Cerebrovascular and Cognitive Improvement by Resveratrol (resVida) and Fruitflow-II (CCIRF-II)
Cerebrovascular and Cognitive Improvement by Resveratrol (resVida) and Fruitflow-II (CCIRF-II)
The purpose of this study is to determine whether Fruitflow-II, Resveratrol (resVida), alone
 or in combination, are effective in the treatment of memory problems in adult patients with
 memory impairment. We also evaluate effects of these medications on blood flow to the brain
 and fitness, to find whether the possible improvement in memory is associated with the
 alterations in these parameters.
Accumulating evidence suggests that tomato consumption has cardiovascular benefits, primarily
 through increasing blood flow in vivo; the active ingredient in tomato, or its extract
 (Fruitflow) have been shown to inhibit glycoprotein IIb/IIIa, similar to aspirin (which has
 antiplatelet activity and is used for secondary prevention of cardiovascular and
 cerebrovascular events in patients). Considering the fact that Fruitflow can improve the
 platelet function and peripheral blood flow, we hypothesized that Fruitflow can also increase
 the blood flow in the brain and thereby possibly enhance memory and cognitive function in
 middle-aged or elderly people who have memory complaints. Therefore, the initial goal of our
 study is to evaluate the effects of Fruitflow on brain blood and cardiovascular function by
 using Transcranial Doppler ultrasound (to check for changes in cerebral blood flow),
 cardiovascular fitness testing (to check for changes in VO2-max and stroke volume), and
 neurocognitive evaluation (to check for changes in memory and executive function).

 Many pathways such as inflammation and oxidative stress are involved in the pathophysiology
 of memory loss with ageing. Recent studies have shown that a natural compound found in the
 skin of red grapes and also in wine, called "Resveratrol", have beneficial effects for
 prevention of cognitive decline by reducing inflammation and improving cardiovascular
 function. Therefore, our next goal is to evaluate whether administration of Resveratrol, by
 itself or in combination with Fruitflow, can improve brain blood flow, VO2-max, and cognitive
 performance.

 Thus our clinical trial will have the following 4 arms: Fruitflow, Resveratrol,
 Fruitflow/Resveratrol combination, and placebo for each supplement.

 The results of the study will potentially provide evidence that these natural supplements can
 have significant cardioprotective and neuroprotective properties in middle-aged and elderly
 adults.

 Subjects (between 50 and 80 years old) complaining of memory problem who have MMSE
 (Mini-Mental State Examination) above 27 will be recruited from patients of Dr. Majid Fotuhi
 (PI at the Neurology Institute for Brain Health and Fitness). Flyers at the institute and
 advertisement in Baltimore will provide information about the opportunity to enroll in an
 observational study for 3 months, along with eligibility criteria. Participants will continue
 to receive routine and standard care, while data on outcome (i.e., dependent) variables and
 mediators will be collected over three study visits:

 Day 1: at the onset of their participation: Assessment of memory and Cardiovascular Fitness
 Testing (CFT)

 Day 2: Blood Test and Transcranial Doppler (TCD) Ultrasound at time 0 and 3 hours after
 taking the first dose of the supplements;

 Month 3: Assessment of memory, Cardiovascular Fitness Testing, and Transcranial Doppler
 Ultrasound 3 months after daily treatment with supplements in each group.
Inclusion Criteria:

 1. Between the ages of 50 and 80;

 2. Having a primary care physician;

 3. Ability to speak, read, and write English;

 4. Logical Memory subtest (of the Wechsler Memory Scale - IV [WMS-IV]) raw score one
 standard deviation or greater below the mean of a younger population;

 5. Be in stable overall health based on medical history and physical examination;

 6. Sedentary or moderately active (< 2 aerobic session / week);

 7. Suspend, for at least one month before participating in the study, the use of dietary
 supplements (fish oil, seed oils, ginkgo biloba, ginseng, resveratrol, fruit powder
 extracts and DHA; subjects who have high intake of these products are asked to take
 off these products for 4 weeks and after this washout period they will be recruited in
 the study). No more than one multivitamins per day is acceptable;

 8. Wine intake not more than 2 glasses per day

 Exclusion Criteria:

 1. Patients reporting severe depression with or without suicidal ideation [Beck
 Depression Inventory (BDI) > 30 and BDI item #9 >1];

 2. Patients with a severe language or hearing and/or vision impairment;

 3. Pregnancy;

 4. Patients presenting with delirium, dementia, or cognitive impairment (Mini-Mental
 Status Examination score < 26);

 5. Current alcohol or substance abuse/dependence;

 6. Major neurological and psychiatric diseases including Parkinson's disease, Alzheimer's
 disease, epilepsy, multiple sclerosis, concussion/traumatic brain injury,
 schizophrenia, bipolar disorder, psychosis, eating disorders;

 7. Uncontrolled high blood pressure (> 180/100 mmHg) or a documented record of
 uncontrolled high blood pressure-related complications such as cerebral vascular
 disease (CVD), and/or large strokes with disability, uncontrolled diabetes mellitus
 (medical report of blood HbA1c > 7 during the last three months; in diabetic patients
 without this record HbA1c will be measured in the first blood testing), or history of
 major cardiopulmonary disease such as congestive heart failure, pulmonary disorders
 (COPD [emphysema or chronic bronchitis] and pulmonary embolism);

 8. Documented evidence of the following findings in the current medical history of
 subjects:

 8-1- Low platelet number (< 170 x 10^9/ L); 8-2- Hematocrit below 40% for males or 30%
 for females; 8-3- Haemoglobin below 120 g/L for males or 110 g/L for females; 8-4-
 Prothrombin time (PT) values outside normal range of approximately 10-16 s;

 9. Current hepatic failure, renal failure, bleeding disorders (hemophilia, Von Willebrand
 disease, esophageal varicoses);

 10. Subjects who have given 500 ml of blood or more for transfusion purposes in the past
 month before entry into the study

 11. Patients who take aspirin more than 325 mg/day

 12. Current medications for cognition such as acetylcholine esterase inhibitors (e.g.,
 tacrine, donepezil, galantamine, rivastigmin) and memantine;

 13. Known history of allergies to tomatoes or tomato-based products;

 14. High habitual intake of tomatoes, grapes, and tomato-based products confirmed by food
 frequency questionnaire (>5 times per day). Subjects who have high intake of these
 products are asked to take off these products for 4 weeks and after this washout
 period they will be reconsidered to participate in the study.