Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
Anna Stockbauer, Leonie Beyer, Maria Huber, Annika Kreuzer, Carla Palleis, Sabrina Katzdobler, Boris‐Stephan Rauchmann, Silvia Morbelli, A. Chincarini, Rose Bruffaerts, Rik Vandenberghe, Milica G. Kramberger, Maja Trošt, Valentina Garibotto, Nicolas Nicastro, Aurélien Lathuilière, Afina W. Lemstra, Bart N.M. van Berckel, Andrea Pilotto, Alessandro Padovani, M.A. Ochoa-Figueroa, Anette Davidsson, Valle Camacho, Enrico Peira, Matteo Bauckneht, Matteo Pardini, Gianmario Sambuceti, Dag Aarsland, Flavio Nobili, Mattes Groß, Jonathan Vöglein, Robert Perneczky, Oliver Pogarell, Katharina Büerger, Nicolai Franzmeier, Adrian Danek, Johannes Levin, Günter U. Höglinger, Peter Bartenstein, Paul Cumming, Axel Rominger, Matthias Brendel
Abstract
PURPOSE: Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA). METHODS: FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level. RESULTS: = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912). CONCLUSION: Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.