Ivayla Apostolova1, Catharina Lange2, Per Suppa3, Lothar Spies3, Susanne Klutmann1, Gerhard Adam1, Michel J Grothe4, Ralph Buchert5. 1. Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. 2. Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. 3. jung diagnostics GmbH, Hamburg, Germany. 4. German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany. 5. Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. r.buchert@uke.de.
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.
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.
Authors: William J Jagust; Dan Bandy; Kewei Chen; Norman L Foster; Susan M Landau; Chester A Mathis; Julie C Price; Eric M Reiman; Daniel Skovronsky; Robert A Koeppe Journal: Alzheimers Dement Date: 2010-05 Impact factor: 21.566
Authors: R D Terry; E Masliah; D P Salmon; N Butters; R DeTeresa; R Hill; L A Hansen; R Katzman Journal: Ann Neurol Date: 1991-10 Impact factor: 10.422
Authors: Eric M Reiman; Kewei Chen; Gene E Alexander; Richard J Caselli; Daniel Bandy; David Osborne; Ann M Saunders; John Hardy Journal: Proc Natl Acad Sci U S A Date: 2003-12-19 Impact factor: 11.205
Authors: Leslie M Shaw; Hugo Vanderstichele; Malgorzata Knapik-Czajka; Christopher M Clark; Paul S Aisen; Ronald C Petersen; Kaj Blennow; Holly Soares; Adam Simon; Piotr Lewczuk; Robert Dean; Eric Siemers; William Potter; Virginia M-Y Lee; John Q Trojanowski Journal: Ann Neurol Date: 2009-04 Impact factor: 10.422
Authors: Eric Guedj; Andrea Varrone; Ronald Boellaard; Nathalie L Albert; Henryk Barthel; Bart van Berckel; Matthias Brendel; Diego Cecchin; Ozgul Ekmekcioglu; Valentina Garibotto; Adriaan A Lammertsma; Ian Law; Iván Peñuelas; Franck Semah; Tatjana Traub-Weidinger; Elsmarieke van de Giessen; Donatienne Van Weehaeghe; Silvia Morbelli Journal: Eur J Nucl Med Mol Imaging Date: 2021-12-09 Impact factor: 10.057