TY - JOUR
T1 - Associations of Advanced Glycation End-Products With Cognitive Functions in Individuals With and Without Type 2 Diabetes: The Maastricht Study
AU - Spauwen, P.J.J.
AU - van Eupen, M.G.A.
AU - Köhler, S.
AU - Stehouwer, C.D.A.
AU - Verhey, F.R.J.
AU - van der Kallen, C.J.H.
AU - Sep, S.J.S.
AU - Koster, A.
AU - Schaper, N.C.
AU - Dagnelie, P.C.
AU - Schalkwijk, C.G.
AU - Schram, M.T.
AU - van Boxtel, M.P.J.
PY - 2015/3
Y1 - 2015/3
N2 - Context: Advanced glycation end-products (AGEs) are thought to be involved in the pathogenesis of Alzheimer's disease. AGEs are products resulting from nonenzymatic 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: The objective of the study was to examine associations between AGEs and cognitive functions.Design, Setting, and 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/high-density lipoprotein cholesterol ratio, triglycerides, and lipid-lowering medication use, higher SAF was significantly associated with worse delayed word recall (regression coefficient, b = - 0.44; P = .04), and response inhibition (b = 0.03; P = .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 = .07; response inhibition, b = 0.02, P = .07). Higher pentosidine levels were associated with worse global cognitive functioning (b = - 0.61; P = .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 noninvasive marker for tissue AGEs) with cognitive performance, which were attenuated after adjustment for vascular risk factors and depression.
AB - Context: Advanced glycation end-products (AGEs) are thought to be involved in the pathogenesis of Alzheimer's disease. AGEs are products resulting from nonenzymatic 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: The objective of the study was to examine associations between AGEs and cognitive functions.Design, Setting, and 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/high-density lipoprotein cholesterol ratio, triglycerides, and lipid-lowering medication use, higher SAF was significantly associated with worse delayed word recall (regression coefficient, b = - 0.44; P = .04), and response inhibition (b = 0.03; P = .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 = .07; response inhibition, b = 0.02, P = .07). Higher pentosidine levels were associated with worse global cognitive functioning (b = - 0.61; P = .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 noninvasive marker for tissue AGEs) with cognitive performance, which were attenuated after adjustment for vascular risk factors and depression.
KW - PARTICIPANTS AGED 24-81
KW - NORMATIVE DATA
KW - CARDIOVASCULAR-DISEASE
KW - ALZHEIMERS-DISEASE
KW - EDUCATION
KW - LEVEL
KW - BETA
KW - ENDPRODUCTS
KW - PERFORMANCE
KW - PENTOSIDINE
U2 - 10.1210/jc.2014-2754
DO - 10.1210/jc.2014-2754
M3 - Article
C2 - 25459912
SN - 0021-972X
VL - 100
SP - 951
EP - 960
JO - Journal of Clinical Endocrinology & Metabolism
JF - Journal of Clinical Endocrinology & Metabolism
IS - 3
ER -