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Associations between methylglyoxal and cerebral small vessel disease and cognitive function – The Maastricht Study

Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Cerebral small vessel disease (CSVD) and dementia are increasingly prevalent in the aging population. Diabetes is a major risk factor for CSVD and cognitive impairment, but the underlying mechanisms remain unclear. Methylglyoxal (MGO), a glycolysis by-product and precursor of advanced glycation endproducts (AGEs), is elevated in diabetes and linked to microvascular complications. The aim of this study is to investigate the association between levels of MGO in plasma with MRI-derived markers of CSVD and cognitive impairment in a population-based setting. METHODS: Cross-sectional data from The Maastricht Study, a population-based cohort with an oversampling of type 2 diabetes (age 59.7 ± 8.2 years, 49.9 % male, 26 % type 2 diabetes), were analysed. Plasma MGO concentrations were measured using UPLC-MS/MS after overnight fasting. Participants underwent MRI (n = 1789) and cognitive testing (n = 2515). CSVD markers included white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds. Logistic and linear regressions, adjusted for confounders, assessed the associations between plasma MGO levels, CSVD markers, and cognitive function. RESULTS: No linear associations were found in any of the outcomes. When dividing the population into tertiles (lowest, intermediate, highest) based on plasma MGO concentration, intermediate compared to lowest levels of plasma MGO were associated with increased odds of having a lacunar infarct (OR: 2.26, 95 %CI: 1.27; 4.01). This was not observed for highest plasma MGO (OR: 1.56, 95 %CI: 0.85; 2.86). CONCLUSION: Intermediate plasma MGO levels were associated with the presence of more lacunar infarcts. Further research is needed to determine whether MGO contributes to lacunar infarct formation in a causal manner.
DOI: 10.1016/j.jstrokecerebrovasdis.2026.108578
Authors: Eline Berends, Simone J.P.M. Eussen, Walter H. Backes, Pieter C. Dagnelie, Jacobus F.A. Jansen, Bastiaan E. de Galan, Marleen M.J. van Greevenbroek, Sebastian Köhler, Miranda T. Schram, Anke Wesselius, Robert J. van Oostenbrugge, Sébastien Foulquier, Casper G. Schalkwijk
Language: English
Open Access status: gold
Estimated APC paid: $2,170
Funders: Sanofi, Health Foundation Limburg, European Foundation for the Study of Diabetes, Ministerie van Economische Zaken, Novo Nordisk, Stichting Sint Annadal, Stichting De Weijerhorst, European Regional Development Fund, CARIM School for Cardiovascular Diseases, Universiteit Maastricht, Care and Public Health Research Institute, Universiteit Maastricht, NUTRIM School of Nutrition and Translational Research in Metabolism, Janssen Nederland
OpenAlex ID: W7126081273
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