{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:03:24Z","timestamp":1784797404184,"version":"3.55.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":193,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzheimer\u2019s Society and Alzheimer\u2019s Research UK"},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Betty Messenger Charitable Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease characterized predominantly by degeneration of both upper and lower motor neurons, thought to occur due to an interplay between genetics and environmental factors. Physical activity has been suggested as a potential risk factor for ALS; however, the exact role of exercise in the onset and progression of the disease is still unclear.<\/jats:p>\n                  <jats:p>We assessed lifetime physical activity in two independent ALS cohorts: post-mortem brain donors from the London Neurodegenerative Diseases Brain Bank (n = 139) and patients from the Motor Neurone Disease (MND) Register of England, Wales and Northern Ireland (n = 166 cases, 196 controls).<\/jats:p>\n                  <jats:p>In both cohorts, highly active individuals developed ALS symptoms at a significantly younger age, 54.2 years (mean, standard deviation = 7.5) in the post-mortem cohort and 58.0 years (median, interquartile range = 15) in the MND Register, compared with 63.9 years (mean, standard deviation = 11.5) and 63.0 years (median, interquartile range = 17.5) in inactive individuals, respectively [one-way analysis of variance (ANOVA), F(2, 136) = 6.10, P = 0.003, \u03b72 = 0.08, 95% confidence interval (CI) 0.02\u20131.00 and Kruskal\u2013Wallis, H(2) = 7.39, P = 0.02, \u03b72 = 0.03, 95% CI 0.003\u20130.12]. Cox regression showed a higher hazard of earlier onset in highly active patients [post-mortem: hazard ratio (HR) 2.84, 95% CI 1.55\u20135.26, P = 0.0008; MND Register: HR 2.34, 95% CI 1.30\u20134.23, P = 0.005].<\/jats:p>\n                  <jats:p>Our findings suggest that strenuous physical activity may be associated with a significantly younger age of ALS onset, replicated in both the post-mortem and MND Register cohorts, but not with an increased risk of developing ALS. Logistic regression analysis confirmed that neither highly active [odds ratio (OR) 1.43, 95% CI 0.69\u20132.99, P = 0.333] nor being active (OR 1.30, 95% CI 0.72\u20132.37, P = 0.386) was significantly associated with ALS risk, whereas a history of head injury was (OR 1.72, 95% CI 1.03\u20132.88, P = 0.038). These results suggest that strenuous exercise may accelerate disease onset in predisposed individuals, while the role of head injury requires further study and the findings may in fact indicate reverse causality.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag272","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:54:36Z","timestamp":1783684476000},"source":"Crossref","is-referenced-by-count":0,"title":["Strenuous physical activity is associated with a younger age of amyotrophic lateral sclerosis onset in two independent cohorts"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0414-0758","authenticated-orcid":false,"given":"Jaimee","family":"Kennedy","sequence":"first","affiliation":[{"name":"Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London , London SE5 9RT ,","place":["UK"]},{"name":"London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology & Neuroscience, Kings College London , London SE8 8AF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7406-9831","authenticated-orcid":false,"given":"Ahmad","family":"Al Khleifat","sequence":"additional","affiliation":[{"name":"Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London , London SE5 9RT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"King","sequence":"additional","affiliation":[{"name":"London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology & Neuroscience, Kings College London , London SE8 8AF ,","place":["UK"]},{"name":"Clinical Neuropathology Department, Kings College Hospital NHS Trust , London SE5 9RS ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Al-Sarraj","sequence":"additional","affiliation":[{"name":"London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology & Neuroscience, Kings College London , London SE8 8AF ,","place":["UK"]},{"name":"Clinical Neuropathology Department, Kings College Hospital NHS Trust , London SE5 9RS ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4924-7712","authenticated-orcid":false,"given":"Ammar","family":"Al-Chalabi","sequence":"additional","affiliation":[{"name":"Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London , London SE5 9RT ,","place":["UK"]},{"name":"Department of Clinical Neurosciences, King\u2019s College Hospital NHS Trust , London SE5 9RS ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline C","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London , London SE5 9RT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Troakes","sequence":"additional","affiliation":[{"name":"Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London , London SE5 9RT ,","place":["UK"]},{"name":"London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology & Neuroscience, Kings College London , London SE8 8AF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"2026072304311570100_fcag272-B1","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/nrdp.2017.71","article-title":"Amyotrophic lateral 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