Frontotemporal dementia associated with granulin (GRN) mutations presents asymmetric brain atrophy. We applied a Minimum Spanning Tree plus an Efficiency Cost Optimization approach to cortical thickness data in order to test whether graph theory measures could identify global or local impairment of connectivity in the presymptomatic phase of pathology.We included 52 symptomatic GRN mutation carriers (SC), 161 presymptomatic GRN mutation carriers (PSC) and 341 non-carriers relatives from the Genetic Frontotemporal dementia research Initiative cohort. Global graph perturbation was selectively impaired in SC compared to non-carriers, with no changes in PSC. At the local level, only SC exhibited perturbation of frontotemporal nodes, but edge connectivity revealed a characteristic pattern of interhemispheric disconnection, involving homologous parietal regions, in PSC. Our results suggest that GRN-related frontotemporal dementia resembles a disconnection syndrome, with interhemispheric disconnection between parietal regions in presymptomatic phases that progresses to frontotemporal areas as symptoms emerge.

Structural brain splitting is a hallmark of Granulin-related Frontotemporal Dementia / Gazzina S., Grassi M., Premi E., Alberici A., Benussi A., Archetti S., Gasparotti R., Bocchetta M., Cash D.M., Todd E.G., Peakman G., Convery R.S., van Swieten J.C., Jiskoot L.C., Seelaar H., Sanchez-Valle R., Moreno F., Laforce R. Jr, Graff,C., Synofzik M., Galimberti,D., Rowe J.B., Masellis M., Tartaglia M.C., Finger E., Vandenberghe R., Mendonça A., Tagliavini F., Butler C.R., Santana I., Gerhard A., Ber I.L., Pasquier F., Ducharme S., Levin J., Danek A., Sorbi S., Otto M., Rohrer J.D., Borroni B., Afonso S., Almeida M.R., Andersson C., Antonell A., Arighi A., Balasa M., Barandiaran M., Bargalló N., Bartha R., Bender B., Bertoux M., Bertrand A., Bessi V., Black S., Borrego-Ecija, S., Bouzigues, A., Bras, J., Brice, A., Bruffaerts, R., Camuzat, A., Cañada, M., Cantoni, V., Caroppo, P., Castelo-Branco, M., Colliot, O., Cope, T., Deramecourt, V., Fede, G.D., Díez, A., Duro, D., Fenoglio C., Ferrari C., Ferreira, C.B., Fox, N., Freedman, M., Fumagalli, G., Funkiewiez, A., Gabilondo, A., Gauthier, S., Giaccone, G., Gorostidi, A., Greaves, C., Guerreiro, R., Heller, C., Hoegen, T., Indakoetxea, B., Jelic, V., Karnath, H.-O., Keren, R., Kuchcinski, G., Langheinrich, T., Lebouvier, T., Leitão, M.J., Lladó, A., Lombardi, G., Lombardi, J., Loosli, S., Maruta, C., Mead, S., Meeter, L., Miltenberger, G., van Minkelen, R., Mitchell, S., Moore, K., Nacmias B., Nelson, A., Nicholas, J., Öijerstedt, L., Olives, J., Ourselin, S., Panman, J., Papma, J.M., Pijnenburg, Y., Polito C., Prioni, S., Prix, C., Rademakers, R., Redaelli, V., Rinaldi, D., Rittman, T., Rogaeva, E., Rollin, A., Rosa-Neto, P., Rossi, G., Rossor, M., Santiago, B., Saracino, D., Sayah, S., Scarpini, E., Schönecker, S., Shafei, R., Shoesmith, C., Swift, I., Tábuas-Pereira, M., Tainta, M., Taipa, R., Tang-Wai, D., Thomas, D.L., Thompson, P., Thonberg, H., Timberlake, C., Tiraboschi, P., Van Damme, P., Vandenbulcke, M., Veldsman, M., Verdelho, A., Villanua, J., Warren, J., Wilke, C., Woollacott, I., Wlasich, E., Zetterberg, H., Zulaica, M., Genetic Frontotemporal dementia Initiative (GENFI). - In: NEUROBIOLOGY OF AGING. - ISSN 0197-4580. - ELETTRONICO. - 114:(2022), pp. 94-104. [10.1016/j.neurobiolaging.2022.02.009]

Structural brain splitting is a hallmark of Granulin-related Frontotemporal Dementia

Sorbi S.;Bessi V.;Ferrari C.;Lombardi G.;Nacmias B.;Polito C.;
2022

Abstract

Frontotemporal dementia associated with granulin (GRN) mutations presents asymmetric brain atrophy. We applied a Minimum Spanning Tree plus an Efficiency Cost Optimization approach to cortical thickness data in order to test whether graph theory measures could identify global or local impairment of connectivity in the presymptomatic phase of pathology.We included 52 symptomatic GRN mutation carriers (SC), 161 presymptomatic GRN mutation carriers (PSC) and 341 non-carriers relatives from the Genetic Frontotemporal dementia research Initiative cohort. Global graph perturbation was selectively impaired in SC compared to non-carriers, with no changes in PSC. At the local level, only SC exhibited perturbation of frontotemporal nodes, but edge connectivity revealed a characteristic pattern of interhemispheric disconnection, involving homologous parietal regions, in PSC. Our results suggest that GRN-related frontotemporal dementia resembles a disconnection syndrome, with interhemispheric disconnection between parietal regions in presymptomatic phases that progresses to frontotemporal areas as symptoms emerge.
114
94
104
Gazzina S., Grassi M., Premi E., Alberici A., Benussi A., Archetti S., Gasparotti R., Bocchetta M., Cash D.M., Todd E.G., Peakman G., Convery R.S., van Swieten J.C., Jiskoot L.C., Seelaar H., Sanchez-Valle R., Moreno F., Laforce R. Jr, Graff,C., Synofzik M., Galimberti,D., Rowe J.B., Masellis M., Tartaglia M.C., Finger E., Vandenberghe R., Mendonça A., Tagliavini F., Butler C.R., Santana I., Gerhard A., Ber I.L., Pasquier F., Ducharme S., Levin J., Danek A., Sorbi S., Otto M., Rohrer J.D., Borroni B., Afonso S., Almeida M.R., Andersson C., Antonell A., Arighi A., Balasa M., Barandiaran M., Bargalló N., Bartha R., Bender B., Bertoux M., Bertrand A., Bessi V., Black S., Borrego-Ecija, S., Bouzigues, A., Bras, J., Brice, A., Bruffaerts, R., Camuzat, A., Cañada, M., Cantoni, V., Caroppo, P., Castelo-Branco, M., Colliot, O., Cope, T., Deramecourt, V., Fede, G.D., Díez, A., Duro, D., Fenoglio C., Ferrari C., Ferreira, C.B., Fox, N., Freedman, M., Fumagalli, G., Funkiewiez, A., Gabilondo, A., Gauthier, S., Giaccone, G., Gorostidi, A., Greaves, C., Guerreiro, R., Heller, C., Hoegen, T., Indakoetxea, B., Jelic, V., Karnath, H.-O., Keren, R., Kuchcinski, G., Langheinrich, T., Lebouvier, T., Leitão, M.J., Lladó, A., Lombardi, G., Lombardi, J., Loosli, S., Maruta, C., Mead, S., Meeter, L., Miltenberger, G., van Minkelen, R., Mitchell, S., Moore, K., Nacmias B., Nelson, A., Nicholas, J., Öijerstedt, L., Olives, J., Ourselin, S., Panman, J., Papma, J.M., Pijnenburg, Y., Polito C., Prioni, S., Prix, C., Rademakers, R., Redaelli, V., Rinaldi, D., Rittman, T., Rogaeva, E., Rollin, A., Rosa-Neto, P., Rossi, G., Rossor, M., Santiago, B., Saracino, D., Sayah, S., Scarpini, E., Schönecker, S., Shafei, R., Shoesmith, C., Swift, I., Tábuas-Pereira, M., Tainta, M., Taipa, R., Tang-Wai, D., Thomas, D.L., Thompson, P., Thonberg, H., Timberlake, C., Tiraboschi, P., Van Damme, P., Vandenbulcke, M., Veldsman, M., Verdelho, A., Villanua, J., Warren, J., Wilke, C., Woollacott, I., Wlasich, E., Zetterberg, H., Zulaica, M., Genetic Frontotemporal dementia Initiative (GENFI)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1281799
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