{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:31:44Z","timestamp":1773315104171,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901273"],"award-info":[{"award-number":["81901273"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Amyotrophic lateral sclerosis (ALS) has a prolonged latency period, though its preclinical characteristics remain poorly understood. This study uses UK Biobank data to explore and compare ALS's pre\u2010diagnostic features, including symptoms and medication use, aiming to provide insights into the disease's underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical symptoms and medications were identified from self\u2010reports, hospital records, and death registry data. Propensity score matching was used to match ALS with Alzheimer's disease (<jats:sc>AD<\/jats:sc>) and Parkinson's disease (PD), ensuring balance in socioeconomic factors to compare symptoms 0\u20135\u2009years before diagnosis. Cox regression analysis was applied to assess the associations between medication use and the risk of incident ALS and mortality after ALS diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 753 ALS cases were observed in 502\u2009417 participants, with an incidence rate of 10.58 per 100\u2009000 person\u2010years. In the ALS cohort, the male\u2010to\u2010female ratio was 2.9, with a median age at onset of 64.61\u2009years (Interquartile range (IQR): 56.80\u201371.31) and a median survival time post\u2010diagnosis of 9.08\u2009months (IQR: 3.18\u201318.98), while females (log\u2010rank <jats:italic>p<\/jats:italic>\u2009=\u20090.038) and individuals with earlier (&lt; 64.61\u2009years) disease onset (log\u2010rank <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) had longer survival periods. In the 5\u2009years prior to diagnosis, ALS showed a higher incidence of falls compared to <jats:sc>ad<\/jats:sc> (11.3% vs. 3.2%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), but a lower incidence than PD (10.7% vs. 28.3%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Additionally, ALS had a lower incidence of depression (4.6% vs. 25.6%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), anxiety (3.5% vs. 18.1%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), sleep disorders (1.4% vs. 7.2%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), hypotension (3.4% vs. 30.5%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), constipation (0.3% vs. 4.9%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and urinary dysfunction (2.2% vs. 8.7%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) compared with PD. The use of calcium channel blockers may be a risk factor for incident ALS (adjusted HR 1.61, 95% CI: 1.22\u20132.12, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pre\u2010diagnostic presentations of falls are more frequent in ALS than in <jats:sc>AD<\/jats:sc>, but less frequent than in PD. However, ALS exhibits fewer psychiatric symptoms and autonomic dysfunction compared with PD. The use of calcium channel blockers may be associated with an increased risk of developing ALS in the future.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.70003","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T09:38:58Z","timestamp":1752226738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prediagnosis Insights Into Amyotrophic Lateral Sclerosis: Clinical Symptoms and Medication Use"],"prefix":"10.1002","volume":"16","author":[{"given":"Chunyang","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Department of Neurology First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University Third Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai East Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaojia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Department of Neurology First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luyi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Department of Neurology First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongsheng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurology Peking University Third Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4058-0738","authenticated-orcid":false,"given":"Binbin","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Department of Neurology First Affiliated Hospital of Wenzhou Medical University  Wenzhou 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