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@ARTICLE{Perovnik:285739,
author = {Perovnik, Matej and Simončič, Urban and Jamšek, Jan and
Gregorič Kramberger, Milica and Brumberg, Joachim and
Meyer, Philipp Tobias and Perani, Daniela and Caminiti,
Silvia Paola and Brendel, Matthias and Stockbauer, Anna and
Camacho, Valle and Alcolea, Daniel and Vandenberghe, Rik and
Van Laere, Koen and Ko, Ji Hyun and Lee, Chong Sik and
Pardini, Matteo and Lombardo, Lorenzo and Padovani,
Alessandro and Pilotto, Andrea and Ochoa-Figueroa, Miguel A
and Davidsson, Anette and Cháfer-Pericás, Consuelo and
Álvarez-Sánchez, Lourdes and Garibotto, Valentina and
Lemstra, Afina W and Ferreira, Daniel and Morbelli, Silvia
Daniela and Tang, Chris C and Eidelberg, David and Trošt,
Maja},
collaboration = {Initiative, Alzheimer’s Disease Neuroimaging},
title = {{M}etabolic brain networks in dementia with {L}ewy bodies:
from prodromal to manifest disease stages.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {97},
number = {4},
issn = {0022-3050},
address = {London},
publisher = {BMJ Publishing Group},
reportid = {DZNE-2026-00296},
pages = {316 - 324},
year = {2026},
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.},
keywords = {Humans / Lewy Body Disease: metabolism / Lewy Body Disease:
diagnostic imaging / Male / Female / Aged /
Positron-Emission Tomography / Cognitive Dysfunction:
metabolism / Cognitive Dysfunction: diagnostic imaging /
Brain: metabolism / Brain: diagnostic imaging /
Fluorodeoxyglucose F18 / Alzheimer Disease: metabolism /
Alzheimer Disease: diagnostic imaging / Aged, 80 and over /
Disease Progression / Biomarkers: metabolism / Prodromal
Symptoms / Middle Aged / ALZHEIMER'S DISEASE (Other) / LEWY
BODY DEMENTIA (Other) / PET, FUNCTIONAL IMAGING (Other) /
Fluorodeoxyglucose F18 (NLM Chemicals) / Biomarkers (NLM
Chemicals)},
cin = {AG Haass},
ddc = {610},
cid = {I:(DE-2719)1110007},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41344886},
doi = {10.1136/jnnp-2025-336935},
url = {https://pub.dzne.de/record/285739},
}