Project Summary/Abstract Alzheimer's disease (AD) is now America's most expensive disease, more costly than cancer and heart disease. Without effective therapies to slow or stop the disease, there is an increasing emphasis on developing methods to prevent and delay the onset. Observational data, and limited clinical trial evidence, suggest that the Mediterranean diet may slow age-related cognitive decline and delay or prevent the onset of AD. There remains a need for rigorous data proving its effectiveness and to develop methods for delivering the diet in a way that enhances adoption and adherence. We have a demonstrated track record of performing rigorous dietary interventions, including a recent pilot Mediterranean diet trial. We have established methods for delivering the intervention and have data indicating we can successfully educate older adults to adopt and adhere to a Mediterranean diet pattern. Our Med+O package includes formal education and counseling, daily prescriptions for olive oil, almonds, and omega-3 fatty acids, and a weekly food box through a partnership with a major grocery chain. We now propose to test this highly scalable and reproducible approach to administering the Med+O diet in a randomized trial testing its effectiveness versus a low fat (control) diet on cognitive change over 1 year in older adults (n = 200 men and women ≥ 65 years). The primary endpoint compares the mean change in pre and post-diet composite global cognition score at 12 months. Additional outcomes include secondary composite indices of memory, executive, and visuospatial function. Aim 2 determines how Med+O impacts brain volume and cerebral antioxidant systems (glutathione and vitamin C). Aim 3 explores the impact of Med+O on cardiometabolic markers (blood pressure, glucose, HbA1c, insulin, advanced lipid testing, C- reactive protein and Lipoprotein-associated phospholipase A2). Aim 4 includes in silico statistical simulations that will determine the most impactful methods and outcomes for a larger, multi-site trial. The results of this project will have important