{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia",
        "Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA",
        "Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia"
      ],
      "name": "Matej Perovnik"
    },
    {
      "affiliations": [
        "Faculty of Mathematics and Physics, University of Ljubljana, Ljubljana, Slovenia"
      ],
      "name": "Urban Simončič"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia"
      ],
      "name": "Jan Jamšek"
    },
    {
      "affiliations": [
        "Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia",
        "Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia",
        "Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Milica Gregorič Kramberger"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Medical Center-University of Freiburg, Freiburg, Germany",
        "Faculty of Medicine, University of Freiburg, Freiburg, Germany"
      ],
      "name": "Joachim Brumberg"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Medical Center-University of Freiburg, Freiburg, Germany",
        "Faculty of Medicine, University of Freiburg, Freiburg, Germany"
      ],
      "name": "Philipp Tobias Meyer"
    },
    {
      "affiliations": [
        "Vita-Salute San Raffaele University, Milan, Italy"
      ],
      "name": "Daniela Perani"
    },
    {
      "affiliations": [
        "Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy"
      ],
      "name": "Silvia Paola Caminiti"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, LMU Hospital, Munich, Germany",
        "German Centre for Neurodegenerative Diseases, Munich, Germany",
        "Munich Cluster for Systems Neurology (SyNergy), Munich, Germany"
      ],
      "name": "Matthias Brendel"
    },
    {
      "affiliations": [
        "Munich Cluster for Systems Neurology (SyNergy), Munich, Germany",
        "Department of Neurology, LMU Hospital, Munich, Germany"
      ],
      "name": "Anna Christina Stockbauer"
    },
    {
      "affiliations": [
        "Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"
      ],
      "name": "Valle Camacho"
    },
    {
      "affiliations": [
        "Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"
      ],
      "name": "Daniel Alcolea"
    },
    {
      "affiliations": [
        "Laboratory for Cognitive Neurology, Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium"
      ],
      "name": "Rik Vandenberghe"
    },
    {
      "affiliations": [
        "Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium"
      ],
      "name": "Koen Van Laere"
    },
    {
      "affiliations": [
        "Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada"
      ],
      "name": "Ji Hyun Ko"
    },
    {
      "affiliations": [
        "CHA Bundang Medical Center, CHA University, Seongnam-si, Korea (the Republic of)"
      ],
      "name": "Chong Sik Lee"
    },
    {
      "affiliations": [
        "Department of Neuroscience, University of Genoa, Genova, Italy"
      ],
      "name": "Matteo Pardini"
    },
    {
      "affiliations": [
        "Department of Neuroscience, University of Genoa, Genova, Italy"
      ],
      "name": "Lorenzo Lombardo"
    },
    {
      "affiliations": [
        "Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy",
        "Department of Continuity of Care and Frailty, Unit of Neurology, ASST Spedali Civili di Brescia, Brescia, Italy"
      ],
      "name": "Alessandro Padovani"
    },
    {
      "affiliations": [
        "Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy",
        "Department of Continuity of Care and Frailty, Unit of Neurology, ASST Spedali Civili di Brescia, Brescia, Italy"
      ],
      "name": "Andrea Pilotto"
    },
    {
      "affiliations": [
        "Department of Clinical Physiology, Institution of Medicine and Health Sciences, Linköping University Hospital, Linköping, Sweden"
      ],
      "name": "Miguel A Ochoa-Figueroa"
    },
    {
      "affiliations": [
        "Department of Clinical Physiology, Institution of Medicine and Health Sciences, Linköping University Hospital, Linköping, Sweden"
      ],
      "name": "Anette Davidsson"
    },
    {
      "affiliations": [
        "Alzheimer’s Disease Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain"
      ],
      "name": "Consuelo Cháfer-Pericás"
    },
    {
      "affiliations": [
        "Alzheimer’s Disease Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain"
      ],
      "name": "Lourdes Álvarez-Sánchez"
    },
    {
      "affiliations": [
        "Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneve, Switzerland",
        "NIMTlab, Geneva University, Geneva, Switzerland"
      ],
      "name": "Valentina Garibotto"
    },
    {
      "affiliations": [
        "Alzheimer Center Amsterdam, Department of Neurology, Amsterdam UMC Locatie De Boelelaan, Amsterdam, The Netherlands"
      ],
      "name": "Afina W Lemstra"
    },
    {
      "affiliations": [
        "Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden",
        "Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain"
      ],
      "name": "Daniel Ferreira"
    },
    {
      "affiliations": [
        "Department of Medical Sciences, University of Turin, Turin, Italy",
        "Nuclear Medicine Unit, Città della Salute e della Scienza Torino, Turin, Italy"
      ],
      "name": "Silvia Daniela Morbelli"
    },
    {
      "affiliations": [
        "Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA"
      ],
      "name": "Chris C Tang"
    },
    {
      "affiliations": [
        "Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA"
      ],
      "name": "David Eidelberg"
    },
    {
      "affiliations": [
        "Department of Neurology, University Medical Centre Ljubljana, Ljubljana, Slovenia",
        "Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia",
        "Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia"
      ],
      "name": "Maja Trošt"
    },
    {
      "affiliations": [],
      "name": "Alzheimer’s Disease Neuroimaging Initiative"
    }
  ],
  "title": "Metabolic brain networks in dementia with Lewy bodies: from prodromal to manifest disease stages",
  "uid": "02813a75-e171-53a6-8b56-d7a2c22de695"
}