Metabolic correlates of dopaminergic loss in dementia with lewy bodies

Maria Huber, Leonie Beyer, Catharina Prix, Sonja Schönecker, Carla Palleis, Boris-Stephan Rauchmann, Silvia Morbelli, Andrea Chincarini, Rose Bruffaerts, Rik Vandenberghe, Koen van Laere, Milica G. Kramberger, Maja Trost, Marko Grmek, Valentina Garibotto, Nicolas Nicastro, Giovanni B. Frisoni, Afina W. Lemstra, Jessica van der Zande, Andrea PilottoAlessandro Padovani, Sara Garcia-Ptacek, Irina Savitcheva, Miguel A. Ochoa-Figueroa, Anette Davidsson, Valle Camacho, Enrico Peira, Dario Arnaldi, Matteo Bauckneht, Matteo Pardini, Gianmario Sambuceti, Jonathan Vöglein, Jonas Schnabel, Marcus Unterrainer, Robert Perneczky, Oliver Pogarell, Katharina Buerger, Cihan Catak, Peter Bartenstein, Paul Cumming, Michael Ewers, Adrian Danek, Johannes Levin, Dag Aarsland, Flavio Nobili, Axel Rominger, Matthias Brendel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18F-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective: We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods: We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest–based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results: There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions: Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies.

Original languageEnglish
Pages (from-to)595-605
Number of pages11
JournalMovement Disorders
Volume35
Issue number4
Early online date16 Dec 2019
DOIs
Publication statusPublished - 1 Apr 2020

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