Abstract
The metabolic serum marker HbA1c has been associated with both impaired cognitive performance and altered white matter integrity in patients suffering from diabetes mellitus. However, it remains unclear if higher levels of HbA1c might also affect brain structure and function in healthy subjects. With the present study we therefore aimed to investigate the relationship between HbA1c levels and cognitive performance as well as white matter microstructure in healthy, young adults. To address this question, associations between HbA1c and cognitive measures (NIH Cognition Toolbox) as well as DTI-derived imaging measures of white matter microstructure were investigated in a publicly available sample of healthy, young adults as part of the Humane Connectome Project (n = 1206, mean age = 28.8 years, 45.5% male). We found that HbA1c levels (range 4.1–6.3%) were significantly inversely correlated with measures of cognitive performance. Higher HbA1c levels were associated with significant and widespread reductions in fractional anisotropy (FA) controlling for age, sex, body mass index, ethnicity, and education. FA reductions were furthermore found to covary with measures of cognitive performance. The same pattern of results could be observed in analyses restricted to participants with HBA1c levels below 5.7%. The present study demonstrates that low-grade HbA1c variation below diagnostic threshold for diabetes is related to both cognitive performance and white matter integrity in healthy, young adults. These findings highlight the detrimental impact of metabolic risk factors on brain physiology and underscore the importance of intensified preventive measures independent of the currently applied diagnostic HbA1c cutoff scores.
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Change history
13 March 2020
A Correction to this paper has been published: https://doi.org/10.1038/s41380-020-0710-z
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Acknowledgements
This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5–1 and DA1151/5–2 to UD; SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). Data were provided [in part] by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University.
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VA is a member of the advisory board of, or has given presentations on behalf of, the following companies: Astra-Zeneca, Janssen-Organon, Lilly, Lundbeck, Servier, Pfizer, Otsuka, and Trommsdorff. These affiliations are of no relevance to the work described in the paper. H. Kugel has received consultation fees from MR: comp GmbH, Testing Services for MR Safety.
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JR and GK made substantial contributions to the conception, design of the work, and drafted the work. SM, KF, DG, and JG made substantial contributions to the analysis of this work and the interpretation of data. VA, BB, and UD have substantially revised the work. NO made substantial contributions to the conception, design of the work, and drafted the work. All authors approved the submitted version and agreed both to be personally accountable for the author’s own contributions and that questions related to the accuracy or integrity of any part of the work are appropriately investigated.
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Repple, J., Karliczek, G., Meinert, S. et al. Variation of HbA1c affects cognition and white matter microstructure in healthy, young adults. Mol Psychiatry 26, 1399–1408 (2021). https://doi.org/10.1038/s41380-019-0504-3
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DOI: https://doi.org/10.1038/s41380-019-0504-3
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