Pomegranate Juice Augments Memory and fMRI Activity in Middle-Aged and Older Adults with Mild Memory Complaints

Despite increasing emphasis on the potential of dietary antioxidants in preventing memory loss and on diet as a precursor of neurological health, rigorous studies investigating the cognitive effects of foods and their components are rare. Recent animal studies have reported memory and other cognitive benefits of polyphenols, found abundantly in pomegranate juice. We performed a preliminary, placebo-controlled randomized trial of pomegranate juice in older subjects with age-associated memory complaints using memory testing and functional brain activation (fMRI) as outcome measures. Thirty-two subjects (28 completers) were randomly assigned to drink 8 ounces of either pomegranate juice or a flavor-matched placebo drink for 4 weeks. Subjects received memory testing, fMRI scans during cognitive tasks, and blood draws for peripheral biomarkers before and after the intervention. Investigators and subjects were all blind to group membership. After 4 weeks, only the pomegranate group showed a significant improvement in the Buschke selective reminding test of verbal memory and a significant increase in plasma trolox-equivalent antioxidant capacity (TEAC) and urolithin A-glucuronide. Furthermore, compared to the placebo group, the pomegranate group had increased fMRI activity during verbal and visual memory tasks. While preliminary, these results suggest a role for pomegranate juice in augmenting memory function through task-related increases in functional brain activity.

[1]  Timothy Q. Duong,et al.  Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia , 2013, NeuroImage.

[2]  M. Dickinson,et al.  Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury. , 2012, ACS nano.

[3]  H. Arrighi,et al.  Mild cognitive impairment: Disparity of incidence and prevalence estimates , 2012, Alzheimer's & Dementia.

[4]  A. Saxena,et al.  Protective effect of treatment with black cumin oil on spatial cognitive functions of rats that suffered global cerebrovascular hypoperfusion. , 2012, Acta neurobiologiae experimentalis.

[5]  G. Gonzales,et al.  Dose–response effect of black maca (Lepidium meyenii) in mice with memory impairment induced by ethanol , 2011, Toxicology mechanisms and methods.

[6]  H. Walter,et al.  Evidence of neuronal compensation during episodic memory in subjective memory impairment. , 2011, Archives of general psychiatry.

[7]  M. Kim,et al.  Punica granatum protects against oxidative stress in PC12 cells and oxidative stress-induced Alzheimer's symptoms in mice. , 2011, Journal of medicinal food.

[8]  M. Weiner,et al.  Magnetic resonance imaging and neuropsychological results from a trial of memantine in Alzheimer’s disease , 2011, Alzheimer's & Dementia.

[9]  N. Seeram,et al.  Antioxidant capacity and phytochemical content of herbs and spices in dry, fresh and blended herb paste form , 2011, International journal of food sciences and nutrition.

[10]  G. Small,et al.  Thickness in Entorhinal and Subicular Cortex Predicts Episodic Memory Decline in Mild Cognitive Impairment , 2011, International journal of Alzheimer's disease.

[11]  N. Mercuri,et al.  Effect of Memantine on Resting State Default Mode Network Activity in Alzheimer’s Disease , 2011, Drugs & aging.

[12]  M. Torres-Ramos,et al.  Neuroprotection by natural polyphenols: molecular mechanisms. , 2010, Central nervous system agents in medicinal chemistry.

[13]  D. Butterfield,et al.  Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer's disease. , 2010, Biochimica et biophysica acta.

[14]  Tiffany A. Nash,et al.  Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. , 2010, The British journal of nutrition.

[15]  Michael A. Cunningham,et al.  Complex antioxidant blend improves memory in community-dwelling seniors. , 2010, Journal of Alzheimer's disease : JAD.

[16]  D. Teplow,et al.  Grape derived polyphenols attenuate tau neuropathology in a mouse model of Alzheimer's disease. , 2010, Journal of Alzheimer's disease : JAD.

[17]  Xi Zhang,et al.  Ellagic acid promotes Abeta42 fibrillization and inhibits Abeta42-induced neurotoxicity. , 2009, Biochemical and biophysical research communications.

[18]  J. Manson,et al.  Vitamin E, Vitamin C, Beta Carotene, and Cognitive Function Among Women With or at Risk of Cardiovascular Disease: The Women’s Antioxidant and Cardiovascular Study , 2009, Circulation.

[19]  D. Klimis-Zacas,et al.  Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity , 2009, Behavioural Brain Research.

[20]  A. Koudinov,et al.  Amyloid-beta, tau protein, and oxidative changes as a physiological compensatory mechanism to maintain CNS plasticity under Alzheimer's disease and other neurodegenerative conditions. , 2009, Journal of Alzheimer's disease : JAD.

[21]  Hyunsu Bae,et al.  Evidence Based Complementary and Alternative Medicine , 2008, Evidence-based complementary and alternative medicine : eCAM.

[22]  Jing-yu Wei,et al.  Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects. , 2008, Nutrition research.

[23]  N. Seeram,et al.  Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. , 2008, Journal of agricultural and food chemistry.

[24]  Arne D. Ekstrom,et al.  Spatial and temporal episodic memory retrieval recruit dissociable functional networks in the human brain. , 2007, Learning & memory.

[25]  D. Holtzman,et al.  Pomegranate Polyphenols and Resveratrol Protect the Neonatal Brain against Hypoxic-Ischemic Injury , 2007, Developmental Neuroscience.

[26]  A. Toga,et al.  Tracking Alzheimer's Disease , 2007, Annals of the New York Academy of Sciences.

[27]  Nancy Cook,et al.  A randomized trial of vitamin E supplementation and cognitive function in women. , 2006, Archives of internal medicine.

[28]  A. Fagan,et al.  Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease , 2006, Neurobiology of Disease.

[29]  David Heber,et al.  Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. , 2006, The Journal of nutrition.

[30]  S. Francis,et al.  The Effect of Flavanol-rich Cocoa on the fMRI Response to a Cognitive Task in Healthy Young People , 2006, Journal of cardiovascular pharmacology.

[31]  Gregory G. Brown,et al.  fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease , 2005, Neurology.

[32]  H. Mukhtar,et al.  Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice , 2005, International journal of cancer.

[33]  Yaakov Stern,et al.  Positive evidence against human hippocampal involvement in working memory maintenance of familiar stimuli. , 2004, Cerebral cortex.

[34]  D. Tomasi,et al.  Practice-induced changes of brain function during visual attention: a parametric fMRI study at 4 Tesla , 2004, NeuroImage.

[35]  A. Bokov,et al.  The role of oxidative damage and stress in aging , 2004, Mechanisms of Ageing and Development.

[36]  M. Albert,et al.  Medial temporal lobe function and structure in mild cognitive impairment , 2004, Annals of neurology.

[37]  Andrew J Saykin,et al.  Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. , 2004, Brain : a journal of neurology.

[38]  D. Foley,et al.  Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study. , 2004, American journal of epidemiology.

[39]  B. Shukitt-Hale,et al.  Blueberry Supplemented Diet: Effects on Object Recognition Memory and Nuclear Factor-kappa B Levels in Aged Rats , 2004, Nutritional neuroscience.

[40]  Deborah Gustafson,et al.  Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. , 2004, Archives of neurology.

[41]  Jing-yu Wei,et al.  Antioxidant activities of peel, pulp and seed fractions of common fruits as determined by FRAP assay , 2003 .

[42]  B. Shukitt-Hale,et al.  Blueberry Supplementation Enhances Signaling and Prevents Behavioral Deficits in an Alzheimer Disease Model , 2003, Nutritional neuroscience.

[43]  W. Willett,et al.  High-dose antioxidant supplements and cognitive function in community-dwelling elderly women. , 2003, The American journal of clinical nutrition.

[44]  R. Mayeux,et al.  Antioxidant vitamin intake and risk of Alzheimer disease. , 2003, Archives of neurology.

[45]  M. Albert,et al.  fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease , 2003, Journal of neurology, neurosurgery, and psychiatry.

[46]  R. S. Sohal,et al.  Mechanisms of aging: an appraisal of the oxidative stress hypothesis. , 2002, Free radical biology & medicine.

[47]  D. Bennett,et al.  Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study , 2022 .

[48]  T. Seeman,et al.  Risk and protective factors for physical functioning in older adults with and without chronic conditions: MacArthur Studies of Successful Aging. , 2002, The journals of gerontology. Series B, Psychological sciences and social sciences.

[49]  Mark S. Cohen,et al.  Patterns of brain activation in people at risk for Alzheimer's disease. , 2000, The New England journal of medicine.

[50]  R. Havlik,et al.  Association of vitamin E and C supplement use with cognitive function and dementia in elderly men , 2000, Neurology.

[51]  Barbara Shukitt-Hale,et al.  Reversals of Age-Related Declines in Neuronal Signal Transduction, Cognitive, and Motor Behavioral Deficits with Blueberry, Spinach, or Strawberry Dietary Supplementation , 1999, The Journal of Neuroscience.

[52]  K. Hall,et al.  Association of antioxidants with memory in a multiethnic elderly sample using the Third National Health and Nutrition Examination Survey. , 1999, American journal of epidemiology.

[53]  A. Saykin,et al.  Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: Patterns of functional MRI activation , 1999, Journal of the International Neuropsychological Society.

[54]  R. Coppola,et al.  Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. , 1999, Cerebral cortex.

[55]  T. Crook,et al.  Estimated Prevalence of Age-Associated Memory Impairment Derived From Standardized Tests of Memory Function , 1994, International Psychogeriatrics.

[56]  S. Ferris,et al.  Age‐associated memory impairment: Proposed diagnostic criteria and measures of clinical change — report of a national institute of mental health work group , 1986 .

[57]  HERMAN BUSCHKE,et al.  Evaluating storage, retention, and retrieval in disordered memory and learning , 1974, Neurology.