The Pasinetti laboratory is currently focused on building a model based on genetic and environmental information to predict cognitive decline in overweight and obese individuals with type 2 diabetes (T2D). Ultimately, the study will allow the prediction of the long-term effects of intensive weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study. In particular, our studies are sequencing individual participants’ genome using whole exome sequencing and developing robust genetic risk models for predicting cognitive decline in subjects with T2D. Moreover, we are identifying causal biomarkers of cognitive decline and building a comprehensive model, integrating genetic and non-genetic biomarkers, for predicting risk of cognitive decline in T2D subjects. Lastly, we will use independent study cohorts from other Biobanks to validate our comprehensive model. Collectively, our studies will be critical for developing and redirecting efforts for potential therapeutic intervention in a subpopulation of T2D subjects who are at high risk for cognitive deterioration.