20.500.12556/DiRROS-28432 Metabolic brain networks in dementia with Lewy bodies from prodromal to manifest disease stages 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. Alzheimer's disease Lewy body dementia FDG PET functional imaging mild cognitive impairment true false true Angleški jezik Ni določen Neznano 2026-03-19 08:58:29 2026-03-19 08:58:30 2026-03-26 03:42:32 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis z dne 9. 12. 2025; str. 316-324 issue 4 Vol. 97 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.8 1468-330X 10.1136/jnnp-2025-336935 260578563 RAZ_Perovnik_Matej_2025.pdf RAZ_Perovnik_Matej_2025.pdf 1 3E2EAA1C72DDC9A17C7B7EEE3BC2A5AB dea09d1537a1917c525e64bc0b29e1084aa3ee17b7d1ba8df4fd2fbd621157b7 9813589d-2369-11f1-8070-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=42086 https://jnnp.bmj.com/content/97/4/316 0 a268af06-2369-11f1-8070-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=42087 Univerzitetni klinični center Ljubljana 0 0 0