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Brain Sciences
Volume 15
Issue 7
10.3390/brainsci15070692
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Brief Report

White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function

by
Rudolph Johnstone
1,
Ida Rangus
2,*,
Natalie Busby
2,
Janina Wilmskoetter
3,
Nicholas Riccardi
2,
Sarah Newman-Norlund
2,
Roger Newman-Norlund
4,
Chris Rorden
4,
Julius Fridriksson
2 and
Leonardo Bonilha
1
1
School of Medicine Columbia, University of South Carolina, 6311 Garners Ferry Rd, Columbia, SC 29209, USA
2
Department of Communication Sciences and Disorders, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USA
3
Department of Rehabilitation Sciences, Medical University of South Carolina, 160 Ashley Avenue, Charleston, SC 29425, USA
4
Department of Psychology, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USA
*
Author to whom correspondence should be addressed.
Brain Sci. 2025, 15(7), 692; https://doi.org/10.3390/brainsci15070692 (registering DOI)
Submission received: 22 May 2025 / Revised: 20 June 2025 / Accepted: 26 June 2025 / Published: 27 June 2025
(This article belongs to the Special Issue Advances in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease)
Review Reports Versions Notes

Abstract

Background: Type 2 diabetes is linked to impaired cognitive function, but the underlying mechanisms remain poorly understood. As white matter hyperintensities (WMHs) are common in diabetes and associated with vascular brain injury, we investigated whether WMH burden mediates the relationship between hemoglobin A1c (HbA1c) levels and cognition. Methods: We quantified WMH load using the Fazekas scale and conducted a mediation analysis with HbA1c as the independent variable, Fazekas scale as the mediator, and MoCA scores as the outcome variable. Results: WMHs partially mediated the relationship between HbA1c levels and MoCA scores (indirect effect = −0.224, 95% CI = −0.619 to −0.050, p = 0.001), accounting for approximately 15.6% of the total effect. Conclusions: This study suggests that WMHs partially mediate the association between chronically elevated blood glucose levels and cognitive impairment in neurologically healthy adults, supporting a potential microvascular mechanism in diabetes-related cognitive impairment.
Keywords: diabetes; cognitive impairment; white matter hyperintensities; dementia; brain aging diabetes; cognitive impairment; white matter hyperintensities; dementia; brain aging

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MDPI and ACS Style

Johnstone, R.; Rangus, I.; Busby, N.; Wilmskoetter, J.; Riccardi, N.; Newman-Norlund, S.; Newman-Norlund, R.; Rorden, C.; Fridriksson, J.; Bonilha, L. White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function. Brain Sci. 2025, 15, 692. https://doi.org/10.3390/brainsci15070692

AMA Style

Johnstone R, Rangus I, Busby N, Wilmskoetter J, Riccardi N, Newman-Norlund S, Newman-Norlund R, Rorden C, Fridriksson J, Bonilha L. White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function. Brain Sciences. 2025; 15(7):692. https://doi.org/10.3390/brainsci15070692

Chicago/Turabian Style

Johnstone, Rudolph, Ida Rangus, Natalie Busby, Janina Wilmskoetter, Nicholas Riccardi, Sarah Newman-Norlund, Roger Newman-Norlund, Chris Rorden, Julius Fridriksson, and Leonardo Bonilha. 2025. "White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function" Brain Sciences 15, no. 7: 692. https://doi.org/10.3390/brainsci15070692

APA Style

Johnstone, R., Rangus, I., Busby, N., Wilmskoetter, J., Riccardi, N., Newman-Norlund, S., Newman-Norlund, R., Rorden, C., Fridriksson, J., & Bonilha, L. (2025). White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function. Brain Sciences, 15(7), 692. https://doi.org/10.3390/brainsci15070692

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