Preclinical Imaging Biomarkers of Alzheimer's Disease Neuropathology in Young Adults With Youth-onset Diabetes: a Proof-of-concept Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Preclinical Imaging Biomarkers of Alzheimer's Disease Neuropathology in Young Adults With Youth-onset Diabetes: a Proof-of-concept Study

Conditions
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Diabetes, Youth Onset, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: PI-2620 tracer


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| T1D<br>Young adults with youth-onset type 1 diabetes (n=5) from the SEARCH for Diabetes in Youth study cohort | Drug: PI-2620 tracer<br>* 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.<br>|
| T2D<br>Young adults with youth-onset type 2 diabetes (n=5) from the SEARCH for Diabetes in Youth study cohort | Drug: PI-2620 tracer<br>* 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.<br>|
| NDM<br>Age-similar group of young adults without diabetes (n=5) | Drug: PI-2620 tracer<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Temporal lobe volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR | Baseline | 
| Temporal lobe cortical thickness in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR | Baseline | 
| Whole brain white matter hyperintensities volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Structural cerebrovascular disease via Sagittal 3D FLAIR | Baseline | 
| Regional homogeneity of the default mode network in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Resting-state functional connectivity via Axial T2* EPI fcMRI | Baseline | 
| Whole brain cerebral blood flow in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Cerebral blood flow or perfusion via Axial 3D pCASL | Baseline | 
| Whole brain fractional anisotropy in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Gray matter and white matter microstructure via Diffusion Kurtosis Imaging | Baseline | 
| Standardized uptake value ratio for hippocampal to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Tau accumulation via positron emission tomography with PI-2620 radiotracer | Baseline | 
| Standardized uptake value ratio for entorhinal to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Tau accumulation via positron emission tomography with PI-2620 radiotracer | Baseline | 
| Standardized uptake value ratio for cerebral to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Tau accumulation via positron emission tomography with PI-2620 radiotracer | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole brain gray matter volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR | Baseline | 
| Whole brain white matter volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR | Baseline | 
| Perivascular space in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Structural cerebrovascular disease via Sagittal 3D FLAIR | Baseline | 
| Atlas based region of interest cerebral blood flow in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Cerebral blood flow via Axial 3D pCASL | Baseline | 
| Atlas based region of interest fractional anisotropy in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes | Gray matter and white matter microstructure via Diffusion Kurtosis Imaging | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetes, Youth Onset, Magnetic Resonance Imaging, Positron Emission Tomography Imaging