Diabetes and "hyperinsulinemia" (high insulin levels) have surfaced as important risk factors for Alzheimer's disease (AD). There are ongoing clinical trials of anti-diabetic agents (e.g. rosiglitazone) in the prevention and treatment of AD based on the hypothesis that reduction of insulin levels will decrease AD progression. However, recent reports of safety concerns with rosiglitazone widely covered by the scientific and lay press have put the use of this medication in the prevention and treatment of AD into question. Dr. Luchsinger proposes to continue a phase II pilot clinical trial of metformin, a safe and effective medication in the prevention and treatment of diabetes and the reduction of insulin levels, in the prevention of cognitive decline among persons with amnestic mild cognitive impairment (AMCI), a transitional stage between normal cognition and AD. Luchsinger will complete recruitment of 40 subjects with grant 270901 from ISOA. With the additional funding raised through the "fund-a-scientist" program, he will continue to follow-up these 40 subjects and will recruit 10 new participants.