verbal memory in non-demented older adults. J Clin Exp Neuropsychol 29:706–718CrossRefPubMedGoogle Scholar
  26. 26.
    Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, Voss JL (2014) Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science 345:1054–1057CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Robinson-Long M, Wang J, Yang QX, Meadowcroft M, Golay X, Eslinger PJ (2009) FMRI Evidence for Binding and consolidation pathways for face-name associations: implications for associative memory disorder. Top Magn Reson Imaging 20:271–278CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Morbelli S, Nobili F (2014) Cognitive reserve and clinical expression of Alzheimer’ disease: evidence and implications for brain PET imaging. Am J Nucl Med Mol Imaging 4:239–247PubMedPubMedCentralGoogle Scholar
  29. 29.
    Westerberg CE, Voss JL, Reber PJ, Paller KA (2012) Medial temporal contributions to successful face-name learning. Hum Brain Mapp 33:1717–1726CrossRefPubMedGoogle Scholar
  30. 30.
  31. 31.
    Comijs HC, Dik MG, Deeg DJ, Jonker C (2004) The course of cognitive decline in older persons: results from the longitudinal aging study Amsterdam. Dement Geriatr Cogn Disord 17:136–142CrossRefPubMedGoogle Scholar
  32. 32.
    Vogel A (2008) Subjective memory complaints in older people. Is it a symptom of dementia? Ugeskr Laeger 170:1728–1733PubMedGoogle Scholar
  33. 33.
    Bridge DJ, Voss JL (2014) Hippocampal binding of novel information with dominant memory traces can support both memory stability and change. J Neurosci 34:2203–2213CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Toni N, Laplagne DA, Zhao C, Lombardi G, Ribak CE, Gage FH, Schinder AF (2008) Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci 11:901–907CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Zheng G, Cheng W, Wang Y, Wang XM, Zhao SZ, Zhou Y, Liu SJ, Wang XT (2011) Ginseng total saponins enhance neurogenesis after focal cerebral ischemia. J Ethnopharmacol 133:724–728CrossRefPubMedGoogle Scholar
  36. 36.
    Pramastya H, Anggadiredja K, Fidriany I (2010) Neuroprotective effect of gotu kola (centella asiatica L urban) in cerebral ischemic rat model. In: Proceeding 3rd International Conference on Mathematical Natural Science 77–90Google Scholar
  37. 37.
    Madhyastha S, Sekhar S, Rao G (2013) Resveratol improves postnatal hippocampal neurogenesis and brain derived neurotrophic factor in prenatally stressed rats. Int J Dev Neurosci 31:580–585CrossRefPubMedGoogle Scholar
  38. 38.
    Chan A, Paskavitz J, Remington R, Rasmussen S, Shea TB (2008) Efficacy of a vitamin / nutraceutical formulation for early-stage Alzeheimers disease: a 1-year, open label pilot study with an 16-month caregiver extension. Am J Alzheimers Dis Other Demen 23:571–585CrossRefPubMedGoogle Scholar
  39. 39.
    Carrasco-Gallardo C, Farias GA, Fuentes P, Crespo F, Maccioni RB (2012) Can nutraceuticals prevent Alzheimer’ disease? Potential therapeutic role of a formulation containing shilajit and complex vitamins. Arch Med Res 43:699–704CrossRefPubMedGoogle Scholar
  40. 40.
    Activity Monitors (2017) Isfit Shine [http://www.misfitwearables.com/flash]. Sense Wear Pro Armband (SWA), Body Media Inc, Pittsburgh, PA. [http://sensewear.bodymedia.com/]. Lifecorder-EX, New-Lifestyles Inc, Lees Summit, MO [http://www.new-lifestyles.com/lifecorderex.html]. Accessed 17 Mar 2017

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Alzheimer’s CorporationAlbuquerqueUSA
  2. 2.Department of Biostatistics, Graduate School of Public HealthUniversity of PittsburghPittsburghUSA

Personalised recommendations