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

Abstract

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 APOEε4 noncarriers and 63 carriers. An automated brain mapping algorithm characterized and compared correlations between higher fasting serum glucose levels and lower [(18)F]-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 APOEε4 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 APOEε4 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.

Figure 1. Association between higher fasting serum glucose levels and reduced rCMRgl in AD-related brain regions

Statistical maps generated from this study were projected onto the lateral and medial surfaces of the left and right cerebral hemispheres and feature brain regions in which elevated serum glucose levels are associated with reduced rCMRgl. Initial findings (p < 0.005) in AD-related search regions (see figure e-1) were corrected for multiple comparisons and yield a similar pattern of results (p < 0.05). AD = Alzheimer disease; rCMRgl = regional cerebral metabolic rate for glucose.

Figure 2. Scatterplot of the highest significant correlation between higher fasting serum glucose levels and reduced rCMRgl

This correlation occurred in an Alzheimer disease–related right parietal cortex voxel (r = −0.41, p = 0.00014) and survived correction for multiple comparisons (p < 0.05). rCMRgl = regional cerebral metabolic rate for glucose.

Figure 3. Association between higher fasting serum glucose and reduced rCMRgl by APOEε4 carrier group in AD-related brain regions

Statistical maps generated from this study were projected onto the lateral and medial surfaces of the left and right cerebral hemispheres and feature brain regions in which elevated serum glucose levels are associated with reduced rCMRgl in noncarriers (A) and carriers (B) of the APOEε4 allele. Initial findings (p < 0.005) in AD-related search regions (see figure e-2) were corrected for multiple comparisons and yield a similar pattern of results (p < 0.05). AD = Alzheimer disease; rCMRgl = regional cerebral metabolic rate for glucose.