Effect of Advanced Glycation End Products on the Progression of Alzheimer's Disease

Background: Shared links between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) have been well-known. A high concentration of advanced glycation end products (AGEs) has been reported to contribute to impaired mobility in patients with AD, but there is limited understanding regarding the longitudinal impact of AGEs on cognitive performance. Objective: This study aims to explore whether the concentrations of AGEs mediate the clinical progression of cognitive performance in patients with AD and T2DM. Methods: Twenty-five patients aged 79.0 +/- 5.8 years who were diagnosed with probable AD with a Clinical Dementia Rating (CDR) of 0.5 or 1 and T2DM were enrolled in this study. When patients participated in the study, the concentration of plasma AGEs was tested. A series of neuropsychological tests, namely the Mini-Mental Status Examination (MMSE), Cognitive Assessment Screening Instrument (CAST), and CDR, were performed annually during follow-up. The association between the concentration of AGEs and changes in overall cognition and cognition related daily living performance was analyzed. Results: After the mean 48.6 +/- 2.1 months of follow-up, AGEs were found to be significantly associated with a change in CDR. A total of 12 (48%) patients experienced a decline in CDR; they had a significantly higher concentration of AGEs than did those whose CDR did not deteriorate (100.5 +/- 14.2 versus 81.5 +/- 17.7; p = 0.007). This difference in CDR remained significant after adjustment for age, sex, education level, and apolipoprotein E4 status (adjusted p = 0.023). Conclusion: In conclusion, this study indicates that a high concentration of AGEs may be a predictor of a long-term decline in cognition related daily living performance in patients with AD and T2DM.