title: RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study.
abstract: OBJECTIVE
  Receptor for advanced glycation end products (AGEs; RAGE) binds to both AGEs and amyloid-beta peptides. RAGE is involved in chronic complications of type 2 diabetes and Alzheimer's disease. We aimed to investigate the roles of RAGE, AGEs and the Gly82Ser polymorphism of RAGE in mild cognitive impairment (MCI) among type 2 diabetes patients.
  
  
  METHODS
  Of the 167 hospitalized type 2 diabetes patients recruited, 82 satisfied the diagnostic criteria for MCI, and 85 matched control individuals were classified as non-MCI. Demographic data were collected, and the soluble RAGE (sRAGE) concentrations, serum AGE-peptide (AGE-P) levels, RAGE Gly82Ser genotype and neuropsychological test results were examined.
  
  
  RESULTS
  The MCI group exhibited a decreased sRAGE level (0.87±0.35 vs. 1.05±0.52 ng/ml, p<0.01) and an increased serum AGE-P level (3.54±1.27 vs. 2.71±1.18 U/ml, p<0.01) compared with the control group. Logistic regression analysis indicated that each unit reduction in the sRAGE concentration increased the MCI risk by 54% (OR 0.46[95% CI 0.22-0.96], p = 0.04) and that each unit increase in the AGE-P level increased the MCI risk by 72% in the type 2 diabetes patients (OR 1.72[95% CI 1.31-2.28], p<0.01). The serum sRAGE level was negatively correlated with the score on the trail making test-B (TMT-B) (r = -0.344, p = 0.002), which indicates early cognitive deficits related to diabetes. Moreover, the AGE-P level was positively correlated with multiple cognitive domains (all p<0.05). No significant differences in the neuropsychological test results or serum RAGE concentrations between the different RAGE genotypes or in the RAGE genotype frequencies between the MCI and control groups were identified (all p>0.05).
  
  
  CONCLUSIONS
  The RAGE pathway partially mediates AGE-induced MCI in diabetic patients. The serum AGE-P level may serve as a serum biomarker of MCI in these individuals, and sRAGE represents a predictor and even a potential intervention target of early cognitive decline in type 2 diabetes patients.
  
  
  BACKGROUND
  Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060.
authors.affiliation: Department of Endocrinology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China.
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of the Intensive Care Unit, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, PR China.
authors.forename: Sen
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Endocrinology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Endocrinology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Cai
authors.affiliation: Department of Endocrinology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Wang
mesh_terms: D000368:Aged; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D003430:Cross-Sectional Studies; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D005838:Genotype; D017127:Glycation End Products, Advanced / Q000097:blood*; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood* / Q000235:genetics; D012306:Risk
chemical_list: C000593871:AGER protein, human; D015415:Biomarkers; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products