# Project 2: Vascular Mechanisms of Cognitive Impairment in Chronic Kidney Disease

> **NIH NIH P20** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $257,097

## Abstract

Cognitive impairment in chronic kidney disease (CKD) patients impacts up to 12 million US adults and is a
major public health problem. The mechanisms that underlie cognitive changes in CKD are unknown; however,
the rates of cognitive impairment increase with worsening kidney function, suggesting an association between
kidney function and cognitive impairment. While vascular disease is highly prevalent in CKD, and a greater
proportion of cognitive impairment has been attributed to vascular causes in CKD, traditional cardiovascular
risk factors do not account for the higher risk of cognitive impairment in CKD compared to those without CKD.
Preliminary data from our lab and others demonstrates that biomarkers of inflammation (C-reactive protein,
Interleukin-6), hemostasis (factor VIII, D-dimer and fibrinogen) and endothelial activation (E-selectin, Vascular
cell adhesion molecule-1, Intercellular adhesion molecule-1) are linked to both CKD and cognitive impairment
independently. As candidate biomarkers in the pathway between CKD and cognitive impairment, we
hypothesize that these biomarkers mediate cognitive impairment in CKD. In addition, little is known about the
trajectory of cognitive function in persons with CKD, as most previous studies have focused on cross-sectional
associations. To address these knowledge gaps, we will study participants in the Reasons for Geographic and
Racial Differences in Stroke (REGARDS) Study. We have repeated measures of global cognitive function
annually and a cognitive battery biannually in a sample of 23,183 black and white adults from across the U.S.,
9% of whom have CKD. Our overall hypothesis is that cognitive decline in CKD is progressive and that there
are unique trajectories and biomarkers of cognitive impairment. In this project, we aim to 1) Characterize the
trajectories of cognitive impairment in CKD among a nationally representative sample and the risk factors for
different trajectories, and 2) Determine the role of activation of inflammation, hemostasis and endothelium in
the association of CKD and cognitive impairment. The innovative aspects of our study include a) the
REGARDS study as a unique, longitudinal dataset with measures of global cognitive function and a cognitive
battery of tests on learning, verbal memory and executive function, b) the use of group-based trajectory
modeling to distinguish different trajectories of cognitive function and identify risk factors for rapid decline, and
c) the ability to measure, in a sub-cohort of 4,000 participants, new analytes reflecting potential mediators of
cognitive decline in CKD including inflammation, hemostatic and endothelial activation. The results of our study
will determine the natural history of cognitive decline in CKD, shed light on vascular mechanisms of CI in CKD,
a critical area of brain health research, and will lay the groundwork for future interventions to reduce cognitive
impairment in CKD.

## Key facts

- **NIH application ID:** 10447830
- **Project number:** 5P20GM135007-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Katharine L. Cheung
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $257,097
- **Award type:** 5
- **Project period:** 2020-08-06 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447830

## Citation

> US National Institutes of Health, RePORTER application 10447830, Project 2: Vascular Mechanisms of Cognitive Impairment in Chronic Kidney Disease (5P20GM135007-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10447830. Licensed CC0.

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