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DIFFERENTIAL ASSOCIATION OF BLOOD INSULIN AND HBA1C WITH CEREBRAL AMYLOID DEPOSITION AND REGIONAL GLUCOSE METABOLISM IN MIDDLE- AND OLD-AGED ADULTS

      Background

      Preclinical studies indicated that insulin may activate beta-amyloid protein (Aβ) clearance through multiple pathways. Recently, a couple of studies have evaluated whether blood insulin or insulin resistance affect brain Aβ deposition in living human, the results were controversial. We aimed to investigate the associations of blood insulin and hemoglobin A1c (HbA1c) with cerebral amyloid burden and regional cerebral glucose metabolism (rCMglu) in cognitively normal middle- and old-aged adults.

      Methods

      One hundred and seventy-four cognitively normal middle- and old-aged adults (mean age = 68.9). Higher levels of blood insulin and HOMA-IR related to lower global PiB retention even after controlling age, gender, APOE4 status, and body mass index (BMI).

      Results

      The relationships was much stronger in old-aged participants (age above 65 years) than in mid-aged ones. In addition, both blood insulin level and HOMA-IR were positively associated with rCMglu in the angular gyrus, hippocampus, and parahippocampal gyrus. In contrast, HbA1c and fasting blood glucose had no association with global PiB retention, but both were negatively associated with rCMglu in all the ROIs after controlling age, gender, APOE4 status, and BMI.

      Conclusions

      Our results indicate that blood insulin itself may contribute to lowering cerebral Aβ deposition and maintaining brain function in cognitively normal middle- and old-aged adults, old-aged in particular, while higher blood glucose level may have negative influence on brain function through non-amyloid mechanism.