{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:51:14Z","timestamp":1785325874260,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 2017SNW5MB"],"award-info":[{"award-number":["PRIN 2017SNW5MB"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009281","name":"Fondation Thierry Latran","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF\u20102016\u201002362405"],"award-info":[{"award-number":["RF\u20102016\u201002362405"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["259867"],"award-info":[{"award-number":["259867"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["GA101017598"],"award-info":[{"award-number":["GA101017598"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["101137074"],"award-info":[{"award-number":["101137074"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cognitive reserve (CR) applies to ALS\u2010related cognitive impairment and education is a CR proxy. The influence of sex on CR in ALS is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We compared brain 2\u2010[\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG\u2010PET metabolism of male (m\u2010ALS,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200995) and female (f\u2010ALS,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200995) patients, matched for age, education, onset, and King's stage, with no significant difference in ECAS scores. In each group, clusters showing a negative\/positive correlation with education were used as seed regions in an interregional correlation analysis (IRCA) to evaluate connectivity. We identified the seed regions including age, onset, King's stage and ECAS as covariates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>M\u2010ALS showed a relative hypometabolism compared to f\u2010ALS in bilateral frontotemporal regions. In f\u2010ALS brain metabolism positively correlated with education in the left fusiform gyrus, cerebellum and pons. The IRCA showed a positive correlation of the seed region with the cerebellum, pons, right fusiform gyrus and cuneus, and the left precuneus, and a negative correlation with the frontal lobes and caudate nuclei. In m\u2010ALS brain metabolism negatively correlated with education in the left frontotemporal and insular cortices. The IRCA showed a positive correlation of the seed region with bilateral frontotemporal and cingulate cortices, and the right parietal cortex, and a negative correlation with bilateral cerebellum and motor cortex, and the left lingual gyrus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>M\u2010ALS showed relative frontotemporal hypometabolism compared to f\u2010ALS, suggesting a male prevalence of CR. In m\u2010ALS the negative correlation of education with left frontotemporal and insular metabolism supports the CR hypothesis. In f\u2010ALS the positive correlation of cerebellar metabolism with education suggests compensatory mechanisms, also supported by the IRCA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70412","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:27:29Z","timestamp":1762522049000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cognitive Reserve in Amyotrophic Lateral Sclerosis: A 2\u2010[\n                    <scp>\n                      <sup>18<\/sup>\n                      F\n                    <\/scp>\n                    ]\n                    <scp>FDG<\/scp>\n                    \u2010\n                    <scp>PET<\/scp>\n                    Study on Sex\u2010Related Differences"],"prefix":"10.1111","volume":"32","author":[{"given":"Antonio","family":"Canosa","sequence":"first","affiliation":[{"name":"ALS Centre, \u2018Rita Levi Montalcini\u2019 Department of Neuroscience University of Turin  Turin Italy"},{"name":"Azienda Ospedaliero\u2010Universitaria Citt\u00e0 della Salute e della Scienza di Torino Neurology Unit 1U  Turin Italy"},{"name":"Institute of Cognitive Sciences and Technologies C.N.R.  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