PROJECT SUMMARY/ABSTRACT Apathy, defined as the absence or lack of motivation and emotional detachment, is a clinical feature of depression. Depressive symptoms and insulin resistance are conditions that are interdependent. Apathy, being a common depressive symptom in the elderly (> 70 years of age) and among individuals with diabetes, is a particularly attractive therapeutic target in interventions designed to improve glucose metabolism. The presence of apathy predicts chronicity of depression and poor response of depressive symptoms to treatment. Current interventions lack the precision needed to address apathy and its underlying mechanisms. We hypothesize that increasing insulin sensitivity in apathetic insulin resistant individuals will reduce apathy. Our preliminary studies show that a low glycemic index (GI) diet and exercise (D+E) intervention for seven days and 12 weeks increases insulin sensitivity in older adults with obesity. The key feature of a low GI diet is its high dietary fiber (DF) content. However, to maintain the benefits of a low GI diet in an elderly population, the fiber must be delivered in DF-dense portions of soft foods. Further, the exercise dose must be sustainable in a real-world setting. We will compare the traditional low GI diet with a low GI diet containing a novel dietary intervention using whole soybean pods (soy). To achieve Aim 1, we will conduct a dose escalation trial in the elderly with obesity and determine the maximum tolerated dose of DF delivered in soft foods including 10g, 20g, and 30g of soy and containing 4g, 8g, and 12g of DF respectively. At each dose, eight subjects will incorporate the foods into their usual diet for one week. We will evaluate tolerability to each dose and measure fecal short chain fatty acids as a biomarker of compliance. The results from Aim 1 will guide the design and implementation of Aim 2 that will determine the effect of a low GI D+E program on insulin sensitivity in elderly subjects with obesity and insulin resistance. To complete this aim we will conduct a 12-week randomized controlled trial of a low GI D+E program (controlled feeding and supervised exercise) with and without soy in 40 insulin resistant subjects with obesity and depressive symptoms including apathy. Aim 3 will determine the effect of the D+E intervention on apathy and whether the effect was mediated by changes in insulin sensitivity. The impact of social, psychosocial, and socioeconomic factors, and the acceptability of the intervention will also be evaluated. This research and training will: 1) provide the advanced transdisciplinary training needed to advance the delivery of D+E interventions in the elderly; 2) position the applicant to emerge as a leader in the development of efficacious D+E regimens for healthy aging; 3) facilitate the exploration of the effect of insulin resistance on apathy in age-related neurodegenerative disorders and; 4) precipitate exploration of the interaction between nutriti...