Identifying Targets for Preventing Neurocognitive Complications in Youth with T1D - PROJECT SUMMARY/ABSTRACT Early childhood is a critical time in brain development for later health and maturation. During this period of rapid brain development, the brain may be especially vulnerable to dysglycemia and other metabolic conditions associated with type 1 diabetes (T1D). The current project seeks to evaluate neurocognitive complications in pre-pubertal onset T1D and identify potential risk and protective factors of brain health. Investigators at Joslin Diabetes Center (JDC) and Boston Children’s Hospital (BCH) seek to become a joint clinical center in the proposed consortium to investigate neurocognitive complications of pediatric T1D. In addition, we will collaborate with Boston Medical Center, an inner city safety net hospital, to ensure inclusion of under-represented and under- resourced participants. We have assembled a multidisciplinary team with expertise in clinical research and advanced diabetes technology use in pediatric T1D, health equity, psychosocial and cognitive implications of T1D, pediatric neurocognitive testing, pediatric neuroimaging, and brain development. In addition, we have engaged a diverse group of stakeholders who will actively participate in the development, design, and execution of the study as well as dissemination of results. In this consortium, we propose to recruit a prospective cohort of 600 (60 at the combined JDC and BCH site) pre-pubertal children, aged 4-8 years with newly diagnosed T1D, representative of the racial, ethnic, and socioeconomic diversity of the US, and a normative control group of 300 (30 at JDC/BCH) healthy children matched for age, sex, race, and ethnicity. Children will undergo structural, diffusion, and resting state functional MRI, neurocognitive and psychological assessments, and clinical evaluations shortly after diagnosis and longitudinally for 2 years. Structural and functional MRI measures and neurocognitive and psychological outcomes of children with T1D will be compared with matched neurotypically developing children from our normative sample, supplemented with publicly available data in large pediatric MRI repositories. To facilitate comparisons, imaging protocols will be adapted from published standard protocols; instruments for assessing cognitive function, psychosocial variables, and social determinants of health and cognition have been curated from standardized collections complemented with specific validated instruments. Clinical and diabetes management data will be assessed via record review and cloud-based data capture integrating device data from continuous glucose monitors (CGM), insulin pumps and pens, and activity monitors. As a member of this consortium: we aim: (1) to describe the impact of a pre-pubertal diagnosis of T1D on brain development; (2) to link functional and structural brain changes to clinical and performance outcomes; and (3) to assess determinants of brain health and identify targets for prevention or early intervention. In this MPI application, we hope to advance understanding of childhood brain development, with potential for direct implications for the clinical management of pediatric T1D to preserve neurocognition.
