Use Muscadine Wine Nutraceuticals to Improve Brain Health, Cognition, and Mental Health

Acute and Chronic Impacts of Muscadine Wine Polyphenols on Cognition, Memory, Mood, and Anxiety in Adults Over 50 Years of Age

Previous studies have shown that polyphenol-rich foods can positively affect cognitive functions, memory, and mood in humans. We hypothesize that both acute and chronic intake of muscadine wine polyphenols will improve cognitive performance and mood through regulating the HPA axis, alleviating inflammation and oxidative stress, and/or inhibiting monoamine oxidase activities

Although the exact biological mechanisms for depression and Alzheimer's Disease are not fully understood, it's believed that they are caused by a combination of factors. An increasing amount of scientific research has proposed several possible pathophysiologies linking depression and AD. For example, increased production of pro-inflammatory cytokines in the nervous system, oxidative stress induced by chronic inflammation leads to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and disturbance in the brain-derived neurotrophic factor signal pathway. Polyphenol has been well recognized for its antioxidant and anti-inflammatory properties. Previous studies have shown that polyphenol-rich food such as concord grape juice, blueberries, blackcurrants, and green oats positively affect cognition, memory, and mood in humans. However, no one has examined the effects of muscadine wine polyphenol on cognitive and mental health. In addition, if they do have effects, through what mechanism? This clinical trial will allow us to investigate the questions raised. We hypothesize that intake of muscadine wine polyphenols enhances cognition and memory and improve depression and anxiety in healthy adults over 50 year-old via regulating the HPA axis, alleviating inflammation and oxidative stress, and/or inhibiting monoamine oxidase activities. The research will provide the first clinical evidence of how muscadine wine polyphenols affect the brain and mental health.

Participants in this arm will consume muscadine wine polyphenol for six weeks and then placebo for another six weeks. The two phases are separated by a 21-day washout period

Participants in this arm will first consume placebo for six weeks and then muscadine wine polyphenol for another six weeks. The two phases are separated by a 21-day washout period

this placebo beverage is formulated with matching sugar and organic acid content to the muscadine wine polyphenol. Food coloring is added to match the color of the intervention

Participants will complete the NIH Toolbox cognitive battery. The test battery incorporates multiple tests that assess various aspects of cognitive performance. The list of tests and the function they measure are the following.1. Flanker inhibitory control and attention test (executive function): scoring is based on a combination of accuracy and reaction time. A 2-vector scoring method is employed that uses accuracy and reaction time, where each of these vectors ranges in value between 0 and 5, and the computed score, combining each vector score, ranges in value 0-10. The higher the score the better the performance. 2. Dimensional Change Card Sort (cognitive flexibility): scoring is the same as Flanker's test.

3. Picture Sequence Test (episodic memory): Item Response Theory (IRT) is used to score this test. score known as a theta score is calculated for each participant; it represents the relative overall ability or performance of the participant. A theta score is very similar to a z-score, which is a statistic with a mean of zero and a standard deviation of one. The higher the score, the better the performance. 4. List Sorting Test (working memory: scored by summing the total number of items correctly recalled and sequenced on the tests, which can range from 0-26. 5. Pattern and Comparison Test (processing speed): The participant's raw score is the number of items answered correctly in 85 seconds of response time, with a range of 0-130. higher score means better performance. Both individual test scores and composite scores will be compared to baseline score

6. Rey's Auditory Verbal Learning Test assesses immediate and delayed (30min) recall of a given list of words that is repeated 5 times. The number of correct words recalled and intrusion words (extraneous word offered by the participant that does not appear on the list) are recorded for scoring

Blood samples will be drawn immediately after the completion test battery. Blood plasma level of monoamine oxidase (MAOs) activity will be determined using the Amplex Red Monoamine Oxidase Assay Kit to assess the inhibitory effects of muscadine wine/juice on MAOs.

Plasma levels of acetylcholine, dopamine, melatonin, serotonin, epinephrine, and γ-aminobutyric acid (GABA) will be quantified using the targeted metabolomic method on UHPLC-MS/MS

Participants will complete the NIH Toolbox emotion battery. The test battery include two self-report measure, Positive affect survey (assess mood): 5-point scale with options ranging from "not at all" to "very much." higher scores are indicative of more positive affect Fear-Affect Survey (assess anxiety): 5-point scale with options ranging from "never" to "always." higher scores are indicative of more feelings of fear and anxiety

Depression score will be assessed with Beck's Depression inventory. The questionnaire consists of 21 items with a four point scale ranges between 0-3. The higher the total score the more severe the depression.

Inflammatory response will be evaluated by measuring the plasma level of pro-inflammatory cytokines IL-1beta, IL-6, and TNF-alpha using Elisa Kits

Inclusion Criteria: Healthy BMI (18.5-29.9) Body weight ≥110 pounds Exclusion Criteria: Pregnancy Breast-feeding Smokers Diabetic Heavy drinkers Subjective but not clinically diagnosed cognitive impairment (Montreal cognitive assessment score <26), Inability to understand the cognitive function tasks Intake of medication that might influence the outcome of the study (e.g. psychostimulant) cannabis product user Clinically diagnosed mental illnesses Cardiovascular and neurological disorders Uncontrolled hypertension

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