# Insulin resistance, cognitive health, and perfusion of the adolescent brain

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $187,150

## Abstract

Project Summary/Abstract
One in five American adolescents are obese, and many of these patients exhibit some level of insulin resistance
(IR). IR is associated with cerebrovascular disease, reduced memory, attention, and cognition, but how IR
contributes to these in the course of adolescent brain development is unclear. The goal of this proposal is to
investigate the extent and mechanisms by which IR drives reductions in neurocognitive function and cerebral
blood flow (CBF) in adolescents at elevated risk of poor brain and cerebrovascular health. We are testing the
overall hypothesis that neurocognitive decline is linked to severity of IR, as are reductions in brain perfusion, due
to dysfunctional insulin signaling. We propose to study acute CBF control in healthy adolescents (12-18 years)
across a range of IR (diabetes excluded) in collaboration with expert childhood neuropsychologists who lead a
comprehensive testing protocol. Next, two complementary MRI methods (ASL and Phase Contrast), along with
a physiologic stressor to challenge CBF, will be used to test whether the impact of IR on brain macrovascular
CBF and microvascular perfusion is regionally specific, with more negative effects in temporal and parietal lobes.
These lobes are some of the initial brain areas to change, and are involved in attention, memory, learning, and
cognition. Finally, this study tests whether the degree of cognitive decline is linked to the CBF stress response
and to severity of IR, and to what extent brain hypoperfusion mediates the IR-driven lower cognitive function.
This study will provide the first comprehensive look at IR in adolescent brains, by utilizing extensive
neuropsychological testing and state-of-the-art MR imaging, and drawing on interdisciplinary collaborations
between developmental neuropsychologists, vascular physiologists, and pediatric endocrinologists. These
studies are designed to uncover fundamental relationships between IR, neurocognitive function, and CBF in
these blossoming adolescent brains. Exciting preliminary data support the aims—particularly uncovered by a
physiologic insulin surge—signifying these findings will serve as a foundation for prospective, mechanistic
studies to reduce the burden of IR and improve brain and cognitive health in this clinically important population.

## Key facts

- **NIH application ID:** 9980475
- **Project number:** 5R21HD097510-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** WILLIAM G SCHRAGE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $187,150
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980475

## Citation

> US National Institutes of Health, RePORTER application 9980475, Insulin resistance, cognitive health, and perfusion of the adolescent brain (5R21HD097510-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9980475. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*