{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:34:19Z","timestamp":1791815659420,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"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":[[2026,5]]},"abstract":"\n Objective<\/jats:title>\n Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f\u2010FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f\u2010FTLD. We used a Bayesian linear mixed\u2010effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Participants included 234 asymptomatic or prodromal carriers of\n C9orf72<\/jats:italic>\n ,\n GRN<\/jats:italic>\n , or\n MAPT<\/jats:italic>\n mutations (including 21 dementia converters) with \u22653 longitudinal magnetic resonance imaging (MRI) T1\u2010weighted scans. The BLME models established individual voxel\u2010wise gray matter trajectories using the first 2 scans. Person\u2010specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time\u2010varying Cox proportional hazard models covarying for age. Receiver\u2010operating characteristic (ROC) curves estimated utility of cluster volume in discriminating which participants converted to dementia within 24\u2009months.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The BLME cluster volume predicted conversion to dementia in f\u2010FTLD mutation carriers overall and separately in\n C9orf72<\/jats:italic>\n ,\n GRN<\/jats:italic>\n , and\n MAPT<\/jats:italic>\n , with comparable hazard ratios observed for atrophy W\u2010maps and regional volumes. Within a 24\u2010month timeframe, BLME cluster volume discriminated dementia converters from non\u2010converters with larger areas under the curve (AUCs) than other approaches.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n Bayesian\u2010modeled individualized atrophy scores predict dementia progression among asymptomatic f\u2010FTLD mutation carriers and may have increased utility compared with other structural imaging methods when studying individuals over shorter timeframes that align with clinical trial design. ANN NEUROL 20269999:n\/a\u2013n\/a<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ana.78167","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T10:35:57Z","timestamp":1769682957000},"page":"1315-1326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Individualized Atrophy\u2010Based Prediction of Dementia Progression in Familial Frontotemporal Lobar Degeneration With Bayesian Linear Mixed\u2010Effects Modeling"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8408-2220","authenticated-orcid":false,"given":"Shubir","family":"Dutt","sequence":"first","affiliation":[{"name":"Department of Neurology, Edward and Pearl Fein Memory and Aging Center University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Leichter","sequence":"additional","affiliation":[{"name":"Department of Neurology, Edward and Pearl Fein Memory and Aging Center University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Cobigo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Edward and Pearl Fein Memory and Aging Center University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Neurology, Edward and Pearl Fein Memory and Aging Center University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kornak","sequence":"additional","affiliation":[{"name":"Department of Neurology, Edward and Pearl Fein Memory and Aging Center University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Neurology, Edward and Pearl Fein Memory and Aging Center University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5023-5893","authenticated-orcid":false,"given":"Lucy L.","family":"Russell","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arabella","family":"Bouzigues","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Cash","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1814-5024","authenticated-orcid":false,"given":"Martina","family":"Bocchetta","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, UCL Queen Square Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly","family":"Olzinski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Edward and Pearl Fein Memory and Aging Center University of California, San Francisco San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Appleby","sequence":"additional","affiliation":[{"name":"Department of Neurology Case Western Reserve University Cleveland OH 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