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 journalArticle

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
JournalMovement Disorders
DOIs
Publication statusAccepted/In press - Jan 1 2019

Keywords

  • dopamine deficiency
  • glucose metabolism
  • Lewy body dementia
  • metabolic connectivity
  • PET imaging

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Huber, M., Beyer, L., Prix, C., Schönecker, S., Palleis, C., Rauchmann, B. S., ... Brendel, M. (Accepted/In press). Metabolic correlates of dopaminergic loss in dementia with lewy bodies. Movement Disorders. https://doi.org/10.1002/mds.27945

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

In: Movement Disorders, 01.01.2019.

Research output: Contribution to journalArticle

Huber, M, Beyer, L, Prix, C, Schönecker, S, Palleis, C, Rauchmann, BS, Morbelli, S, Chincarini, A, Bruffaerts, R, Vandenberghe, R, Van Laere, K, Kramberger, MG, Trost, M, Grmek, M, Garibotto, V, Nicastro, N, Frisoni, GB, Lemstra, AW, van der Zande, J, Pilotto, A, Padovani, A, Garcia-Ptacek, S, Savitcheva, I, Ochoa-Figueroa, MA, Davidsson, A, Camacho, V, Peira, E, Arnaldi, D, Bauckneht, M, Pardini, M, Sambuceti, G, Vöglein, J, Schnabel, J, Unterrainer, M, Perneczky, R, Pogarell, O, Buerger, K, Catak, C, Bartenstein, P, Cumming, P, Ewers, M, Danek, A, Levin, J, Aarsland, D, Nobili, F, Rominger, A & Brendel, M 2019, 'Metabolic correlates of dopaminergic loss in dementia with lewy bodies', Movement Disorders. https://doi.org/10.1002/mds.27945
Huber M, Beyer L, Prix C, Schönecker S, Palleis C, Rauchmann BS et al. Metabolic correlates of dopaminergic loss in dementia with lewy bodies. Movement Disorders. 2019 Jan 1. https://doi.org/10.1002/mds.27945
Huber, Maria ; Beyer, Leonie ; Prix, Catharina ; Schönecker, Sonja ; Palleis, Carla ; Rauchmann, Boris Stephan ; Morbelli, Silvia ; Chincarini, Andrea ; Bruffaerts, Rose ; Vandenberghe, Rik ; Van Laere, Koen ; Kramberger, Milica G. ; Trost, Maja ; Grmek, Marko ; Garibotto, Valentina ; Nicastro, Nicolas ; Frisoni, Giovanni B. ; Lemstra, Afina W. ; van der Zande, Jessica ; Pilotto, Andrea ; Padovani, Alessandro ; Garcia-Ptacek, Sara ; Savitcheva, Irina ; Ochoa-Figueroa, Miguel A. ; Davidsson, Anette ; Camacho, Valle ; Peira, Enrico ; Arnaldi, Dario ; Bauckneht, Matteo ; Pardini, Matteo ; Sambuceti, Gianmario ; Vöglein, Jonathan ; Schnabel, Jonas ; Unterrainer, Marcus ; Perneczky, Robert ; Pogarell, Oliver ; Buerger, Katharina ; Catak, Cihan ; Bartenstein, Peter ; Cumming, Paul ; Ewers, Michael ; Danek, Adrian ; Levin, Johannes ; Aarsland, Dag ; Nobili, Flavio ; Rominger, Axel ; Brendel, Matthias. / Metabolic correlates of dopaminergic loss in dementia with lewy bodies. In: Movement Disorders. 2019.
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title = "Metabolic correlates of dopaminergic loss in dementia with lewy bodies",
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.",
keywords = "dopamine deficiency, glucose metabolism, Lewy body dementia, metabolic connectivity, PET imaging",
author = "Maria Huber and Leonie Beyer and Catharina Prix and Sonja Sch{\"o}necker and Carla Palleis and Rauchmann, {Boris Stephan} and Silvia Morbelli and Andrea Chincarini and Rose Bruffaerts and Rik Vandenberghe and {Van Laere}, Koen and Kramberger, {Milica G.} and Maja Trost and Marko Grmek and Valentina Garibotto and Nicolas Nicastro and Frisoni, {Giovanni B.} and Lemstra, {Afina W.} and {van der Zande}, Jessica and Andrea Pilotto and Alessandro Padovani and Sara Garcia-Ptacek and Irina Savitcheva and Ochoa-Figueroa, {Miguel A.} and Anette Davidsson and Valle Camacho and Enrico Peira and Dario Arnaldi and Matteo Bauckneht and Matteo Pardini and Gianmario Sambuceti and Jonathan V{\"o}glein and Jonas Schnabel and Marcus Unterrainer and Robert Perneczky and Oliver Pogarell and Katharina Buerger and Cihan Catak and Peter Bartenstein and Paul Cumming and Michael Ewers and Adrian Danek and Johannes Levin and Dag Aarsland and Flavio Nobili and Axel Rominger and Matthias Brendel",
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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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