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024 7 _ |a 10.1136/jnnp-2025-336935
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024 7 _ |a pmid:41344886
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024 7 _ |a 0022-3050
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024 7 _ |a 0266-8637
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024 7 _ |a 0368-329X
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024 7 _ |a 1468-330X
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024 7 _ |a 2753-0477
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024 7 _ |a 2753-0485
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037 _ _ |a DZNE-2026-00296
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Perovnik, Matej
|0 0000-0001-8595-7773
|b 0
245 _ _ |a Metabolic brain networks in dementia with Lewy bodies: from prodromal to manifest disease stages.
260 _ _ |a London
|c 2026
|b BMJ Publishing Group
336 7 _ |a article
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520 _ _ |a 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.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.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.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.
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650 _ 7 |a ALZHEIMER'S DISEASE
|2 Other
650 _ 7 |a LEWY BODY DEMENTIA
|2 Other
650 _ 7 |a PET, FUNCTIONAL IMAGING
|2 Other
650 _ 7 |a Fluorodeoxyglucose F18
|0 0Z5B2CJX4D
|2 NLM Chemicals
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Lewy Body Disease: metabolism
|2 MeSH
650 _ 2 |a Lewy Body Disease: diagnostic imaging
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Positron-Emission Tomography
|2 MeSH
650 _ 2 |a Cognitive Dysfunction: metabolism
|2 MeSH
650 _ 2 |a Cognitive Dysfunction: diagnostic imaging
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Brain: diagnostic imaging
|2 MeSH
650 _ 2 |a Fluorodeoxyglucose F18
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: diagnostic imaging
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Disease Progression
|2 MeSH
650 _ 2 |a Biomarkers: metabolism
|2 MeSH
650 _ 2 |a Prodromal Symptoms
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
700 1 _ |a Simončič, Urban
|b 1
700 1 _ |a Jamšek, Jan
|b 2
700 1 _ |a Gregorič Kramberger, Milica
|b 3
700 1 _ |a Brumberg, Joachim
|0 0000-0003-0959-4776
|b 4
700 1 _ |a Meyer, Philipp Tobias
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700 1 _ |a Perani, Daniela
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700 1 _ |a Caminiti, Silvia Paola
|b 7
700 1 _ |a Brendel, Matthias
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700 1 _ |a Stockbauer, Anna
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700 1 _ |a Camacho, Valle
|0 0000-0003-0748-0847
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700 1 _ |a Alcolea, Daniel
|0 0000-0002-3819-3245
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700 1 _ |a Vandenberghe, Rik
|0 0000-0001-6237-2502
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700 1 _ |a Van Laere, Koen
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700 1 _ |a Ko, Ji Hyun
|b 14
700 1 _ |a Lee, Chong Sik
|b 15
700 1 _ |a Pardini, Matteo
|b 16
700 1 _ |a Lombardo, Lorenzo
|b 17
700 1 _ |a Padovani, Alessandro
|b 18
700 1 _ |a Pilotto, Andrea
|0 P:(DE-2719)9000943
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700 1 _ |a Ochoa-Figueroa, Miguel A
|b 20
700 1 _ |a Davidsson, Anette
|b 21
700 1 _ |a Cháfer-Pericás, Consuelo
|b 22
700 1 _ |a Álvarez-Sánchez, Lourdes
|b 23
700 1 _ |a Garibotto, Valentina
|0 0000-0003-2422-698X
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700 1 _ |a Lemstra, Afina W
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700 1 _ |a Ferreira, Daniel
|b 26
700 1 _ |a Morbelli, Silvia Daniela
|b 27
700 1 _ |a Tang, Chris C
|b 28
700 1 _ |a Eidelberg, David
|b 29
700 1 _ |a Trošt, Maja
|b 30
700 1 _ |a Initiative, Alzheimer’s Disease Neuroimaging
|b 31
|e Collaboration Author
773 _ _ |a 10.1136/jnnp-2025-336935
|g Vol. 97, no. 4, p. 316 - 324
|0 PERI:(DE-600)1480429-3
|n 4
|p 316 - 324
|t Journal of neurology, neurosurgery, and psychiatry
|v 97
|y 2026
|x 0022-3050
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