{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:40:29Z","timestamp":1792658429365,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"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"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Behavioral impairment is common in amyotrophic lateral sclerosis (ALS) and strongly affects autonomy, caregiver burden, and outcomes, yet predictors of vulnerability remain unclear. We investigated whether premorbid regulatory traits and socio\u2010educational exposures are associated with behavioral phenotypes in ALS within a behavioral reserve framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 965 consecutively assessed patients with ALS from a prospective tertiary\u2010center cohort. Behavioral impairment was measured using the Frontal Systems Behavior Scale (FrSBe; family\u2010rated before and after onset) and, in a subset (n\u2009=\u2009633), the Edinburgh Cognitive and Behavioural ALS Screen\u2013Carer Interview (ECAS\u2010CI). Theory\u2010driven hierarchical logistic regression models tested associations between behavioral outcomes and premorbid behavioral regulation, education, occupation, and a Social Interaction Index, including interaction effects. Prespecified sensitivity analyses addressed potential bias in premorbid estimates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Premorbid behavioral regulation showed the strongest associations with behavioral impairment across all FrSBe models. Higher combined educational attainment and social exposure were associated with lower odds of impairment, with a significant interaction across multiple behavioral domains. These patterns persisted in restricted sensitivity analyses. Reserve proxies were not significantly associated with ECAS\u2010CI total impairment, although domain\u2010specific effects were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These findings provide empirical support for a behavioral reserve framework in ALS, in which premorbid regulatory traits and socio\u2010educational exposures are associated with behavioral vulnerability. Although causal inference is limited, reserve\u2010related factors may contribute to non\u2010motor heterogeneity in ALS and may inform future approaches to early behavioral risk stratification. ANN NEUROL 2026;100:934\u2013947<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78315","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:30:06Z","timestamp":1785400206000},"page":"934-947","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toward a Behavioral Reserve Model in Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"100","author":[{"given":"Francesca","family":"Palumbo","sequence":"first","affiliation":[{"name":"ALS Center, \u201cRita Levi Montalcini\u201d Department of Neuroscience, University of Torino  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Iazzolino","sequence":"additional","affiliation":[{"name":"ALS Center, \u201cRita Levi Montalcini\u201d Department of Neuroscience, University of Torino  Turin 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