TY - JOUR
T1 - Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
AU - Stockbauer, Anna
AU - Beyer, Leonie
AU - Huber, Maria
AU - Kreuzer, Annika
AU - Palleis, Carla
AU - Katzdobler, Sabrina
AU - Rauchmann, Boris-Stephan
AU - Morbelli, Silvia
AU - Chincarini, Andrea
AU - Bruffaerts, Rose
AU - Vandenberghe, Rik
AU - Kramberger, Milica G.
AU - Trost, Maja
AU - Garibotto, Valentina
AU - Nicastro, Nicolas
AU - Lathuilière, Aurélien
AU - Lemstra, Afina W.
AU - van Berckel, Bart N. M.
AU - Pilotto, Andrea
AU - Padovani, Alessandro
AU - Ochoa-Figueroa, Miguel A.
AU - Davidsson, Anette
AU - Camacho, Valle
AU - Peira, Enrico
AU - Bauckneht, Matteo
AU - Pardini, Matteo
AU - Sambuceti, Gianmario
AU - Aarsland, Dag
AU - Nobili, Flavio
AU - Gross, Mattes
AU - Vöglein, Jonathan
AU - Perneczky, Robert
AU - Pogarell, Oliver
AU - Buerger, Katharina
AU - Franzmeier, Nicolai
AU - Danek, Adrian
AU - Levin, Johannes
AU - Höglinger, G. nter U.
AU - Bartenstein, Peter
AU - Cumming, Paul
AU - Rominger, Axel
AU - Brendel, Matthias
N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. LB was funded by the Munich-Clinician-Scientist Program (LMU Munich). RB is supported by a Collen-Francqui Start-Up grant. VG was supported by the Swiss National Science Foundation (projects 320030_169876, 320030_185028), the Schmidheiny foundation, the Fondation privée des HUG and the Velux foundation. SK received funding from the Lüneburg heritage, the Ehrmann Foundation and the Deutsche Forschungsgemeinschaft (DFG) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198) as well as research funding from CurePSP. C.P. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). The Lüneburg Heritage and Friedrich-Baur-Stiftung have supported the work of C.P. RP is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), the Davos Alzheimer’s Collaborative, the VERUM Foundation, the Robert-Vogel-Foundation, the German Center for Neurodegenerative Diseases (DZNE), the Sheffield National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) and the University of Cambridge – Ludwig-Maximilians-University Munich Strategic Partnership within the framework of the German Excellence Initiative and Excellence Strategy. MT received funding from the Slovenian Research Agency, Grant Number: J7-2600 and P1-0389. Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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: Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R 2 = 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.
AB - 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: Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R 2 = 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.
KW - DaT-Scan
KW - Dementia with Lewy bodies
KW - FDG-PET
KW - Metabolic connectivity
UR - http://www.scopus.com/inward/record.url?scp=85176556433&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00259-023-06493-w
DO - https://doi.org/10.1007/s00259-023-06493-w
M3 - Article
C2 - 37971501
SN - 1619-7070
JO - European journal of nuclear medicine and molecular imaging
JF - European journal of nuclear medicine and molecular imaging
ER -