# Neurocognition in youth with prediabetes

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $209,375

## 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:** 10413361
- **Project number:** 3R01DK114169-05S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** SONIA CAPRIO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,375
- **Award type:** 3
- **Project period:** 2017-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413361

## Citation

> US National Institutes of Health, RePORTER application 10413361, Neurocognition in youth with prediabetes (3R01DK114169-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10413361. Licensed CC0.

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