Metabolic brain networks in dementia with Lewy bodies: from prodromal to manifest disease stages

Perovnik, Matej ; Simončič, Urban; Jamšek, Jan; Gregorič Kramberger, Milica; Brumberg, Joachim ; Meyer, Philipp Tobias; Perani, Daniela; Caminiti, Silvia Paola; Brendel, Matthias ; Stockbauer, Anna Christina; Camacho, Valle ; Alcolea, Daniel ; Vandenberghe, Rik ; Laere, Koen Van; Ko, Ji Hyun; Lee, Chong Sik; Pardini, Matteo; Lombardo, Lorenzo; Padovani, Alessandro; Pilotto, Andrea ; Ochoa-Figueroa, Miguel A; Davidsson, Anette; Cháfer-Pericás, Consuelo; Álvarez-Sánchez, Lourdes; Garibotto, Valentina ; Lemstra, Afina W; Ferreira, Daniel; Morbelli, Silvia Daniela; Tang, Chris C; Eidelberg, David und Trošt, Maja (2026): Metabolic brain networks in dementia with Lewy bodies: from prodromal to manifest disease stages. In: Journal of Neurology, Neurosurgery & Psychiatry, Vol. 97: pp. 316-324

Abstract

Background Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia, yet it remains under-recognised and misdiagnosed, which delays treatment, causes inaccurate prognosis and limits research opportunities. Imaging with 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is a supportive DLB biomarker. We evaluated a multivariate, quantifiable metabolic network biomarker, termed DLB-related pattern (DLBRP), for its further clinical translation across centres and disease stages.

Methods We analysed demographic, clinical and FDG PET imaging data of 1180 participants from 14 tertiary centres and two multicentre datasets. We included 379 DLB, 28 mild cognitive impairment-LB (MCI-LB), 195 dementia due to Alzheimer’s disease (ADD), 172 MCI-AD without α-synuclein co-pathology (MCI-AD-S–), and 73 MCI-AD with α-synuclein co-pathology (S+) patients, along with a comparative group of 333 normal controls (NCs). From the scans, we calculated the expression of DLBRP, AD-related pattern (ADRP) and Parkinson’s disease-related pattern (PDRP) and compared them across groups. DLBRP scores were correlated with clinical measurements.

Results Across independent cohorts, DLBRP robustly distinguished DLB from NCs (sensitivity >89%, specificity >90%), and scores correlated with Unified Parkinson’s Disease Rating Scale Part III and independently predicted Mini–Mental State Examination. DLBRP was elevated already in MCI-LB. In a small longitudinal dataset, we observed steady increases in DLBRP expression with scores exceeding the diagnostic threshold prior to dementia onset. DLBRP and PDRP discriminated DLB from ADD (sensitivity, 74%–90%; specificity, 80%). In MCI-AD groups, ADRP was expressed, whereas DLBRP and PDRP were increased only in MCI-AD-S+, although comparatively less than in MCI-LB.

Conclusions This study demonstrates the value of DLBRP in diagnosing prodromal and manifest DLB and distinguishing them from their AD counterparts. While overlap between patterns may reflect actual co-pathology, this possibility cannot be accepted without thorough pathological confirmation. The current findings support the use of DLBRP in patient evaluation and in future trial design.

• Item Type: Journal article
• Faculties: Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Medical Center of the University of Munich > Neurological Clinic and Polyclinic with Friedrich Baur Institute; Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Nuclear Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0022-3050
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198