Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

Tsvetanov, K.A.; Gazzina, S.; Jones, P.S.; van Swieten, J.; Borroni, B.; Sanchez-Valle, R.; Moreno, F.; Laforce, R.; Graff, C.; Synofzik, M.; Galimberti, D.; Masellis, M.; Tartaglia, M.C.; Finger, E.; Vandenberghe, R.; de Mendonca, A.; Tagliavini, F.; Santana, I.; Ducharme, S.; Butler, C.; Gerhard, A.; Danek, A.; Levin, J.; Otto, M.; Frisoni, G.; Ghidoni, R.; Sorbi, S.; Rohrer, J.D.; Rowe, J.B.; Afonso, S.; Almeida, M.R.; Anderl-Straub, S.; Andersson, C.; Antonell, A.; Archetti, S.; Arighi, A.; Balasa, M.; Barandiaran, M.; Bargallo, N.; Bartha, R.; Bender, B.; Benussi, L.; Bessi, V.; Binetti, G.; Black, S.; Bocchetta, M.; Borrego-Ecija, S.; Bras, J.; Bruffaerts, R.; Caroppo, P.; Cash, D.; Castelo-Branco, M.; Convery, R.; Cope, T.; Cosseddu, M.; de Arriba, M.; Di Fede, G.; Diaz, Z.; Moore, K.M.; Duro, D.; Fenoglio, C.; Ferrari, C.; Ferreira, C.; Ferreira, C.B.; Flanagan, T.; Fox, N.; Freedman, M.; Fumagalli, G.; Gabilondo, A.; Gasparotti, R.; Gauthier, S.; Gazzina, S.; Giaccone, G.; Gorostidi, A.; Greaves, C.; Guerreiro, R.; Heller, C.; Hoegen, T.; Indakoetxea, B.; Jelic, V.; Jiskoot, L.; Karnath, H.-.; Institutet, K.; Keren, R.; Langheinrich, T.; Leitao, M.J.; Llado, A.; Lombardi, G.; Loosli, S.; Maruta, C.; Mead, S.; Meeter, L.; Miltenberger, G.; van Minkelen, R.; Mitchell, S.; Nacmias, B.; Neason, M.; Nicholas, J.; Olives, J.; Padovani, A.; Panman, J.; Papma, J.; Piaceri, I.; Pievani, M.; Pijnenburg, Y.; Polito, C.; Premi, E.; Prioni, S.; Prix, C.; Rademakers, R.; Redaelli, V.; Rittman, T.; Rogaeva, E.; Rosa-Neto, P.; Rossi, G.; Rossor, M.; Santiago, B.; Scarpini, E.; Schonecker, S.; Semler, E.; Shafei, R.; Shoesmith, C.; Tabuas-Pereira, M.; Tainta, M.; Taipa, R.; Tang-Wai, D.; Thomas, D.L.; Thompson, P.; Thonberg, H.; Timberlake, C.; Tiraboschi, P.; Vandamme, P.; Vandenbulcke, M.; Veldsman, M.; Verdelho, A.; Villanua, J.; Warren, J.; Wilke, C.; Woollacott, I.; Wlasich, E.; Zetterberg, H.; Zulaica, M.

doi:10.1002/alz.12209

Introduction: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. Results: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. Discussion: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance. (Genetic FTD Initiative) GENFI (GENFI)

Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia / K.A. Tsvetanov, S. Gazzina, P.S. Jones, J. van Swieten, B. Borroni, R. Sanchez-Valle, F. Moreno, R. Laforce, C. Graff, M. Synofzik, D. Galimberti, M. Masellis, M.C. Tartaglia, E. Finger, R. Vandenberghe, A. de Mendonca, F. Tagliavini, I. Santana, S. Ducharme, C. Butler, A. Gerhard, A. Danek, J. Levin, M. Otto, G. Frisoni, R. Ghidoni, S. Sorbi, J.D. Rohrer, J.B. Rowe, S. Afonso, M.R. Almeida, S. Anderl-Straub, C. Andersson, A. Antonell, S. Archetti, A. Arighi, M. Balasa, M. Barandiaran, N. Bargallo, R. Bartha, B. Bender, L. Benussi, V. Bessi, G. Binetti, S. Black, M. Bocchetta, S. Borrego-Ecija, J. Bras, R. Bruffaerts, P. Caroppo, D. Cash, M. Castelo-Branco, R. Convery, T. Cope, M. Cosseddu, M. de Arriba, G. Di Fede, Z. Diaz, K.M. Moore, D. Duro, C. Fenoglio, C. Ferrari, C. Ferreira, C.B. Ferreira, T. Flanagan, N. Fox, M. Freedman, G. Fumagalli, A. Gabilondo, R. Gasparotti, S. Gauthier, S. Gazzina, G. Giaccone, A. Gorostidi, C. Greaves, R. Guerreiro, C. Heller, T. Hoegen, B. Indakoetxea, V. Jelic, L. Jiskoot, H.-. Karnath, K. Institutet, R. Keren, T. Langheinrich, M.J. Leitao, A. Llado, G. Lombardi, S. Loosli, C. Maruta, S. Mead, L. Meeter, G. Miltenberger, R. van Minkelen, S. Mitchell, B. Nacmias, M. Neason, J. Nicholas, J. Olives, A. Padovani, J. Panman, J. Papma, I. Piaceri, M. Pievani, Y. Pijnenburg, C. Polito, E. Premi, S. Prioni, C. Prix, R. Rademakers, V. Redaelli, T. Rittman, E. Rogaeva, P. Rosa-Neto, G. Rossi, M. Rossor, B. Santiago, E. Scarpini, S. Schonecker, E. Semler, R. Shafei, C. Shoesmith, M. Tabuas-Pereira, M. Tainta, R. Taipa, D. Tang-Wai, D.L. Thomas, P. Thompson, H. Thonberg, C. Timberlake, P. Tiraboschi, P. Vandamme, M. Vandenbulcke, M. Veldsman, A. Verdelho, J. Villanua, J. Warren, C. Wilke, I. Woollacott, E. Wlasich, H. Zetterberg, M. Zulaica. - In: ALZHEIMER'S & DEMENTIA. - ISSN 1552-5260. - 17:3(2021 Mar 21), pp. 500-514. [10.1002/alz.12209]

Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

Tsvetanov K. A.;Gazzina S.;Jones P. S.;van Swieten J.;Borroni B.;Sanchez-Valle R.;Moreno F.;Laforce R.;Graff C.;Synofzik M.;D. Galimberti^{Primo

Membro del Collaboration Group};Masellis M.;Tartaglia M. C.;Finger E.;Vandenberghe R.;de Mendonca A.;Tagliavini F.;Santana I.;Ducharme S.;Butler C.;Gerhard A.;Danek A.;Levin J.;Otto M.;Frisoni G.;Ghidoni R.;Sorbi S.;Rohrer J. D.;Rowe J. B.;Afonso S.;Almeida M. R.;Anderl-Straub S.;Andersson C.;Antonell A.;Archetti S.;Arighi A.;Balasa M.;Barandiaran M.;Bargallo N.;Bartha R.;Bender B.;Benussi L.;Bessi V.;Binetti G.;Black S.;Bocchetta M.;Borrego-Ecija S.;Bras J.;Bruffaerts R.;Caroppo P.;Cash D.;Castelo-Branco M.;Convery R.;Cope T.;Cosseddu M.;de Arriba M.;Di Fede G.;Diaz Z.;Moore K. M.;Duro D.;Fenoglio C.;Ferrari C.;Ferreira C.;Ferreira C. B.;Flanagan T.;Fox N.;Freedman M.;Fumagalli G.;Gabilondo A.;Gasparotti R.;Gauthier S.;Gazzina S.;Giaccone G.;Gorostidi A.;Greaves C.;Guerreiro R.;Heller C.;Hoegen T.;Indakoetxea B.;Jelic V.;Jiskoot L.;Karnath H. -O.;Institutet K.;Keren R.;Langheinrich T.;Leitao M. J.;Llado A.;Lombardi G.;Loosli S.;Maruta C.;Mead S.;Meeter L.;Miltenberger G.;van Minkelen R.;Mitchell S.;Nacmias B.;Neason M.;Nicholas J.;Olives J.;Padovani A.;Panman J.;Papma J.;Piaceri I.;Pievani M.;Pijnenburg Y.;Polito C.;Premi E.;Prioni S.;Prix C.;Rademakers R.;V. Redaelli^{Membro del Collaboration Group};Rittman T.;Rogaeva E.;Rosa-Neto P.;Rossi G.;Rossor M.;Santiago B.;E. Scarpini^{Membro del Collaboration Group};Schonecker S.;Semler E.;Shafei R.;Shoesmith C.;Tabuas-Pereira M.;Tainta M.;Taipa R.;Tang-Wai D.;Thomas D. L.;Thompson P.;Thonberg H.;Timberlake C.;Tiraboschi P.;Vandamme P.;Vandenbulcke M.;Veldsman M.;Verdelho A.;Villanua J.;Warren J.;Wilke C.;Woollacott I.;Wlasich E.;Zetterberg H.;Zulaica M.

2021

Abstract

Introduction: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. Results: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. Discussion: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance. (Genetic FTD Initiative) GENFI (GENFI)

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	Parole chiave
	
				frontotemporal dementia (FTD); functional magnetic resonance imaging (fMRI); network connectivity; presymptomatic; Atrophy; Brain; C9orf72 Protein; Cognition; Frontotemporal Dementia; Humans; Internationality; Magnetic Resonance Imaging; Middle Aged; Mutation; tau Proteins; Prodromal Symptoms
			
	Settori scientifico-disciplinari dell'articolo (sola visualizzazione)
	
				Settore BIO/13 - Biologia Applicata
Settore MED/26 - Neurologia
			
	Data di pubblicazione
	
				21-mar-2021
			
	Rivista in ANCE
	
				ALZHEIMER'S & DEMENTIA
			
	DOI
	
				https://dx.doi.org/10.1002/alz.12209
			
	Tipologia
	
				Article (author)
			
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				01 - Articolo su periodico

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