{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:27:54Z","timestamp":1791224874075,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T00:00:00Z","timestamp":1423699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DC010367"],"award-info":[{"award-number":["R01 DC010367"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG11378"],"award-info":[{"award-number":["R01 AG11378"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 AG016574"],"award-info":[{"award-number":["P50 AG016574"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["NIRG-12-242215"],"award-info":[{"award-number":["NIRG-12-242215"]}],"id":[{"id":"10.13039\/100000957","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":[[2015,5]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>The aim of our study was to determine the utility of longitudinal magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) measurements as potential biomarkers in the main genetic variants of frontotemporal dementia (<jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content>), including microtubule\u2010associated protein tau (<jats:italic><jats:styled-content style=\"fixed-case\">MAPT<\/jats:styled-content><\/jats:italic>) and progranulin (<jats:italic><jats:styled-content style=\"fixed-case\">GRN<\/jats:styled-content><\/jats:italic>) mutations and <jats:italic>C9<jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>72<\/jats:italic> repeat expansions, as well as sporadic <jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this longitudinal study, 58 subjects were identified who had at least two <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> and <jats:italic><jats:styled-content style=\"fixed-case\">MAPT<\/jats:styled-content><\/jats:italic> mutations (<jats:italic>n<\/jats:italic>\u00a0=\u00a021), <jats:italic><jats:styled-content style=\"fixed-case\">GRN<\/jats:styled-content><\/jats:italic> mutations (<jats:italic>n<\/jats:italic>\u00a0=\u00a011), <jats:italic>C9<jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>72<\/jats:italic> repeat expansions (<jats:italic>n<\/jats:italic>\u00a0=\u00a011) or sporadic <jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0=\u00a015). A total of 198 serial <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> measurements were analyzed. Rates of whole brain atrophy were calculated using the boundary shift integral. Regional rates of atrophy were calculated using tensor\u2010based morphometry. Sample size estimates were calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Progressive brain atrophy was observed in all groups, with fastest rates of whole brain atrophy in <jats:italic><jats:styled-content style=\"fixed-case\">GRN<\/jats:styled-content><\/jats:italic>, followed by sporadic <jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content>,<jats:italic> C9<jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>72<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">MAPT<\/jats:styled-content><\/jats:italic>. All variants showed greatest rates in the frontal and temporal lobes, with parietal lobes also strikingly affected in <jats:italic><jats:styled-content style=\"fixed-case\">GRN<\/jats:styled-content><\/jats:italic>. Regional rates of atrophy across all lobes were greater in <jats:italic><jats:styled-content style=\"fixed-case\">GRN<\/jats:styled-content><\/jats:italic> compared to the other groups. <jats:italic>C9<jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>72<\/jats:italic> showed greater rates of atrophy in the left cerebellum and right occipital lobe than <jats:italic><jats:styled-content style=\"fixed-case\">MAPT<\/jats:styled-content><\/jats:italic>, and sporadic <jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> showed greater rates in the anterior cingulate than <jats:italic>C9<jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>72<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">MAPT<\/jats:styled-content><\/jats:italic>. Sample size estimates were lowest using temporal lobe rates in <jats:italic><jats:styled-content style=\"fixed-case\">GRN<\/jats:styled-content><\/jats:italic>, ventricular rates in <jats:italic><jats:styled-content style=\"fixed-case\">MAPT<\/jats:styled-content><\/jats:italic> and <jats:italic>C9<jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>72<\/jats:italic>, and whole brain rates in sporadic <jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data support the utility of using rates of atrophy as outcome measures in future drug trials in <jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content> and show that different imaging biomarkers may offer advantages in the different variants of <jats:styled-content style=\"fixed-case\">FTD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.12675","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T10:14:34Z","timestamp":1423822474000},"page":"745-752","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":117,"title":["Brain atrophy over time in genetic and sporadic frontotemporal dementia: a study of 198 serial magnetic resonance images"],"prefix":"10.1111","volume":"22","author":[{"given":"J. L.","family":"Whitwell","sequence":"first","affiliation":[{"name":"Department of Radiology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. F.","family":"Boeve","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. D.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. L.","family":"Senjem","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic Rochester MN USA"},{"name":"Department of Information Technology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L.","family":"Gunter","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic Rochester MN USA"},{"name":"Department of Information Technology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"DeJesus\u2010Hernandez","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. S.","family":"Knopman","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z. K.","family":"Wszolek","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. C.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Rademakers","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"C. R.","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. A.","family":"Josephs","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/31508"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05017"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.011"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.010"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e31815c345e"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr361"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.12.088"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318268452e"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000343851.46573.67"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318227047f"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl241"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.6.1546"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.4.506"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31821103e6"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm336"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.04.030"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1109\/42.640753"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.10325"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2007.06.004"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000386"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0978"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0318-1"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181b9c8b9"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.12675","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.12675","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T21:03:12Z","timestamp":1695502992000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.12675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,12]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1111\/ene.12675"],"URL":"https:\/\/doi.org\/10.1111\/ene.12675","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,12]]},"assertion":[{"value":"2014-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}