# Neurocognition in youth with prediabetes

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $778,047

## Abstract

SUMMARY
Accumulating evidence links human obesity and diabetes with cognitive dysfunction and dementia 1-51. While
the causality is unknown in humans, and likely bi-directional, it is clear from work in rodents that diet induced
obesity and associated metabolic dysfunction cause impaired cognition52-56. The mechanisms supporting this
effect and the relative contribution of adiposity, diet and metabolic dysfunction remain unknown. Of particular
interest to the funding opportunity announcement to which we respond is elucidating the link between glucose
regulation and cognition. Although glucose intolerance is diagnostic of type 2 diabetes (T2D), a recent systematic
review of 86 papers examining T2D and cognition only found a weak association between glycaemia and
cognition 68 and there is even less evidence for an association with other measures of peripheral glucose
regulation (e.g., insulin concentration, insulin action, insulin resistance)68. This represents a major gap in
knowledge because it impedes the development of strategies to mitigate the risk of neurocognitive
complications. The proposed research directly addresses this gap in knowledge. More specifically, we aim to
provide a definitive test of the role of peripheral glucose intolerance on neurocognition, by longitudinal evaluation
of cognitive and brain function in youth enrolled in the Pathogenesis of Youth Onset Diabetes (PYOD) study
(R01DK111038) who are either glucose tolerant or intolerant but matched for age, gender, BMI and central
adiposity. The PYOD cohort provides an exceptional opportunity to study cognitive impairment in T2D because
the participants are pre-diabetic and thus do not suffer from chronic conditions associated with T2D. We also
propose to use a new neuroimaging paradigm developed to assess central insulin resistance (IR) so that we
may disentangle the effects of central and peripheral IR on neurocognition 46 and an indirect marker of striatal
dopamine signaling to investigate the relation between IR, dopamine and neurocognition. More specifically, our
aims are to (1) To test whether impaired peripheral glucose tolerance (IGT) and/or central IR influence
neurocognitive function independently from adiposity; (2) To test whether change in glucose
metabolism and/or adiposity predicts and precedes change in neurocognition; and (3) To test whether
cognitive dysfunction and decline is associated with dopamine signaling. We anticipate that these results
will inform the development of strategies to mitigate the risk of developing neurocognitive impairment, aid in the
identification of individuals who are at-risk and who might benefit from additional therapy, provide a novel
therapeutic target for pharmacological intervention and provide critical information about the rate of cognitive
decline.

## Key facts

- **NIH application ID:** 9991829
- **Project number:** 5R01DK114169-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** SONIA CAPRIO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $778,047
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991829

## Citation

> US National Institutes of Health, RePORTER application 9991829, Neurocognition in youth with prediabetes (5R01DK114169-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991829. Licensed CC0.

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