(21-10-15) Associations of advanced glycation endproducts with cognitive functions in individuals with and without type 2 diabetes.

Spauwen PJ1, van Eupen MG, Köhler S, Stehouwer CD, Verhey FR, van der Kallen CJ, Sep SJ, Koster A, Schaper NC, Dagnelie PC,Schalkwijk CG, Schram MT, van Boxtel MP.
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Abstract
Context: Advanced glycation endproducts (AGEs) are thought to be involved in the pathogenesis of Alzheimer's disease. AGEs are products resulting from non-enzymatic chemical reactions between reduced sugars and proteins, which accumulate during natural aging and their accumulation is accelerated in hyperglycemic conditions such as type 2 diabetes mellitus. Objective: Examine associations between AGEs and cognitive functions Design, setting, participants: This study was performed as part of The Maastricht study, a population-based cohort study, in which, by design, 215 participants (28.1%) had type 2 diabetes mellitus. Main outcome measures: We examined associations of skin autofluorescence (SAF) (N=764), an overall estimate of skin AGEs, and specific plasma protein-bound AGEs (N=781) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition. Results: After adjustment for demographics, diabetes, smoking, alcohol, waist circumference, total cholesterol/HDL cholesterol ratio, triglycerides, and lipid-lowering medication use, higher SAF was significantly associated with worse delayed word recall (regression coefficient b=-0.44, P=0.04), and response inhibition (b=0.03, P=0.04). After further adjustment for systolic blood pressure, cardiovascular disease, estimated glomerular filtration rate, and depression, associations were attenuated (delayed word recall: b=-0.38, P=0.07; response inhibition: b=0.02, P=0.07). Higher pentosidine levels were associated with worse global cognitive functioning (b=-0.61, P=0.04) after full adjustment, but other plasma AGEs were not. Associations did not differ between individuals with and without diabetes. Conclusion: We found inverse associations of SAF, a non-invasive marker for tissue AGES, with cognitive performance, which were attenuated after adjustment for vascular risk factors and depression.


Source: J Clin Endocrinol Metab. 2014 Dec 2:jc20142754. [Epub ahead of print]

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