Impact of plasma glucose level on the pattern of brain FDG uptake and the predictive power of FDG PET in mild cognitive impairment.

Abstract

Increased blood glucose level (BGL) has been reported to cause alterations of FDG uptake in the brain that mimic Alzheimer's disease (AD), even within the "acceptable" range ≤ 160mg/dl. The aim of this study was (i) to confirm this in a large sample of well-characterized normal control (NC) subjects, and (ii) to analyze its impact on the prediction of AD dementia (ADD) in mild cognitive impairment (MCI). The study included NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that were cognitively stable for ≥36months after PET (n = 87, 74.2 ± 5.3 y), and ADNI MCIs with ≥36months follow-up if not progressed to ADD earlier (n = 323, 71.1 ± 7.1 y). Seventy-three of the MCIs had progressed to ADD within 36months. In the NCs, parenchyma-scaled FDG uptake was tested for clusters of correlation with BGL on the family-wise, error-corrected 5% level. In the MCIs, ROC analysis was used to assess the power of FDG uptake in a predefined AD-typical region for prediction of ADD. ROC analysis was repeated after correcting mean FDG uptake in the AD-typical region for BGL based on linear regression in the NCs. In the NCs, BGL (59-149mg/dl) was negatively correlated with FDG uptake in a cluster comprising the occipital cortex and precuneus but sparing the posterior cingulate, independent of amyloid-β and ApoE4 status. In the MCIs, FDG uptake in the AD-typical region provided an area of 0.804 under the ROC curve for prediction of ADD. Correcting FDG uptake in the AD-typical region for BGL (55-189mg/dl) did not change predictive performance (area = 0.808, p = 0.311). Increasing BGL is associated with relative reduction of FDG uptake in the posterior cortex even in the "acceptable" range ≤ 160mg/dl. The BGL-associated pattern is similar to the typical AD pattern, but not identical. BGL-associated variability of regional FDG uptake has no relevant impact on the power of FDG PET for prediction of MCI-to-ADD progression.