The Relationship Between Fasting Serum Glucose, Brain Metabolism and Neuropsychological Functioning in Older and Younger Adults

Abstract

Objective: To characterize the association between longitudinal changes in fasting serum glucose and changes in flourodeoxyglucose Positron Emission Tomography (FDG PET) measurements of regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer's disease (AD). A secondary objective was to investigate whether higher fasting serum glucose levels are associated with lower rCMRgl in younger adults within these same AD relevant brain areas. Methods: For the primary study, baseline, interim, and 4.4 ± 1.0-year follow-up fasting serum glucose and PET CMRgl were analyzed in 80 cognitively unimpaired, non-diabetic, 61.5 ± 5 year-old persons with a first-degree family history of AD, including 38 carriers and 42 non-carriers of the apolipoprotein E (APOE) ε 4 allele. An automated brain-mapping algorithm was used to characterize associations between changes in fasting serum glucose levels and changes in rCMRgl. Longitudinal changes in fasting serum glucose levels and their correlation with changes in six pre-selected neuropsychological test measures of memory, attention and processing speed were also assessed with linear regression. The secondary study included a cross sectional sample of 31 cognitively unimpaired, non-diabetic participants, 31.2 ±5.4 years of age. General linear model-based voxel-wise analyses were performed to examine the correlation between fasting serum glucose and rCMRgl. Results: In the primary study of older adults, average fasting serum glucose levels increased over longitudinal measurement, and changes in these levels were inversely associated with longitudinal CMRgl changes in the vicinity of brain regions preferentially affected by AD (p<0.05, corrected for multiple comparisons). Fasting serum glucose was also inversely associated with performance on a measure of visuospatial memory (p<0.05, corrected for multiple comparisons). In the younger sample, fasting serum glucose levels were inversely associated with rCMRgl in left frontal pole and right primary visual cortex regions (p<.05, corrected for multiple comparisons).Conclusions: In older adults, fasting serum glucose increases across time and is inversely related to rCMRgl in AD relevant regions and to visual memory test scores. This relationship between serum glucose and regional brain metabolism may begin in metabolically sensitive areas at a younger age.