{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T13:47:32Z","timestamp":1777124852013,"version":"3.51.4"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Mixed pathology of Alzheimer\u2019s disease (AD) and dementia with Lewy bodies (DLB) are frequently observed in patients with cognitive impairment, and complicate clinical diagnosis. We aimed to develop a classification model using\n                      <jats:sup>18<\/jats:sup>\n                      F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to improve diagnostic accuracy for these challenging cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed FDG-PET images from 277 participants who were categorized into AD, DLB, mixed disease, and healthy control (HC) groups. Deep learning-based classification models were trained on seven binary classification tasks and one multiclass classification task and subsequently integrated into an ensemble model to predict AD, DLB, mixed disease or HC groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The model achieved an AUROC of 0.73 (95% CI, 0.69\u20130.78) for AD, 0.90 (95% CI, 0.89\u20130.91) for DLB, 0.71 (95% CI, 0.66\u20130.75) for Mixed, and 0.87 (95% CI, 0.84\u20130.89) for HC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The model represents the state-of-the-art in automatic FDG-PET-based classification of AD, DLB, Mixed, and HC. This study highlights the utility of FDG-PET as a biomarker for differentiating AD, DLB, Mixed, and HC groups, resolving diagnostic challenges caused by overlapping clinical features.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1780858","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:58:18Z","timestamp":1772693898000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Deep learning for FDG-PET classification in patients with Alzheimer\u2019s disease, dementia with Lewy bodies and their mixed pathology: a solution for diagnostic heterogeneity"],"prefix":"10.3389","volume":"18","author":[{"given":"Seonggyu","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Electronic Engineering, Hanyang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seun","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yonsei University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwonhwi","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Artificial Intelligence, Hanyang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungwoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hanyang Seoul Hospital, Hanyang University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungkyu","family":"Bang","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, Hanyang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byoung Seok","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yonsei University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, Hanyang University","place":["Seoul, Republic of Korea"]},{"name":"Department of Artificial Intelligence, Hanyang University","place":["Seoul, Republic of Korea"]},{"name":"Department of Biomedical Engineering, Hanyang University","place":["Seoul, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimers Dement."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1002\/ana.26453","article-title":"\u03b1\u2010synuclein seed amplification in CSF and brain from patients with different brain distributions of pathological \u03b1-synuclein in the context of co-pathology and non-LBD diagnoses","volume":"92","author":"Arnold","year":"2022","journal-title":"Ann. Neurol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.media.2007.06.004","article-title":"Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain","volume":"12","author":"Avants","year":"2008","journal-title":"Med. Image Anal."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3988\/jcn.2022.0021","article-title":"Cortical thickness and brain glucose metabolism in healthy aging","volume":"19","author":"Baik","year":"2023","journal-title":"J. Clin. Neurol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"19024","DOI":"10.1038\/s41598-019-54204-z","article-title":"Predicting clinical decline and conversion to Alzheimer\u2019s disease or dementia using novel Elecsys a\u03b2 (1\u201342), pTau and tTau CSF immunoassays","volume":"9","author":"Blennow","year":"2019","journal-title":"Sci. Rep."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13195-019-0473-4","article-title":"Brain glucose metabolism in Lewy body dementia: implications for diagnostic criteria","volume":"11","author":"Caminiti","year":"2019","journal-title":"Alzheimer's Res. Ther."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.12779\/dnd.2018.17.1.11","article-title":"Re-standardization of the Korean-instrumental activities of daily living (K-IADL): clinical usefulness for various neurodegenerative diseases","volume":"17","author":"Chin","year":"2018","journal-title":"Dement. Neurocogn. Disord."},{"key":"ref8","volume-title":"Proceedings of the IEEE\/CVF Conference on Computer Vision and Pattern Recognition","author":"Cubuk","year":"2019"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s00259-021-05483-0","article-title":"A 3D deep learning model to predict the diagnosis of dementia with Lewy bodies, Alzheimer's disease, and mild cognitive impairment using brain 18F-FDG PET","volume":"49","author":"Etminani","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e231442","DOI":"10.1148\/radiol.231442","article-title":"AmyloidPETNet: classification of amyloid positivity in brain PET imaging using end-to-end deep learning","volume":"311","author":"Fan","year":"2024","journal-title":"Radiology"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1212\/wnl.62.2.181","article-title":"DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging","volume":"62","author":"Ferman","year":"2004","journal-title":"Neurology"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1111\/j.1750-3639.2000.tb00269.x","article-title":"Lewy bodies in Alzheimer's disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry","volume":"10","author":"Hamilton","year":"2000","journal-title":"Brain Pathol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e209453","DOI":"10.1212\/WNL.0000000000209453","article-title":"Neuropathologic validation and diagnostic accuracy of presynaptic dopaminergic imaging in the diagnosis of parkinsonism","volume":"102","author":"Hastings","year":"2024","journal-title":"Neurology"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria","volume":"32","author":"H\u00f6glinger","year":"2017","journal-title":"Mov. Disord."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/s1474-4422(16)30291-5","article-title":"Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis","volume":"16","author":"Irwin","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"4952","DOI":"10.1002\/hbm.24750","article-title":"Automated brain extraction of multisequence MRI using artificial neural networks","volume":"40","author":"Isensee","year":"2019","journal-title":"Hum. Brain Mapp."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.cogsys.2018.12.015","article-title":"Convolutional neural network based Alzheimer\u2019s disease classification from magnetic resonance brain images","volume":"57","author":"Jain","year":"2019","journal-title":"Cogn. Syst. Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.neurobiolaging.2019.10.007","article-title":"Presynaptic dopaminergic function in early-onset Alzheimer's disease: an FP-CIT image study","volume":"86","author":"Jang","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13195-018-0350-6","article-title":"Clinical prevalence of Lewy body dementia","volume":"10","author":"Kane","year":"2018","journal-title":"Alzheimer's Res. Ther."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"14394","DOI":"10.1038\/s41598-021-93442-y","article-title":"Implication of metabolic and dopamine transporter PET in dementia with Lewy bodies","volume":"11","author":"Kang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"3105","DOI":"10.1111\/ene.15995","article-title":"Striatal dopamine transporter uptake, parkinsonism and cognition in Alzheimer's disease","volume":"30","author":"Kang","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13195-024-01429-4","article-title":"Alteration of medial temporal lobe metabolism related to Alzheimer's disease and dementia with Lewy bodies","volume":"16","author":"Kang","year":"2024","journal-title":"Alzheimer's Res. Ther."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s00401-017-1717-7","article-title":"Impact of multiple pathologies on the threshold for clinically overt dementia","volume":"134","author":"Kapasi","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"72726","DOI":"10.1109\/access.2019.2920448","article-title":"Transfer learning with intelligent training data selection for prediction of Alzheimer\u2019s disease","volume":"7","author":"Khan","year":"2019","journal-title":"IEEE Access"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1002\/ana.26355","article-title":"Effects of Alzheimer and Lewy body disease pathologies on brain metabolism","volume":"91","author":"Lee","year":"2022","journal-title":"Ann. Neurol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1136\/jnnp-2016-313775","article-title":"Concomitant AD pathology affects clinical manifestation and survival in dementia with Lewy bodies","volume":"88","author":"Lemstra","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.2967\/jnumed.109.065870","article-title":"The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies","volume":"50","author":"Lim","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/s0002-9440(10)65722-7","article-title":"Lewy bodies contain altered alpha-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes","volume":"153","author":"Lippa","year":"1998","journal-title":"Am. J. Pathol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e0217566","DOI":"10.1371\/journal.pone.0217566","article-title":"Faster cognitive decline in dementia due to Alzheimer disease with clinically undiagnosed Lewy body disease","volume":"14","author":"Malek-Ahmadi","year":"2019","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e12515","DOI":"10.1002\/dad2.12515","article-title":"Combined 18F-FDG PET-CT markers in dementia with Lewy bodies","volume":"15","author":"Mattoli","year":"2023","journal-title":"Alzheimers Dement. 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Neurol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"A121","DOI":"10.1038\/jcbfm.1991.47","article-title":"A regional covariance approach to the analysis of functional patterns in positron emission tomographic data","volume":"11","author":"Moeller","year":"1991","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"390","DOI":"10.2967\/jnumed.107.045385","article-title":"Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias","volume":"49","author":"Mosconi","year":"2008","journal-title":"J. Nucl. Med."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/jnen\/nlx099","article-title":"The amygdala as a locus of pathologic misfolding in neurodegenerative diseases","volume":"77","author":"Nelson","year":"2018","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.2967\/jnumed.114.143347","article-title":"18F-FDG PET and perfusion SPECT in the diagnosis of Alzheimer and Lewy body dementias","volume":"55","author":"O'Brien","year":"2014","journal-title":"J. Nucl. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1212\/wnl.51.2.351","article-title":"Cognitive decline is faster in Lewy body variant than in Alzheimer's disease","volume":"51","author":"Olichney","year":"1998","journal-title":"Neurology"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.neuroimage.2011.02.046","article-title":"A Bayesian model of shape and appearance for subcortical brain segmentation","volume":"56","author":"Patenaude","year":"2011","journal-title":"NeuroImage"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1005731","DOI":"10.3389\/fnagi.2022.1005731","article-title":"Automated differential diagnosis of dementia syndromes using FDG PET and machine learning","volume":"14","author":"Perovnik","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1212\/WNL.0b013e3181cb3e25","article-title":"Alzheimer's disease neuroimaging initiative (ADNI): clinical characterization","volume":"74","author":"Petersen","year":"2010","journal-title":"Neurology"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1093\/brain\/awz030","article-title":"Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study","volume":"142","author":"Postuma","year":"2019","journal-title":"Brain"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"116189","DOI":"10.1016\/j.neuroimage.2019.116189","article-title":"Automated anatomical labelling atlas 3","volume":"206","author":"Rolls","year":"2020","journal-title":"NeuroImage"},{"key":"ref46","volume-title":"Proceedings of the IEEE International Conference on Computer Vision","author":"Selvaraju","year":"2017"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"274","DOI":"10.2967\/jnumed.122.264213","article-title":"Differential effects of tau stage, Lewy body pathology, and substantia Nigra degeneration on 18F-FDG PET patterns in clinical Alzheimer disease","volume":"64","author":"Silva-Rodriguez","year":"2023","journal-title":"J. Nucl. Med."},{"key":"ref48","article-title":"Very deep convolutional networks for large-scale image recognition","author":"Simonyan","year":"2014"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s40478-019-0787-2","article-title":"Unique \u03b1-synuclein pathology within the amygdala in Lewy body dementia: implications for disease initiation and progression","volume":"7","author":"Sorrentino","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1111\/jon.12104","article-title":"Syndrome-specific patterns of regional cerebral glucose metabolism in posterior cortical atrophy in comparison to dementia with Lewy bodies and Alzheimer's disease--a [F-18]-FDG pet study","volume":"25","author":"Spehl","year":"2015","journal-title":"J. Neuroimaging"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1109\/tmi.2010.2046908","article-title":"N4ITK: improved N3 bias correction","volume":"29","author":"Tustison","year":"2010","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1007\/s00259-016-3312-x","article-title":"[(123)]FP-CIT SPECT scans initially rated as normal became abnormal over time in patients with probable dementia with Lewy bodies","volume":"43","author":"van der Zande","year":"2016","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"190","DOI":"10.3389\/fnagi.2018.00190","article-title":"EEG characteristics of dementia with Lewy bodies, Alzheimer's disease and mixed pathology","volume":"10","author":"van der Zande","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1007\/s00330-024-11257-7","article-title":"Separating dementia with Lewy bodies from Alzheimer's disease dementia using a volumetric MRI classifier","volume":"35","author":"van Gils","year":"2024","journal-title":"Eur. Radiol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1017\/s0033291713000494","article-title":"The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies","volume":"44","author":"Vann Jones","year":"2014","journal-title":"Psychol. Med."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neurobiolaging.2019.10.020","article-title":"Distinguishing between dementia with Lewy bodies and Alzheimer's disease using metabolic patterns","volume":"87","author":"Ye","year":"2020","journal-title":"Neurobiol. 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