Journal Article

DZNE-2026-00296

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Metabolic brain networks in dementia with Lewy bodies: from prodromal to manifest disease stages.

Perovnik, M. ; Simončič, U. ; Jamšek, J. ; Gregorič Kramberger, M. ; Brumberg, J. ; Meyer, P. T. ; Perani, D. ; Caminiti, S. P. ; Brendel, M.DZNE* ; Stockbauer, A.Extern* ; Camacho, V. ; Alcolea, D. ; Vandenberghe, R. ; Van Laere, K. ; Ko, J. H. ; Lee, C. S. ; Pardini, M. ; Lombardo, L. ; Padovani, A. ; Pilotto, A. ; Ochoa-Figueroa, M. A. ; Davidsson, A. ; Cháfer-Pericás, C. ; Álvarez-Sánchez, L. ; Garibotto, V. ; Lemstra, A. W. ; Ferreira, D. ; Morbelli, S. D. ; Tang, C. C. ; Eidelberg, D. ; Trošt, M. ; Initiative, A. D. N. (Collaboration Author)

2026
BMJ Publishing Group London

This record in other databases:    

Please use a persistent id in citations: doi:10.1136/jnnp-2025-336935

Abstract: 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.

Keyword(s): Humans (MeSH) ; Lewy Body Disease: metabolism (MeSH) ; Lewy Body Disease: diagnostic imaging (MeSH) ; Male (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Positron-Emission Tomography (MeSH) ; Cognitive Dysfunction: metabolism (MeSH) ; Cognitive Dysfunction: diagnostic imaging (MeSH) ; Brain: metabolism (MeSH) ; Brain: diagnostic imaging (MeSH) ; Fluorodeoxyglucose F18 (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Aged, 80 and over (MeSH) ; Disease Progression (MeSH) ; Biomarkers: metabolism (MeSH) ; Prodromal Symptoms (MeSH) ; Middle Aged (MeSH) ; ALZHEIMER'S DISEASE ; LEWY BODY DEMENTIA ; PET, FUNCTIONAL IMAGING ; Fluorodeoxyglucose F18 ; Biomarkers

---

Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---