The journal of nutrition, health & aging

, Volume 22, Issue 7, pp 837–846 | Cite as

A Combination of Essential Fatty Acids, Panax Ginseng Extract, and Green Tea Catechins Modifies Brain fMRI Signals in Healthy Older Adults

  • Owen T. Carmichael
  • S. Pillai
  • P. Shankapal
  • A. McLellan
  • D. G. Kay
  • B. T. Gold
  • J. N. Keller



To assess the effects of a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides on cognition and brain functioning in healthy older adults.


Double-blind, placebo-controlled, crossover design randomized controlled trial with 26-day intervention phases and a 30-day washout period.


The Institute for Dementia Research and Prevention at the Pennington Biomedical Research Center.


Ten independently-living, cognitively-healthy older adults (mean age: 67.3 + 2.01 years). Intervention: Daily consumption of an investigational product (trade name “Cerbella TM”) consisting of an emulsified liquid combination of standardized fish oil, panax ginseng extract, and green tea catechins in a flavored base of lecithin phospholipids optimized to maximize bioavailability of the active ingredients.


Before and after supplementation with the investigational product or placebo, participants completed cognitive tests including the Mini Mental State Exam (MMSE), Stroop test, Digit Symbol Substitution Test (DSST), and Immediate and Delayed Recall tests, as well as functional magnetic resonance imaging (fMRI) during a standard cognitive task switching paradigm.


Performance on the MMSE, Stroop test, and DSST increased significantly over one month of supplementation with the investigational product (one-sample t tests, p<.05) although differences between these changes and corresponding changes during supplementation with placebo were not significant (two-sample t tests, p>.05). During supplementation with the investigational product, brain activation during task performance increased significantly more than during supplementation with placebo in brain regions known to be activated by this task (anterior and posterior cingulate cortex). Functional connectivity during task execution between task regions (middle frontal gyrus and anterior cingulate cortex) increased significantly during supplementation with the investigational product, relative to placebo. Functional connectivity during rest between task regions (precentral gyrus and middle frontal gyrus) and default mode network regions (medial frontal gyrus and precuneus) decreased during supplementation with the investigational product relative to placebo, suggesting greater segregation of task and rest related brain activity.


One-month supplementation with a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides was associated with suggestive changes in cognitive functioning as well as modification of brain activation and brain functional connectivity in cognitively healthy older adults.

Key words

Cognitive aging fMRI fish oil panax ginseng extract green tea catechins 


  1. 1.
    Moore, K.E. and J.E. Brennan. ALPHA/Sim simulation software tutorial. in Proceedings of the 28th conference on Winter simulation. 1996. IEEE Computer Society.Google Scholar
  2. 2.
    Mather, M., Fact Sheet: Aging in the United States. Population Reference Bureau, 2016.Google Scholar
  3. 3.
    Kriegeskorte, N., et al., Circular analysis in systems neuroscience: the dangers of double dipping. Nat Neurosci, 2009. 12(5): p. 535–40.CrossRefPubMedGoogle Scholar
  4. 4.
    Dirnagl, U., C. Iadecola, and M.A. Moskowitz, Pathobiology of ischaemic stroke: an integrated view. Trends in Neurosciences, 1999. 22(9): p. 391–397.CrossRefPubMedGoogle Scholar
  5. 5.
    Bejot, Y., et al., Trends in Incidence, Risk Factors, and Survival in Symptomatic Lacunar Stroke in Dijon, France, From 1989 to 2006 A Population-Based Study. Stroke, 2008. 39: p. 1945–1951.CrossRefPubMedGoogle Scholar
  6. 6.
    Hebert, L.E., et al., Alzheimer Disease in the US Population: Prevalence Estimates Using the 2000 Census. Arch Neurol, 2003. 60(8): p. 1119–1122.CrossRefPubMedGoogle Scholar
  7. 7.
    Tilvis, R.S., et al., Predictors of cognitive decline and mortality of aged people over a 10-year period. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2004. 59(3): p. M268–M274.CrossRefGoogle Scholar
  8. 8.
    Wimo, A., et al., The worldwide economic impact of dementia 2010. Alzheimer’s & Dementia, 2013. 9(1): p. 1–11. e3.CrossRefGoogle Scholar
  9. 9.
    Ravina, B., et al., Neuroprotective agents for clinical trials in Parkinson’s disease A systematic assessment. Neurology, 2003. 60(8): p. 1234–1240.CrossRefPubMedGoogle Scholar
  10. 10.
    Scapagnini, G., et al., Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. Molecular neurobiology, 2011. 44(2): p. 192–201.CrossRefPubMedGoogle Scholar
  11. 11.
    Kelsey, N.A., H.M. Wilkins, and D.A. Linseman, Nutraceutical antioxidants as novel neuroprotective agents. Molecules, 2010. 15(11): p. 7792–7814.CrossRefPubMedGoogle Scholar
  12. 12.
    Brookmeyer, R., et al., Forecasting the global burden of Alzheimer’s disease. Alzheimer’s & dementia, 2007. 3(3): p. 186–191.CrossRefGoogle Scholar
  13. 13.
    Becker, R.E. and N.H. Greig, Alzheimer’s disease drug development in 2008 and beyond: problems and opportunities. Current Alzheimer Research, 2008. 5(4): p. 346–357.CrossRefPubMedGoogle Scholar
  14. 14.
    Schneider, L.S. and D.K. Lahiri, The perils of Alzheimer’s drug development. Current Alzheimer Research, 2009. 6(1): p. 77–78.CrossRefPubMedGoogle Scholar
  15. 15.
    Cole, G.M., Q.-L. Ma, and S.A. Frautschy, Omega-3 fatty acids and dementia. Prostaglandins, Leukotrienes and Essential Fatty Acids, 2009. 81(2): p. 213–221.CrossRefGoogle Scholar
  16. 16.
    Calon, F. and G. Cole, Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies. Prostaglandins, Leukotrienes and Essential Fatty Acids, 2007. 77(5): p. 287–293.CrossRefGoogle Scholar
  17. 17.
    Zhang, W., et al., Omega-3 polyunsaturated fatty acids in the brain: metabolism and neuroprotection. Frontiers in bioscience (Landmark edition), 2010. 16: p. 2653–2670.CrossRefGoogle Scholar
  18. 18.
    Ng, T.-P., et al., Tea consumption and cognitive impairment and decline in older Chinese adults. The American journal of clinical nutrition, 2008. 88(1): p. 224–231.CrossRefPubMedGoogle Scholar
  19. 19.
    Kuriyama, S., et al., Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project. The American journal of clinical nutrition, 2006. 83(2): p. 355–361.CrossRefPubMedGoogle Scholar
  20. 20.
    Schaefer, E.J., et al., Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Archives of neurology, 2006. 63(11): p. 1545–1550.CrossRefPubMedGoogle Scholar
  21. 21.
    Morris, M.C., et al., Fish consumption and cognitive decline with age in a large community study. Archives of neurology, 2005. 62(12): p. 1849–1853.CrossRefPubMedGoogle Scholar
  22. 22.
    van Gelder, B.M., et al., Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. The American journal of clinical nutrition, 2007. 85(4): p. 1142–1147.CrossRefPubMedGoogle Scholar
  23. 23.
    He, K., et al., Fish consumption and risk of stroke in men. Jama, 2002. 288(24): p. 3130–3136.CrossRefPubMedGoogle Scholar
  24. 24.
    Arab, L., W. Liu, and D. Elashoff, Green and black tea consumption and risk of stroke. Stroke, 2009. 40(5): p. 1786–1792.CrossRefPubMedGoogle Scholar
  25. 25.
    Kokubo, Y., et al., The impact of green tea and coffee consumption on the reduced risk of stroke incidence in Japanese population. Stroke, 2013. 44(5): p. 1369–1374.CrossRefPubMedGoogle Scholar
  26. 26.
    Noguchi-Shinohara, M., et al., Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline. PLoS One, 2014. 9(5): p. e96013.CrossRefPubMedGoogle Scholar
  27. 27.
    Petursdottir, A.L., et al., Effect of dietary n-3 polyunsaturated fatty acids on brain lipid fatty acid composition, learning ability, and memory of senescence-accelerated mouse. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2008. 63(11): p. 1153–1160.CrossRefGoogle Scholar
  28. 28.
    Ehrnhoefer, D.E., et al., Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington’s disease models. Human molecular genetics, 2006. 15(18): p. 2743–2751.CrossRefPubMedGoogle Scholar
  29. 29.
    Bastianetto, S., et al., Neuroprotective effects of green and black teas and their catechin gallate esters against β-amyloid-induced toxicity. European Journal of Neuroscience, 2006. 23(1): p. 55–64.CrossRefPubMedGoogle Scholar
  30. 30.
    Zhang, G., et al., Panax ginseng ginsenoside-Rg 2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia. Journal of ethnopharmacology, 2008. 115(3): p. 441–448.CrossRefPubMedGoogle Scholar
  31. 31.
    Eckert, G.P., Traditional used plants against cognitive decline and Alzheimer disease. Frontiers in pharmacology, 2010. 1: p.138.CrossRefPubMedGoogle Scholar
  32. 32.
    Heo, J.H., et al., An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer’s disease. European Journal of Neurology, 2008. 15(8): p. 865–868.CrossRefPubMedGoogle Scholar
  33. 33.
    Ahmed, T., et al., Ginsenoside Rb1 as a neuroprotective agent: A review. Brain research bulletin, 2016. 125: p. 30–43.CrossRefPubMedGoogle Scholar
  34. 34.
    Yurko-Mauro, K., et al., Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimer’s & Dementia, 2010. 6(6): p. 456–464.CrossRefGoogle Scholar
  35. 35.
    Bauer, I., et al., Omega-3 supplementation improves cognition and modifies brain activation in young adults. Human Psychopharmacology: Clinical and Experimental, 2014. 29(2): p. 133–144.CrossRefGoogle Scholar
  36. 36.
    Boespflug, E., et al., Fish oil supplementation increases event-related posterior cingulate activation in older adults with subjective memory impairment. The journal of nutrition, health & aging, 2016. 20(2): p.161.CrossRefGoogle Scholar
  37. 37.
    Feng, L., et al., Tea Consumption Reduces the Incidence of Neurocognitive Disorders: Findings from the Singapore Longitudinal Aging Study. J Nutr Health Aging, 2016. 20(10): p. 1002–1009.CrossRefPubMedGoogle Scholar
  38. 38.
    Pan, C.-W., et al., Tea consumption and health-related quality of life in older adults. The journal of nutrition, health & aging, 2017. 21(5): p. 480–486.CrossRefGoogle Scholar
  39. 39.
    Park, S.-K., et al., A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebocontrolled study. Journal of medicinal food, 2011. 14(4): p. 334–343.CrossRefPubMedGoogle Scholar
  40. 40.
    Schmidt, A., et al., Green tea extract enhances parieto-frontal connectivity during working memory processing. Psychopharmacology, 2014. 231(19): p. 3879–3888.CrossRefPubMedGoogle Scholar
  41. 41.
    Geng, J., et al., Ginseng for cognition. The Cochrane Library, 2010.Google Scholar
  42. 42.
    Shergis, J.L., et al., Panax ginseng in randomised controlled trials: a systematic review. Phytotherapy Research, 2013. 27(7): p. 949–965.CrossRefPubMedGoogle Scholar
  43. 43.
    Lee, M.S., et al., Ginseng for cognitive function in Alzheimer’s disease: a systematic review. Journal of Alzheimer’s Disease, 2009. 18(2): p. 339–344.CrossRefPubMedGoogle Scholar
  44. 44.
    Fotuhi, M., P. Mohassel, and K. Yaffe, Fish consumption, long-chain omega-3 fatty acids and risk of cognitive decline or Alzheimer disease: a complex association. Nature Clinical Practice Neurology, 2009. 5(3): p. 140–152.PubMedGoogle Scholar
  45. 45.
    Dangour, A.D., et al., Omega 3 fatty acids and cognitive health in older people. British Journal of Nutrition, 2012. 107(S2): p. S152–S158.CrossRefPubMedGoogle Scholar
  46. 46.
    Bos, D.J., et al., Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: What is the evidence? European Neuropsychopharmacology, 2016. 26(3): p. 546–561.CrossRefPubMedGoogle Scholar
  47. 47.
    Bolling, B.W., C.-Y.O. Chen, and J.B. Blumberg, Tea and health: preventive and therapeutic usefulness in the elderly? Current opinion in clinical nutrition and metabolic care, 2009. 12(1): p.42.CrossRefPubMedGoogle Scholar
  48. 48.
    Feng, L., et al., Pharmacokinetics, tissue distribution, metabolism, and excretion of ginsenoside Rg1 in rats. Archives of pharmacal research, 2010. 33(12): p. 1975–1984.CrossRefPubMedGoogle Scholar
  49. 49.
    Stough, C., et al., Neuropsychological changes after 30-day Ginkgo biloba administration in healthy participants. The The International Journal of Neuropsychopharmacology, 2001. 4(2): p. 131–134.CrossRefPubMedGoogle Scholar
  50. 50.
    Akhondzadeh, S., et al., Passionflower in the treatment of generalized anxiety: A pilot double-blind randomized controlled trial with oxazepam. Journal of clinical pharmacy and therapeutics, 2001. 26(5): p. 363–367.CrossRefPubMedGoogle Scholar
  51. 51.
    Bourin, M., et al., A combination of plant extracts in the treatment of outpatients with adjustment disorder with anxious mood: controlled study versus placebo. Fundamental & clinical pharmacology, 1997. 11(2): p. 127–132.CrossRefGoogle Scholar
  52. 52.
    Malsch, U. and M. Kieser, Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology, 2001. 157(3): p. 277–283.CrossRefPubMedGoogle Scholar
  53. 53.
    Connor, K. and J. Davidson, A placebo-controlled study of Kava kava in generalized anxiety disorder. International clinical psychopharmacology, 2002. 17(4): p. 185–188.CrossRefPubMedGoogle Scholar
  54. 54.
    Gastpar, M. and H. Klimm, Treatment of anxiety, tension and restlessness states with Kava special extract WS® 1490 in general practice: A randomized placebo-controlled double-blind multicenter trial. Phytomedicine, 2003. 10(8): p. 631–639.CrossRefPubMedGoogle Scholar
  55. 55.
    Jacobs, B.P., et al., An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine, 2005. 84(4): p. 197–207.CrossRefPubMedGoogle Scholar
  56. 56.
    Sarris, J., et al., The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology, 2009. 205(3): p. 399–407.CrossRefPubMedGoogle Scholar
  57. 57.
    Sarris, J., et al., St. John’s wort and Kava in treating major depressive disorder with comorbid anxiety: a randomised double-blind placebo-controlled pilot trial. Human Psychopharmacology: Clinical and Experimental, 2009. 24(1): p. 41–48.Google Scholar
  58. 58.
    File, S.E., et al., Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function. Menopause, 2005. 12(2): p. 193–201.CrossRefPubMedGoogle Scholar
  59. 59.
    Elsabagh, S., D.E. Hartley, and S.E. File, Limited cognitive benefits in Stage+ 2 postmenopausal women after 6 weeks of treatment with Ginkgo biloba. Journal of Psychopharmacology, 2005. 19(2): p. 173–181.CrossRefPubMedGoogle Scholar
  60. 60.
    Cao, J., et al., Incorporation and clearance of omega-3 fatty acids in erythrocyte membranes and plasma phospholipids. Clinical chemistry, 2006. 52(12): p. 2265–2272.CrossRefPubMedGoogle Scholar
  61. 61.
    Fung, S.-T., et al., Comparison of catechin profiles in human plasma and urine after single dosing and regular intake of green tea (Camellia sinensis). British Journal of Nutrition, 2013. 109(12): p. 2199–2207.CrossRefPubMedGoogle Scholar
  62. 62.
    Reay, J.L., A.B. Scholey, and D.O. Kennedy, Panax ginseng (G115) improves aspects of working memory performance and subjective ratings of calmness in healthy young adults. Human Psychopharmacology: Clinical and Experimental, 2010. 25(6): p. 462–471.CrossRefGoogle Scholar
  63. 63.
    Folstein, M.F., S.E. Folstein, and P.R. McHugh, «Mini-mental state». A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res, 1975. 12(3): p. 189–98.CrossRefPubMedGoogle Scholar
  64. 64.
    Wechsler, D., WAIS-R manual: Wechsler adult intelligence scale-revised. 1981: Psychological Corporation.Google Scholar
  65. 65.
    Lamers, M.J., A. Roelofs, and I.M. Rabeling-Keus, Selective attention and response set in the Stroop task. Memory & Cognition, 2010. 38(7): p. 893–904.CrossRefGoogle Scholar
  66. 66.
    Lezak, M.D., Neuropsychological assessment. 2004: Oxford University Press, USA.Google Scholar
  67. 67.
    Glover, G.H., T.Q. Li, and D. Ress, Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magnetic Resonance in Medicine, 2000. 44(1): p. 162–167.CrossRefPubMedGoogle Scholar
  68. 68.
    Gold, B.T., et al., Lifelong bilingualism maintains neural efficiency for cognitive control in aging. Journal of Neuroscience, 2013. 33(2): p. 387–396.CrossRefPubMedGoogle Scholar
  69. 69.
    Hakun, J.G., et al., Evidence for reduced efficiency and successful compensation in older adults during task switching. Cortex, 2015. 64: p. 352–62.CrossRefPubMedGoogle Scholar
  70. 70.
    Sohn, M.-H., et al., The role of prefrontal cortex and posterior parietal cortex in task switching. Proceedings of the National Academy of Sciences, 2000. 97(24): p. 13448–13453.CrossRefGoogle Scholar
  71. 71.
    Dreher, J.-C., et al., The roles of timing and task order during task switching. Neuroimage, 2002. 17(1): p. 95–109.CrossRefPubMedGoogle Scholar
  72. 72.
    Pearson, J.M., et al., Posterior cingulate cortex: adapting behavior to a changing world. Trends in cognitive sciences, 2011. 15(4): p. 143–151.CrossRefPubMedGoogle Scholar
  73. 73.
    Yeung, N., et al., Between-task competition and cognitive control in task switching. Journal of Neuroscience, 2006. 26(5): p. 1429–1438.CrossRefPubMedGoogle Scholar
  74. 74.
    Luft, A.R., et al., Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial. Jama, 2004. 292(15): p. 1853–1861.CrossRefPubMedGoogle Scholar
  75. 75.
    Chiaravalloti, N.D., et al., Increased cerebral activation after behavioral treatment for memory deficits in MS. Journal of neurology, 2012. 259(7): p. 1337–1346.CrossRefPubMedGoogle Scholar
  76. 76.
    Rushworth, M., et al., Role of the human medial frontal cortex in task switching: a combined fMRI and TMS study. Journal of neurophysiology, 2002. 87(5): p. 2577–2592.CrossRefPubMedGoogle Scholar
  77. 77.
    Rissman, J., A. Gazzaley, and M. D’Esposito, Measuring functional connectivity during distinct stages of a cognitive task. Neuroimage, 2004. 23(2): p. 752–63.CrossRefPubMedGoogle Scholar
  78. 78.
    Biswal, B.B., et al., Toward discovery science of human brain function. Proc Natl Acad Sci U S A, 2010. 107(10): p. 4734–9.CrossRefPubMedGoogle Scholar
  79. 79.
    Fox, M.D., et al., The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the United States of America, 2005. 102(27): p. 9673–9678.CrossRefPubMedGoogle Scholar
  80. 80.
    Sridharan, D., D.J. Levitin, and V. Menon, A critical role for the right frontoinsular cortex in switching between central-executive and default-mode networks. Proceedings of the National Academy of Sciences, 2008. 105(34): p. 12569–12574.CrossRefGoogle Scholar
  81. 81.
    Goulden, N., et al., The salience network is responsible for switching between the default mode network and the central executive network: replication from DCM. Neuroimage, 2014. 99: p. 180–190.CrossRefPubMedGoogle Scholar
  82. 82.
    Greicius, M., Resting-state functional connectivity in neuropsychiatric disorders. Current Opinion in Neurology, 2008. 21(4): p. 424–430.CrossRefPubMedGoogle Scholar
  83. 83.
    Greicius, M.D., et al., Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A, 2004. 101(13): p. 4637–42.CrossRefPubMedGoogle Scholar
  84. 84.
    He, J., et al., Influence of functional connectivity and structural MRI measures on episodic memory. Neurobiol Aging, 2012. 33(11): p. 2612–2620.CrossRefPubMedGoogle Scholar
  85. 85.
    Seeley, W.W., et al., Neurodegenerative diseases target large-scale human brain networks. Neuron, 2009. 62(1): p. 42–52.CrossRefPubMedGoogle Scholar
  86. 86.
    Daniels, J.K., et al., Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity. Journal of psychiatry & neuroscience: JPN, 2010. 35(4): p.258.CrossRefGoogle Scholar
  87. 87.
    Whitfield-Gabrieli, S. and J.M. Ford, Default mode network activity and connectivity in psychopathology. Annual review of clinical psychology, 2012. 8: p. 49–76.CrossRefPubMedGoogle Scholar
  88. 88.
    Utevsky, A.V., D.V. Smith, and S.A. Huettel, Precuneus is a functional core of the default-mode network. Journal of Neuroscience, 2014. 34(3): p. 932–940.CrossRefPubMedGoogle Scholar
  89. 89.
    Tsukada, H., et al., Docosahexaenoic acid (DHA) improves the age-related impairment of the coupling mechanism between neuronal activation and functional cerebral blood flow response: a PET study in conscious monkeys. Brain research, 2000. 862(1): p. 180–186.CrossRefPubMedGoogle Scholar
  90. 90.
    Wurtman, R.J., Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents. Metabolism, 2008. 57: p. S6–S10.CrossRefPubMedGoogle Scholar
  91. 91.
    Tassoni, D., et al., The role of eicosanoids in the brain. Asia Pacific journal of clinical nutrition, 2008. 17(S1): p. 220–228.PubMedGoogle Scholar
  92. 92.
    Dyall, S.C., Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Frontiers in aging neuroscience, 2015.7.Google Scholar
  93. 93.
    Mandel, S. and M.B. Youdim, Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radical Biology and Medicine, 2004. 37(3): p. 304–317.CrossRefPubMedGoogle Scholar
  94. 94.
    Mandel, S.A., et al., Simultaneous manipulation of multiple brain targets by green tea catechins: a potential neuroprotective strategy for Alzheimer and Parkinson diseases. CNS neuroscience & therapeutics, 2008. 14(4): p. 352–365.CrossRefGoogle Scholar
  95. 95.
    Radad, K., R. Moldzio, and W.D. Rausch, Ginsenosides and their CNS targets. CNS neuroscience & therapeutics, 2011. 17(6): p. 761–768.CrossRefGoogle Scholar
  96. 96.
    Kim, H.J., P. Kim, and C.Y. Shin, A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. Journal of ginseng research, 2013. 37(1): p.8.CrossRefPubMedGoogle Scholar
  97. 97.
    Sperling, R.A., et al., 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. Alzheimer’s & Dementia, 2011. 7(3): p. 280–292.CrossRefGoogle Scholar
  98. 98.
    Jack, C.R., et al., Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. The Lancet Neurology, 2013. 12(2): p. 207–216.CrossRefPubMedGoogle Scholar
  99. 99.
    Villemagne, V.L., et al., Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. The Lancet Neurology, 2013. 12(4): p. 357–367.CrossRefPubMedGoogle Scholar
  100. 100.
    Eklund, A., T.E. Nichols, and H. Knutsson, Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences of the United States of America, 2016. 113(28): p. 7900–7905.CrossRefPubMedGoogle Scholar

Copyright information

© Serdi and Springer-Verlag France SAS, part of Springer Nature 2018

Authors and Affiliations

  • Owen T. Carmichael
    • 1
  • S. Pillai
    • 1
  • P. Shankapal
    • 2
  • A. McLellan
    • 3
  • D. G. Kay
    • 3
  • B. T. Gold
    • 4
  • J. N. Keller
    • 1
  1. 1.Pennington Biomedical Research CenterBaton RougeUSA
  2. 2.MS Ramaiah University of Applied SciencesBengaluruIndia
  3. 3.Neurodyn, IncCharlottetown, Prince Edward IslandCanada
  4. 4.University of KentuckyLexingtonUSA

Personalised recommendations