Prodromal frontotemporal dementia: clinical features and predictors of progression

Abstract Background The prodromal phase of frontotemporal dementia (FTD) is still not well characterized, and conversion rates to dementia and predictors of progression at 1-year follow-up are currently unknown. Methods In this retrospective study, disease severity was assessed using the global CDR...

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Autores principales:	Alberto Benussi, Nicholas J. Ashton, Thomas K. Karikari, Antonella Alberici, Claudia Saraceno, Roberta Ghidoni, Luisa Benussi, Henrik Zetterberg, Kaj Blennow, Barbara Borroni
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Frontotemporal dementia Serum neurofilament light Prodromal Mild Progression Conversion Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/7434446daf234058909f16d1c6cc2be3
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spelling	oai:doaj.org-article:7434446daf234058909f16d1c6cc2be32021-11-21T12:40:24ZProdromal frontotemporal dementia: clinical features and predictors of progression10.1186/s13195-021-00932-21758-9193https://doaj.org/article/7434446daf234058909f16d1c6cc2be32021-11-01T00:00:00Zhttps://doi.org/10.1186/s13195-021-00932-2https://doaj.org/toc/1758-9193Abstract Background The prodromal phase of frontotemporal dementia (FTD) is still not well characterized, and conversion rates to dementia and predictors of progression at 1-year follow-up are currently unknown. Methods In this retrospective study, disease severity was assessed using the global CDR plus NACC FTLD. 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. Results 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, p < 0.001). Conclusions 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.Alberto BenussiNicholas J. AshtonThomas K. KarikariAntonella AlbericiClaudia SaracenoRoberta GhidoniLuisa BenussiHenrik ZetterbergKaj BlennowBarbara BorroniBMCarticleFrontotemporal dementiaSerum neurofilament lightProdromalMildProgressionConversionNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENAlzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Frontotemporal dementia Serum neurofilament light Prodromal Mild Progression Conversion Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Frontotemporal dementia Serum neurofilament light Prodromal Mild Progression Conversion Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Alberto Benussi Nicholas J. Ashton Thomas K. Karikari Antonella Alberici Claudia Saraceno Roberta Ghidoni Luisa Benussi Henrik Zetterberg Kaj Blennow Barbara Borroni Prodromal frontotemporal dementia: clinical features and predictors of progression
description	Abstract Background The prodromal phase of frontotemporal dementia (FTD) is still not well characterized, and conversion rates to dementia and predictors of progression at 1-year follow-up are currently unknown. Methods In this retrospective study, disease severity was assessed using the global CDR plus NACC FTLD. 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. Results 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, p < 0.001). Conclusions 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.
format	article
author	Alberto Benussi Nicholas J. Ashton Thomas K. Karikari Antonella Alberici Claudia Saraceno Roberta Ghidoni Luisa Benussi Henrik Zetterberg Kaj Blennow Barbara Borroni
author_facet	Alberto Benussi Nicholas J. Ashton Thomas K. Karikari Antonella Alberici Claudia Saraceno Roberta Ghidoni Luisa Benussi Henrik Zetterberg Kaj Blennow Barbara Borroni
author_sort	Alberto Benussi
title	Prodromal frontotemporal dementia: clinical features and predictors of progression
title_short	Prodromal frontotemporal dementia: clinical features and predictors of progression
title_full	Prodromal frontotemporal dementia: clinical features and predictors of progression
title_fullStr	Prodromal frontotemporal dementia: clinical features and predictors of progression
title_full_unstemmed	Prodromal frontotemporal dementia: clinical features and predictors of progression
title_sort	prodromal frontotemporal dementia: clinical features and predictors of progression
publisher	BMC
publishDate	2021
url	https://doaj.org/article/7434446daf234058909f16d1c6cc2be3
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Prodromal frontotemporal dementia: clinical features and predictors of progression

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