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

Title: Metabolic brain networks in dementia with Lewy bodies: from prodromal to manifest disease stages
Authors: Perovnik, Matej; Simoncic, Urban; Jamsek, Jan; Gregoric Kramberger, Milica; Brumberg, Joachim; Meyer, Philipp Tobias; Perani, Daniela; Caminiti, Silvia Paola; Brendel, Matthias; Stockbauer, Anna Christina; Camacho, Valle; Alcolea, Daniel; Vandenberghe, Rik; Van Laere, Koen; Ko, Ji Hyun; Lee, Chong Sik; Pardini, Matteo; Lombardo, Lorenzo; Padovani, Alessandro; Pilotto, Andrea; Ochoa-Figueroa, Miguel A.; Davidsson, Anette; Chafer-Pericas, Consuelo; Alvarez-Sanchez, Lourdes; Garibotto, Valentina; Lemstra, Afina W.; Ferreira, Daniel; Morbelli, Silvia Daniela; Tang, Chris C.; Eidelberg, David; Trost, Maja
Source: ISSN:0022-3050 ; ISSN:1468-330X ; Journal Of Neurology Neurosurgery And Psychiatry, vol. 97 (4.
Publisher Information: BMJ Publishing Group
Publication Year: 2026
Subject Terms: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Psychiatry; Surgery; Neurosciences & Neurology; LEWY BODY DEMENTIA; ALZHEIMER'S DISEASE; PET; FUNCTIONAL IMAGING; IMAGE-RECONSTRUCTION ALGORITHMS; DIAGNOSTIC PERFORMANCE; ALZHEIMERS-DISEASE; AMYLOID-PET; PATTERNS; F-18-FDG-PET; MANAGEMENT; EXPRESSION; Humans; Lewy Body Disease; Male; Female; Aged; Positron-Emission Tomography; Cognitive Dysfunction; Brain; Fluorodeoxyglucose F18; Alzheimer Disease; 80 and over; Disease Progression
Description: 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 ...
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://lirias.kuleuven.be/handle/20.500.12942/779173; https://pubmed.ncbi.nlm.nih.gov/41344886
DOI: 10.1136/jnnp-2025-336935
Availability: https://lirias.kuleuven.be/handle/20.500.12942/779173; https://hdl.handle.net/20.500.12942/779173; https://lirias.kuleuven.be/retrieve/8628ee1e-cb83-400c-a0fc-7f7f50e11430; https://doi.org/10.1136/jnnp-2025-336935; https://pubmed.ncbi.nlm.nih.gov/41344886
Rights: info:eu-repo/semantics/openAccess ; public ; https://creativecommons.org/licenses/by-nc/4.0/
Accession Number: edsbas.7C3D4F4
Database: BASE