title: Associations of advanced glycation end-products with cognitive functions in individuals with and without type 2 diabetes: the maastricht study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry and Neuropsychology (P.J.J.S., S.K., F.R.J.V., M.P.J.v.B.), Maastricht University Medical Centre (MUMC+), 6200 MD, Maastricht, The Netherlands; School for Mental Health and Neuroscience (P.J.J.S., S.K., F.R.J.V., M.P.J.v.B.), Maastricht University, 6200 MD, Maastricht, The Netherlands; Department of Internal Medicine (M.G.A.v.E., C.D.A.S., C.J.H.v.d.K., S.J.S.S., N.C.S., C.G.S., M.T.S.), MUMC+, 6200 MD, Maastricht, The Netherlands; and Cardiovascular Research Institute Maastricht (M.G.A.v.E., C.D.A.S., C.J.H.v.d.K., S.J.S.S., N.C.S., P.C.D., C.G.S., M.T.S.), Department of Social Medicine (A.K.), School for Public Health and Primary Care (A.K., P.C.D.), and Department of Epidemiology (P.C.D.), Maastricht University, 6200 MD, Maastricht, The Netherlands.
authors.forename: P J J
authors.initials: PJ
authors.lastname: Spauwen
authors.forename: M G A
authors.initials: MG
authors.lastname: van Eupen
authors.forename: S
authors.initials: S
authors.lastname: Köhler
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: F R J
authors.initials: FR
authors.lastname: Verhey
authors.forename: C J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.forename: S J S
authors.initials: SJ
authors.lastname: Sep
authors.forename: A
authors.initials: A
authors.lastname: Koster
authors.forename: N C
authors.initials: NC
authors.lastname: Schaper
authors.forename: P C
authors.initials: PC
authors.lastname: Dagnelie
authors.forename: C G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: M T
authors.initials: MT
authors.lastname: Schram
authors.forename: M P J
authors.initials: MP
authors.lastname: van Boxtel
mesh_terms: D000368:Aged; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000523:psychology*; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007266:Inhibition, Psychological; D007361:Intelligence Tests; D008297:Male; D008568:Memory; D011939:Mental Recall; D008875:Middle Aged
chemical_list: D017127:Glycation End Products, Advanced