Glucose metabolism, advanced glycation endproducts, and cognition

Abstract

The accumulation of advanced glycation endproducts (AGEs) has been implicated in the pathogenesis of diabetic complications and aging. Diabetes mellitus is associated with moderate cognitive deficit. The AGEs may exert several actions on central nervous system. To explore a possible role of AGEs for cognitive impairment, we have examined the association between serum AGEs and cognitive function in diabetic patients.We studied 198 diabetic patients with a mean age of 74 years. Serum AGE (N‐epsilon‐ carboxymethyllysine, CML) was measured with the enzyme immunoassay. The several domains of cognitive function were assessed using the WAIS‐R, Stroop test, and Benton test. Diabetic patients had more impairment of complex pychomotor skill and visual memory as assessed with the digit symbol substitution test and Benton test than non‐diabetic subjects. Among the diabetic patients, a marker of hyperglycemia, HbA1c level was associated with the cognitive impairment, while short‐term glucose control partially improved the cognitive impairment. Serum AGE levels correlated with age, duration of diabetes, and HbA1c. Serum AGE levels were significantly associated with the impairment of complex psychomotor skills independent of HbA1c. In conclusion, hyperglycemia and increased AGE accumulation were associated with the cognitive impairment in patients with diabetes mellitus as a model of accelerated aging.