Project Summary Children with type 1 diabetes (T1D) have an increased likelihood of mild cognitive dysfunction and altered brain development compared to healthy children, which can appear soon after disease onset. Younger age at diagnosis, poorer metabolic control, episodes of diabetic ketoacidosis (DKA), and hypoglycemic events have been identified as possible risk factors, but how they interact to affect brain development, and who is most vulnerable remain poorly understood. To investigate the impacts of T1D on cognition and brain development without interference from puberty, this planned research will enroll as many as 1,000 prepubertal children, half of whom were diagnosed with T1D within the previous year, and perform MRI and cognitive tests at baseline and at two-to-three 18-month intervals. Biomedical data will also be collected. Outcomes include cognitive function and academic achievement, as well as MRI-based microstructural, volumetric, functional and physiological measures. Their relationship to glycemic variability and multiple biomedical factors will be assessed. Differences in neurocognitive development between participants with and without T1D will be compared. Our team has successfully recruited large, diverse cohorts, including children with and without diabetes, who have been followed over extended periods of time, recruited from multiple clinical sites, and assessed with a broad series of biomedical tests, continuous glucose monitoring, neurocognitive and psychosocial measures, and state-of-the-art neuroimaging techniques. With PIs and Co-Investigators with expertise in neurocognitive studies in T1D, imaging in young children, management of diabetes in children, data management, quality control, statistical analysis, cognitive assessments, neuroimaging methods, continuous glucose monitoring, and stakeholder engagement, our team has the necessary experience to succeed in the proposed study.