Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations

Bouzigues, A.; Russell, L. L.; Peakman, G.; Bocchetta, M.; Greaves, C. V.; Convery, R. S.; Todd, E.; Rowe, J. B.; Borroni, B.; Galimberti, D.; Tiraboschi, P.; Masellis, M.; Tartaglia, M. C.; Finger, E.; van Swieten, J. C.; Seelaar, H.; Jiskoot, L.; Sorbi, S.; Butler, C. R.; Graff, C.; Gerhard, A.; Langheinrich, T.; Laforce, R.; Sanchez-Valle, R.; de Mendonça, A.; Moreno, F.; Synofzik, M.; Vandenberghe, R.; Ducharme, S.; Le Ber, I.; Levin, J.; Danek, A.; Otto, M.; Pasquier, F.; Santana, I.; Rohrer, J. D.; Esteve, A. S.; Nelson, A.; Heller, C.; Greaves, C. V.; Cash, D.; Thomas, D. L.; Benotmane, H.; Zetterberg, H.; Swift, I. J.; Nicholas, J.; Samra, K.; Russell, L. L.; Shafei, R.; Convery, R. S.; Timberlake, C.; Cope, T.; Rittman, T.; Benussi, A.; Premi, E.; Gasparotti, R.; Archetti, S.; Gazzina, S.; Cantoni, V.; Arighi, A.; Fenoglio, C.; Scarpini, E.; Fumagalli, G.; Borracci, V.; Rossi, G.; Giaccone, G.; Caroppo, P.; Prioni, S.; Redaelli, V.; Tang-Wai, D.; Rogaeva, E.; Castelo-Branco, M.; Keren, R.; Black, S.; Mitchell, S.; Shoesmith, C.; Bartha, R.; Rademakers, R.; Poos, J.; Papma, J. M.; Giannini, L.; Minkelen, R.; Pijnenburg, Y.; Nacmias, B.; Ferrari, C.; Polito, C.; Lombardi, G.; Bessi, V.; Veldsman, M.; Andersson, C.; Thonberg, H.; Öijerstedt, L.; Jelic, V.; Thompson, P.; Lladó, A.; Antonell, A.; Olives, J.; Balasa, M.; Bargalló, N.; Borrego-Ecija, S.; Verdelho, A.; Maruta, C.; Ferreira, C. B.; Miltenberger, G.; do Couto, F. S.; Gabilondo, A.; Gorostidi, A.; Villanua, J.; Cañada, M.; Tainta, M.; Zulaica, M.; Barandiaran, M.; Alves, P.; Bender, B.; Wilke, C.; Graf, L.; Vogels, A.; Vandenbulcke, M.; Van Damme, P.; Bruffaerts, R.; Poesen, K.; Rosa-Neto, P.; Gauthier, S.; Camuzat, A.; Brice, A.; Bertrand, A.; Funkiewiez, A.; Rinaldi, D.; Saracino, D.; Colliot, O.; Sayah, S.; Prix, C.; Wlasich, E.; Wagemann, O.; Loosli, S.; Schönecker, S.; Hoegen, T.; Lombardi, J.; Anderl-Straub, S.; Rollin, A.; Kuchcinski, G.; Bertoux, M.; Lebouvier, T.; Deramecourt, V.; Santiago, B.; Duro, D.; Leitão, M. J.; Almeida, M. R.; Tábuas-Pereira, M.; Afonso, S.; Engel, A.; Polyakova, M.; The Genetic FTD Initiative,; Genf,

doi:10.1007/s00415-022-11068-0

Introduction A third of frontotemporal dementia (FTD) is caused by an autosomal-dominant genetic mutation in one of three genes: microtubule-associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72) and progranulin (GRN). Prior studies of prodromal FTD have identified impaired executive function and social cognition early in the disease but few have studied naming in detail. Methods We investigated performance on the Boston Naming Test (BNT) in the GENetic Frontotemporal dementia Initiative cohort of 499 mutation carriers and 248 mutation-negative controls divided across three genetic groups: C9orf72, MAPT and GRN. Mutation carriers were further divided into 3 groups according to their global CDR plus NACC FTLD score: 0 (asymptomatic), 0.5 (prodromal) and 1 + (fully symptomatic). Groups were compared using a bootstrapped linear regression model, adjusting for age, sex, language and education. Finally, we identified neural correlates of anomia within carriers of each genetic group using a voxel-based morphometry analysis. Results All symptomatic groups performed worse on the BNT than controls with the MAPT symptomatic group scoring the worst. Furthermore, MAPT asymptomatic and prodromal groups performed significantly worse than controls. Correlates of anomia in MAPT mutation carriers included bilateral anterior temporal lobe regions and the anterior insula. Similar bilateral anterior temporal lobe involvement was seen in C9orf72 mutation carriers as well as more widespread left frontal atrophy. In GRN mutation carriers, neural correlates were limited to the left hemisphere, and involved frontal, temporal, insula and striatal regions. Conclusion This study suggests the development of early anomia in MAPT mutation carriers, likely to be associated with impaired semantic knowledge. Clinical trials focused on the prodromal period within individuals with MAPT mutations should use language tasks, such as the BNT for patient stratification and as outcome measures.

Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations / Bouzigues A., Russell L.L., Peakman G., Bocchetta M., Greaves C.V., Convery R.S., Todd E., Rowe J.B., Borroni B., Galimberti D., Tiraboschi P., Masellis M., Tartaglia M.C., Finger E., van Swieten J.C., Seelaar H., Jiskoot L., Sorbi S., Butler C.R., Graff C., Gerhard A., Langheinrich T., Laforce R., Sanchez-Valle R., de Mendonça A., Moreno F., Synofzik M., Vandenberghe R., Ducharme S., Le Ber I., Levin J., Danek A., Otto M., Pasquier F., Santana I., Rohrer J.D., Esteve A.S., Nelson A., Heller C., Greaves C.V., Cash D., Thomas D.L., Benotmane H., Zetterberg H., Swift I.J., Nicholas J., Samra K., Russell L.L., Shafei R., Convery R.S., Timberlake C., Cope T., Rittman T., Benussi A., Premi E., Gasparotti R., Archetti S., Gazzina S., Cantoni V., Arighi A., Fenoglio C., Scarpini E., Fumagalli G., Borracci V., Rossi G., Giaccone G., Caroppo P., Prioni S., Redaelli V., Tang-Wai D., Rogaeva E., Castelo-Branco M., Keren R., Black S., Mitchell S., Shoesmith C., Bartha R., Rademakers R., Poos J., Papma J.M., Giannini L., Minkelen R., Pijnenburg Y., Nacmias B., Ferrari C., Polito C., Lombardi G., Bessi V., Veldsman M., Andersson C., Thonberg H., Öijerstedt L., Jelic V., Thompson P., Lladó A., Antonell A., Olives J., Balasa M., Bargalló N., Borrego-Ecija S., Verdelho A., Maruta C., Ferreira C.B., Miltenberger G., do Couto F.S., Gabilondo A., Gorostidi A., Villanua J., Cañada M., Tainta M., Zulaica M., Barandiaran M., Alves P., Bender B., Wilke C., Graf L., Vogels A., Vandenbulcke M., Van Damme P., Bruffaerts R., Poesen K., Rosa-Neto P., Gauthier S., Camuzat A., Brice A., Bertrand A., Funkiewiez A., Rinaldi D., Saracino D., Colliot O., Sayah S., Prix C., Wlasich E., Wagemann O., Loosli S., Schönecker S., Hoegen T., Lombardi J., Anderl-Straub S., Rollin A., Kuchcinski G., Bertoux M., Lebouvier T., Deramecourt V., Santiago B., Duro D., Leitão M.J., Almeida M.R., Tábuas-Pereira M., Afonso S., Engel A., Polyakova M., The Genetic FTD Initiative, GENF. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - ELETTRONICO. - 269:(2022), pp. 4322-4332. [10.1007/s00415-022-11068-0]