{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T11:27:25Z","timestamp":1793618845377,"version":"4.5.0"},"reference-count":71,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010275","name":"Deutsche Gesellschaft f\u00fcr Muskelkranke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.ebiom.2026.106505","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:53:34Z","timestamp":1791528814000},"page":"106505","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis"],"prefix":"10.1016","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2078-1997","authenticated-orcid":false,"given":"Isabell","family":"Cordts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-5292","authenticated-orcid":false,"given":"Ana","family":"Galhoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7643-3232","authenticated-orcid":false,"given":"Laura","family":"Tzeplaeff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Gr\u00fcndel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Kohlmayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schwersenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Marschalkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Bjelica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Panitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sva\u010dina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Rau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 C.","family":"Dorigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Deschauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Witzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen H.","family":"Weishaupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Bublitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Lorenzl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Hagenacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-7386","authenticated-orcid":false,"given":"Martin","family":"Regensburger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmar C.","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike F.","family":"Dohrn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Dorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Guenther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1874-8872","authenticated-orcid":false,"given":"Christoph","family":"Neuwirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan C.","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Boentert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-7662","authenticated-orcid":false,"given":"Markus","family":"Weiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Petri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Weyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Grehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Menden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-7096","authenticated-orcid":false,"given":"Paul","family":"Lingor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ebiom.2026.106505_bib1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/brain\/awab404","article-title":"Preventing amyotrophic lateral sclerosis: insights from pre-symptomatic neurodegenerative diseases","volume":"145","author":"Benatar","year":"2022","journal-title":"Brain"},{"key":"10.1016\/j.ebiom.2026.106505_bib2","doi-asserted-by":"crossref","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":"10.1016\/j.ebiom.2026.106505_bib3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1001\/archneur.58.3.397","article-title":"Mild cognitive impairment represents early-stage alzheimer disease","volume":"58","author":"Morris","year":"2001","journal-title":"Arch Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib4","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1136\/jnnp.2007.128728","article-title":"Detection of Huntington\u2019s disease decades before diagnosis: the Predict-HD study","volume":"79","author":"Paulsen","year":"2008","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.1016\/j.ebiom.2026.106505_bib5","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.biopsych.2006.11.034","article-title":"Psychiatric symptoms in Huntington\u2019s disease before diagnosis: the Predict-HD study","volume":"62","author":"Duff","year":"2007","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.ebiom.2026.106505_bib6","doi-asserted-by":"crossref","first-page":"3500","DOI":"10.1093\/brain\/awac185","article-title":"Mild motor impairment as prodromal state in amyotrophic lateral sclerosis: a new diagnostic entity","volume":"145","author":"Benatar","year":"2022","journal-title":"Brain"},{"key":"10.1016\/j.ebiom.2026.106505_bib7","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/21678421.2016.1267768","article-title":"Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): revised diagnostic criteria","volume":"18","author":"Strong","year":"2017","journal-title":"Amyotroph Lateral Scler Front Degener"},{"key":"10.1016\/j.ebiom.2026.106505_bib8","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/s41582-024-00961-z","article-title":"The Miami framework for ALS and related neurodegenerative disorders: an integrated view of phenotype and biology","volume":"20","author":"Benatar","year":"2024","journal-title":"Nat Rev Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib9","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3109\/21678421.2012.735240","article-title":"Premorbid body mass index and risk of amyotrophic lateral sclerosis","volume":"14","author":"O\u2019Reilly","year":"2013","journal-title":"Amyotroph Lateral Scler Front Degener"},{"key":"10.1016\/j.ebiom.2026.106505_bib10","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1136\/jnnp-2018-319611","article-title":"Early weight loss in amyotrophic lateral sclerosis: outcome relevance and clinical correlates in a population-based cohort","volume":"90","author":"Moglia","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.1016\/j.ebiom.2026.106505_bib11","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1136\/jnnp-2020-322909","article-title":"Prognostic value of weight loss in patients with amyotrophic lateral sclerosis: a population-based study","volume":"91","author":"Janse Van Mantgem","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.1016\/j.ebiom.2026.106505_bib12","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1136\/jnnp-2017-315795","article-title":"Hypothalamic atrophy is related to body mass index and age at onset in amyotrophic lateral sclerosis","volume":"88","author":"Gorges","year":"2017","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.1016\/j.ebiom.2026.106505_bib13","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.1007\/s00415-024-12455-5","article-title":"Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions","volume":"271","author":"Bjelica","year":"2024","journal-title":"J Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib14","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/S1474-4422(14)70219-4","article-title":"Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study","volume":"13","author":"Al-Chalabi","year":"2014","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib15","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1474-4422(21)00414-2","article-title":"Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib16","first-page":"7","article-title":"Amyotrophic lateral sclerosis and environmental factors","volume":"31","author":"Bozzoni","year":"2016","journal-title":"Funct Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neurol.2015.11.002","article-title":"Epidemiology of amyotrophic lateral sclerosis: a review of literature","volume":"172","author":"Couratier","year":"2016","journal-title":"Rev Neurol (Paris)"},{"key":"10.1016\/j.ebiom.2026.106505_bib18","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1001\/jamaneurol.2025.5379","article-title":"Long-term exposure to air pollution and risk and prognosis of motor neuron disease","volume":"83","author":"Wu","year":"2026","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neuro.2016.06.015","article-title":"Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis","volume":"61","author":"Wang","year":"2017","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.ebiom.2026.106505_bib20","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nrneurol.2013.203","article-title":"The epidemiology of ALS: a conspiracy of genes, environment and time","volume":"9","author":"Al-Chalabi","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/146608200300079536","article-title":"El escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis","volume":"1","author":"Brooks","year":"2000","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"key":"10.1016\/j.ebiom.2026.106505_bib23","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1212\/WNL.0000000000200799","article-title":"Hastening the diagnosis of amyotrophic lateral sclerosis","volume":"99","author":"Mitsumoto","year":"2022","journal-title":"Neurology"},{"key":"10.1016\/j.ebiom.2026.106505_bib24","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000213917","article-title":"Proposed research criteria for mild motor impairment as a prodromal syndrome in amyotrophic lateral sclerosis","volume":"105","author":"Benatar","year":"2025","journal-title":"Neurology"},{"key":"10.1016\/j.ebiom.2026.106505_bib25","first-page":"1","article-title":"Prodromal symptoms in amyotrophic lateral sclerosis from the perspective of the patient and of the caregiver","author":"Van Wijk","year":"2025","journal-title":"Amyotroph Lateral Scler Front Degener"},{"key":"10.1016\/j.ebiom.2026.106505_bib26","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1212\/01.wnl.0000286948.99150.16","article-title":"Clinical, electrophysiologic, and pathologic evidence for sensory abnormalities in ALS","volume":"69","author":"Hammad","year":"2007","journal-title":"Neurology"},{"key":"10.1016\/j.ebiom.2026.106505_bib27","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.1007\/s00415-023-11954-1","article-title":"Sensory neuropathy in amyotrophic lateral sclerosis: a systematic review","volume":"270","author":"Bombaci","year":"2023","journal-title":"J Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib28","doi-asserted-by":"crossref","DOI":"10.1155\/2024\/1228194","article-title":"Amyotrophic lateral sclerosis and pain: a narrative review from pain assessment to therapy","volume":"2024","author":"Pota","year":"2024","journal-title":"Behav Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib29","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S1474-4422(16)30358-1","article-title":"Pain in amyotrophic lateral sclerosis","volume":"16","author":"Chi\u00f2","year":"2017","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.clineuro.2019.105540","article-title":"Pain at the onset of Amyotrophic Lateral Sclerosis: a cross-sectional study","volume":"186","author":"Taga","year":"2019","journal-title":"Clin Neurol Neurosurg"},{"key":"10.1016\/j.ebiom.2026.106505_bib31","doi-asserted-by":"crossref","DOI":"10.1177\/22143602261422971","article-title":"Characteristics of muscle cramps as a prodromal symptom of sporadic amyotrophic lateral sclerosis","author":"Komori","year":"2026","journal-title":"J Neuromuscul Dis"},{"key":"10.1016\/j.ebiom.2026.106505_bib32","first-page":"18","article-title":"Timeliness of diagnosis in motor neurone disease: a population-based study","volume":"77","author":"Donaghy","year":"2008","journal-title":"Ulster Med J"},{"key":"10.1016\/j.ebiom.2026.106505_bib33","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1227\/01.NEU.0000180028.64385.d3","article-title":"Incidence and characteristics of spinal decompression surgery after the onset of symptoms of amyotrophic lateral sclerosis","volume":"57","author":"Yoshor","year":"2005","journal-title":"Neurosurgery"},{"key":"10.1016\/j.ebiom.2026.106505_bib34","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1750-1326-7-6","article-title":"Spinal cord trauma and the molecular point of no return","volume":"7","author":"Yip","year":"2012","journal-title":"Mol Neurodegener"},{"key":"10.1016\/j.ebiom.2026.106505_bib35","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adm7580","article-title":"Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models","volume":"17","author":"Guillot","year":"2025","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.ebiom.2026.106505_bib36","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cortex.2021.11.009","article-title":"Clinicoanatomical substrates of selfish behaviour in amyotrophic lateral sclerosis \u2013 an observational cohort study","volume":"146","author":"Lul\u00e9","year":"2022","journal-title":"Cortex"},{"key":"10.1016\/j.ebiom.2026.106505_bib37","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S1474-4422(13)70026-7","article-title":"Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment","volume":"12","author":"Goldstein","year":"2013","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib38","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fnbeh.2017.00189","article-title":"Mistakes, too few to mention? Impaired self-conscious emotional processing of errors in the behavioral variant of frontotemporal dementia","volume":"11","author":"Scherling","year":"2017","journal-title":"Front Behav Neurosci"},{"key":"10.1016\/j.ebiom.2026.106505_bib39","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1016\/j.concog.2011.09.005","article-title":"Loss of emotional insight in behavioral variant frontotemporal dementia or \u201cfrontal anosodiaphoria\u201d","volume":"20","author":"Mendez","year":"2011","journal-title":"Conscious Cogn"},{"key":"10.1016\/j.ebiom.2026.106505_bib40","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00702-024-02850-7","article-title":"Mild cognitive impairment in amyotrophic lateral sclerosis: current view","volume":"132","author":"Jellinger","year":"2025","journal-title":"J Neural Transm"},{"key":"10.1016\/j.ebiom.2026.106505_bib41","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/s00702-024-02841-8","article-title":"The spectrum of behavioral disorders in amyotrophic lateral sclerosis: current view","volume":"132","author":"Jellinger","year":"2025","journal-title":"J Neural Transm"},{"key":"10.1016\/j.ebiom.2026.106505_bib42","first-page":"1239","article-title":"Health care resource utilization and costs across stages of amyotrophic lateral sclerosis in the United States","volume":"30","author":"Stenson","year":"2024","journal-title":"J Manag Care Spec Pharm"},{"key":"10.1016\/j.ebiom.2026.106505_bib43","doi-asserted-by":"crossref","first-page":"748","DOI":"10.3390\/brainsci11060748","article-title":"Informal caregiving in amyotrophic lateral sclerosis (ALS): a high caregiver burden and drastic consequences on caregivers\u2019 lives","volume":"11","author":"Schischlevskij","year":"2021","journal-title":"Brain Sci"},{"key":"10.1016\/j.ebiom.2026.106505_bib44","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.1119","article-title":"Are people with amyotrophic lateral sclerosis (ALS) particularly nice? An international online case\u2013control study of the big five personality factors","volume":"8","author":"Parkin Kullmann","year":"2018","journal-title":"Brain Behav"},{"key":"10.1016\/j.ebiom.2026.106505_bib45","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1212\/01.wnl.0000277463.87361.8c","article-title":"Lifetime occupation, education, smoking, and risk of ALS","volume":"69","author":"Sutedja","year":"2007","journal-title":"Neurology"},{"key":"10.1016\/j.ebiom.2026.106505_bib46","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1080\/21678421.2021.1905847","article-title":"Occupation and amyotrophic lateral sclerosis risk: a case-control study in the isolated island population of Malta","volume":"22","author":"Farrugia Wismayer","year":"2021","journal-title":"Amyotroph Lateral Scler Front Degener"},{"key":"10.1016\/j.ebiom.2026.106505_bib47","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2023.1177431","article-title":"Risk factors of amyotrophic lateral sclerosis: a global meta-summary","volume":"17","author":"Duan","year":"2023","journal-title":"Front Neurosci"},{"key":"10.1016\/j.ebiom.2026.106505_bib48","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neubiorev.2016.04.007","article-title":"Physical activity, and physical activity related to sports, leisure and occupational activity as risk factors for ALS: a systematic review","volume":"66","author":"Lacorte","year":"2016","journal-title":"Neurosci Biobehav Rev"},{"key":"10.1016\/j.ebiom.2026.106505_bib49","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1093\/brain\/awac470","article-title":"Physical activity as an exogenous risk factor for amyotrophic lateral sclerosis: a review of the evidence","volume":"146","author":"Chapman","year":"2023","journal-title":"Brain"},{"key":"10.1016\/j.ebiom.2026.106505_bib50","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1001\/jamaneurol.2016.0594","article-title":"Association of environmental toxins with amyotrophic lateral sclerosis","volume":"73","author":"Su","year":"2016","journal-title":"JAMA Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18332\/tid\/175731","article-title":"Association of smoking with amyotrophic lateral sclerosis: a systematic review, and meta-analysis, including dose-response analysis","volume":"22","author":"Kim","year":"2024","journal-title":"Tob Induc Dis"},{"key":"10.1016\/j.ebiom.2026.106505_bib52","doi-asserted-by":"crossref","DOI":"10.1001\/archneurol.2010.367","article-title":"Smoking and risk of amyotrophic lateral sclerosis: a pooled analysis of 5 prospective cohorts","volume":"68","author":"Wang","year":"2011","journal-title":"Arch Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib53","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S1474-4422(21)00042-9","article-title":"Associations between lifestyle and amyotrophic lateral sclerosis stratified by C9orf72 genotype: a longitudinal, population-based, case-control study","volume":"20","author":"Westeneng","year":"2021","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib54","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1136\/jnnp-2018-318559","article-title":"Association between alcohol exposure and the risk of amyotrophic lateral sclerosis in the Euro-MOTOR study","volume":"90","author":"D\u2019Ovidio","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.1016\/j.ebiom.2026.106505_bib55","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.3390\/ijms21072316","article-title":"Role of alcohol drinking in alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis","volume":"21","author":"Peng","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.ebiom.2026.106505_bib56","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/mds.25076","article-title":"Caffeine and risk of Parkinson\u2019s disease in a large cohort of men and women","volume":"27","author":"Palacios","year":"2012","journal-title":"Mov Disord"},{"key":"10.1016\/j.ebiom.2026.106505_bib57","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3109\/21678421.2015.1020813","article-title":"Intakes of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis: results from five cohort studies","volume":"16","author":"Fondell","year":"2015","journal-title":"Amyotroph Lateral Scler Front Degener"},{"key":"10.1016\/j.ebiom.2026.106505_bib58","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/jnr.23185","article-title":"Effects of chronic caffeine intake in a mouse model of amyotrophic lateral sclerosis","volume":"91","author":"Potenza","year":"2013","journal-title":"J Neurosci Res"},{"key":"10.1016\/j.ebiom.2026.106505_bib59","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/aje\/kww140","article-title":"Body mass index and amyotrophic lateral sclerosis: a study of US military veterans","volume":"185","author":"Mariosa","year":"2017","journal-title":"Am J Epidemiol"},{"key":"10.1016\/j.ebiom.2026.106505_bib60","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/mus.26749","article-title":"Loss of appetite in amyotrophic lateral sclerosis is associated with weight loss and decreased calorie consumption independent of dysphagia","volume":"61","author":"Mezoian","year":"2020","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.ebiom.2026.106505_bib61","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1007\/s00415-009-5100-z","article-title":"Hypermetabolism in ALS patients: an early and persistent phenomenon","volume":"256","author":"Bouteloup","year":"2009","journal-title":"J Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib62","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s10654-017-0318-z","article-title":"Life course body mass index and risk and prognosis of amyotrophic lateral sclerosis: results from the ALS registry Swabia","volume":"32","author":"Peter","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"10.1016\/j.ebiom.2026.106505_bib63","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/nan.12709","article-title":"Loss of the metabolism and sleep regulating neuronal populations expressing orexin and oxytocin in the hypothalamus in amyotrophic lateral sclerosis","volume":"47","author":"Gabery","year":"2021","journal-title":"Neuropathol Appl Neurobiol"},{"key":"10.1016\/j.ebiom.2026.106505_bib64","doi-asserted-by":"crossref","first-page":"9119","DOI":"10.1038\/s41598-021-88755-x","article-title":"Loss of appetite in patients with amyotrophic lateral sclerosis is associated with weight loss and anxiety\/depression","volume":"11","author":"Wang","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.ebiom.2026.106505_bib65","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.genm.2010.11.010","article-title":"Effects of gender in amyotrophic lateral sclerosis","volume":"7","author":"McCombe","year":"2010","journal-title":"Gend Med"},{"key":"10.1016\/j.ebiom.2026.106505_bib66","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jns.2010.03.028","article-title":"The diagnostic pathway and prognosis in bulbar-onset amyotrophic lateral sclerosis","volume":"294","author":"Turner","year":"2010","journal-title":"J Neurol Sci"},{"key":"10.1016\/j.ebiom.2026.106505_bib67","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s00586-015-4052-5","article-title":"Gender differences in patients scheduled for lumbar disc herniation surgery: a National Register Study including 15,631 operations","volume":"25","author":"Str\u00f6mqvist","year":"2016","journal-title":"Eur Spine J"},{"key":"10.1016\/j.ebiom.2026.106505_bib68","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.3390\/ijerph15102094","article-title":"Differences in the incidence of symptomatic cervical and lumbar disc herniation according to age, sex and national health insurance eligibility: a pilot study on the disease\u2019s association with work","volume":"15","author":"Kim","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"10.1016\/j.ebiom.2026.106505_bib69","first-page":"533","article-title":"Relationship between physical work load and lumbar disc herniation","volume":"22","author":"Ahsan","year":"2013","journal-title":"Mymensingh Med J MMJ"},{"key":"10.1016\/j.ebiom.2026.106505_bib70","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/ana.26933","article-title":"Sex differences in amyotrophic lateral sclerosis survival and progression: a multidimensional analysis","volume":"96","author":"Grassano","year":"2024","journal-title":"Ann Neurol"},{"key":"10.1016\/j.ebiom.2026.106505_bib71","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.1038\/s41467-024-49196-y","article-title":"Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target","volume":"15","author":"Caldi Gomes","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.ebiom.2026.106505_bib72","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s42466-025-00417-9","article-title":"Identification of a presymptomatic and early disease signature for amyotrophic lateral sclerosis (ALS): protocol of the premodiALS study","volume":"7","author":"Tzeplaeff","year":"2025","journal-title":"Neurol Res Pract"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396426003890?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396426003890?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T10:50:21Z","timestamp":1793616621000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396426003890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":71,"alternative-id":["S2352396426003890"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2026.106505","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"EARLY-ALS: a multicentre study on prodromal amyotrophic lateral sclerosis","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2026.106505","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"106505"}}