{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:23:26Z","timestamp":1787203406749,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons in the brain and spinal cord. Most patients survive 3 to 5\u2009years after diagnosis, although some live 10\u2009years or more. Prognostic factors are incompletely understood, but previous case\u2013control studies suggest that exposure to persistent organic pollutants (POPs) may be associated with ALS survival, but this has not been explored within prospective analysis of POP biomarkers. In this study, we aimed to prospectively investigate the relationship between exposure to POPs\u2014assessed in pre\u2010disease plasma samples\u2014and survival with ALS in the Danish Diet, Cancer, and Health study cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified 166 incident ALS cases using the Danish National Patient Register via International Classification of Diseases (ICD) codes. We measured concentrations of 13 polychlorinated biphenyls (PCBs), 9 organochlorine pesticides, and 3 polybrominated diphenyl ethers in plasma samples collected at inclusion in the study (baseline). To assess the relationship between POP exposures and ALS survival, we used separate Cox models for each POP group adjusting for diagnosis age, sex, smoking status, body mass index, and marital status. We selected the most relevant POP groups for ALS survival using an elastic net penalized Cox proportional hazards regression model and then ran a model using a summary environmental risk score (ERS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Single\u2010pollutant Cox models showed that exposure to non\u2010dioxin like PCBs, hexachlorobenzene (HCB), \u03b2\u2010hexachlorocyclohexane (\u03b2\u2010HCH), and chlordane compounds were associated with shorter survival. Elastic net penalized Cox proportional hazards regression selected HCB and chlordane compounds as the most relevant POPs for survival. The ERS Cox model showed a significant association with shorter survival (hazard ratio [HR]: 1.4, 95% confidence interval [CI]: 1.1\u20131.7). A 1 standard deviation (SD) higher ERS score was associated with an HR for death of 1.4 (95% CI: 1.1\u20131.7). Predicted median survival for those with an ERS score 1 SD higher than the mean was 12\u2009months shorter (26 vs 38\u2009months).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our study suggests that pre\u2010disease exposure to some POPs such as HCB and chlordane compounds could negatively influence ALS survival. ANN NEUROL 2026<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78334","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:23:43Z","timestamp":1787199823000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations between Pre\u2010Disease Biomarkers of Persistent Organic Pollutants and Amyotrophic Lateral Sclerosis Survival in the Danish Diet, Cancer and Health Study Cohort"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8430-0102","authenticated-orcid":false,"given":"Aline","family":"Davias","sequence":"first","affiliation":[{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Knekt","sequence":"additional","affiliation":[{"name":"Department of Public Health Finnish Institute for Health and Welfare  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panu","family":"Rantakokko","sequence":"additional","affiliation":[{"name":"Department of Health Finnish Institute for Health and Welfare  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnni","family":"Hansen","sequence":"additional","affiliation":[{"name":"Danish Cancer Institute, Danish Cancer Society  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-9834","authenticated-orcid":false,"given":"Marc G.","family":"Weisskopf","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston MA USA"},{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"225","volume-title":"In: handbook of clinical neurology","author":"Talbott EO","year":"2016"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3109\/17482960802566824","article-title":"Prognostic factors in ALS: a critical review","volume":"10","author":"Chi\u00f2 A","year":"2009","journal-title":"Amyotroph Lateral Scler"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1212\/01.WNL.0000049472.47709.3B","article-title":"Prognosis in amyotrophic lateral sclerosis","volume":"60","author":"Aguila MA","year":"2003","journal-title":"Neurology"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1136\/jnnp-2016-313793","article-title":"Influence of cigarette smoking on ALS outcome: a population\u2010based study","volume":"87","author":"Calvo A","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1136\/jnnp-2023-332121","article-title":"Environmental risk scores of persistent organic pollutants associate with higher ALS risk and shorter survival in a new Michigan case\/control cohort","volume":"95","author":"Goutman SA","year":"2024","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1136\/jnnp-2018-319785","article-title":"High plasma concentrations of organic pollutants negatively impact survival in amyotrophic lateral sclerosis","volume":"90","author":"Goutman SA","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1136\/jnnp-2024-333978","article-title":"Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self\u2010reported exposures: a case\u2010control study","volume":"96","author":"Jang DG","year":"2025","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_2_9_9_1","unstructured":"United Nations Environment Programme.Stockholm Convention on persistent organic pollutants (POPs) [Internet]. [date unknown];[cited 2025 Mar 21 ] Available at:https:\/\/www.pops.int\/TheConvention\/Overview\/TextoftheConvention\/tabid\/2232\/Default.aspx."},{"key":"e_1_2_9_10_1","unstructured":"UN Environment Programme.PCBs \u2010 a forgotten legacy? [Internet] 2017. 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