TY - JOUR
T1 - Metabolic correlates of dopaminergic loss in dementia with lewy bodies
AU - Huber, Maria
AU - Beyer, Leonie
AU - Prix, Catharina
AU - Schönecker, Sonja
AU - Palleis, Carla
AU - Rauchmann, Boris Stephan
AU - Morbelli, Silvia
AU - Chincarini, Andrea
AU - Bruffaerts, Rose
AU - Vandenberghe, Rik
AU - Van Laere, Koen
AU - Kramberger, Milica G.
AU - Trost, Maja
AU - Grmek, Marko
AU - Garibotto, Valentina
AU - Nicastro, Nicolas
AU - Frisoni, Giovanni B.
AU - Lemstra, Afina W.
AU - van der Zande, Jessica
AU - Pilotto, Andrea
AU - Padovani, Alessandro
AU - Garcia-Ptacek, Sara
AU - Savitcheva, Irina
AU - Ochoa-Figueroa, Miguel A.
AU - Davidsson, Anette
AU - Camacho, Valle
AU - Peira, Enrico
AU - Arnaldi, Dario
AU - Bauckneht, Matteo
AU - Pardini, Matteo
AU - Sambuceti, Gianmario
AU - Vöglein, Jonathan
AU - Schnabel, Jonas
AU - Unterrainer, Marcus
AU - Perneczky, Robert
AU - Pogarell, Oliver
AU - Buerger, Katharina
AU - Catak, Cihan
AU - Bartenstein, Peter
AU - Cumming, Paul
AU - Ewers, Michael
AU - Danek, Adrian
AU - Levin, Johannes
AU - Aarsland, Dag
AU - Nobili, Flavio
AU - Rominger, Axel
AU - Brendel, Matthias
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - dopamine deficiency
KW - glucose metabolism
KW - Lewy body dementia
KW - metabolic connectivity
KW - PET imaging
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U2 - 10.1002/mds.27945
DO - 10.1002/mds.27945
M3 - Article
C2 - 31840326
AN - SCOPUS:85076721003
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
ER -