Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
Authors: Stockbauer Anna , Beyer Leonie , Huber Maria , Kreuzer Annika , Palleis Carla , Katzdobler Sabrina , Rauchmann Boris-Stephan , Morbelli Silvia , Chincarini Andrea , Bruffaerts Rose , Vandenberghe Rik , Kramberger Milica G. , Trost Maja , Garibotto Valentina , Nicastro Nicolas , Lathuilière Aurélien , Lemstra Afina W. , van Berckel Bart N. M. , Pilotto Andrea , Padovani Alessandro , Ochoa-Figueroa Miguel A. , Davidsson Anette , Camacho Valle , Peira Enrico , Bauckneht Matteo , Pardini Matteo , Sambuceti Gianmario , Aarsland Dag , Nobili Flavio , Gross Mattes , Vöglein Jonathan , Perneczky Robert , Pogarell Oliver , Buerger Katharina , Franzmeier Nicolai , Danek Adrian , Levin Johannes , Höglinger Günter U. , Bartenstein Peter , Cumming Paul , Rominger Axel , Brendel Matthias 
Published: November 2023

Abstract
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 (R2 = 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.