Grape Science Center

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Cognitive (Mind) Health

Cognitive Health

We invite you to discover the emerging science behind Concord grapes. While more research is needed to confirm Concord grapes’ link to health, in this section you will find the very latest information on grape science.

Please note: The following research overviews are based on a thorough assessment of the studies, but they are intended to be summaries only. Please refer to publications in each section for further details. As always, please keep study designs and limitations in mind when assessing how this research may or may not relate to your health or the health of your clients.


Researchers have begun investigating the role of Concord grapes in cognitive function. The research in this area is very preliminary. However, emerging science suggests that Concord grapes may offer certain health benefits for the mind.1,2,4,5

Science indicates that the polyphenols in Concord grapes help support flexible arteries6-10 which, in turn, may help promote healthy blood flow to the mind.11

  • According to a review by Nash and Fillet published in the American Journal of Cardiology (2006), cardiovascular risk factors appear to play a role in the development of cognitive decline.11

Oxidative stress, caused by free radicals in the body, can have a damaging effect on the brain.12 The brain is particularly vulnerable to oxidative damage because of its high use of oxygen relative to its size and few antioxidant defense systems, among other factors.12 Oxidative damage can affect enzymatic activities in many proteins including glutamine synthetase, which converts glutamate to glutamine. Glutamate is neurotoxic, and thus a buildup of this amino acid can be harmful. In the brain, oxidative damage effects important neurochemical processes such as dopamine synthesis.12 Polyphenols help neutralize free radicals and thus may help to combat the effects of oxidative stress.

  • In a 2004 double-blind, crossover study in 20 adults with coronary artery disease (CAD), Albers and colleagues found drinking Concord grape juice daily for two weeks (7 mL/kg/d) decreased superoxide production (a free radical) and a marker of inflammation (platelet-dependent), possibly due to the juice’s polyphenol antioxidant content.13 These findings were supported by a similar study conducted by Freedman and colleagues on healthy adults, which found that platelet aggregation (clotting) was inhibited, superoxide release was decreased, and drinking grape juice stimulated the production of nitric oxide by platelets, which has a relaxing effect on blood vessels.9
  • Two recent reviews, by Joseph and Spencer et al., elaborate on potential mechanisms by which polyphenolic compounds, like those found in Concord grapes and other fruits and vegetables, may support cognitive function. They suggest that, while more science is necessary, the ability of polyphenols to potentially reverse the damaging effects of progressive oxidative stress is related to protecting, enhancing, and stimulating neuronal development.14,15

Recent studies suggest that Concord grape juice may help slow the progression of age-related memory decline and motor function in older adults.2-4

  • A randomized, double-blind, placebo-controlled pilot study of 12 older adults with early memory deficits (i.e., forgetfulness, prospective memory lapses) by Krikorian et al. found cognitive improvements after 12 weeks of Concord grape juice consumption. Five subjects consuming Concord grape juice (6-9 mL/kg/d) experienced significant improvement in list learning and trended toward improved verbal recall and spatial memory compared to controls. The 12 weeks of juice consumption did not have an effect on mood. Also, neither weight nor waist circumference were impacted by the intervention; however, there was a slight increase in fasting insulin for those consuming the grape juice.2
  • Building on this earlier research, Krikorian and colleagues demonstrated that Concord grape juice can increase blood flow to certain regions of the brain, as well as improve memory function compared to those consuming a grape-flavored placebo. In this study, 21 older adults (average age = 77) were given either Concord grape juice or the placebo daily for 16 weeks, and were tested in various areas releated to long-term memory. Those who drank Concord grape juice were less susceptible to distraction when asked to remember what they had previously learned. Test scores in other areas like learning and retention did not improve with the juice.3
    • Also, using functional magnetic resonance imaging (fMRI), researchers monitored specific areas of the brain in a subset of eight study participants while they performed a working memory task. The researchers found that the group consuming Concord grape juice had increased neural activity (indicating an increase in blood flow) in two regions of the brain involved in working memory, compared to the placebo.3
  • Laboratory studies indicate that Concord grape juice has a positive impact on short-term memory and motor function. In a 2006 study by Shukitt-Hale et al., aged rats were treated with either: 0% (sugar water), 10% or 50% dilutions of Concord grape juice. The Concord grape juice-treated groups experienced beneficial results in cognitive performance (10% dilution) and in psychomotor function (50% dilution), compared to those receiving the placebo. These findings suggest that it takes a higher concentration of grape juice to enhance motor function. The authors hypothesized that the potential reversal of neuronal and behavioral effects may be related to cell-signaling, as well as antioxidant properties of Concord grape juice.4

Additional research with grape seed extract and other grape-derived polyphenol extracts have shown positive results in slowing progression of neurodegenerative diseases, such as Alzheimer's disease, in laboratory studies through preventing build-up of certain proteins in the brain associated with such diseases.5,16-19 Whether these findings extend to grapes and other grape products, as well as in humans, remains to be determined.

  • Wang and Ho et al. have conducted research on polyphenols extracted from grapes. These researchers concur that, subject to further research, grape polyphenol extracts, including extracts from Concord grapes, have the potential to positively impact cognitive deterioration in certain groups.5,16-19
    • The presence and accumulation of amyloid- β peptides play a key role in the development of Alzheimer’s disease. In vivo and in vitro research presented by Ho and colleagues at Experimental Biology in 2010 found that select polyphenols from red wine and Concord grape juice may have the ability to inhibit the production and accumulation of amyloid-β peptides.5
    • Previous reports from their laboratory have shown that polyphenol extracts from grape seeds reduced the generation and accumulation of amyloid β-protein in in vitro and ex vivo (mice) models of Alzheimer’s disease.19 A possible mechanism they’ve discovered suggests that grape seed extract interferes with certain protein (tau) aggregation, which is ultimately involved in the development of neurodegenerative disorders.16
    • In a mini-review, these researchers summarize their laboratory findings supporting the hypothesis that grape seed polyphenol extract may play a role in slowing the progression of certain neurodegenerative disorders, such as Alzheimer’s disease.17 However, they stress that further trials are needed to explain potential benefits in humans.

Bottom Line

Studies suggest that a diet rich in antioxidants, such as those found in fruits, vegetables, and their juices, can help slow and possibly even reverse age-related cognitive decline.11 The findings presented are exciting, but most research has taken place in a laboratory setting. More clinical research needs to be conducted to truly understand if Concord grapes can impact cognitive health in humans.

Bibliography

  1. Vislocky LM and Fernandez MLF. Biomedical Effects of Grape Products. Nutrition Reviews. 2010. 68(11): 656-670. onlinelibrary.wiley.com/doi/10.1111/j.1753-4887.2010.00335.x/abstract
  2. Krikorian R, Nash TA, Shidler MD, Shukitt-Hale B and Joseph JA. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010. 103(5):730-734. www.ncbi.nlm.nih.gov/pubmed/20028599
  3. Krikorian R, Boespflug EL, Fleck DE, Stein AL, Wightman JD, Shidler MD and Sadat-Hossieny S. Concord grape juice supplementation and neurocognitive function in human aging. J Agric Food Chem. 2012. 60(23):5736-5742. www.ncbi.nlm.nih.gov/pubmed/22468945
  4. Shukitt-Hale B, Carey A, Simon L, Mark DA NS Joseph JA. Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition. 2006. 22(3):295-302. www.ncbi.nlm.nih.gov/pubmed/16412610
  5. Ho L, Ferruzzi MG, Janle EM, Lobo J, Chen TY, Talcott ST, Simon J, Wu QL, Wang J, Cheng A, Weaver CM, Percival SS and Pasinetti GM. Bioavailability of grape-derived polyphenolics and implications in Alzheimer’s disease prevention and therapy. Presented at Experimental Biology 2010. Anaheim CA. April 24-28, 2010.
  6. Anselm E, Chataigneau M, Ndiaye M, Chataigneau T and Schini-Kerth VB. Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS. Cardiovasc Res. 2007. 73(2):404-413. www.ncbi.nlm.nih.gov/pubmed/16962569
  7. Chou EJ, Keevil JG, Aeschlimann S, Wiebe DA, Folts JD and Stein JH. Effect of ingestion of purple grape juice on endothelial function in patients with coronary heart disease. Am J Cardiol. 2001. 88(5):553-555. www.ncbi.nlm.nih.gov/pubmed/11524068
  8. Fitzpatrick DF, Hirschfield SL and Coffey RG. Endothelium-dependent vasorelaxing activity of wine and other grape products. Am J Physiol. 1993. 265(2 Pt 2):H774-778. www.ncbi.nlm.nih.gov/pubmed/8396352
  9. Freedman JE, Parker C, 3rd, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Iafrati MD and Folts JD. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation. 2001. 103(23):2792-2798. www.ncbi.nlm.nih.gov/pubmed/11401934
  10. Stein JH, Keevil JG, Wiebe DA, Aeschlimann S and Folts JD. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation. 1999. 100(10):1050-1055. www.ncbi.nlm.nih.gov/pubmed/10477529
  11. Nash DT and Fillit H. Cardiovascular disease risk factors and cognitive impairment. Am J Cardiol. 2006. 97(8):1262-1265. www.ncbi.nlm.nih.gov/pubmed/16616038
  12. Floyd RA and Carney JM. Free radical damage to protein and DNA: Mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann Neurol. 1992. 32(S1):S22-S27. www.ncbi.nlm.nih.gov/pubmed/1510377
  13. Albers AR, Varghese S, Vitseva O, Vita JA and Freedman JE. The antiinflammatory effects of purple grape juice consumption in subjects with stable coronary artery disease. Arterioscler Thromb Vasc Biol. 2004. 24(11):e179-180. www.ncbi.nlm.nih.gov/pubmed/15528483
  14. Joseph JA, Shukitt-Hale B and Casadesus G. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr. 2005. 81(1 Suppl):313S-316S. www.ncbi.nlm.nih.gov/pubmed/15640496
  15. Spencer JP. Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proc Nutr Soc. 2008. 67(2):238-252. www.ncbi.nlm.nih.gov/pubmed/18412998
  16. Ho L, Yemul S, Wang J and Pasinetti GM. Grape seed polyphenolic extract as a potential novel therapeutic agent in tauopathies. J Alzheimers Dis. 2009. 16(2):433-439. www.ncbi.nlm.nih.gov/pubmed/19221432
  17. Pasinetti GM, Ksiezak-Reding H, Santa-Maria I, Wang J and Ho L. Development of a grape seed polyphenolic extract with anti-oligomeric activity as a novel treatment in progressive supranuclear palsy and other tauopathies. J. Neurochem. 2010. 114(6):1557–1568. www.ncbi.nlm.nih.gov/pubmed/20569300
  18. Ho L, Chen LH, Wang J, Zhao W, Talcott ST, Ono K, Teplow D, Humala N, Cheng A, Percival SS, Feruzzi M, Janle E, Dickstein DL and Pasinetti GM. Heterogeneity in red wine polyphenolic contents differentially influences Alzheimer's disease-type neuropathology and cognitive deterioration. J Alzheimers Dis. 2009. 16(1):59-72. www.ncbi.nlm.nih.gov/pubmed/19158422
  19. Wang J, Ho L, Zhao W, Ono K, Rosensweig C, Chen L, Humala N, Teplow DB and Pasinetti GM Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's disease. J Neurosci. 2008. 28(25):6388-6392. www.ncbi.nlm.nih.gov/pubmed/18562609
Eating a balanced diet rich in a variety of fruits and vegetables is important for maintaining overall health. Delicious Concord grapes and 100% grape juice are part of a nutritious diet, but they should not be used to treat health problems. If you are worried about your health or are faced with a medical concern, be sure to consult with your doctor.

Guide to Navigating Research Studies

The definition of scientific research is performing a methodical study in order to prove a theory or answer a question. The following is a brief overview of different types of research used in health and nutrition exploration 1:

Case-Control Study
Clinical Study
Cohort Study
Cross-Sectional Study
Observational Study
Pilot Study
Preclinical or Laboratory Studies
Randomized Controlled Trials

Reference:

1. Hulley SB, Cummings SR, Browner WS, Grady D, Hearst N, Newman TB. Designing Clinical Research: An Epidemiologic Approach. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.


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An observational study, usually a retrospective study (a study that looks backward in time) that compares two groups of people: 1) those with the specific condition (e.g., disease) being studied (cases) and, 2) a similar group of people without that condition (controls). Researchers compare these two groups of people and important characteristics, such as certain lifestyle choices, to determine what factors may be associated with the condition under investigation.

A type of study that often includes patients with specific health conditions who could benefit from receiving a new treatment. These studies can also be performed in healthy subjects. The end goal of a clinical study (also called clinical research or clinical trial) is to determine effectiveness and safety of a health intervention in humans.

An observational study, usually prospective (looking forward), that follows a group of similar people over time. The goal is to determine which factors and exposures affect the development of a specific outcome or health condition (e.g., disease) during the study’s time period.

A type of observational study, often given as a survey, that examines a group of subjects during a single occasion, or over a very short period of time. This type of study aims to describe the relationship between health-related conditions (e.g., metabolic syndrome, hypertension) and other factors that exist in the general population (e.g., dietary intake, physical activity levels), during a particular time period.

A type of study in which researchers simply observe subjects and measure the associations between certain characteristics (e.g., fruit/vegetable intake) and specific outcomes (e.g., obesity). Examples of observational studies include case-control studies, cross-sectional studies, and cohort studies. While these studies gather important information, they cannot prove that a specific treatment or factor affects health.

A small scale, preliminary study that is conducted to determine the potential for a larger study.

A stage of research that often occurs prior to trials involving humans. This type of research can help determine mechanisms of action of a treatment, or how the treatment is causing the effect, as well as help ensure the safety of treatment in subsequent human trials.

In vitro
Testing performed in a controlled environment, such as a test tube or a Petri dish, instead of living organisms. In vitro literally means "within the glass" in Latin.

Ex vivo
These experiments are performed on tissue (e.g., animal or human cells) taking place outside of the organism, such as in a laboratory setting. In Latin, this means "out of the living."

In vivo
These tests are done on whole, living organisms. Technically, animal and human testing are two forms of in vivo research, which means "within the living." These experiments may be performed outside of a laboratory setting.

A study designed to provide the most credible information about the cause and effects of treatment. These types of studies are recognized as unbiased because they involve the random assignment of treatments to subjects being studied.

Bias
The tendency throughout any stage of research to generate findings that may not reflect "true values." In clinical trials, researchers try to avoid many kinds of bias, including selection by randomizing subjects, measurement by creating placebos and performing blind trials, and confounding by carefully designing the study and analyzing the findings.

Blind
Study in which subjects do not know whether they receive the treatment or the placebo, which assists in prevention of bias. Double-blinded studies are a higher level of scientific rigor because neither the participants nor the investigators know who is receiving the treatment or the placebo. A double-blind crossover study means each participant undergoes both the treatment and control scenario, typically with a wash-out period in between.

Placebo-controlled
Study that allows researchers to isolate the effect size of the treatment by comparing a group given a simulated treatment (e.g., grape flavored drink) to those with the real treatment (e.g., Concord grape juice), which reduces measurement bias. The placebo should match as closely as possible to the treatment without containing the active ingredients.

Randomized
Study involving participants who are randomly assigned to either the treatment or the placebo group, reducing selection bias.