Higher levels of advanced glycation endproducts are inversely associated with cognitive function – The Maastricht Study

Peggy Spauwen, Marcelle van Eupen, Sebastian Köhler, Casper Schalkwijk, Coen Stehouwer, Frans Verhey, Carla van der Kallen, Simone Sep, Annemarie Koster, Nicolaas Schaper, Pieter Dagnelie, Miranda Schram, Martin van Boxtel

Advanced glycation endproducts (AGEs) are thought to be involved in the pathogenesis of Alzheimer’s disease. We examined the association of skin autofluorescence (SAF) (N=762), an overall estimate of skin AGEs, and specific plasma protein-bound AGEs (N=779) with cognitive functions in The Maastricht Study, in which, by design, 214 participants (28.1%) had type 2 diabetes.  After adjustment for demographics, diabetes, smoking, alcohol, waist circumference, total cholesterol/HDL cholesterol, triglyceride, and lipid-lowering medication use, SAF was significantly associated with delayed word recall (regression coefficient b=-0.44, P=0.03), and response inhibition (b=0.03, P=0.03). 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=0.08). Pentosidine was associated with global cognitive functioning (b=-0.61, P=0.04) after full adjustment, but other AGEs were not. Associations did not differ between individuals with and without diabetes. In conclusion, SAF and pentosidine may be involved in the development of cognitive impairment, possibly in part through vascular risk factors. Future longitudinal studies need to demonstrate this.