Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetes, Youth Onset
Conditions
Keywords
Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetes, Youth Onset, Magnetic Resonance Imaging, Positron Emission Tomography Imaging
Brief summary
The goal of the study is to characterize preclinical Alzheimer's Disease and related dementias (AD/ADRD) neuropathology in a selected group of young adults with youth-onset diabetes, and an age-similar group of young adults without diabetes.
Detailed description
The goal of the current proof-of-concept study is to characterize brain structural, functional, and molecular imaging biomarkers of preclinical Alzheimer's Disease and related dementias (AD/ADRD) neuropathology in a selected group of young adults with youth-onset diabetes (Y-DM; type 1 diabetes \[T1D\], n=5; type 2 diabetes \[T2D\], n=5) from the SEARCH for Diabetes in Youth study cohort, and an age-similar group of young adults without diabetes (n=5). This study will quantify structural and functional imaging biomarkers of AD/ADRD neuropathology via magnetic resonance imaging by assessing gray matter (GM) volume/cortical thickness, as well as GM and white matter (WM) microstructure, resting state functional network connectivity (rsfMRI), and cerebral blood flow (CBF) and WM hyperintensity volume. This study will additionally quantify brain tau density via positron emission tomography as the gold-standard measure of preclinical AD/ADRD neuropathology.
Interventions
DRUGPI-2620 tracer
Following published manufacturer guidelines for Flutemetamol (VizamylTM), Flortaucipir (TauvidTM) and PI-2620 tracer administration162, all participants will be given a 370 MBq (10 mCi) single intravenous bolus (total volume 10mL) of the radiotracer, followed with an intravenous flush of 0.9% sodium chloride injection. Radiotracer administration and participant monitoring will be conducted by trained personnel from the CU-RIC.
Sponsors
American College of Radiology
University of Colorado, Denver
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Part of the SEARCH for Diabetes in Youth study cohort or * Age 18-40 * Without diabetes
Exclusion criteria
* Head trauma with loss of consciousness \>30 minutes * Claustrophobia * Metal in the body * Major psychiatric disorder (eg. schizophrenia, bipolar, and major depression) * Neurological conditions affecting cognition (eg. epilepsy) * Stroke * If female, breastfeeding, plan to become pregnant or are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Standardized uptake value ratio for cerebral to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Tau accumulation via positron emission tomography with PI-2620 radiotracer |
| Regional homogeneity of the default mode network in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Resting-state functional connectivity via Axial T2\* EPI fcMRI |
| Whole brain cerebral blood flow in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Cerebral blood flow or perfusion via Axial 3D pCASL |
| Whole brain fractional anisotropy in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Gray matter and white matter microstructure via Diffusion Kurtosis Imaging |
| Standardized uptake value ratio for hippocampal to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Tau accumulation via positron emission tomography with PI-2620 radiotracer |
| Standardized uptake value ratio for entorhinal to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Tau accumulation via positron emission tomography with PI-2620 radiotracer |
| Temporal lobe volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR |
| Temporal lobe cortical thickness in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR |
| Whole brain white matter hyperintensities volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Structural cerebrovascular disease via Sagittal 3D FLAIR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whole brain white matter volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR |
| Perivascular space in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Structural cerebrovascular disease via Sagittal 3D FLAIR |
| Atlas based region of interest cerebral blood flow in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Cerebral blood flow via Axial 3D pCASL |
| Atlas based region of interest fractional anisotropy in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Gray matter and white matter microstructure via Diffusion Kurtosis Imaging |
| Whole brain gray matter volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Baseline | Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR |
Countries
United States
Outcome results
None listed