# Metabolomics of Neurocognitive Risk for Dementia in Diabetes

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $757,624

## Abstract

Type 2 diabetes (T2D) is a major epidemic associated with significant burdens on patients, families, and the
public healthcare system. Its rise in prevalence is concomitant with an increase in diabetes-related
comorbidities. Among these, diabetes has emerged as a reproducible risk factor for cognitive impairment and
dementia. However, the mechanisms underlying the risk for dementia in the disproportionately burdened T2D
populations are poorly understood. The primary goal of this study is to evaluate the hypothesis that
metabolomic signatures of neurocognitive trajectory are present in diabetes and these signatures explain, in
part, race disparities in cognitive decline between European Americans and African Americans with T2D. This
hypothesis will be explored by re-examining the Diabetes Heart Study (DHS) cohort for neurocognitive
trajectory using a well-established cognitive battery, literacy testing, and adjudicated physician diagnosis of
dementia. Because neurodegenerative conditions, representative of cognitive decline, are progressive with
pathology developing years prior to the observation of clinical symptoms and functional deficits, untargeted
metabolomic analysis will be performed on baseline samples collected >10 years prior and correlated with
cognitive trajectory. This approach offers the potential to identify relevant biomarkers before onset of overt
disease. Finally, a comprehensive genetic analysis of the DHS participants to examine the genetic architecture
of neurocognitive measures and metabolomic signatures of neurocognitive change will be performed. The
composition of this study, inclusive of European American and African Americans participants, will provide
generalizability of the findings. The timing of this study is critical to contrast changes in midlife to early-late
adulthood to identify first stage pathophysiological changes facilitating the identification of relevant biomarkers
with potential to improve the diagnosis, prognosis and treatment of cognitive impairment and dementia.

## Key facts

- **NIH application ID:** 9882933
- **Project number:** 5R01AG058921-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Nicholette D. Allred
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $757,624
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882933

## Citation

> US National Institutes of Health, RePORTER application 9882933, Metabolomics of Neurocognitive Risk for Dementia in Diabetes (5R01AG058921-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9882933. Licensed CC0.

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