Sporadic Creutzfeldt-Jakob Disease is associated with reorganization of metabolic connectivity in a pathological brain network
Tomaž Rus 1 2 , Jernej Mlakar 3 , Luka Ležaić 4 , An Vo 5 , Nha Nguyen 6 , Chris Tang 5 , Michele Fiorini 7 , Elena Prieto 8 , Gloria Marti-Andres 9 , Javier Arbizu 8 , David Eidelberg 5 , Maja Trošt 1 2 4
Background: Although sporadic Creutzfeldt-Jakob's disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, we investigated metabolic brain network associated with sCJD and explored its internal network organization.
Methods: We explored FDG-PET brain scans of 29 sCJD patients, 56 normal controls (NC) and 46 other dementia patients from two independent centers. sCJD-related pattern (CJDRP) was identified in a cohort of 16 pathologically proven sCJD patients and 16 age-matched NC using Scaled Subprofile Modelling/Principal Component Analysis and prospectively validated on an independent cohort of 13 sCJD patients and 20 NC. Pattern's specificity was tested on other dementia patients and its clinical relevance by clinical correlations. We further studied pattern's internal organization using graph theory methods.
Results: CJDRP was characterized by relative hypometabolism in bilateral caudate, thalami, middle and superior frontal gyri, parietal lobe and posterior cingulum in association with relative hypermetabolism in hippocampi, parahippocampal gyri and cerebellum. The pattern's expression significantly discriminated sCJD from NC and other dementia patients (p<0.005; ROC analysis CJD vs NC: AUC=0.90-0.96, sCJD vs AD: AUC=0.78, sCJD vs bvFTD AUC=0.84). The pattern's expression significantly correlated with cognitive, functional decline and disease duration. The metabolic connectivity analysis revealed inefficient information transfer with specific network reorganization.
Conclusions: CJDRP is a robust metabolic biomarker of sCJD. Due to its excellent clinical correlations it has a potential to monitor disease in emerging disease-modifying trials.
CITA DEL ARTÍCULO Eur J Neurol. 2022 Dec 30. doi: 10.1111/ene.15669