{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:29:00Z","timestamp":1787840940111,"version":"build-2784847793"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS045893"],"award-info":[{"award-number":["R01 NS045893"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015326","name":"Common Fund","doi-asserted-by":"publisher","award":["R01 CA49449"],"award-info":[{"award-number":["R01 CA49449"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015326","name":"Common Fund","doi-asserted-by":"publisher","award":["U01 CA164973"],"award-info":[{"award-number":["U01 CA164973"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015326","name":"Common Fund","doi-asserted-by":"publisher","award":["U01 CA167552"],"award-info":[{"award-number":["U01 CA167552"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015326","name":"Common Fund","doi-asserted-by":"publisher","award":["UM1 CA186107"],"award-info":[{"award-number":["UM1 CA186107"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our goal was to examine whether pre\u2010diagnostic plasma carotenoids and tocopherols are associated with amyotrophic lateral sclerosis (ALS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A nested case\u2013control study within 4 United States cohorts, where 154 participants with pre\u2010diagnostic blood\u2010draw, were diagnosed during follow\u2010up with amyotrophic lateral sclerosis\u00a0(ALS). Controls were randomly selected from participants alive on the date a case was diagnosed, matched 2:1 by cohort, sex, age, race\/ethnicity, fasting\u2010status, time of blood\u2010draw. Carotenoid and tocopherol levels were quantified by high\u2010performance liquid\u2010chromatography with diode array\u2010detector. ALS incidence or death rate ratios (RR) were estimated using conditional logistic regression adjusting for body mass index, smoking status, physical activity, cholesterol, and urate levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The association between beta\u2010carotene and ALS varied by sex (\n                      <jats:italic>p<\/jats:italic>\n                      \u2010for\u2010interaction\u2009=\u20090.007). After matched\u2010 and multivariable\u2010adjustment, women with higher cis\u2010, trans\u2010 and total beta\u2010carotene had lower incidence of ALS (RR for 1\u2010standard deviation [SD] increase in total beta\u2010carotene: 0.68; 95% CI: 0.48\u20130.98;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.038), whereas a positive association was seen in men (1\u2010SD increase: RR\u2009=\u20091.44; 95% CI: 1.03\u20132.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.033). However, after further adjustment for other correlated carotenoids, the association in men was attenuated, whereas it remained significant in women. Women with higher beta\u2010cryptoxanthin, but not men, had a lower risk of ALS (1\u2010SD increase: RR\u2009=\u20090.67; 95% CI: 0.48\u20130.94;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02;\n                      <jats:italic>p<\/jats:italic>\n                      \u2010for\u2010interaction\u2009=\u20090.12). Alpha\u2010carotene, lutein\u2010zeaxanthin, lycopene, retinol, and tocopherols were not associated with ALS, except for a borderline inverse association of gamma\u2010tocopherol in men (RR\u2009=\u20090.74; 95% CI: 0.54\u20131.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.059).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Higher pre\u2010diagnostic plasma levels of beta\u2010carotene and beta\u2010cryptoxanthin in women and gamma\u2010tocopherol in men were suggestively associated with lower ALS risk. Other carotenoids or tocopherols were not clearly associated with ALS. ANN NEUROL 2026;100:426\u2013435<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78240","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:38:00Z","timestamp":1777955880000},"page":"426-435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pre\u2010Diagnostic Plasma Carotenoids, Tocopherols and Retinol Levels, and Risk of Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"100","author":[{"given":"\u00c9ilis J.","family":"O'Reilly","sequence":"first","affiliation":[{"name":"School of Public Health University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2892-6986","authenticated-orcid":false,"given":"Kjetil","family":"Bjornevik","sequence":"additional","affiliation":[{"name":"Department of Nutrition Harvard T.H. Chan School of Public Health  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy D.","family":"Furtado","sequence":"additional","affiliation":[{"name":"Department of Nutrition Harvard T.H. Chan School of Public Health  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpa V.","family":"Patel","sequence":"additional","affiliation":[{"name":"American Cancer Society  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"American Cancer Society  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence N.","family":"Kolonel","sequence":"additional","affiliation":[{"name":"Epidemiology Program University of Hawaii Cancer Center  Honolulu HI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Le Marchand","sequence":"additional","affiliation":[{"name":"Epidemiology Program University of Hawaii Cancer Center  Honolulu HI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ascherio","sequence":"additional","affiliation":[{"name":"Departments of Nutrition and Epidemiology Harvard T.H. Chan School of Public Health  Boston MA USA"},{"name":"Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.71"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25153453"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23820"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20316"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq416"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000201563"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1179\/1476830513Y.0000000071"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1418002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuaa008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.2016.303338"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)90542-W"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.101970"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a010213"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/CPJ.0b013e3182a1b8ab"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh179"},{"key":"e_1_2_9_17_1","first-page":"232","article-title":"Simultaneous determination of retinol, tocopherols, carotenes and lycopene in plasma by means of high\u2010performance liquid chromatography on reversed phase","volume":"61","author":"Hess D","year":"1991","journal-title":"Int J Vitam Nutr Res"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/76.1.172"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/122.9.1792"},{"key":"e_1_2_9_20_1","first-page":"283","article-title":"Associations of plasma carotenoid concentrations and dietary intake of specific carotenoids in samples of two prospective cohort studies using a new carotenoid database","volume":"7","author":"Michaud DS","year":"1998","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1418005"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwn217"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/1047-2797(94)90036-1"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2012.745570"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/951786"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.78240","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.78240","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.78240","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:33:20Z","timestamp":1787837600000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.78240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ana.78240"],"URL":"https:\/\/doi.org\/10.1002\/ana.78240","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"assertion":[{"value":"2025-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}