{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:01:42Z","timestamp":1790449302464,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      The presymptomatic phase of frontotemporal dementia and amyotrophic lateral sclerosis associated with C\n                      <jats:italic>9orf72<\/jats:italic>\n                      repeat expansion features widespread structural brain changes. We aimed at fulfilling the unmet need of quantitative magnetic resonance imaging (MRI)\u2010derived measures suitable for disease tracking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We compared the profile of longitudinal gray (GM) and white matter (WM) changes in 66 presymptomatic carriers and 52 controls over 3\u2010year follow\u2010up and appraised their annualized rate of change (ARC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Both putamen (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      &lt;\u00a00.01) and left insula (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      =\u00a00.005) volumes declined the most in carriers over 40, with an ARC up to four\u2010fold higher than in controls. Increases in mean diffusivity occurred first in the left uncinate fasciculus, followed by thalamo\u2010cortical bundles (\n                      <jats:italic>p\u00a0<\/jats:italic>\n                      &lt;\u00a00.05), associated with higher neurofilament levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our study highlighted the GM and WM structures showing the greatest longitudinal decline during the preclinical stage, whose ARC may serve as an MRI\u2010derived biomarker for longitudinal surveillance and therapeutic outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CLINICAL TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>NCT02590276 and NCT05358431.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            We studied longitudinal multimodal MRI changes in presymptomatic\n                            <jats:italic>C9orf72<\/jats:italic>\n                            disease.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Carriers displayed faster atrophy in putamen, insula and cerebellar regions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Mean diffusivity increased mainly in uncinate and thalamo\u2010cortical tracts.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These differences were even more significant in older (&gt;\u00a040) participants.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We proposed targeted annualized rate of change as a quantitative biomarker.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70902","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:15:20Z","timestamp":1765343720000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Quantifying multimodal longitudinal brain changes in presymptomatic\n                    <i>C9orf72<\/i>\n                    disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Dario","family":"Saracino","sequence":"first","affiliation":[{"name":"Paris Brain Institute\u2014Institut du 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