Maria Huber1, Leonie Beyer1, Catharina Prix2, Sonja Schönecker2, Carla Palleis2, Boris-Stephan Rauchmann3,4, Silvia Morbelli5,6, Andrea Chincarini7, Rose Bruffaerts8,9, Rik Vandenberghe8,9, Koen Van Laere10, Milica G Kramberger11, Maja Trost11,12, Marko Grmek12, Valentina Garibotto13, Nicolas Nicastro14,15, Giovanni B Frisoni16, Afina W Lemstra17, Jessica van der Zande17, Andrea Pilotto18,19, Alessandro Padovani18, Sara Garcia-Ptacek20,21, Irina Savitcheva22, Miguel A Ochoa-Figueroa23,24,25, Anette Davidsson23, Valle Camacho26, Enrico Peira7,27, Dario Arnaldi5,27, Matteo Bauckneht5,6, Matteo Pardini5,27, Gianmario Sambuceti5,6, Jonathan Vöglein2,28, Jonas Schnabel1, Marcus Unterrainer1, Robert Perneczky3,28,29,30, Oliver Pogarell3, Katharina Buerger28,30, Cihan Catak30, Peter Bartenstein1,31, Paul Cumming32,33, Michael Ewers28, Adrian Danek2, Johannes Levin2,28,31, Dag Aarsland34,35, Flavio Nobili5,27, Axel Rominger1,31,32, Matthias Brendel1,31. 1. Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany. 2. Department of Neurology, University Hospital of Munich, LMU Munich, Munich, Germany. 3. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany. 4. Department of Radiology, University Hospital of Munich, LMU Munich, Munich, Germany. 5. IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 6. Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa, Italy. 7. National Institute of Nuclear Physics (INFN), Genoa section, Genoa, Genoa, Italy. 8. Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium. 9. Department of Neurology, University Hospitals Leuven, Leuven, Belgium. 10. Department of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium. 11. Department of Neurology, University Medical Centre, Ljubljana, Slovenia. 12. Department for Nuclear Medicine, University Medical Centre, Ljubljana, Slovenia. 13. Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals and NIMTLab, Geneva University, Geneva, Switzerland. 14. Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland. 15. Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom. 16. LANVIE (Laboratoire de Neuroimagerie du Vieillissement), Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland. 17. VU Medical Center Alzheimer Center, Amsterdam, The Netherlands. 18. Neurology Unit, University of Brescia, Brescia, Italy. 19. Parkinson's Disease Rehabilitation Centre, FERB ONLUS-S. Isidoro Hospital, Trescore Balneario (BG), Italy. 20. Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. 21. Internal Medicine, section for Neurology, Sädersjukhuset, Stockholm, Sweden. 22. Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden. 23. Department of Clinical Physiology, Institution of Medicine and Health Sciences, Linköping University Hospital, Linköping, Sweden. 24. Department of Diagnostic Radiology, Linköping University Hospital, Linköping, Sweden. 25. Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden. 26. Servicio de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, España. 27. Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy. 28. DZNE-German Center for Neurodegenerative Diseases, Munich, Germany. 29. Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College, London, United Kingdom. 30. Institut for Stroke and Dementia Research, University of Munich, Munich, Germany. 31. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. 32. Department of Nuclear Medicine, University of Bern, Inselspital, Bern, Switzerland. 33. School of Psychology and Counselling and IHBI, Queensland University of Technology, Brisbane, Australia. 34. Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, Stavanger, Norway. 35. Wolfson Centre for Age-Related Diseases, King's College London, London, United Kingdom.
Abstract
BACKGROUND: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123 I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18 F-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.
BACKGROUND: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123 I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18 F-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 dopaminedeficiency and glucose metabolism of 84 dementia with Lewy bodypatients 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 dopaminedeficiency 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.
Authors: Euna Choi; Ji Won Han; Seung Wan Suh; Jong Bin Bae; Ji Hyun Han; Subin Lee; Sang Eun Kim; Ki Woong Kim Journal: Front Neurol Date: 2022-08-08 Impact factor: 4.086
Authors: Sung Woo Kang; Seun Jeon; Young-Gun Lee; Mincheol Park; Kyoungwon Baik; Jin Ho Jung; Seok Jong Chung; Han Soo Yoo; Seong Ho Jeong; Mijin Yun; Phil Hyu Lee; Young H Sohn; Alan C Evans; Byoung Seok Ye Journal: Sci Rep Date: 2021-07-13 Impact factor: 4.379
Authors: Young-Gun Lee; Seun Jeon; Sung Woo Kang; Mincheol Park; Kyoungwon Baik; Han Soo Yoo; Seok Jong Chung; Seong Ho Jeong; Jin Ho Jung; Phil Hyu Lee; Young Ho Sohn; Alan C Evans; Byoung Seok Ye Journal: Alzheimers Dement (Amst) Date: 2021-05-21