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

Eur J Nucl Med Mol Imaging. 2018 Jul;45(8):1417-1422. doi: 10.1007/s00259-018-3985-4. Epub 2018 Mar 3.

Abstract

Purpose: 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 ≤ 160 mg/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).

Methods: The study included NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that were cognitively stable for ≥36 months after PET (n = 87, 74.2 ± 5.3 y), and ADNI MCIs with ≥36 months 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 36 months. 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.

Results: In the NCs, BGL (59-149 mg/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 (55-189 mg/dl) did not change predictive performance (area = 0.808, p = 0.311).

Conclusions: Increasing BGL is associated with relative reduction of FDG uptake in the posterior cortex even in the "acceptable" range ≤ 160 mg/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.

Keywords: F-18-fluorodesoxyglucose; Healthy controls; MCI; Plasma glucose.

MeSH terms

  • Aged
  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnostic imaging*
  • Blood Glucose / metabolism*
  • Brain
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Male
  • Positron-Emission Tomography*

Substances

  • Blood Glucose
  • Fluorodeoxyglucose F18