Resveratrol for Improved Performance in the Elderly (RIPE)

• Cognitive Outcomes [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  Executive function measured by N-back and Controlled Oral Word Association test, Processing Speed measuring by Trails A & B, Memory Function measured by word recall.
• Physical Outcomes [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  Physical function measured by performance on the 400 meter walk test, physical activity levels as measured by accelerometer.

• Cognitive Outcomes [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  Executive function measured by N-back and Controlled Oral Word Association test, Processing Speed measuring by Trails A & B, Memory Function measured by word recall.
• Physical Outcomes [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  Physical function measured by performance on the 400 meter walk test, physical activity levels as measured by accelerometer.

The investigators aim to conduct a randomized placebo controlled pilot study to determine whether resveratrol, a dietary ingredient, supplementation is safe and improves memory and physical performance in older adults. Loss in memory and physical performance is a frequent complaint in older adults and a growing public health issue. Additionally, later adulthood is associated with a normative decline in both working and primary memory as well as domains including attention, speed of processing and executive function. Resveratrol is safely tolerated in pre-clinical models and in dose-escalation human studies. It also has demonstrated beneficial effects on memory and performance in pre-clinical models. Therefore, this study will take the next step in understanding the longer-term safety (3 months) and efficacy of resveratrol supplementation on age-related health conditions.

Enrolled participants will complete psychological questionnaires and a multi-measure cognitive test battery, physical function, as well as provide blood samples, to determine blood chemistry. These will include complete blood count and complete metabolic count [(Na, K, Cl, CO2, BUN, Creatinine, Glucose, Total Protein, Albumin, Calcium, Phosphorous, Aspartate Aminotransferase (AST), Alkaline Phos, Total Bilirubin, and Alanine Amino Transferase (ALT)] and any others deemed necessary by the study physician. They will return to the laboratory to perform a muscular endurance test and MRI evaluation at the Brain Institute. Eligible participants will be randomly assigned with equal probability to either receive resveratrol (300 mg/d or 1000 mg/d) or placebo for twelve weeks. Immediately following completion of the MRI, participants will be given a month's supply of resveratrol or placebo. All participants will be closely monitored for safety and toxicity during the first 10 days (range 8-12 days are acceptable) of the trial. During this initial evaluation period, blood chemistries (complete metabolic profiles) will be evaluated every 3 (range 1-2 days are acceptable) days. Following one month, participants will be asked to return to clinic. At their monthly visits, memory tests, blood samples will be collected to monitor cognitive adaptations and ensure that no adverse changes have occurred. Participants' compliance with the supplementation regimen will also be checked through pill counts, and participants will be given a month's supply of product at each of their monthly visits. After 12 weeks of taking either resveratrol or a placebo on a daily basis, participants will complete a final test battery, an MRI scan, a blood draw collection. A follow-up evaluation will be provided at 10 and 30 days following completion of the final post-treatment assessment.

• Dietary Supplement: Placebo
  2 capsules of placebo daily for 12 weeks
• Drug: Low dose Resveratrol
  2 capsules daily for 12 weeks containing 300 mg/d (combined) of resveratrol active ingredient
  Other Name: ReserveAge
• Drug: High dose Resveratrol
  2 capsules daily for 12 weeks containing 1000 mg/d (combined) of resveratrol active ingredient
  Other Name: ReserveAge

• Placebo Comparator: Placebo
  Dietary Supplement: placebo
  Intervention: Dietary Supplement: Placebo
• Experimental: 300 mg/d Resveratrol
  Dietary Supplement: 300 mg/d Resveratrol
  Intervention: Drug: Low dose Resveratrol
• Experimental: 1000 mg/d Resveratrol
  Dietary Supplement: 1000 mg/d Resveratrol
  Intervention: Drug: High dose Resveratrol

Inclusion Criteria:

• Men and women aged 65-100 years
• Body mass index > = 25 and < = 35
• Willing and able to participate in all aspects of the study
• Willing to be randomized to either treatment group
• Sedentary to moderately active lifestyle (<120 min aerobic activity/week)
• Report of ability to walk one mile
• MMSE > 24
• Non-smoking
• Telephone Interview for cognitive status (TICS)

Exclusion Criteria:

• Active treatment for cancer, stroke (< 6 mo), peripheral vascular disease, coronary artery disease (myocardial infarction <6 mo), state III, IV Congestive Heart Failure, valvular heart disease, major psychiatric disease, severe anemia, liver or renal disease, diabetes, severe osteoarthritis, blindness or deafness, fracture in upper or lower extremity within the last 6 months, upper or lower extremity amputation, anticoagulant therapy (aspirin use is permitted), parkinsons disease
• Failure to give consent
• Anabolic medications (growth hormone or testosterone)
• High amounts of physical activity (i.e. running, bicycling etc) > 120 min/week.
• Dementing illness
• Excessive alcohol use (>2 drinks per day)
• Resting heart rate > 120 bpm
• Systolic blood pressure > 180 mmHg
• Diastolic blood pressure > 100 mmHg
• Dietary supplementation of grape seed extract or ginko biloba
• History of significant head injury
• Vision or hearing impairment
• Anticholinesterase inhibitor (such as Aricept)
• Contraindications to MRI (e.g. cardiac pacemaker, implanted cardiac defibrillator, aneurysm clip, claustrophobia, etc.)
• Consumption of red wine/dealcoholized red wine/red or purple grape juice more than once weekly; consumption of any dietary supplements containing resveratrol, quercetin, or P. cuspidatum in the previous 90 days;
• Subject is participating in another clinical trial or has received an investigational product within 30 days prior to screening/enrollment
• Current Use of Antidepressant Medications
• CES-D Score > 20