White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-06-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/15/7/692 |
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| author | Rudolph Johnstone Ida Rangus Natalie Busby Janina Wilmskoetter Nicholas Riccardi Sarah Newman-Norlund Roger Newman-Norlund Chris Rorden Julius Fridriksson Leonardo Bonilha |
| author_facet | Rudolph Johnstone Ida Rangus Natalie Busby Janina Wilmskoetter Nicholas Riccardi Sarah Newman-Norlund Roger Newman-Norlund Chris Rorden Julius Fridriksson Leonardo Bonilha |
| author_sort | Rudolph Johnstone |
| collection | DOAJ |
| description | 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, <i>p</i> = 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. |
| format | Article |
| id | doaj-art-426d612f8d5e41ee9a5c61df6eda2b40 |
| institution | DOAJ |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj-art-426d612f8d5e41ee9a5c61df6eda2b402025-08-20T02:45:45ZengMDPI AGBrain Sciences2076-34252025-06-0115769210.3390/brainsci15070692White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive FunctionRudolph Johnstone0Ida Rangus1Natalie Busby2Janina Wilmskoetter3Nicholas Riccardi4Sarah Newman-Norlund5Roger Newman-Norlund6Chris Rorden7Julius Fridriksson8Leonardo Bonilha9School of Medicine Columbia, University of South Carolina, 6311 Garners Ferry Rd, Columbia, SC 29209, USADepartment of Communication Sciences and Disorders, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USADepartment of Communication Sciences and Disorders, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USADepartment of Rehabilitation Sciences, Medical University of South Carolina, 160 Ashley Avenue, Charleston, SC 29425, USADepartment of Communication Sciences and Disorders, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USADepartment of Communication Sciences and Disorders, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USADepartment of Psychology, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USADepartment of Psychology, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USADepartment of Communication Sciences and Disorders, University of South Carolina, 915 Greene Street, Columbia, SC 29208, USASchool of Medicine Columbia, University of South Carolina, 6311 Garners Ferry Rd, Columbia, SC 29209, USABackground: 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, <i>p</i> = 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.https://www.mdpi.com/2076-3425/15/7/692diabetescognitive impairmentwhite matter hyperintensitiesdementiabrain aging |
| spellingShingle | Rudolph Johnstone Ida Rangus Natalie Busby Janina Wilmskoetter Nicholas Riccardi Sarah Newman-Norlund Roger Newman-Norlund Chris Rorden Julius Fridriksson Leonardo Bonilha White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function Brain Sciences diabetes cognitive impairment white matter hyperintensities dementia brain aging |
| title | White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function |
| title_full | White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function |
| title_fullStr | White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function |
| title_full_unstemmed | White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function |
| title_short | White Matter Hyperintensities Mediate the Negative Impact of HbA1c Levels on Cognitive Function |
| title_sort | white matter hyperintensities mediate the negative impact of hba1c levels on cognitive function |
| topic | diabetes cognitive impairment white matter hyperintensities dementia brain aging |
| url | https://www.mdpi.com/2076-3425/15/7/692 |
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