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Prodromal FTD was defined to reflect mild cognitive or behavioural impairment with relatively preserved functional independence (global CDR plus NACC = 0.5) as well as mild, moderate and severe dementia (classified as global CDR plus NACC = 1, 2, 3, respectively). Disease progression at 1-year follow-up and serum NfL measurements were acquired in a subgroup of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 563 participants, 138 were classified as prodromal FTD, 130 as mild, 175 as moderate and 120 as severe FTD. In the prodromal and mild phases, we observed an early increase in serum NfL levels followed by behavioural disturbances and deficits in executive functions. Negative symptoms, such as apathy, inflexibility and loss of insight, predominated in the prodromal phase. Serum NfL levels were significantly increased in the prodromal phase compared with healthy controls (average difference 14.5, 95% CI 2.9 to 26.1 pg\/mL), but lower than in patients with mild FTD (average difference -15.5, 95% CI -28.4 to -2.7 pg\/mL). At 1-year follow-up, 51.2% of patients in the prodromal phase had converted to dementia. Serum NfL measurements at baseline were the strongest predictors of disease progression at 1-year follow-up (OR 1.07, 95% CI 1.03 to 1.11,<jats:italic>p<\/jats:italic>&lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Prodromal FTD is a mutable stage with high rate of progression to fully symptomatic disease at 1-year follow-up. High serum NfL levels may support prodromal FTD diagnosis and represent a helpful marker to assess disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13195-021-00932-2","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T15:03:04Z","timestamp":1636988584000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Prodromal frontotemporal dementia: clinical features and predictors of progression"],"prefix":"10.1186","volume":"13","author":[{"given":"Alberto","family":"Benussi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas K.","family":"Karikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Alberici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Saraceno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Ghidoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Benussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9340-9814","authenticated-orcid":false,"given":"Barbara","family":"Borroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"issue":"11","key":"932_CR1","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1212\/WNL.0b013e31821103e6","volume":"76","author":"ML Gorno-Tempini","year":"2011","unstructured":"Gorno-Tempini ML, Hillis AE, Weintraub S, et al. 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Ann Clin Transl Neurol. 2016;3(3):216\u201325 http:\/\/eutils.ncbi.nlm.nih.gov\/entrez\/eutils\/elink.fcgi?dbfrom=pubmed&id=27042681&retmode=ref&cmd=prlinks.","journal-title":"Ann Clin Transl Neurol"}],"container-title":["Alzheimer's Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-021-00932-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13195-021-00932-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-021-00932-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T05:26:06Z","timestamp":1726118766000},"score":1,"resource":{"primary":{"URL":"https:\/\/alzres.biomedcentral.com\/articles\/10.1186\/s13195-021-00932-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,15]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["932"],"URL":"https:\/\/doi.org\/10.1186\/s13195-021-00932-2","relation":{},"ISSN":["1758-9193"],"issn-type":[{"value":"1758-9193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,15]]},"assertion":[{"value":"15 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Full written informed consent was obtained from all subjects according to the Declaration of Helsinki. The Brescia Ethics Committee approved the study protocol.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"HZ has served at scientific advisory boards for Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies and CogRx, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD\/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics and Siemens Healthineers and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"188"}}