Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions

Objective: To investigate whether higher fasting serum glucose levels in cognitively normal, nondiabetic adults were associated with lower regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer disease (AD). Methods: This is a cross-sectional study of 124 cognitively normal persons aged 64 +/- 6 years with a first-degree family history of AD, including 61 APOE epsilon 4 noncarriers and 63 carriers. An automated brain mapping algorithm characterized and compared correlations between higher fasting serum glucose levels and lower [F-18]-fluorodeoxyglucose-PET rCMRgl measurements. Results: As predicted, higher fasting serum glucose levels were significantly correlated with lower rCMRgl and were confined to the vicinity of brain regions preferentially affected by AD. A similar pattern of regional correlations occurred in the APOE epsilon 4 noncarriers and carriers. Conclusions: Higher fasting serum glucose levels in cognitively normal, nondiabetic adults may be associated with AD pathophysiology. Findings suggest that the risk imparted by higher serum glucose levels may be independent of APOE epsilon 4 status. This study raises additional questions about the role of the metabolic process in the predisposition to AD and supports the possibility of targeting these processes in presymptomatic AD trials.