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51. Design and implementation of a Stroke Rehabilitation Registry for the systematic assessment of processes and outcomes and the development of data-driven prediction models: The STRATEGY study protocol

Author: Chiavilli, Marco, primary, Campagnini, Silvia, additional, Baretta, Teresa, additional, Castagnoli, Chiara, additional, Paperini, Anita, additional, Politi, Angela Maria, additional, Pellicciari, Leonardo, additional, Baccini, Marco, additional, Basagni, Benedetta, additional, Marignani, Sara, additional, Bardi, Donata, additional, Sodero, Alessandro, additional, Lombardi, Gemma, additional, Guolo, Erika, additional, Navarro, Jorge Solano, additional, Galeri, Silvia, additional, Montesano, Angelo, additional, Falco, Lucia, additional, Rovaris, Marco Giuseppe, additional, Carrozza, Maria Chiara, additional, Macchi, Claudio, additional, Mannini, Andrea, additional, and Cecchi, Francesca, additional
Published: 2022
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52. Comparison of arterial spin labeling registration strategies in the multi‐center GENetic frontotemporal dementia initiative (GENFI)

Author: Mutsaerts, Henri J.M.M., Petr, Jan, Thomas, David L., De Vita, Enrico, Cash, David M., van Osch, Matthias J.P., Golay, Xavier, Groot, Paul F.C., Ourselin, Sebastien, van Swieten, John, Laforce, Robert, Jr, Tagliavini, Fabrizio, Borroni, Barbara, Galimberti, Daniela, Rowe, James B., Graff, Caroline, Pizzini, Francesca B., Finger, Elizabeth, Sorbi, Sandro, Castelo Branco, Miguel, Rohrer, Jonathan D., Masellis, Mario, MacIntosh, Bradley J., Rossor, Martin, Fox, Nick, Warren, Jason, Bocchetta, Martina, Dick, Katrina, Pievani, Michela, Ghidoni, Roberta, Benussi, Luisa, Padovani, Alessandro, Cosseddu, Maura, Mendonça, Alexandre, Frisoni, Giovanni, Premi, Enrico, Archetti, Silvana, Scarpini, Elio, Fumagalli, Giorgio, Arighi, Andrea, Fenoglio, Chiara, Prioni, Sara, Redaelii, Veronica, Grisoli, Marina, Tiraboschi, Pietro, Black, Sandra, Rogaeva, Ekaterina, Freedman, Morris, Tartaglia, Maria Carmela, Tang‐Wai, David, Keren, Ron, Panman, Jessica, Meeter, Lieke, Jiskoot, Lize, van Minkelen, Rick, Lombardi, Gemma, Polito, Cristina, Nacmias, Benedetta, Jelic, Vesna, Andersson, Christin, Öijerstedt, Linn, Fallström, Marie, Thonberg, Hakan, Verdelho, Ana, and Maruta, Carolina
Published: 2018
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53. Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study

Author: van der Ende, Emma L, Heller, Carolin, Papma, Janne M, Maruta, Carolina, Mead, Simon, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Meeter, Lieke H, Ourselin, Sebastien, Padovani, Alessandro, Peakman, Georgia, Pievani, Michela, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Dopper, Elise G P, Rittman, Tim, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rossi, Giacomina, Rosser, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Bocchetta, Martina, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Cash, David, Zulaica, Miren, Graff, Caroline, Synofzik, Matthis, Moreno, Fermin, Finger, Elizabeth, Sogorb-Esteve, Aitana, Sanchez-Valle, Raquel, Vandenberghe, Rik, Laforce, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B, Butler, Chris, Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Swift, Imogen J, Levin, Johannes, Pijnenburg, Yolande A L, Otto, Markus, Borroni, Barbara, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Galimberti, Daniela, Sorbi, Sandro, Zetterberg, Henrik, McFall, David, Huang, Eric, van Swieten, John C, Rohrer, Jonathan D, Seelaar, Harro, Initiative, Genetic Frontotemporal Dementia, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Bessi, Valentina, Bouzigues, Arabella, Binetti, Giuliano, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Poos, Jackie M, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Jiskoot, Lize C, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Panman, Jessica L, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Langheinrich, Tobias, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Apollo - University of Cambridge Repository, Levin, Johannes [0000-0001-5092-4306], Repositório da Universidade de Lisboa, Genetic Frontotemporal Dementia Initiative (GENFI), Neurology, Erasmus MC other, Clinical Psychology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Biomarker, Complement, Frontotemporal dementia, Neuroinflammation, Immunology, Medizin, diagnostic imaging [Frontotemporal Dementia], Cohort Studies, Cellular and Molecular Neuroscience, CEREBROSPINAL-FLUID, Pick Disease of the Brain, Settore BIO/13 - Biologia Applicata, CRITERIA, Humans, ddc:610, C3, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Biology, Science & Technology, C9orf72 Protein, General Neuroscience, Complement C1q, Research, Neurosciences, Biomarkers, Complement System Proteins, Frontotemporal Dementia, ALZHEIMERS-DISEASE, Neurology, CHAIN, Neurosciences & Neurology, Human medicine, genetics [Complement System Proteins], Life Sciences & Biomedicine
Abstract: Funder: The Bluefield Project, Funder: UK Dementia Research Institute; doi: http://dx.doi.org/10.13039/501100017510, Funder: Alzheimer's Society; doi: http://dx.doi.org/10.13039/501100000320, Funder: schorling foundation, Funder: Swedish brain foundation, Funder: swedish alzheimer foundation, Funder: Stockholm Council ALF, Funder: Demensfonden; doi: http://dx.doi.org/10.13039/501100021594, Funder: Gun och Bertil Stohnes Stiftelse; doi: http://dx.doi.org/10.13039/100009673, Funder: Stiftelsen för Gamla Tjänarinnor; doi: http://dx.doi.org/10.13039/100010815, Funder: Karolinska Institutet; doi: http://dx.doi.org/10.13039/501100004047, Funder: Stratneuro, Funder: Mady Browaeys Fonds, Funder: Knut och Alice Wallenbergs Stiftelse; doi: http://dx.doi.org/10.13039/501100004063, BACKGROUND: Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers. METHODS: We measured the complement proteins C1q and C3b in CSF by ELISAs in 224 presymptomatic and symptomatic GRN, C9orf72 or MAPT mutation carriers and non-carriers participating in the Genetic Frontotemporal Dementia Initiative (GENFI), a multicentre cohort study. Next, we used multiplex immunoassays to measure a panel of 14 complement proteins in plasma of 431 GENFI participants. We correlated complement protein levels with corresponding clinical and neuroimaging data, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). RESULTS: CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers. In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers. In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP. In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores. CONCLUSIONS: Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD. Intriguingly, correlations with several disease measures in presymptomatic carriers suggest that complement protein levels might increase before symptom onset. Although the overlap between groups precludes their use as diagnostic markers, further research is needed to determine their potential to monitor dysregulation of the complement system in FTD.
Published: 2022
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54. Rethinking on the concept of biomarkers in preclinical Alzheimer’s disease

Author: Berti, Valentina, Polito, Cristina, Lombardi, Gemma, Ferrari, Camilla, Sorbi, Sandro, and Pupi, Alberto
Published: 2016
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55. Assessing Relationships between Physically Demanding Work and Late-Life Disability in Italian Nonagenarian Women Living in a Rural Area

Author: Lombardi, Gemma, primary, Pancani, Silvia, additional, Lorenzini, Francesca, additional, Vannetti, Federica, additional, Pasquini, Guido, additional, Frandi, Roberta, additional, Turcan, Nona, additional, Razzolini, Lorenzo, additional, Molino Lova, Raffaello, additional, Cecchi, Francesca, additional, and Macchi, Claudio, additional
Published: 2022
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56. Corrigendum to “Dissemination in time and space in presymptomatic granulin mutation carriers: A spatial chronnectome study” [Neurobiology of Aging Volume 108, December 2021, Pages 155–167]

Author: Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bouzigues, Arabella, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gauthier, Serge, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Lombardi, Jolina, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Panman, Jessica, Papma, Janne M., Pijnenburg, Yolande, Polito, Cristina, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Premi, Enrico, Giunta, Marcello, Iraji, Armin, Rachakonda, Srinivas, Calhoun, VinceD., Gazzina, Stefano, Benussi, Alberto, Gasparotti, Roberto, Archetti, Silvana, Bocchetta, Martina, Cash, Dave, Todd, Emily, Peakman, Georgia, Convery, Rhian, van Swieten, John C., Jiskoot, Lize, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, JamesB., Masellis, Mario, Tartaglia, Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Gerhard, Alexander, Ber, Isabelle Le, Pasquier, Florence, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Sorbi, Sandro, Otto, Markus, Rohrer, Jonathan D., and Borroni, Barbara
Published: 2022
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57. The CBI-R detects early behavioural impairment in genetic frontotemporal dementia

Author: Nelson, Annabel, Russell, Lucy L., Moreno, Fermin, Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Sanchez-Valle, Raquel, Papma, Janne M., Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Laforce, Robert, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Graff, Caroline, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L., Masellis, Mario, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Tartaglia, Maria Carmela, Warren, Jason, Wilke, Carlo, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Peakman, Georgia, Galimberti, Daniela, Vandenberghe, Rik, Mendonça, Alexandre, Butler, Chris R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Convery, Rhian S., Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Bouzigues, Arabella, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Greaves, Caroline V., Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Cash, David M., Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Swieten, John C., Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans Otto, Keren, Ron, Kuchcinski, Gregory, Jiskoot, Lize, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Neurology, Clinical Genetics, Genetic FTD Initiative (GENFI), Russell, Lucy L [0000-0001-5023-5893], Bocchetta, Martina [0000-0003-1814-5024], Sanchez-Valle, Raquel [0000-0001-7750-896X], Laforce, Robert [0000-0002-2031-490X], Borroni, Barbara [0000-0001-9340-9814], Finger, Elizabeth [0000-0003-4461-7427], Synofzik, Matthis [0000-0002-2280-7273], Galimberti, Daniela [0000-0002-9284-5953], Ducharme, Simon [0000-0002-7309-1113], Le Ber, Isabelle [0000-0002-2508-5181], Rohrer, Jonathan D [0000-0002-6155-8417], Apollo - University of Cambridge Repository, and Amsterdam Neuroscience - Neurodegeneration
Subjects: FUNCTIONAL BRAIN CONNECTIVITY, Clinical Neurology, Medizin, PROGRESSION, tau Proteins, C9orf72 Protein, Humans, Progranulins, Frontotemporal Dementia, Pick Disease of the Brain, ATROPHY, genetics [Progranulins], diagnosis [Frontotemporal Dementia], mental disorders, ddc:610, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Research Articles, Science & Technology, HEXANUCLEOTIDE REPEAT, MUTATIONS, General Neuroscience, TEMPORAL VARIANT, Neurosciences, genetics [tau Proteins], Neurosciences & Neurology, Neurology (clinical), TAU, FTLD, Life Sciences & Biomedicine, Research Article
Abstract: Funder: UK Dementia Research Institute, Funder: NIHR UCL/H Biomedical Research Centre, Funder: The Wolfson Foundation, Funder: Brain Research UK; Id: http://dx.doi.org/10.13039/100013790, Funder: Alzheimer’s Research UK; Id: http://dx.doi.org/10.13039/501100002283, INTRODUCTION: Behavioural dysfunction is a key feature of genetic frontotemporal dementia (FTD) but validated clinical scales measuring behaviour are lacking at present. METHODS: We assessed behaviour using the revised version of the Cambridge Behavioural Inventory (CBI-R) in 733 participants from the Genetic FTD Initiative study: 466 mutation carriers (195 C9orf72, 76 MAPT, 195 GRN) and 267 non-mutation carriers (controls). All mutation carriers were stratified according to their global CDR plus NACC FTLD score into three groups: asymptomatic (CDR = 0), prodromal (CDR = 0.5) and symptomatic (CDR = 1+). Mixed-effects models adjusted for age, education, sex and family clustering were used to compare between the groups. Neuroanatomical correlates of the individual domains were assessed within each genetic group. RESULTS: CBI-R total scores were significantly higher in all CDR 1+ mutation carrier groups compared with controls [C9orf72 mean 70.5 (standard deviation 27.8), GRN 56.2 (33.5), MAPT 62.1 (36.9)] as well as their respective CDR 0.5 groups [C9orf72 13.5 (14.4), GRN 13.3 (13.5), MAPT 9.4 (10.4)] and CDR 0 groups [C9orf72 6.0 (7.9), GRN 3.6 (6.0), MAPT 8.5 (13.3)]. The C9orf72 and GRN 0.5 groups scored significantly higher than the controls. The greatest impairment was seen in the Motivation domain for the C9orf72 and GRN symptomatic groups, whilst in the symptomatic MAPTgroup, the highest-scoring domains were Stereotypic and Motor Behaviours and Memory and Orientation. Neural correlates of each CBI-R domain largely overlapped across the different mutation carrier groups. CONCLUSIONS: The CBI-R detects early behavioural change in genetic FTD, suggesting that it could be a useful measure within future clinical trials.
Published: 2022
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58. Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Author: Wilson, Katherine M, Katona, Eszter, Knowles, Kathryn, Lebouvier, Thibaud, Leitão, Maria João, Levin, Johannes, Lladó, Albert, Lombardi, Gemma, Lombardi, Jolina, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Miltenberger, Gabriel, Patil, Saurabh, Minkelen, Rick van, Mitchell, Sara, Moreno, Fermin, Nacmias, Benedetta, Nelson, Annabel, Nicholas, Jennifer, Öijerstedt, Linn, Papma, Janne M, Pasquier, Florence, Peakman, Georgia, Mohapatra, Susovan, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Liu, Yuanjing, Rossi, Giacomina, Rossor, Martin, Santana, Isabel, Santiago, Beatriz, Saracino, Dario, Scarpini, Elio, Schönecker, Sonja, Shafei, Rachelle, Shoesmith, Christen, Sorbi, Sandro, Goyal, Jaya, Tábuas-Pereira, Miguel, Tagliavini, Fabrizio, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Sanchez-Valle, Raquel, Damme, Philip Van, Vandenbulcke, Mathieu, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Wlasich, Elisabeth, Zulaica, Miren, Laforce, Robert Jr, Synofzik, Matthis, Rowe, James B, Finger, Elizabeth, Glaria, Idoia, Vandenberghe, Rik, Butler, Christopher R, Gerhard, Alexander, Van Swieten, John C, Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, de Mendonça, Alexandre, Masellis, Mario, Tartaglia, M Carmela, Carcolé, Mireia, Otto, Markus, Graff, Caroline, Ducharme, Simon, Schott, Jonathan M, Malaspina, Andrea, Zetterberg, Henrik, Boyanapalli, Ramakrishna, Rohrer, Jonathan D, Isaacs, Adrian M, Initiative, Genetic FTD, Swift, Imogen J, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Sogorb-Esteve, Aitana, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Heller, Carolin, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Convery, Rhian, Bouzigues, Arabella, Cope, Thomas, Danek, Adrian, Deramecourt, Vincent, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Heslegrave, Amanda J, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Graf, Lisa, Keshavan, Ashvini, Greaves, Caroline, Guerreiro, Rita, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Ber, Isabelle Le, and Neurology
Subjects: Frontotemporal dementia, motor disease, Biomarkers, C9orf72 Protein, DNA Repeat Expansion, Humans, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, C9ORF72 EXPANSION, PROTEINS, SENSE, Medizin, diagnosis [Amyotrophic Lateral Sclerosis], genetics [DNA Repeat Expansion], Clinical Neurology, FRONTOTEMPORAL DEMENTIA, MOTOR NEURON DISEASE, DIAGNOSIS, TOXICITY, diagnosis [Frontotemporal Dementia], SDG 3 - Good Health and Well-being, ddc:150, Settore BIO/13 - Biologia Applicata, CRITERIA, ddc:610, Motor neuron disease, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Frontotemporale Demenz, Psychiatry, Science & Technology, HEXANUCLEOTIDE REPEAT, DDC 150 / Psychology, ANTISENSE TRANSCRIPTS, Myatrophische Lateralsklerose, Biomarker, Motoneuron, genetics [Amyotrophic Lateral Sclerosis], Psychiatry and Mental health, Cerebrospinal fluid, cerebrospinal fluid [Biomarkers], RNA FOCI, metabolism [Frontotemporal Dementia], cerebrospinal fluid [Amyotrophic Lateral Sclerosis], Surgery, Neurosciences & Neurology, Neurology (clinical), ALS, Life Sciences & Biomedicine, DDC 610 / Medicine & health
Abstract: ObjectiveA GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay.MethodsWe used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS.Results and conclusionsWe show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze–thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts., publishedVersion
Published: 2022
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59. Progranulin plasma levels predict the presence of GRN mutations in asymptomatic subjects and do not correlate with brain atrophy: results from the GENFI study

Author: Andersson, Christin, Archetti, Silvana, Arighi, Andrea, Benussi, Luisa, Binetti, Giuliano, Black, Sandra, Cash, David, Cosseddu, Maura, Dick, Katrina M., Fallström, Marie, Ferreira, Carlos, Finger, Elizabeth, Fox, Nick, Freedman, Morris, Frisoni, Giovanni, Gazzina, Stefano, Ghidoni, Roberta, Grisoli, Marina, Jelic, Vesna, Jiskoot, Lize, Keren, Ron, Laforce, Robert, Lombardi, Gemma, Maruta, Carolina, Mead, Simon, Meeter, Lieke, van Minkelen, Rick, Nacmias, Benedetta, Öijerstedt, Linn, Ourselin, Sebastien, Panman, Jessica, Pievani, Michela, Polito, Cristina, Prioni, Sara, Rademakers, Rosa, Redaelli, Veronica, Rogaeva, Ekaterina, Rossi, Giacomina, Besta, Carlo, Rossor, Martin, Rowe, James, Sorbi, Sandro, Tang-Wai, David, Thomas, David L., Thonberg, Hakan, Tiraboschi, Pietro, Verdelho, Ana, Warren, Jason, Galimberti, Daniela, Fumagalli, Giorgio G., Fenoglio, Chiara, Cioffi, Sara M.G., Serpente, Maria, Borroni, Barbara, Padovani, Alessandro, Tagliavini, Fabrizio, Masellis, Mario, Tartaglia, Maria Carmela, van Swieten, John, Graff, Caroline, de Mendonça, Alexandre, Bocchetta, Martina, Rohrer, Jonathan D., and Scarpini, Elio
Published: 2018
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60. Structural brain splitting is a hallmark of Granulin-related frontotemporal dementia

Author: Gazzina, Stefano, primary, Grassi, Mario, additional, Premi, Enrico, additional, Alberici, Antonella, additional, Benussi, Alberto, additional, Archetti, Silvana, additional, Gasparotti, Roberto, additional, Bocchetta, Martina, additional, Cash, David M., additional, Todd, Emily G., additional, Peakman, Georgia, additional, Convery, Rhian S., additional, van Swieten, John C., additional, Jiskoot, Lize C., additional, Seelaar, Harro, additional, Sanchez-Valle, Raquel, additional, Moreno, Fermin, additional, Laforce, Robert, additional, Graff, Caroline, additional, Synofzik, Matthis, additional, Galimberti, Daniela, additional, Rowe, James B., additional, Masellis, Mario, additional, Tartaglia, Maria Carmela, additional, Finger, Elizabeth, additional, Vandenberghe, Rik, additional, de Mendonça, Alexandre, additional, Tagliavini, Fabrizio, additional, Butler, Chris R., additional, Santana, Isabel, additional, Gerhard, Alexander, additional, Ber, Isabelle Le, additional, Pasquier, Florence, additional, Ducharme, Simon, additional, Levin, Johannes, additional, Danek, Adrian, additional, Sorbi, Sandro, additional, Otto, Markus, additional, Rohrer, Jonathan D., additional, Borroni, Barbara, additional, Afonso, Sónia, additional, Almeida, Maria Rosario, additional, Andersson, Christin, additional, Antonell, Anna, additional, Arighi, Andrea, additional, Balasa, Mircea, additional, Barandiaran, Myriam, additional, Bargalló, Nuria, additional, Bartha, Robart, additional, Bender, Benjamin, additional, Bertoux, Maxime, additional, Bertrand, Anne, additional, Bessi, Valentina, additional, Black, Sandra, additional, Borrego-Ecija, Sergi, additional, Bouzigues, Arabella, additional, Bras, Jose, additional, Brice, Alexis, additional, Bruffaerts, Rose, additional, Camuzat, Agnès, additional, Cañada, Marta, additional, Cantoni, Valentina, additional, Caroppo, Paola, additional, Castelo-Branco, Miguel, additional, Colliot, Olivier, additional, Cope, Thomas, additional, Deramecourt, Vincent, additional, Fede, Giuseppe Di, additional, Díez, Alina, additional, Duro, Diana, additional, Fenoglio, Chiara, additional, Ferrari, Camilla, additional, Ferreira, Catarina B., additional, Fox, Nick, additional, Freedman, Morris, additional, Fumagalli, Giorgio, additional, Funkiewiez, Aurélie, additional, Gabilondo, Alazne, additional, Gauthier, Serge, additional, Giaccone, Giorgio, additional, Gorostidi, Ana, additional, Greaves, Caroline, additional, Guerreiro, Rita, additional, Heller, Carolin, additional, Hoegen, Tobias, additional, Indakoetxea, Begoña, additional, Jelic, Vesna, additional, Karnath, Hans-Otto, additional, Keren, Ron, additional, Kuchcinski, Gregory, additional, Langheinrich, Tobias, additional, Lebouvier, Thibaud, additional, Leitão, Maria João, additional, Lladó, Albert, additional, Lombardi, Gemma, additional, Lombardi, Jolina, additional, Loosli, Sandra, additional, Maruta, Carolina, additional, Mead, Simon, additional, Meeter, Lieke, additional, Miltenberger, Gabriel, additional, van Minkelen, Rick, additional, Mitchell, Sara, additional, Moore, Katrina, additional, Nacmias, Benedetta, additional, Nelson, Annabel, additional, Nicholas, Jennifer, additional, Öijerstedt, Linn, additional, Olives, Jaume, additional, Ourselin, Sebastien, additional, Panman, Jessica, additional, Papma, Janne M., additional, Pijnenburg, Yolande, additional, Polito, Cristina, additional, Prioni, Sara, additional, Prix, Catharina, additional, Rademakers, Rosa, additional, Redaelli, Veronica, additional, Rinaldi, Daisy, additional, Rittman, Tim, additional, Rogaeva, Ekaterina, additional, Rollin, Adeline, additional, Rosa-Neto, Pedro, additional, Rossi, Giacomina, additional, Rossor, Martin, additional, Santiago, Beatriz, additional, Saracino, Dario, additional, Sayah, Sabrina, additional, Scarpini, Elio, additional, Schönecker, Sonja, additional, Shafei, Rachelle, additional, Shoesmith, Christen, additional, Swift, Imogen, additional, Tábuas-Pereira, Miguel, additional, Tainta, Mikel, additional, Taipa, Ricardo, additional, Tang-Wai, David, additional, Thomas, David L, additional, Thompson, Paul, additional, Thonberg, Hakan, additional, Timberlake, Carolyn, additional, Tiraboschi, Pietro, additional, Van Damme, Philip, additional, Vandenbulcke, Mathieu, additional, Veldsman, Michele, additional, Verdelho, Ana, additional, Villanua, Jorge, additional, Warren, Jason, additional, Wilke, Carlo, additional, Woollacott, Ione, additional, Wlasich, Elisabeth, additional, Zetterberg, Henrik, additional, and Zulaica, Miren, additional
Published: 2022
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61. Predictors of Mortality in 433 Nonagenarians Inside the Mugello Study: A 10 Years Follow-Up Study

Author: Pancani, Silvia, primary, Lombardi, Gemma, additional, Sofi, Francesco, additional, Gori, Anna Maria, additional, Boni, Roberta, additional, Castagnoli, Chiara, additional, Paperini, Anita, additional, Pasquini, Guido, additional, Vannetti, Federica, additional, Molino Lova, Raffaello, additional, Macchi, Claudio, additional, and Cecchi, Francesca, additional
Published: 2022
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62. Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia

Author: Heller, Carolin, Foiani, Martha S, Shafei, Rachelle, Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Fede, Giuseppe Di, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Van Swieten, John C, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Moreno, Fermin, Veldsman, Michele, Flanagan, Toby, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Semler, Elisa, Anderl-Straub, Sarah, Benussi, Luisa, Sanchez-Valle, Raquel, Binetti, Giuliano, Ghidoni, Roberta, Pievani, Michela, Lombardi, Gemma, Nacmias, Benedetta, Ferrari, Camilla, Bessi, Valentina, Borroni, Barbara, Laforce, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Moore, Katrina, Rowe, James B, Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonca, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Christopher R, Gerhard, Alex, Convery, Rhian, Levin, Johannes, Danek, Adrian, Frisoni, Giovanni, Sorbi, Sandro, Otto, Markus, Heslegrave, Amanda J, Zetterberg, Henrik, Rohrer, Jonathan D, GENFI, Rossor, Martin N, Bocchetta, Martina, Warren, Jason D, Fox, Nick C, Guerreiro, Rita, Bras, Jose, Nicholas, Jennifer, Mead, Simon, Jiskoot, Lize, Meeter, Lieke, Panman, Jessica, Papma, Janne, Neason, Mollie, Minkelen, Rick van, Pijnenburg, Yolanda, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Arriba, Maria de, Gorostidi, Ana, Zulaica, Miren, Villanua, Jorge, Cash, David M, Diaz, Zigor, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargallo, Nuria, Premi, Enrico, Cosseddu, Maura, Gazzina, Stefano, Thomas, David, Padovani, Alessandro, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Öijerstedt, Linn, Greaves, Caroline V, Andersson, Christin, Jelic, Vesna, Thonberg, Hakan, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Woollacott, Ione Oc, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans-Otto, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B, Amsterdam Neuroscience - Neurodegeneration, Neurology, Heller, Carolin [0000-0002-1934-6162], Foiani, Martha S [0000-0003-4157-2606], Moore, Katrina [0000-0002-4458-8390], Convery, Rhian [0000-0002-9477-1812], Bocchetta, Martina [0000-0003-1814-5024], Neason, Mollie [0000-0001-9419-7171], Thomas, David [0000-0003-1491-1641], Greaves, Caroline V [0000-0002-6446-1960], Woollacott, Ione Oc [0000-0003-1166-6417], Shafei, Rachelle [0000-0002-4760-8684], Van Swieten, John C [0000-0001-6278-6844], Borroni, Barbara [0000-0001-9340-9814], Rowe, James B [0000-0001-7216-8679], Finger, Elizabeth [0000-0003-4461-7427], Otto, Markus [0000-0002-6647-5944], Rohrer, Jonathan D [0000-0002-6155-8417], Apollo - University of Cambridge Repository, Repositório da Universidade de Lisboa, and Woollacott, Ione OC [0000-0003-1166-6417]
Subjects: blood [Frontotemporal Dementia], Male, blood [Neurofilament Proteins], Gastroenterology, genetics [Progranulins], Progranulins, 0302 clinical medicine, Neurofilament Proteins, C9orf72, blood [Glial Fibrillary Acidic Protein], genetics [Frontotemporal Dementia], 0303 health sciences, blood [Biomarkers], Glial fibrillary acidic protein, biology, Middle Aged, Astrogliosis, Psychiatry and Mental health, Frontotemporal Dementia, Biomarker (medicine), Female, Frontotemporal dementia, Adult, medicine.medical_specialty, genetics [Mutation], tau Proteins, 03 medical and health sciences, Atrophy, Internal medicine, Glial Fibrillary Acidic Protein, medicine, Humans, ddc:610, Neurodegeneration, genetics [C9orf72 Protein], Pathological, Aged, 030304 developmental biology, C9orf72 Protein, business.industry, Case-control study, medicine.disease, genetics [tau Proteins], Case-Control Studies, Mutation, biology.protein, Surgery, Neurology (clinical), business, GENFI, Biomarkers, 030217 neurology & neurosurgery
Abstract: © Author(s) (or their employer(s)). No commercial re-use. See rights and permissions. Published by BMJ., Background: There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to be explored as potential biomarker. Methods: Plasma GFAP and neurofilament light chain (NfL) concentration were measured in 469 individuals enrolled in the Genetic FTD Initiative: 114 C9orf72 expansion carriers (74 presymptomatic, 40 symptomatic), 119 GRN mutation carriers (88 presymptomatic, 31 symptomatic), 53 MAPT mutation carriers (34 presymptomatic, 19 symptomatic) and 183 non-carrier controls. Biomarker measures were compared between groups using linear regression models adjusted for age and sex with family membership included as random effect. Participants underwent standardised clinical assessments including the Mini-Mental State Examination (MMSE), Frontotemporal Lobar Degeneration-Clinical Dementia Rating scale and MRI. Spearman's correlation coefficient was used to investigate the relationship of plasma GFAP to clinical and imaging measures. Results: Plasma GFAP concentration was significantly increased in symptomatic GRN mutation carriers (adjusted mean difference from controls 192.3 pg/mL, 95% CI 126.5 to 445.6), but not in those with C9orf72 expansions (9.0, -61.3 to 54.6), MAPT mutations (12.7, -33.3 to 90.4) or the presymptomatic groups. GFAP concentration was significantly positively correlated with age in both controls and the majority of the disease groups, as well as with NfL concentration. In the presymptomatic period, higher GFAP concentrations were correlated with a lower cognitive score (MMSE) and lower brain volume, while in the symptomatic period, higher concentrations were associated with faster rates of atrophy in the temporal lobe. Conclusions: Raised GFAP concentrations appear to be unique to GRN-related FTD, with levels potentially increasing just prior to symptom onset, suggesting that GFAP may be an important marker of proximity to onset, and helpful for forthcoming therapeutic prevention trials., The GENFI study has been supported by the Medical Research Council UK (MR/M023664/1), the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, as well as other individual funding to investigators. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, Alzheimer’s Research UK, the Brain Research Trust and the Wolfson Foundation as well as an Alzheimer's Society grant (AS-PG-16-007). The biomarker measurements were funded in part by the UK Dementia Research Institute at UCL and by a Wellcome Trust Multi-User Equipment Grant. KM has received funding from an Alzheimer’s Society PhD studentship. IOCW is supported by a MRC Clinical Research Training Fellowship (MR/M018288/1). RS-V is supported by an Alzheimer's Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2). JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontemporal Dementias Research Grant 2009, The Netherlands Organization for Scientific Research (NWO) grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield project. CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Initiative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. DG received support from the EU Joint Programme—Neurodegenerative Disease Research (JPND) and the Italian Ministry of Health (PreFrontALS) grant 733051042. RS-V has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). JBR has received funding from the Wellcome Trust (103838) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. MO has received funding from BMBF (FTLDc). MM has received funding from a Canadian Institutes of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. EF has received funding from a CIHR grant #327387. HZ is a Wallenberg Academy Fellow. JR is a MRC Clinician Scientist (MR/M008525/1) and has received funding from the NIHR Rare Diseases Translational Research Collaboration (BRC149/NS/MH), the Bluefield Project and the Association for Frontotemporal Degeneration.
Published: 2020
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63. Faster Cortical Thinning and Surface Area Loss in Presymptomatic and Symptomatic C9orf72 Repeat Expansion Adult Carriers

Author: Le Blanc, Gabriella, Jetté Pomerleau, Vincent, Graff, Caroline, Rittman, Tim, Rogaeva, Ekaterina, Rosa‐Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Masellis, Mario, Tábuas‐Pereira, Miguel, Tainta, Mikel, Tang‐Wai, David, Thomas, David L, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Tartaglia, Maria C., Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Zetterberg, Henrik, Zulaica, Miren, Rowe, James B., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, Mendonça, Alexandre, Santana, Isabel, Butler, Chris, McCarthy, Jillian, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Frisoni, Giovanni, Sorbi, Sandro, Rohrer, Jonathan D., Ducharme, Simon, Almeida, Maria Rosario, Anderl‐Straub, Sarah, Borroni, Barbara, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Luisa, Binetti, Giuliano, Swieten, John, Black, Sandra, Bocchetta, Martina, Borrego, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo‐Branco, Miguel, Convery, Rhian, Cope, Thomas, Galimberti, Daniela, Arriba, María, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M, Duro, Diana, Fenoglio, Chiara, Ferreira, Carlos, Ferreira, Catarina B., Flanagan, Toby, Fox, Nick, Sanchez‐Valle, Raquel, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gauthier, Serge, Ghidoni, Roberta, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, LaForce, Robert, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans‐Otto, Keren, Ron, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Moreno, Fermin, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Synofzik, Matthis, Olives, Jaume, Panman, Jessica, Papma, Janne, Patzig, Maximilian, Pievani, Michela, Pijnenburg, Yolande, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Neurology, Ducharme, Simon [0000-0002-7309-1113], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, diagnostic imaging [Frontotemporal Dementia], 03 medical and health sciences, Young Adult, 0302 clinical medicine, Atrophy, C9orf72, Internal medicine, diagnostic imaging [Cerebral Cortex], medicine, Humans, ddc:610, Young adult, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Aged, Aged, 80 and over, Cerebral Cortex, DNA Repeat Expansion, medicine.diagnostic_test, C9orf72 Protein, business.industry, Magnetic resonance imaging, diagnostic imaging [Atrophy], Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Neurology, Cerebral cortex, Frontotemporal Dementia, Cardiology, Female, Neurology (clinical), Trinucleotide repeat expansion, business, Asymptomatic carrier, 030217 neurology & neurosurgery, Frontotemporal dementia, genetics [Atrophy]
Abstract: Objective C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD). We examined aging trajectories of cortical thickness (CTh) and surface area in C9orf72 expansion adult carriers compared to healthy controls to characterize preclinical cerebral changes leading to symptoms. Methods Data were obtained from the Genetic Frontotemporal Dementia Initiative. T1-weighted magnetic resonance imaging scans were processed with CIVET 2.1 to extract vertex-wide CTh and cortical surface area (CSA). Symptomatic and presymptomatic subjects were compared to age-matched controls using mixed-effects models, controlling for demographic variables. Aging trajectories were compared between carriers and noncarriers by testing the "age by genetic status" interaction. False discovery rate corrections were applied to all vertex-wide analyses. Results The sample included 640 scans from 386 subjects, including 54 symptomatic C9orf72 carriers (72.2% behavioral variant FTD), 83 asymptomatic carriers, and 249 controls (age range = 18-86 years). Symptomatic carriers showed fairly symmetric reduction in CTh/CSA in most of the frontal lobes, in addition to large temporoparietal areas. Presymptomatic subjects had reduced CTh/CSA in more restricted areas of the medial frontoparietal lobes, in addition to scattered lateral frontal, parietal, and temporal areas. These differences were explained by faster cortical thinning linearly throughout adulthood in a similar anatomical distribution, with differences emerging in the early 30s. CSA reduction was also faster in mutation carriers predominantly in the ventrofrontal regions. Interpretation C9orf72 mutation carriers have faster cortical thinning and surface loss throughout adulthood in regions that show atrophy in symptomatic subjects. This suggests that the pathogenic effects of the mutation lead to structural cerebral changes decades prior to symptoms. ANN NEUROL 2020 ANN NEUROL 2020;88:113-122.
Published: 2020
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64. Network structure and transcriptomic vulnerability shape atrophy in frontotemporal dementia

Author: Shafiei, Golia, Bazinet, Vincent, Dadar, Mahsa, Manera, Ana L., Collins, D. Louis, Dagher, Alain, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Butler, Chris, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Jiskoot, Lize C., Seelaar, Harro, van Swieten, John C., Rohrer, Jonathan D., Misic, Bratislav, Ducharme, Simon, Rosen, Howard, Dickerson, Bradford C., Domoto-Reilly, Kimoko, Knopman, David, Boeve, Bradley F., Boxer, Adam L., Kornak, John, Miller, Bruce L., Seeley, William W., Gorno-Tempini, Maria-Luisa, McGinnis, Scott, Mandelli, Maria Luisa, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Heller, Carolin, Greaves, Caroline V., Cash, David, Thomas, David L., Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J., Nicholas, Jennifer, Samra, Kiran, Russell, Lucy L., Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S., Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, van Der Ende, Emma, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger, Gabriel, Simões do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Fede, Giuseppe Di, do Couto, Frederico Simões, Shafiei, Golia [0000-0002-2036-5571], Dadar, Mahsa [0000-0003-4008-2672], Collins, D Louis [0000-0002-8432-7021], Dagher, Alain [0000-0002-0945-5779], Sanchez-Valle, Raquel [0000-0001-7750-896X], Graff, Caroline [0000-0002-9949-2951], Synofzik, Matthis [0000-0002-2280-7273], Masellis, Mario [0000-0002-6244-2096], Jiskoot, Lize C [0000-0002-8120-7366], Seelaar, Harro [0000-0003-1989-7527], Misic, Bratislav [0000-0003-0307-2862], Ducharme, Simon [0000-0002-7309-1113], and Apollo - University of Cambridge Repository
Subjects: Aging, connectome, disease epicentre, frontotemporal dementia, gene expression, network spreading, GENetic Frontotemporal dementia Initiative, Medizin, Neurodegenerative, Neuropsychological Tests, Alzheimer's Disease, diagnostic imaging [Frontotemporal Dementia], Medical and Health Sciences, Pick Disease of the Brain, Settore BIO/13 - Biologia Applicata, pathology [Brain], Frontotemporal Lobar Degeneration Neuroimaging Initiative, Acquired Cognitive Impairment, Connectome, 2.1 Biological and endogenous factors, Humans, ddc:610, Aetiology, genetics [Frontotemporal Dementia], pathology [Atrophy], Neurology & Neurosurgery, Psychology and Cognitive Sciences, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain, Magnetic Resonance Imaging, Brain Disorders, Frontotemporal Dementia (FTD), pathology [Pick Disease of the Brain], Neurological, pathology [Frontotemporal Dementia], Dementia, Neurology (clinical), Atrophy, Transcriptome
Abstract: Copyright © The Author(s) 2022. Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioural variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). First, we identified distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbours, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicentre of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and antero-medial temporal areas. We found that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability, providing an explanation as to how heterogenous pathological entities can lead to the same clinical syndrome. Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative. B.M. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant RGPIN #017-04265) and from the Canada Research Chairs Program. S.D. receives salary support from the Fonds de Recherche du Québec—Santé (FRQS). G.S. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Fonds de recherche du Québec—Nature et Technologies (FRQNT). V.B. acknowledges support from the Fonds de recherche du Québec—Nature et Technologies (FRQNT). FTLDNI data collection and sharing was funded by the Frontotemporal Lobar Degeneration Neuroimaging Initiative (National Institutes of Health Grant R01 AG032306) and is coordinated through the University of California, San Francisco, Memory and Aging Center. FTLDNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Published: 2022
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65. Conceptual framework for the definition of preclinical and prodromal frontotemporal dementia

Author: Benussi, Alberto, Alberici, Antonella, Jiskoot, Lize C, Olives, Jaume, Otto, Markus, Ourselin, Sebastien, Panman, Jessica, Papma, Janne M, Pasquier, Florence, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Le Ber, Isabelle, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Masellis, Mario, Santana, Isabel, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Schroeter, Matthias, Shafei, Rachelle, Shoesmith, Christen, Sorbi, Sandro, Nacmias, Benedetta, Swift, Imogen, Tábuas-Pereira, Miguel, Tagliavini, Fabrizio, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Tartaglia, Carmela, Thomas, David L, Thompson, Paul, Rowe, James B, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Van Damme, Philip, Vandenberghe, Rik, Vandenbulcke, Mathieu, van Swieten, John C, Veldsman, Michele, Verdelho, Ana, Sanchez-Valle, Raquel, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Seelaar, Harro, Synofzik, Matthis, Consortium, GENFI, Rohrer, Jonathan D, Samra, Kiran, Borroni, Barbara, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Russell, Lucy L, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bouzigues, Arabella, Bras, Jose, Greaves, Caroline V, Brice, Alexis, Bruffaerts, Rose, Butler, Chris R, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Bocchetta, Martina, Convery, Rhian, Cope, Thomas, Danek, Adrian, de Mendonça, Alexandre, Deramecourt, Vincent, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ducharme, Simon, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Funkiewiez, Aurélie, Gabilondo, Alazne, Gauthier, Serge, Gazzina, Stefano, Gerhard, Alexander, Giaccone, Giorgio, Gorostidi, Ana, Finger, Elizabeth, Graff, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans Otto, Keren, Ron, Kuchcinski, Gregory, Laforce, Robert, Fumagalli, Giorgio, Waldo, Maria Landqvist, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Levin, Johannes, Lladó, Albert, Lombardi, Gemma, Lombardi, Jolina, Loosli, Sandra, Maruta, Carolina, Galimberti, Daniela, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Moreno, Fermin, Nelson, Annabel, Nicholas, Jennifer, Öijerstedt, Linn, Erasmus MC other, Neurology, Clinical Genetics, Clinical Psychology, Rowe, James [0000-0001-7216-8679], Apollo - University of Cambridge Repository, and GENFI Consortium
Subjects: Epidemiology, Health Policy, prodromal, Prodromal Symptoms, frontotemporal dementia, Psychiatry and Mental health, Cellular and Molecular Neuroscience, presymptomatic, diagnosis [Frontotemporal Dementia], mild cognitive impairment, Developmental Neuroscience, SDG 3 - Good Health and Well-being, frontotemporal lobar degeneration, mental disorders, preclinical, Humans, definition, Neurology (clinical), ddc:610, Geriatrics and Gerontology, mild cognitive and/or behavioral and/or motor impairment, genetics [Frontotemporal Dementia]
Abstract: Funder: EU Joint Programme – Neurodegenerative Disease Research; Id: http://dx.doi.org/10.13039/100013278, Funder: UK Dementia Research Institute; Id: http://dx.doi.org/10.13039/501100017510, The presymptomatic stages of frontotemporal dementia (FTD) are still poorly defined and encompass a long accrual of progressive biological (preclinical) and then clinical (prodromal) changes, antedating the onset of dementia. The heterogeneity of clinical presentations and the different neuropathological phenotypes have prevented a prior clear description of either preclinical or prodromal FTD. Recent advances in therapeutic approaches, at least in monogenic disease, demand a proper definition of these predementia stages. It has become clear that a consensus lexicon is needed to comprehensively describe the stages that anticipate dementia. The goal of the present work is to review existing literature on the preclinical and prodromal phases of FTD, providing recommendations to address the unmet questions, therefore laying out a strategy for operationalizing and better characterizing these presymptomatic disease stages.
Published: 2022
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66. Practice effects in genetic frontotemporal dementia and at-risk individuals: a GENFI study

Author: Öijerstedt, Linn, Andersson, Christin, Synofzik, Matthis, Peakman, Georgia, Pievani, Michela, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Galimberti, Daniela, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Rowe, James Benedict, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Håkan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Masellis, Mario, Damme, Philip Van, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Tartaglia, Maria Carmela, Zulaica, Miren, Finger, Elizabeth, Vandenberghe, Rik, de Mendonca, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Jelic, Vesna, Ducharme, Simon, Butler, Christopher R, Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni B, Ghidoni, Roberta, Sorbi, Sandro, Rohrer, Jonathan Daniel, van Swieten, John Cornelis, Graff, Caroline, Initiative, Genetic Frontotemporal Dementia, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Jiskoot, Lize C, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Seelaar, Harro, Bras, Jose, Bruffaerts, Rose, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, Fede, Giuseppe Di, Borroni, Barbara, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Sanchez-Valle, Raquel, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Karnath, Hans Otto, Moreno, Fermin, Keren, Ron, Langheinrich, Tobias, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Laforce, Robert, Minkelen, Rick van, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nicholas, Jennifer, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Öijerstedt, Linn [0000-0003-0635-6377], van Swieten, John Cornelis [0000-0001-6278-6844], Jiskoot, Lize C [0000-0002-1120-1858], Seelaar, Harro [0000-0003-1989-7527], Borroni, Barbara [0000-0001-9340-9814], Galimberti, Daniela [0000-0002-9284-5953], Rowe, James Benedict [0000-0001-7216-8679], Finger, Elizabeth [0000-0003-4461-7427], Ducharme, Simon [0000-0002-7309-1113], Gerhard, Alexander [0000-0002-8071-6062], Danek, Adrian [0000-0001-8857-5383], Otto, Markus [0000-0002-6647-5944], Sorbi, Sandro [0000-0002-0380-6670], Rohrer, Jonathan Daniel [0000-0002-6155-8417], and Apollo - University of Cambridge Repository
Subjects: C9orf72 Protein, physiology [Cognition], Neuropsychological Tests, frontotemporal dementia, psychology [Frontotemporal Dementia], Cognition, Practice, Psychological, Frontotemporal Dementia, Mutation, Humans, ddc:610, C9ORF, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia]
Published: 2022
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67. CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia

Author: Woollacott, Ione O C, Swift, Imogen J, Heslegrave, Amanda, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Rowe, James B, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Borroni, Barbara, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Galimberti, Daniela, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Tiraboschi, Pietro, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Masellis, Mario, Tábuas-Pereira, Miguel, Afonso, Sónia, Tartaglia, Maria Carmela, Finger, Elizabeth, van Swieten, John C, Seelaar, Harro, Sogorb-Esteve, Aitana, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R, Graff, Caroline, Gerhard, Alexander, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Heller, Carolin, Vandenberghe, Rik, Ducharme, Simon, Ber, Isabelle Le, Levin, Johannes, Otto, Markus, Pasquier, Florence, Santana, Isabel, Zetterberg, Henrik, Rohrer, Jonathan D, Genetic FTD Initiative, GENFI, Knowles, Kathryn, Nelson, Annabel, Bocchetta, Martina, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Bouzigues, Arabella, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Russell, Lucy L, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Peakman, Georgia, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Greaves, Caroline V, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Convery, Rhian, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Genetic FTD Initiative, GENFI, Russell, Lucy L [0000-0001-5023-5893], Borroni, Barbara [0000-0001-9340-9814], Galimberti, Daniela [0000-0002-9284-5953], Tiraboschi, Pietro [0000-0002-2171-1720], Tartaglia, Maria Carmela [0000-0002-5944-8497], Finger, Elizabeth [0000-0003-4461-7427], Laforce, Robert [0000-0002-2031-490X], Sanchez-Valle, Raquel [0000-0001-7750-896X], Synofzik, Matthis [0000-0002-2280-7273], Ducharme, Simon [0000-0002-7309-1113], Otto, Markus [0000-0003-4273-4267], Rohrer, Jonathan D [0000-0002-6155-8417], Apollo - University of Cambridge Repository, Repositório da Universidade de Lisboa, Neurology, Clinical Genetics, and Amsterdam Neuroscience - Neurodegeneration
Subjects: C9orf72 Protein, General Neuroscience, Medizin, diagnosis [Frontotemporal Dementia], cerebrospinal fluid [Biomarkers], Pick Disease of the Brain, Settore BIO/13 - Biologia Applicata, Frontotemporal Dementia, genetics [Chitinase-3-Like Protein 1], Humans, ddc:610, Chitinase-3-Like Protein 1, Human medicine, Neurology (clinical), genetics [C9orf72 Protein], Neuroglia, Biomarkers
Abstract: Funder: Alzheimer's Research UK, Funder: Brain Research UK; Id: http://dx.doi.org/10.13039/100013790, Funder: The Wolfson Foundation; Id: http://dx.doi.org/10.13039/501100001320, Funder: Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, Funder: UK Dementia Research Institute; Id: http://dx.doi.org/10.13039/501100017510, Funder: UK DRI Ltd; Id: http://dx.doi.org/10.13039/501100017510, Funder: MRC UK GENFI, Funder: Bluefield Project, Funder: Dioraphte Foundation; Id: http://dx.doi.org/10.13039/501100010573, Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479, Funder: Ontario Brain Institute; Id: http://dx.doi.org/10.13039/100008914, Funder: Cambridge University Centre for Frontotemporal Dementia, Funder: EU Joint Programme – Neurodegenerative Disease Research; Id: http://dx.doi.org/10.13039/100013278, Funder: the Olav Thon Foundation; Id: http://dx.doi.org/10.13039/501100021720, Funder: Erling‐Persson Family Foundation; Id: http://dx.doi.org/10.13039/100007436, Funder: Stiftelsen för Gamla Tjänarinnor; Id: http://dx.doi.org/10.13039/100010815, Funder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659, BACKGROUND: Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD. METHODS: We investigated the cerebrospinal fluid concentrations of TREM2, YKL-40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation-negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias-corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini-Mental State Examination (MMSE) score using non-parametric partial correlations adjusting for age. Age-adjusted z-scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls. RESULTS: Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL-40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL-40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers. CONCLUSIONS: Although chitotriosidase concentrations in GRN mutation carriers were the only significantly raised glia-derived biomarker as a group, a subset of mutation carriers in all three groups, particularly for chitotriosidase and TREM2, had elevated concentrations. Further work is required to understand the variability in concentrations and the extent of neuroinflammation across the genetic forms of FTD. However, the current findings suggest limited utility of these measures in forthcoming trials.
Published: 2022
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68. Additional file 1 of 12-month survival in nonagenarians inside the Mugello study: on the way to live a century

Author: Pancani, Silvia, Lombardi, Gemma, Sofi, Francesco, Gori, Anna Maria, Boni, Roberta, Castagnoli, Chiara, Paperini, Anita, Pasquini, Guido, Vannetti, Federica, Lova, Raffaello Molino, Macchi, Claudio, and Cecchi, Francesca
Subjects: Data_FILES
Abstract: Additional file 1.
Published: 2022
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69. Comparison of clinical rating scales in genetic frontotemporal dementia within the GENFI cohort

Author: Peakman, Georgia, Russell, Lucy L., Convery, Rhian S., Nicholas, Jennifer M., van Swieten, John C., Jiskoot, Lize C., Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alex, Ducharme, Simon, Le Ber, Isabelle, Tagliavini, Fabrizio, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M., Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L., Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Neurology, Amsterdam Neuroscience - Neurodegeneration, University College of London [London] (UCL), London School of Hygiene and Tropical Medicine (LSHTM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Donostia International Physics Center - DIPC (SPAIN), Donostia International Physics Center (DIPC), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU)-University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre Hospitalier Université Laval [Quebec] (CHUL), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Karolinska Institutet [Stockholm], University of Toronto, University of Cambridge [UK] (CAM), University of Brescia, University of Western Ontario (UWO), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Lusófona University [Lisbon], University of Oxford, University of Manchester [Manchester], McGill University = Université McGill [Montréal, Canada], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Coimbra [Portugal] (UC), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ludwig-Maximilians-Universität München (LMU), University of Ulm (UUlm), Università degli Studi di Firenze = University of Florence (UniFI), HAL-SU, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Oxford [Oxford], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Peakman, Georgia [0000-0002-3319-138X], Convery, Rhian S [0000-0002-9477-1812], Van Swieten, John C [0000-0001-6278-6844], Jiskoot, Lize C [0000-0002-1120-1858], Rowe, James B [0000-0001-7216-8679], Borroni, Barbara [0000-0001-9340-9814], Finger, Elizabeth [0000-0003-4461-7427], Galimberti, Daniela [0000-0002-9284-5953], Gerhard, Alex [0000-0002-8071-6062], Ducharme, Simon [0000-0002-7309-1113], Le Ber, Isabelle [0000-0002-2508-5181], Danek, Adrian [0000-0001-8857-5383], Otto, Markus [0000-0002-6647-5944], Sorbi, Sandro [0000-0002-0380-6670], Rohrer, Jonathan D [0000-0002-6155-8417], Apollo - University of Cambridge Repository, and Genetic FTD Initiative (GENFI)
Subjects: Oncology, Medizin, LANGUAGE, Disease, Genetic FTD Initiative (GENFI), Cohort Studies, 0302 clinical medicine, diagnosis [Frontotemporal Dementia], ddc:150, C9orf72, CRITERIA, 030212 general & internal medicine, frontotemporal dementia, C9orf72 Protein, Cross-Sectional Studies, Disease Progression, Frontotemporal Dementia, Humans, Mutation, tau Proteins, Mental Status and Dementia Tests, VERSION, 11 Medical and Health Sciences, Psychiatry, UTILITY, DDC 150 / Psychology, biology, FTD, 17 Psychology and Cognitive Sciences, Psychiatry and Mental health, Mutation (genetic algorithm), Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, FTLD, Life Sciences & Biomedicine, Alzheimer’s disease, Frontotemporal dementia, medicine.medical_specialty, Clinical Dementia Rating, Tau protein, Clinical Neurology, Alzheimerkrankheit, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, DIAGNOSIS, Asymptomatic, VALIDATION, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, mental disorders, medicine, ddc:610, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurodegeneration, Science & Technology, Neurology & Neurosurgery, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, MUTATIONS, medicine.disease, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, biology.protein, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Surgery, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract: BackgroundTherapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD.MethodsThe CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-associated protein tau (MAPT), 187 GRN, 193 C9orf72) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72) and 145 non-carriers had available longitudinal data at a follow-up time point.ResultsCross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p, publishedVersion
Published: 2022
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70. Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study

Author: Wilke, Carlo, Reich, Selina, Swieten, John C., Borroni, Barbara, Sanchez‐Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria C., Finger, Elizabeth, Vandenberghe, Rik, Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Sorbi, Sandro, Bocchetta, Martina, Todd, Emily, Kuhle, Jens, Barro, Christian, Afonso, Sónia, Almeida, Maria Rosario, Anderl‐Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Borrego‐Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo‐Branco, Miguel, Convery, Rhian, Cope, Thomas, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans‐Otto, Keren, Ron, Langheinrich, Tobias, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M., Peakman, Georgia, Pievani, Michela, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Rosa‐Neto, Pedro, Rossi, Giacomina, Rosser, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas‐Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang‐Wai, David, Thomas, David L., Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Rohrer, Jonathan D., Synofzik, Matthis, Repositório da Universidade de Lisboa, Neurology, and Clinical Genetics
Subjects: blood [Frontotemporal Dementia], Male, Oncology, Medizin, blood [Neurofilament Proteins], Disease, Cohort Studies, 0302 clinical medicine, Settore BIO/13 - Biologia Applicata, Neurofilament Proteins, C9orf72, CRITERIA, Longitudinal Studies, Stage (cooking), 0303 health sciences, blood [Biomarkers], FTD, Middle Aged, 3. Good health, Neurology, Frontotemporal Dementia, Cohort, Biomarker (medicine), Female, Life Sciences & Biomedicine, Frontotemporal dementia, Treatment response, medicine.medical_specialty, Clinical Neurology, C9ORF72, IMMUNOASSAY, 03 medical and health sciences, Atrophy, Internal medicine, NEUROFILAMENT LIGHT-CHAIN, medicine, Humans, ddc:610, Aged, 030304 developmental biology, Science & Technology, HEXANUCLEOTIDE REPEAT, MUTATIONS, business.industry, DISEASE PROGRESSION, Neurosciences, medicine.disease, Biomarkers, Neurosciences & Neurology, Neurology (clinical), TAU, business, 030217 neurology & neurosurgery
Abstract: © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Objective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: the conversion stage. Methods: We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single-molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation-negative within-family controls. Results: In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra-individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage-dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity-to-onset. We estimate stage-dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Interpretation: Blood NfL and pNfH provide dynamic stage-dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD., W. and M.S. are members of the European Reference Network for Rare Neurological Diseases Project ID No. 739510. This work was supported by the Horizon 2020 research and innovation program (grant 779257 Solve-RD to M.S.), the National Ataxia Foundation (grant to C.W. and M.S.), the Wilhelm Vaillant Stiftung (grant to C.W.), the EU Joint Programme – Neurodegenerative Disease Research (JPND) “GENFI-prox” through participating national funding agencies (by DLR/BMBF to M.S., J.D.R., B.B., C.G., and M.O.), and the European Union's Horizon 2020 research and innovation programme under grant agreement No. 643417. J.C.S. and H.S. received funding by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813 and 733050103) in the Netherlands and the Bluefield Project to Cure Frontotemporal Dementia. J.B.R. was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and the Medical Research Council (SUAG/051 G101400). C.B. is supported by a postdoctoral fellowship from the Swiss National Science Foundation (P400PM_191077). J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248).
Published: 2021
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71. Predictive factors of progression to total loss of language and functional autonomy in primary progressive aphasia related to Alzheimer's disease

Author: Mazzeo, Salvatore, Polito, Cristina, Mattei, Marta, Padiglioni, Sonia, Berti, Valentina, Bagnoli, Silvia, Lombardi, Gemma, Carraro, Marco, De Cristofaro, Maria Teresa, Passeri, Alessandro, Ferrari, Camilla, Nacmias, Benedetta, Sorbi, Sandro, and Bessi, Valentina
Published: 2021
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72. Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements

Author: Nerattini, Matilde, primary, Rubino, Federica, additional, Arnone, Annachiara, additional, Polito, Cristina, additional, Mazzeo, Salvatore, additional, Lombardi, Gemma, additional, Puccini, Giulia, additional, Nacmias, Benedetta, additional, De Cristofaro, Maria Teresa, additional, Sorbi, Sandro, additional, Pupi, Alberto, additional, Sciagrà, Roberto, additional, Bessi, Valentina, additional, and Berti, Valentina, additional
Published: 2021
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73. Diagnostic Validity of the Smart Aging Serious Game: An Innovative Tool for Digital Phenotyping of Mild Neurocognitive Disorder

Author: Isernia, Sara, primary, Cabinio, Monia, additional, Di Tella, Sonia, additional, Pazzi, Stefania, additional, Vannetti, Federica, additional, Gerli, Filippo, additional, Mosca, Irene Eleonora, additional, Lombardi, Gemma, additional, Macchi, Claudio, additional, Sorbi, Sandro, additional, and Baglio, Francesca, additional
Published: 2021
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74. The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia: The chronnectome fingerprint

Author: Premi, Enrico, Calhoun, Vince D, Galimberti, Daniela, Panman, Jessica, Papma, Janne, Patzig, Maximilian, Pievani, Michela, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Sanchez-Valle, Raquel, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Laforce, Robert, Tang-Wai, David, Thomas, David L, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Moreno, Fermin, Warren, Jason, Wilke, Carlo, Zetterberg, Henrik, Zulaica, Miren, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James, Vandenberghe, Rik, Diano, Matteo, Finger, Elizabeth, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Butler, Chris, Ducharme, Simon, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Gazzina, Stefano, Frisoni, Giovanni, Cappa, Stefano, Sorbi, Sandro, Padovani, Alessandro, Rohrer, Jonathan D, Borroni, Barbara, Genetic FTD Initiative, GENFI, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Cosseddu, Maura, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Luisa, Binetti, Giuliano, Black, Sandra, Alberici, Antonella, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, de Arriba, María, Archetti, Silvana, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M, Duro, Diana, Fenoglio, Chiara, Ferreira, Carlos, Ferreira, Catarina B, Flanagan, Toby, Fox, Nick, Freedman, Morris, Paternicò, Donata, Fumagalli, Giorgio, Gabilondo, Alazne, Gauthier, Serge, Ghidoni, Roberta, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Gasparotti, Roberto, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans-Otto, Keren, Ron, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, van Swieten, John, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Rowe, James [0000-0001-7216-8679], Apollo - University of Cambridge Repository, Neurology, National Institutes of Health (US), National Science Foundation (US), Wellcome Trust, and Repositório da Universidade de Lisboa
Subjects: Male, Time Factors, MOTION, Gene mutation, physiopathology [Frontotemporal Dementia], methods [Connectome], 0302 clinical medicine, C9orf72, physiopathology [Nerve Net], BEHAVIORAL VARIANT, Medicine, genetics [Frontotemporal Dementia], 11 Medical and Health Sciences, dult Connectome/*methods Female Frontotemporal Dementia/diagnostic imaging/genetics/*physiopathology Heterozygote Humans Magnetic Resonance Imaging Male Middle Aged Nerve Net/diagnostic imaging/*physiopathology *Prodromal Symptoms Time Factors C9orf72 Chronnectome Dynamic brain functional connectivity Frontotemporal dementia Granulin Microtuble associate protein tau Mutation resting-state fMRI, medicine.diagnostic_test, Radiology, Nuclear Medicine & Medical Imaging, 05 social sciences, Genetic FTD Initiative, GENFI, Middle Aged, Magnetic Resonance Imaging, Demência Frontotemporal, 17 Psychology and Cognitive Sciences, DYNAMIC FUNCTIONAL CONNECTIVITY, Chronnectome, Dynamic brain functional connectivity, Frontotemporal dementia, Granulin, Microtuble associate protein tau, Mutation, resting-state fMRI, Adult, Connectome, Female, Frontotemporal Dementia, Heterozygote, Humans, Nerve Net, Prodromal Symptoms, Neurology, SENSITIVITY, Life Sciences & Biomedicine, Cognitive Neuroscience, Neuroimaging, FREQUENCY, diagnostic imaging [Frontotemporal Dementia], Article, 050105 experimental psychology, 03 medical and health sciences, mental disorders, 0501 psychology and cognitive sciences, LOBAR DEGENERATION, ddc:610, Dynamic functional connectivity, RESTING-STATE NETWORKS, Neurology & Neurosurgery, Science & Technology, Resting state fMRI, SUBJECT, diagnostic imaging [Nerve Net], business.industry, Neurosciences, medicine.disease, FMRI DATA, PATTERNS, Neurosciences & Neurology, business, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract: © 2019 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials., This work was supported in part by grants from the NIH (R01REB020407, P20GM103472), NSF grant 1539067 and the Well- come Trust grant (JBR 103838).
Published: 2019
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75. Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: Initial application to the GENFI cohort

Author: Cury, Claire, Durrleman, Stanley, Cash, David, Lorenzi, Marco, Nicholas, Jennifer, Bocchetta, Martina, Van Swieten, John, Borroni, Barbara, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James, Graff, Caroline, Tagliavini, Fabrizio, Frisoni, Giovanni, Laforce, Robert, Finger, Elizabeth, de Mendonça, Alexandre, Sorbi, Sandro, Ourselin, Sébastien, Rohrer, Jonathan, Modat, Marc, Andersson, Christin, Archetti, Silvana, Arighi, Andrea, Benussi, Luisa, Black, Sandra, Cosseddu, Maura, Fallstrm, Marie, Ferreira, Carlos, Fenoglio, Chiara, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gazzina, Stefano, Ghidoni, Robert, Grisoli, Marina, Jelic, Vesna, Jiskoot, Lize, Keren, Ron, Lombardi, Gemma, Maruta, Carolina, Meeter, Lieke, van Minkelen, Rick, Nacmias, Benedetta, Ijerstedt, Linn, Padovani, Alessandro, Panman, Jessica, Pievani, Michela, Polito, Cristina, Premi, Enrico, Prioni, Sara, Rademakers, Rosa, Redaelli, Veronica, Rogaeva, Ekaterina, Rossi, Giacomina, Rossor, Martin, Scarpini, Elio, Tang-Wai, David, Thonberg, Hakan, Tiraboschi, Pietro, Verdelho, Ana, Warren, Jason, Department of Medical Physics and Biomedical Engineering (UCL), University College of London [London] (UCL), Dementia Research Centre [London] (DRC), Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), London School of Hygiene and Tropical Medicine (LSHTM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Brescia, Centro Dino Ferrari [Milano], Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Sunnybrook Research Institute [Toronto] (SRI), Sunnybrook Health Sciences Centre, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, University of Cambridge [UK] (CAM), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia = University of Brescia (UniBs), Université Laval [Québec] (ULaval), University of Western Ontario (UWO), Faculdade de Medicina [Lisboa], Universidade de Lisboa = University of Lisbon (ULISBOA), Università degli Studi di Firenze = University of Florence (UniFI), Imaging Sciences and Biomedical Engineering Division [London], Guy's and St Thomas' Hospital [London]-King‘s College London, Civic Hospital of Brescia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, IRCCS Fatebenefratelli - Brescia, Institut de Recherche en Génie Civil et Mécanique (GeM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), UCL, Institute of Neurology [London], Toronto Western Hospital, Neuroimaging and Telemedicine (LENITEM), Mayo Clinic [Jacksonville], Marco Lorenzi received funding from the EPSRC (EP/J020990/1). Jennifer Nicholas is supported by UK Medical Research Council (grant MR/M023664/1). David Cash is supported by grants from the Alzheimer Society(AS-PG-15-025), Alzheimers Research UK (ARUK-PG2014-1946) and Medical Research Council UK (MR/M023664/1). JBR is supported by the Wellcome Trust (103838). Jonathan D. Rohrer is an MRC Clinician Scientist and has received funding from the NIHR Rare Diseases Translational Research Collaboration. Se361 bastien Ourselin receives funding from the EPSRC (EP/H046410/1, EP/K005278), the MRC (MR/J01107X/1), the NIHR Biomedical Research Unit (Dementia) at UCL and the National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative- BW.mn.BRC10269). Marc Modat is supported by the UCL Leonard Wolfson Experimental Neurology Centre, ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), European Project: 601055,EC:FP7:ICT,FP7-ICT-2011-9,VPH-DARE@IT(2013), European Project: 666992,H2020 Pilier Societal Challenges,H2020-PHC-2015-two-stage,EuroPOND(2016), European Project: 678304,H2020 ERC,ERC-2015-STG,LEASP(2016), Cury, Claire, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, Idex UCA JEDI - - UCA JEDI2015 - ANR-15-IDEX-0001 - IDEX - VALID, VPH Dementia Research Enabled by IT - VPH-DARE@IT - - EC:FP7:ICT2013-04-01 - 2017-03-31 - 601055 - VALID, Data-driven models for Progression Of Neurological Disease - EuroPOND - - H2020 Pilier Societal Challenges2016-01-01 - 2019-12-31 - 666992 - VALID, Learning spatiotemporal patterns in longitudinal image data sets of the aging brain - LEASP - - H2020 ERC2016-09-01 - 2021-08-31 - 678304 - VALID, Neurology, Empenn, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Brescia [Brescia], Universidade de Lisboa (ULISBOA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Prodromal Symptoms, Neuroimaging, Middle Aged, Magnetic Resonance Imaging, Article, Shape analysis, Clustering, Cohort Studies, Computational anatomy, Spatio-Temporal Analysis, Thalamus, Frontotemporal Dementia, ddc:618.97, Parallel transport, Spatiotemporal geodesic regression, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract: Brain atrophy as measured from structural MR images, is one of the primary imaging biomarkers used to track neurodegenerative disease progression. In diseases such as frontotemporal dementia or Alzheimer's disease, atrophy can be observed in key brain structures years before any clinical symptoms are present. Atrophy is most commonly captured as volume change of key structures and the shape changes of these structures are typically not analysed despite being potentially more sensitive than summary volume statistics over the entire structure. In this paper we propose a spatiotemporal analysis pipeline based on Large Diffeomorphic Deformation Metric Mapping (LDDMM) to detect shape changes from volumetric MRI scans. We applied our framework to a cohort of individuals with genetic variants of frontotemporal dementia and healthy controls from the Genetic FTD Initiative (GENFI) study. Our method, take full advantage of the LDDMM framework, and relies on the creation of a population specific average spatiotemporal trajectory of a relevant brain structure of interest, the thalamus in our case. The residuals from each patient data to the average spatiotemporal trajectory are then clustered and studied to assess when presymptomatic mutation carriers differ from healthy control subjects. We found statistical differences in shape in the anterior region of the thalamus at least five years before the mutation carrier subjects develop any clinical symptoms. This region of the thalamus has been shown to be predominantly connected to the frontal lobe, consistent with the pattern of cortical atrophy seen in the disease., Graphical abstract Image 1, Highlights • Clustering shape parametrisation allows local shape analysis. • Thalamic shape changes appear 5 years before onset of fronto temporal dementia. • Shape changes seem to occur before volume changes. • Pre-symptomatic shape changes in thalamus are dorsofrontal, where connecting to temporal lobes.
Published: 2019
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76. Education modulates brain maintenance in presymptomatic frontotemporal dementia

Author: Gazzina, Stefano, Grassi, Mario, Laforce, Robert Jr, Pijnenburg, Yolande, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Moreno, Fermin, Santiago, Beatriz, Scarpini, Elio, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Tang-Wai, David, Thomas, David L, Thonberg, Hakan, Synofzik, Matthis, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Wilke, Carlo, Zetterberg, Henrik, Zulaica, Miren, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B, Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, Premi, Enrico, de Mendonça, Alexandre, Santana, Isabel, Butler, Christopher R, Ducharme, Simon, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Frisoni, Giovanni, Sorbi, Sandro, Cosseddu, Maura, Padovani, Alessandro, Rohrer, Jonathan D, Borroni, Barbara, Genetic FTD Initiative, GENFI, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Alberici, Antonella, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Luisa, Binetti, Giuliano, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Archetti, Silvana, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, Arriba, María de, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M, Gasparotti, Roberto, Duro, Diana, Ferreira, Carlos, Ferreira, Catarina B, Flanagan, Toby, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gauthier, Serge, Ghidoni, Roberta, Van Swieten, John, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans-Otto, Galimberti, Daniela, Keren, Ron, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick van, Sanchez-Valle, Raquel, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Panman, Jessica, Papma, Janne, Patzig, Maximilian, Pievani, Michela, and Neurology
Subjects: Male, Longitudinal study, Audiology, genetics [Progranulins], Progranulins, 0302 clinical medicine, pathology [Brain], pathology [Gray Matter], pathology [White Matter], Gray Matter, genetics [Frontotemporal Dementia], Cerebrospinal Fluid, Cognitive reserve, Principal Component Analysis, 0303 health sciences, Brain, Cognition, Organ Size, Middle Aged, Mental Status and Dementia Tests, White Matter, psychology [Frontotemporal Dementia], diagnostic imaging [Cerebrospinal Fluid], Psychiatry and Mental health, medicine.anatomical_structure, Frontotemporal Dementia, Educational Status, Female, Frontotemporal dementia, Adult, medicine.medical_specialty, tau Proteins, Grey matter, diagnostic imaging [Frontotemporal Dementia], diagnostic imaging [White Matter], 03 medical and health sciences, medicine, Humans, Dementia, Genetic Predisposition to Disease, ddc:610, diagnostic imaging [Brain], genetics [C9orf72 Protein], Pathological, 030304 developmental biology, Adult Frontotemporal dementia magnetic resonance imaging graph theory, Environmental enrichment, C9orf72 Protein, business.industry, diagnostic imaging [Gray Matter], medicine.disease, genetics [tau Proteins], Asymptomatic Diseases, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: ObjectiveCognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time.MethodsTwo-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling.ResultsHighly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers.ConclusionsThis longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.
Published: 2019
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77. MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia

Author: Manera, Ana L, Dadar, Mahsa, Van Swieten, John Cornelis, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce Jr, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James Benedict, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, De Mendonca, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Butler, Christopher R, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Sorbi, Sandro, Rohrer, Jonathan Daniel, Ducharme, Simon, Collins, D Louis, FTLDNI Investigators, Rosen, Howard, Dickerson, Bradford C., Domoto-Reilly, Kimoko, Knopman, David, Boeve, Bradley F., Boxer, Adam L., Kornak, John, Miller, Bruce L., Seeley, William W., Gorno-Tempini, Maria-Luisa, McGinnis, Scott, Mandelli, Maria Luisa, GENFI Consortium, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, Cosseddu, Maura, Arriba, María De, Fede, Giuseppe Di, Díaz, Zigor, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Carlos, Ferreira, Catarina B., Flanagan, Toby, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans-Otto, Keren, Ron, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick Van, Mitchell, Sara, Moore, Katrina M, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne, Peakman, Georgia, Piaceri, Irene, Pievani, Michela, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Neurology, Amsterdam Neuroscience - Neurodegeneration, Repositório da Universidade de Lisboa, Manera, Ana L [0000-0003-1639-6858], Dadar, Mahsa [0000-0003-4008-2672], Van Swieten, John Cornelis [0000-0001-6278-6844], Borroni, Barbara [0000-0001-9340-9814], Galimberti, Daniela [0000-0002-9284-5953], Rowe, James Benedict [0000-0001-7216-8679], Finger, Elizabeth [0000-0003-4461-7427], Otto, Markus [0000-0002-6647-5944], Rohrer, Jonathan Daniel [0000-0002-6155-8417], Ducharme, Simon [0000-0002-7309-1113], Apollo - University of Cambridge Repository, and Clinical Genetics
Subjects: medicine.medical_specialty, Audiology, Cross-validation, 03 medical and health sciences, 0302 clinical medicine, Text mining, Cognitive neurology, Neuroimaging, SDG 3 - Good Health and Well-being, Medicine, ddc:610, 030304 developmental biology, 0303 health sciences, business.industry, Semantic fluency, medicine.disease, 3. Good health, Random forest, Psychiatry and Mental health, Cohort, Surgery, Neurology (clinical), Differential diagnosis, business, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ., Introduction: Structural brain imaging is paramount for the diagnosis of behavioural variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis. Methods: A total of 515 subjects from two different bvFTD cohorts (training and independent validation cohorts) were used to perform voxel-wise morphometric analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from deformation-based morphometry differences in isolation and together with semantic fluency. Tenfold cross validation was used to assess the performance of the classifier within the training cohort. A second held-out cohort of genetically confirmed bvFTD cases was used for additional validation. Results: Average 10-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In the separate validation cohort of definite bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added semantic fluency scores. Conclusion: Our results show that structural MRI and semantic fluency can accurately predict bvFTD at the individual subject level within a completely independent validation cohort coming from a different and independent database., Data collection and sharing for this project was funded by the Frontotemporal Lobar Degeneration Neuroimaging Initiative (National Institutes of Health Grant R01 AG032306). The study is coordinated through the University of California, San Francisco, Memory and Aging Center. FTLDNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Brain scan acquisition at the McConnell Brain Imaging was supported by the Brain Canada Foundation with support from Health Canada and the Canada Foundation for Innovation (CFI Project 34874). This work was supported by Italian Ministry of Health (CoEN015 and Ricerca Corrente).
Published: 2021
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78. Neurofilament Light Chain and Intermediate HTT Alleles as Combined Biomarkers in Italian ALS Patients

Author: Ingannato, Assunta, primary, Bagnoli, Silvia, additional, Mazzeo, Salvatore, additional, Bessi, Valentina, additional, Matà, Sabrina, additional, Del Mastio, Monica, additional, Lombardi, Gemma, additional, Ferrari, Camilla, additional, Sorbi, Sandro, additional, and Nacmias, Benedetta, additional
Published: 2021
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79. The Revised Self-Monitoring Scale detects early impairment of social cognition in genetic frontotemporal dementia within the GENFI cohort

Author: Franklin, Hannah D, Russell, Lucy L, Jiskoot, Lize, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Moreno, Fermin, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Sanchez-Valle, Raquel, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Borroni, Barbara, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Laforce, Robert, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Masellis, Mario, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Rowe, James B, Peakman, Georgia, Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alex, Levin, Johannes, Greaves, Caroline V, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D, Genetic FTD Initiative, GENFI, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Bocchetta, Martina, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Nicholas, Jennifer, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Poos, Jackie, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Convery, Rhian S, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Cash, David M, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans Otto, van Swieten, John, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Rohrer, Jonathan D. [0000-0002-6155-8417], Apollo - University of Cambridge Repository, Bocchetta, Martina [0000-0003-1814-5024], Rowe, James B [0000-0001-7216-8679], Rohrer, Jonathan D [0000-0002-6155-8417], Neurology, Clinical Psychology, Clinical Genetics, and Repositório da Universidade de Lisboa
Subjects: Social Cognition, Neurology, Medizin, RSMS, PROGRESSION, Audiology, genetics [Progranulins], 0302 clinical medicine, Progranulins, Familial, C9orf72, MAPT, Medicine, CDR® plus NACC FTLD, VBM, genetics [Frontotemporal Dementia], 11 Medical and Health Sciences, Socioemotional selectivity theory, 05 social sciences, Prodromal Stage, Genetic FTD Initiative, GENFI, Frontotemporal dementia, GRN, C9orf72 Protein, Humans, Magnetic Resonance Imaging, Mutation, tau Proteins, Frontotemporal Dementia, ORBITOFRONTAL CORTEX, Life Sciences & Biomedicine, RC321-571, medicine.medical_specialty, Cognitive Neuroscience, Clinical Neurology, Neurosciences. Biological psychiatry. Neuropsychiatry, genetics [Mutation], diagnostic imaging [Frontotemporal Dementia], 050105 experimental psychology, Temporal lobe, 03 medical and health sciences, mental disorders, 0501 psychology and cognitive sciences, ddc:610, RC346-429, genetics [C9orf72 Protein], Science & Technology, CDR (R) plus NACC FTLD, business.industry, Research, Neurosciences, medicine.disease, DYSFUNCTION, genetics [tau Proteins], Orbitofrontal cortex, Neurology. Diseases of the nervous system, Neurosciences & Neurology, Neurology (clinical), business, Insula, 030217 neurology & neurosurgery
Abstract: © The Author(s). 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: Although social cognitive dysfunction is a major feature of frontotemporal dementia (FTD), it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts. Methods: We used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional sensitivity in 730 participants from the genetic FTD initiative (GENFI) observational study: 269 mutation-negative healthy controls, 193 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. All participants underwent the standardised GENFI clinical assessment including the 'CDR® plus NACC FTLD' scale and RSMS. The RSMS total score and its two subscores, socioemotional expressiveness (EX score) and modification of self-presentation (SP score) were measured. Volumetric T1-weighted magnetic resonance imaging was available from 377 mutation carriers for voxel-based morphometry (VBM) analysis. Results: The RSMS was decreased in symptomatic mutation carriers in all genetic groups but at a prodromal stage only in the C9orf72 (for the total score and both subscores) and GRN (for the modification of self-presentation subscore) groups. RSMS score correlated with disease severity in all groups. The VBM analysis implicated an overlapping network of regions including the orbitofrontal cortex, insula, temporal pole, medial temporal lobe and striatum. Conclusions: The RSMS indexes socioemotional impairment at an early stage of genetic FTD and may be a suitable outcome measure in forthcoming trials., The Dementia Research Centre is supported by Alzheimer’s Research UK, Brain Research Trust and The Wolfson Foundation. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility as well as an Alzheimer’s Society grant [AS-PG-16-007]. This work was also supported by the MRC UK GENFI grant [MR/M023664/1], the Italian Ministry of Health (CoEN015 and Ricerca Corrente) and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant, The Bluefield Project and the JPND GENFI-PROX grant [2019-02248]. JDR is supported by an MRC Clinician Scientist Fellowship [MR/M008525/1] and has received funding from the NIHR Rare Disease Translational Research Collaboration [BRC149/NS/MH], the Bluefield Project and the Association for Frontotemporal Degeneration. MB is supported by a Fellowship award from the Alzheimer’s Society, UK [AS-JF-19a-004-517]. JBR is supported by the Wellcome Trust [103838], the Medical Research Council and NIHR Cambridge Biomedical Research Centre. This work was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology [EXC 2145 SyNergy – ID 390857198]. Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.
Published: 2021
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80. Differential early subcortical involvement in genetic FTD within the GENFI cohort

Author: Bocchetta, Martina, Todd, Emily G, Seelaar, Harro, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Borroni, Barbara, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Galimberti, Daniela, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sanchez-Valle, Raquel, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Laforce, Robert, Tang-Wai, David, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Moreno, Fermin, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Carmela Tartaglia, Maria, Peakman, Georgia, Rowe, James B, Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Butler, Chris R, Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Cash, David M, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D, Initiative, Genetic Frontotemporal dementia, Afonso, Sónia, Rosario Almeida, Maria, Anderl-Straub, Sarah, Convery, Rhian S, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Russell, Lucy L, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Thomas, David L, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Eugenio Iglesias, Juan, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, van Swieten, John C, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans Otto, Jiskoot, Lize C, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, João Leitão, Maria, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Neurology, Amsterdam Neuroscience - Neurodegeneration, Alzheimer's Research UK, Alzheimer Society, Brain Research UK, Wolfson Foundation, National Institute for Health Research (UK), University College London, Dementia Research Institute (UK), Medical Research Council (UK), Ministero della Salute, Canadian Institutes of Health Research, NVIDIA Corporation, Association for Frontotemporal Degeneration (US), European Research Council, European Commission, National Institutes of Health (US), Wellcome Trust, German Research Foundation, Munich Cluster for Systems Neurology, Repositório da Universidade de Lisboa, Clinical Genetics, Clinical Psychology, Genetic Frontotemporal dementia Initiative (GENFI), Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository
Subjects: Pathology, SEGMENTATION, Medizin, Hippocampus, Presymptomatic stage, genetics [Progranulins], Progranulins, 0302 clinical medicine, Limbic system, Basal ganglia, BRAIN ATROPHY, skin and connective tissue diseases, genetics [Frontotemporal Dementia], 05 social sciences, Subiculum, Regular Article, DEGENERATION, Magnetic Resonance Imaging, 3. Good health, Brain volumetry, medicine.anatomical_structure, Neurology, Frontotemporal Dementia, MRI imaging, Life Sciences & Biomedicine, Frontotemporal dementia, medicine.medical_specialty, Cognitive Neuroscience, Computer applications to medicine. Medical informatics, Thalamus, R858-859.7, Prodromal Symptoms, Neuroimaging, tau Proteins, genetics [Mutation], Grey matter, Biology, diagnostic imaging [Frontotemporal Dementia], Genetic frontotemporal dementia, 050105 experimental psychology, Temporal lobe, 03 medical and health sciences, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, PROGRANULIN, RC346-429, genetics [C9orf72 Protein], Science & Technology, C9orf72 Protein, PATHWAYS, FRONTOTEMPORAL DEMENTIA, C9ORF72 MUTATION, medicine.disease, Atrophy, Mutation, PATHOLOGY, genetics [tau Proteins], nervous system, Neurosciences & Neurology, sense organs, Neurology. Diseases of the nervous system, Neurology (clinical), TAU, NEUROPATHOLOGY, 030217 neurology & neurosurgery
Abstract: © 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), Background: Studies have previously shown evidence for presymptomatic cortical atrophy in genetic FTD. Whilst initial investigations have also identified early deep grey matter volume loss, little is known about the extent of subcortical involvement, particularly within subregions, and how this differs between genetic groups. Methods: 480 mutation carriers from the Genetic FTD Initiative (GENFI) were included (198 GRN, 202 C9orf72, 80 MAPT), together with 298 non-carrier cognitively normal controls. Cortical and subcortical volumes of interest were generated using automated parcellation methods on volumetric 3 T T1-weighted MRI scans. Mutation carriers were divided into three disease stages based on their global CDR® plus NACC FTLD score: asymptomatic (0), possibly or mildly symptomatic (0.5) and fully symptomatic (1 or more). Results: In all three groups, subcortical involvement was seen at the CDR 0.5 stage prior to phenoconversion, whereas in the C9orf72 and MAPT mutation carriers there was also involvement at the CDR 0 stage. In the C9orf72 expansion carriers the earliest volume changes were in thalamic subnuclei (particularly pulvinar and lateral geniculate, 9-10%) cerebellum (lobules VIIa-Crus II and VIIIb, 2-3%), hippocampus (particularly presubiculum and CA1, 2-3%), amygdala (all subregions, 2-6%) and hypothalamus (superior tuberal region, 1%). In MAPT mutation carriers changes were seen at CDR 0 in the hippocampus (subiculum, presubiculum and tail, 3-4%) and amygdala (accessory basal and superficial nuclei, 2-4%). GRN mutation carriers showed subcortical differences at CDR 0.5 in the presubiculum of the hippocampus (8%). Conclusions: C9orf72 expansion carriers show the earliest and most widespread changes including the thalamus, basal ganglia and medial temporal lobe. By investigating individual subregions, changes can also be seen at CDR 0 in MAPT mutation carriers within the limbic system. Our results suggest that subcortical brain volumes may be used as markers of neurodegeneration even prior to the onset of prodromal symptoms., This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant, the Alzheimer's Society grant (AS-PG-16-007), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248). MB is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). MB’s work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. MB acknowledges the support of NVIDIA Corporation with the donation of the Titan V GPU used for part of the analyses in this research. JDR is an MRC Clinician Scientist (MR/M008525/1) and has received funding from the NIHR Rare Diseases Translational Research Collaboration (BRC149/NS/MH), the Bluefield Project and the Association for Frontotemporal Degeneration. JEI is supported by the European Research Council (Starting Grant 677697, project BUNGEE-TOOLS), Alzheimer’s Research UK (ARUK-IRG2019A003) and NIH 1RF1MH123195-01. JBR is funded by the Wellcome Trust (103838) and the National Institute for Health Research Cambridge Biomedical Research Centre. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). Several authors of this publication (JCvS, MS, RSV, AD, MO, JDR) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) - Project ID No 739510.
Published: 2021
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81. Error in Article Information

Author: Benussi, Alberto, Premi, Enrico, Laforce, Robert, Lladò, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Graff, Caroline, Nacmias, Benedetta, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, M Papma, Janne, Pievani, Michela, Pijnenburg, Yolande, Synofzik, Matthis, Polito, Cristina, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Galimberti, Daniela, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Masellis, Mario, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, L Thomas, David, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Tartaglia, Carmela, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Rowe, James B, Zetterberg, Henrik, Zulaica, Miren, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Gazzina, Stefano, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R, Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Brattini, Chiara, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Peakman, Georgia, Bocchetta, Martina, Rohrer, Jonathan D, Borroni, Barbara, Initiative, Genetic FTD, Afonso, Sònia, Bonomi, Elisa, Rosario Almeida, Maria, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargallò, Nuria, Bartha, Robart, Alberici, Antonella, Bender, Benjamin, Benussi, Luisa, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Jiskoot, Lize, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Convery, Rhian, Cope, Thomas, Cosseddu, Maura, van Swieten, John C, Deramecourt, Vincent, de Arriba, Marìa, Di Fede, Giuseppe, Dìez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, B Ferreira, Catarina, Fox, Nick, Freedman, Morris, Sanchez-Valle, Raquel, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Moreno, Fermin, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, and João Leitão, Maria
Subjects: ddc:610
Published: 2021
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82. Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia

Author: Benussi, Alberto, Premi, Enrico, Laforce, Robert, Lladò, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Graff, Caroline, Nacmias, Benedetta, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, M Papma, Janne, Pievani, Michela, Pijnenburg, Yolande, Synofzik, Matthis, Polito, Cristina, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Galimberti, Daniela, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Masellis, Mario, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, L Thomas, David, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Tartaglia, Carmela, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Rowe, James B, Zetterberg, Henrik, Zulaica, Miren, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Gazzina, Stefano, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R, Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Brattini, Chiara, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Peakman, Georgia, Bocchetta, Martina, Rohrer, Jonathan D, Borroni, Barbara, Initiative, Genetic FTD, Afonso, Sònia, Bonomi, Elisa, Rosario Almeida, Maria, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargallò, Nuria, Bartha, Robart, Alberici, Antonella, Bender, Benjamin, Benussi, Luisa, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Jiskoot, Lize, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Convery, Rhian, Cope, Thomas, Cosseddu, Maura, van Swieten, John C, Deramecourt, Vincent, de Arriba, Marìa, Di Fede, Giuseppe, Dìez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, B Ferreira, Catarina, Fox, Nick, Freedman, Morris, Sanchez-Valle, Raquel, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Moreno, Fermin, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, João Leitão, Maria, Genetic FTD Initiative (GENFI), Repositório da Universidade de Lisboa, Neurology, Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository
Subjects: Male, Longitudinal study, Pediatrics, Hallucinations, FEATURES, VARIANT, Medizin, Anxiety, physiopathology [Frontotemporal Dementia], 0302 clinical medicine, Interquartile range, Medicine, Apathy, Longitudinal Studies, genetics [Frontotemporal Dementia], Depression (differential diagnoses), Granulins, Original Investigation, Depression, Aged, C9orf72 Protein, Canada, Compulsive Behavior, Disease Progression, Europe, Female, Humans, Middle Aged, tau Proteins, Frontotemporal Dementia, General Medicine, 3. Good health, Online Only, Neurology, Compulsive behavior, medicine.symptom, Life Sciences & Biomedicine, Frontotemporal dementia, Cohort study, medicine.medical_specialty, genetics [Granulins], DIAGNOSTIC-CRITERIA, epidemiology [Frontotemporal Dementia], MAPT protein, human, 03 medical and health sciences, Medicine, General & Internal, 030225 pediatrics, General & Internal Medicine, mental disorders, ddc:610, LOBAR DEGENERATION, genetics [C9orf72 Protein], Science & Technology, business.industry, Research, DISEASE PROGRESSION, Correction, medicine.disease, genetics [tau Proteins], ONSET, Other, C9orf72 protein, human, business, 030217 neurology & neurosurgery
Abstract: © 2021 Benussi A et al. JAMA Network Open. This is an open access article distributed under the terms of the CC-BY License., Importance: Behavioral disturbances are core features of frontotemporal dementia (FTD); however, symptom progression across the course of disease is not well characterized in genetic FTD. Objective: To investigate behavioral symptom frequency and severity and their evolution and progression in different forms of genetic FTD. Design, setting, and participants: This longitudinal cohort study, the international Genetic FTD Initiative (GENFI), was conducted from January 30, 2012, to May 31, 2019, at 23 multicenter specialist tertiary FTD research clinics in the United Kingdom, the Netherlands, Belgium, France, Spain, Portugal, Italy, Germany, Sweden, Finland, and Canada. Participants included a consecutive sample of 232 symptomatic FTD gene variation carriers comprising 115 with variations in C9orf72, 78 in GRN, and 39 in MAPT. A total of 101 carriers had at least 1 follow-up evaluation (for a total of 400 assessments). Gene variations were included only if considered pathogenetic. Main outcomes and measures: Behavioral and neuropsychiatric symptoms were assessed across disease duration and evaluated from symptom onset. Hierarchical generalized linear mixed models were used to model behavioral and neuropsychiatric measures as a function of disease duration and variation. Results: Of 232 patients with FTD, 115 (49.6%) had a C9orf72 expansion (median [interquartile range (IQR)] age at evaluation, 64.3 [57.5-69.7] years; 72 men [62.6%]; 115 White patients [100%]), 78 (33.6%) had a GRN variant (median [IQR] age, 63.4 [58.3-68.8] years; 40 women [51.3%]; 77 White patients [98.7%]), and 39 (16.8%) had a MAPT variant (median [IQR] age, 56.3 [49.9-62.4] years; 25 men [64.1%]; 37 White patients [94.9%]). All core behavioral symptoms, including disinhibition, apathy, loss of empathy, perseverative behavior, and hyperorality, were highly expressed in all gene variant carriers (>50% patients), with apathy being one of the most common and severe symptoms throughout the disease course (51.7%-100% of patients). Patients with MAPT variants showed the highest frequency and severity of most behavioral symptoms, particularly disinhibition (79.3%-100% of patients) and compulsive behavior (64.3%-100% of patients), compared with C9orf72 carriers (51.7%-95.8% of patients with disinhibition and 34.5%-75.0% with compulsive behavior) and GRN carriers (38.2%-100% with disinhibition and 20.6%-100% with compulsive behavior). Alongside behavioral symptoms, neuropsychiatric symptoms were very frequently reported in patients with genetic FTD: anxiety and depression were most common in GRN carriers (23.8%-100% of patients) and MAPT carriers (26.1%-77.8% of patients); hallucinations, particularly auditory and visual, were most common in C9orf72 carriers (10.3%-54.5% of patients). Most behavioral and neuropsychiatric symptoms increased in the early-intermediate phases and plateaued in the late stages of disease, except for depression, which steadily declined in C9orf72 carriers, and depression and anxiety, which surged only in the late stages in GRN carriers. Conclusions and relevance: This cohort study suggests that behavioral and neuropsychiatric disturbances differ between the common FTD gene variants and have different trajectories throughout the course of disease. These findings have crucial implications for counseling patients and caregivers and for the design of disease-modifying treatment trials in genetic FTD., This work is supported by the Joint Programme–Neurodegenerative Disease Research grant no. JPND2019-466-090 “GENFI-prox” (Drs Synofzik, van Swieten, Otto, Graff, Rohrer, and Borroni), the Centre d’Investigation Clinique grant no. ANR/DGOS PRTS 2015-2019 PREV-DEMALS (Dr Le Ber), the Centre pour l’Acquisition et le Traitement des Images platform grant no. ANR-10-IAIHU-06 (Dr Le Ber), the UK Medical Research Council grant no. MR/M023664/1 (Dr Rohrer), the Italian Ministry of Health grant no. 733051042 (Dr Galimberti), and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant no. MOP 327387 (Dr Masellis), a Canadian Institutes of Health Research operating grant.
Published: 2021
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83. Impairment of episodic memory in genetic frontotemporal dementia

Author: Poos, Jackie M, Russell, Lucy L, Pijnenburg, Yolande A L, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B, Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Borroni, Barbara, Caroppo, Paola, Di Fede, Giuseppe, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Sanchez-Valle, Raquel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Veldsman, Michele, Thompson, Paul, Langheinrich, Tobias, Prix, Catharina, Hoegen, Tobias, Moreno, Fermin, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Anderl-Straub, Sarah, Lombardi, Jolina, Bargalló, Nuria, Benussi, Alberto, Cantoni, Valentina, Bertoux, Maxime, Bertrand, Anne, Laforce, Robert, Brice, Alexis, Camuzat, Agnès, Colliot, Olivier, Sayah, Sabrina, Funkiewiez, Aurélie, Rinaldi, Daisy, Lombardi, Gemma, Nacmias, Benedetta, Saracino, Dario, Bessi, Valentina, Graff, Caroline, Ferrari, Camilla, Cañada, Marta, Deramecourt, Vincent, Kuchcinski, Gregory, Lebouvier, Thibaud, Ourselin, Sebastien, Polito, Cristina, Rollin, Adeline, Synofzik, Matthias, Galimberti, Daniela, Rowe, James B, Masellis, Mario, Peakman, Georgia, Tartaglia, Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Medonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R, Santana, Isabel, Ber, Isabelle Le, Gerhard, Alex, Ducharme, Simon, Bocchetta, Martina, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, van Swieten, John C, Rohrer, Jonathan D, Genetic FTD Initiative, GENF, Rossor, Martin N, Fox, Nick C, Greaves, Caroline V, Warren, Jason D, Moore, Katrina, Convery, Rhian, Swift, Imogen J, Shafei, Rachelle, Heller, Carolin, Todd, Emily, Bouzigues, Arabella, Cash, David, Woollacott, Ione, Jiskoot, Lize C, Zetterberg, Henrik, Nelson, Annabel, Nicholas, Jennifer, Guerreiro, Rita, Bras, Jose, Thomas, David L, Mead, Simon, Meeter, Lieke, Panman, Jessica, van Minkelen, Rick, van der Ende, Emma L, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Gorostidi, Ana, Zulaica, Miren, Díez, Alina, Villanua, Jorge, Borrego-Ecija, Sergi, Jaume, Olives, Seelaar, Harro, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargallo, Nuria, Premi, Enrico, Gazzina, Stefano, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Papma, Janne M, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Thonberg, Hakan, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Arighi, Andrea, Fenoglio, Chiara, van den Berg, Esther, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans-Otto, Apollo - University of Cambridge Repository, Repositório da Universidade de Lisboa, Rowe, James [0000-0001-7216-8679], Rowe, James B [0000-0001-7216-8679], Neurology, Amsterdam Neuroscience - Neurodegeneration, Genetic FTD Initiative, GENFI, Radiology & Nuclear Medicine, Neurosurgery, Clinical Psychology, and Clinical Genetics
Subjects: cognition, Medizin, neuropsychology, Audiology, frontotemporal dementia, DISEASE, 0302 clinical medicine, COGNITIVE & BEHAVIORAL ASSESSMENT, C9orf72, BEHAVIORAL VARIANT, CRITERIA, voxel‐based morphometry, ALZHEIMERS, Episodic memory, 0303 health sciences, episodic memory, CARRIERS, frontal lobe, Psychiatry and Mental health, Frontal lobe, Life Sciences & Biomedicine, Frontotemporal dementia, temporal lobe, Cognition, Executive function, Genetic disorders, Neuropsychology, Temporal lobe, Voxel-based morphometry, medicine.medical_specialty, Clinical Neurology, DIAGNOSIS, RESEARCH ARTICLE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Memory impairment, voxel-based morphometry, genetic disorders, ddc:610, PROGRANULIN, RC346-429, 030304 developmental biology, 0604 Genetics, Science & Technology, Recall, business.industry, RC952-954.6, Neurosciences, PROFILES, medicine.disease, executive function, Geriatrics, VOLUME, Genetic FTD Initiative, GENF, Neurology (clinical), Neurology. Diseases of the nervous system, Neurosciences & Neurology, business, 1109 Neurosciences, 030217 neurology & neurosurgery
Abstract: © 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule-associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel-based morphometry to investigate the underlying neural substrates of the FCSRT. Results: All symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers. Discussion: The FCSRT detects presymptomatic deficits in C9orf72- and MAPT-associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD., The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK. J. D. Rohrer is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1); the Bluefield Project; the JPND GENFI-PROX grant (2019-02248); the Dioraphte Foundation (grant numbers 09-02-00); the Association for Frontotemporal Dementias Research Grant 2009; The Netherlands Organization for Scientific Research (NWO; grant HCMI 056-13-018); ZonMw Memorabel (Deltaplan Dementie, project numbers 733 050 103 and 733 050 813); JPND PreFrontAls consortium (project number 733051042). J. M. Poos is supported by a Fellowship award from Alzheimer Nederland (WE.15-2019.02). This work was conducted using the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.
Published: 2021
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84. Association of rs3027178 polymorphism in the circadian clock gene PER1 with susceptibility to Alzheimer's disease and longevity in an Italian population

Author: Bacalini Maria Giulia, Palombo, Flavia, Garagnani, Paolo, Giuliani, Cristina, Fiorini, Claudio, Caporali, Leonardo, Maserati Michelangelo Stanzani, Capellari, Sabina, Romagnoli, Martina, De Fanti Sara, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Galimberti, Daniela, Scarpini, Elio, Arcaro, Marina, Bonanni, Enrica, Siciliano, Gabriele, Maestri, Michelangelo, Guarnieri, Biancamaria, Cucchiara, Federico, Schirru, Alessandro, Lo Gerfo Annalisa, Lombardi, Gemma, Arnaldi, Dario, Mattioli, Pietro, Nobili, Flavio, Cerroni, Gianluigi, Bartoli, Antonella, Manni, Raffaele, Elena, Sinforian, Terzaghi, Michele, Arena, Maria Grazia, Silvestri, Rosalia, Di Perri Maria Caterina, Franzoni, Ferdinando, Tognoni, Gloria, Mancuso, Michelangelo, Sorbi, Sandro, Bonuccelli, Ubaldo, Faraguna, Ugo, Martucci, Morena, Monti, Daniela, Carelli, Valerio, Franceschi, Claudio, La Morgia Chiara, Santoro, Aurelia, Bacalini, Maria Giulia, Palombo, Flavia, Garagnani, Paolo, Giuliani, Cristina, Fiorini, Claudio, Caporali, Leonardo, Stanzani Maserati, Michelangelo, Capellari, Sabina, Romagnoli, Martina, De Fanti, Sara, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Galimberti, Daniela, Scarpini, Elio, Arcaro, Marina, Bonanni, Enrica, Siciliano, Gabriele, Maestri, Michelangelo, Guarnieri, Biancamaria, Martucci, Morena, Monti, Daniela, Carelli, Valerio, Franceschi, Claudio, La Morgia, Chiara, and Santoro, Aurelia
Subjects: Aged, 80 and over, Aging, CLOCK gene, Longevity, Period Circadian Proteins, Aging · Alzheimer’s disease · Centenarians · CLOCK genes · Polymorphism · Circadian rhythms, Alzheimer’s disease, CLOCK genes, Centenarians, Circadian rhythms, Polymorphism, Circadian Rhythm, Humans, Italy, Alzheimer Disease, Circadian Clocks, Settore BIO/13 - Biologia Applicata, 80 and over, Centenarian, Geriatrics and Gerontology, Aged
Abstract: Many physiological processes in the human body follow a 24-h circadian rhythm controlled by the circadian clock system. Light, sensed by retina, is the predominant “zeitgeber” able to synchronize the circadian rhythms to the light-dark cycles. Circadian rhythm dysfunction and sleep disorders have been associated with aging and neurodegenerative diseases including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). In the present study, we aimed at investigating the genetic variability of clock genes in AD patients compared to healthy controls from Italy. We also included a group of Italian centenarians, considered as super-controls in association studies given their extreme phenotype of successful aging. We analyzed the exon sequences of eighty-four genes related to circadian rhythms, and the most significant variants identified in this first discovery phase were further assessed in a larger independent cohort of AD patients by matrix assisted laser desorption/ionization-time of flight mass spectrometry. The results identified a significant association between the rs3027178 polymorphism in the PER1 circadian gene with AD, the G allele being protective for AD. Interestingly, rs3027178 showed similar genotypic frequencies among AD patients and centenarians. These results collectively underline the relevance of circadian dysfunction in the predisposition to AD and contribute to the discussion on the role of the relationship between the genetics of age-related diseases and of longevity.
Published: 2021

85. Impairment of episodic memory in genetic frontotemporal dementia:A genfi study

Author: Poos, Jackie M., Russell, Lucy L., Peakman, Georgia, Bocchetta, Martina, Greaves, Caroline V., Jiskoot, Lize C., van der Ende, Emma L., Seelaar, Harro, Papma, Janne M., van den Berg, Esther, Pijnenburg, Yolande A.L., Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthias, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Carmela, Finger, Elizabeth, Vandenberghe, Rik, Medonça, Alexandre de, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Ber, Isabelle Le, Gerhard, Alex, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, van Swieten, John C., Rohrer, Jonathan D., Rossor, Martin N., Fox, Nick C., Warren, Jason D., Moore, Katrina, Convery, Rhian, Swift, Imogen J., Shafei, Rachelle, Heller, Carolin, Todd, Emily, Bouzigues, Arabella, Cash, David, Woollacott, Ione, Zetterberg, Henrik, Nelson, Annabel, Nicholas, Jennifer, Guerreiro, Rita, Bras, Jose, Thomas, David L., Mead, Simon, Meeter, Lieke, Pan-Man, Jessica, Minkelen, Rick van, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Gorostidi, Ana, Zulaica, Miren, Díez, Alina, Vil-Lanua, Jorge, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargalló, Nuria, Premi, Enrico, Gazzina, Stefano, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Thon-Berg, Hakan, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoe-Smith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans Otto, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Math Ieu, Ferreira, Catarina B., Miltenberger, Gabriel, Mpsych, Carolina Maruta, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Fede, Giuseppe Di, Giac-Cone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Velds-Man, Michele, Thompson, Paul, Langheinrich, Tobias, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Anderl-Straub, Sarah, Lombardi, Jolina, Benussi, Alberto, Cantoni, Valentina, Bertoux, Maxime, Bertrand, Anne, Brice, Alexis, Camuzat, Agnès, Colliot, Olivier, Sayah, Sabrina, Funkiewiez, Aurélie, Rinaldi, Daisy, Lombardi, Gemma, Nacmias, Benedetta, Saracino, Dario, Bessi, Valentina, Ferrari, Camilla, Cañada, Marta, Deramecourt, Vincent, Kuchcinski, Gregory, Lebouvier, Thibaud, Ourselin, Sebastien, Polito, Cristina, Rollin, Adeline, Poos, Jackie M., Russell, Lucy L., Peakman, Georgia, Bocchetta, Martina, Greaves, Caroline V., Jiskoot, Lize C., van der Ende, Emma L., Seelaar, Harro, Papma, Janne M., van den Berg, Esther, Pijnenburg, Yolande A.L., Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthias, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Carmela, Finger, Elizabeth, Vandenberghe, Rik, Medonça, Alexandre de, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Ber, Isabelle Le, Gerhard, Alex, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, van Swieten, John C., Rohrer, Jonathan D., Rossor, Martin N., Fox, Nick C., Warren, Jason D., Moore, Katrina, Convery, Rhian, Swift, Imogen J., Shafei, Rachelle, Heller, Carolin, Todd, Emily, Bouzigues, Arabella, Cash, David, Woollacott, Ione, Zetterberg, Henrik, Nelson, Annabel, Nicholas, Jennifer, Guerreiro, Rita, Bras, Jose, Thomas, David L., Mead, Simon, Meeter, Lieke, Pan-Man, Jessica, Minkelen, Rick van, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Gorostidi, Ana, Zulaica, Miren, Díez, Alina, Vil-Lanua, Jorge, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargalló, Nuria, Premi, Enrico, Gazzina, Stefano, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Thon-Berg, Hakan, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoe-Smith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans Otto, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Math Ieu, Ferreira, Catarina B., Miltenberger, Gabriel, Mpsych, Carolina Maruta, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Fede, Giuseppe Di, Giac-Cone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Velds-Man, Michele, Thompson, Paul, Langheinrich, Tobias, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Anderl-Straub, Sarah, Lombardi, Jolina, Benussi, Alberto, Cantoni, Valentina, Bertoux, Maxime, Bertrand, Anne, Brice, Alexis, Camuzat, Agnès, Colliot, Olivier, Sayah, Sabrina, Funkiewiez, Aurélie, Rinaldi, Daisy, Lombardi, Gemma, Nacmias, Benedetta, Saracino, Dario, Bessi, Valentina, Ferrari, Camilla, Cañada, Marta, Deramecourt, Vincent, Kuchcinski, Gregory, Lebouvier, Thibaud, Ourselin, Sebastien, Polito, Cristina, and Rollin, Adeline
Abstract: Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progran-ulin [GRN], and 73 microtubule-associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel-based morphometry to investigate the underlying neural substrates of the FCSRT. Results: All symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers. Discussion: The FCSRT detects presymptomatic deficits in C9orf72-and MAPT-associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD.
Published: 2021

86. Behavioural disorders in A lzheimer's disease: the descriptive and predictive role of brain 18 F ‐fluorodesoxyglucose‐positron emission tomography

Author: Cappelletto, Pietro, primary, Polito, Cristina, additional, Berti, Valentina, additional, Lombardi, Gemma, additional, Lucidi, Giulia, additional, Bessi, Valentina, additional, Sorbi, Sandro, additional, and Ferrari, Camilla, additional
Published: 2021
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87. Matching Clinical Diagnosis and Amyloid Biomarkers in Alzheimer’s Disease and Frontotemporal Dementia

Author: Giacomucci, Giulia, primary, Mazzeo, Salvatore, additional, Bagnoli, Silvia, additional, Casini, Matteo, additional, Padiglioni, Sonia, additional, Polito, Cristina, additional, Berti, Valentina, additional, Balestrini, Juri, additional, Ferrari, Camilla, additional, Lombardi, Gemma, additional, Ingannato, Assunta, additional, Sorbi, Sandro, additional, Nacmias, Benedetta, additional, and Bessi, Valentina, additional
Published: 2021
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88. Multicenter Study on Sleep and Circadian Alterations as Objective Markers of Mild Cognitive Impairment and Alzheimer’s Disease Reveals Sex Differences

Author: Guarnieri, Biancamaria, primary, Maestri, Michelangelo, additional, Cucchiara, Federico, additional, Lo Gerfo, Annalisa, additional, Schirru, Alessandro, additional, Arnaldi, Dario, additional, Mattioli, Pietro, additional, Nobili, Flavio, additional, Lombardi, Gemma, additional, Cerroni, Gianluigi, additional, Bartoli, Antonella, additional, Manni, Raffaele, additional, Sinforiani, Elena, additional, Terzaghi, Michele, additional, Arena, Maria Grazia, additional, Silvestri, Rosalia, additional, La Morgia, Chiara, additional, Di Perri, Maria Caterina, additional, Franzoni, Ferdinando, additional, Tognoni, Gloria, additional, Mancuso, Michelangelo, additional, Sorbi, Sandro, additional, Bonuccelli, Ubaldo, additional, Siciliano, Gabriele, additional, Faraguna, Ugo, additional, and Bonanni, Enrica, additional
Published: 2020
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89. Analysis of Feasibility, Adherence, and Appreciation of a Newly Developed Tele-Rehabilitation Program for People With MCI and VCI

Author: Mosca, Irene Eleonora, primary, Salvadori, Emilia, additional, Gerli, Filippo, additional, Fabbri, Laura, additional, Pancani, Silvia, additional, Lucidi, Giulia, additional, Lombardi, Gemma, additional, Bocchi, Leonardo, additional, Pazzi, Stefania, additional, Baglio, Francesca, additional, Vannetti, Federica, additional, Sorbi, Sandro, additional, and Macchi, Claudio, additional
Published: 2020
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90. Challenges in Alzheimer’s Disease Diagnostic Work-Up: Amyloid Biomarker Incongruences

Author: Lombardi, Gemma, primary, Pupi, Alberto, additional, Bessi, Valentina, additional, Polito, Cristina, additional, Padiglioni, Sonia, additional, Ferrari, Camilla, additional, Lucidi, Giulia, additional, Berti, Valentina, additional, De Cristofaro, Maria Teresa, additional, Piaceri, Irene, additional, Bagnoli, Silvia, additional, Nacmias, Benedetta, additional, and Sorbi, Sandro, additional
Published: 2020
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91. Concordance among neuropsychological profile, functional neuroimaging and pathological biomarkers in Primary Progressive Aphasia. A single-centre experience (675)

Author: Mazzeo, Salvatore, primary, Polito, Cristina, additional, Padiglioni, Sonia, additional, Berti, Valentina, additional, Bagnoli, Silvia, additional, Lombardi, Gemma, additional, Piaceri, Irene, additional, Carraro, Marco, additional, Ferrari, Camilla, additional, Nacmias, Benedetta, additional, Sorbi, Sandro, additional, and Bessi, Valentina, additional
Published: 2020
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92. Structural magnetic resonance imaging for the early diagnosis of dementia due to Alzheimer's disease in people with mild cognitive impairment

Author: Lombardi, Gemma, primary, Crescioli, Giada, additional, Cavedo, Enrica, additional, Lucenteforte, Ersilia, additional, Casazza, Giovanni, additional, Bellatorre, Alessandro-Giacco, additional, Lista, Chiara, additional, Costantino, Giorgio, additional, Frisoni, Giovanni, additional, Virgili, Gianni, additional, and Filippini, Graziella, additional
Published: 2020
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93. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study

Author: Moore, Katrina M, primary, Nicholas, Jennifer, additional, Grossman, Murray, additional, McMillan, Corey T, additional, Irwin, David J, additional, Massimo, Lauren, additional, Van Deerlin, Vivianna M, additional, Warren, Jason D, additional, Fox, Nick C, additional, Rossor, Martin N, additional, Mead, Simon, additional, Bocchetta, Martina, additional, Boeve, Bradley F, additional, Knopman, David S, additional, Graff-Radford, Neill R, additional, Forsberg, Leah K, additional, Rademakers, Rosa, additional, Wszolek, Zbigniew K, additional, van Swieten, John C, additional, Jiskoot, Lize C, additional, Meeter, Lieke H, additional, Dopper, Elise GP, additional, Papma, Janne M, additional, Snowden, Julie S, additional, Saxon, Jennifer, additional, Jones, Matthew, additional, Pickering-Brown, Stuart, additional, Le Ber, Isabelle, additional, Camuzat, Agnès, additional, Brice, Alexis, additional, Caroppo, Paola, additional, Ghidoni, Roberta, additional, Pievani, Michela, additional, Benussi, Luisa, additional, Binetti, Giuliano, additional, Dickerson, Bradford C, additional, Lucente, Diane, additional, Krivensky, Samantha, additional, Graff, Caroline, additional, Öijerstedt, Linn, additional, Fallström, Marie, additional, Thonberg, Håkan, additional, Ghoshal, Nupur, additional, Morris, John C, additional, Borroni, Barbara, additional, Benussi, Alberto, additional, Padovani, Alessandro, additional, Galimberti, Daniela, additional, Scarpini, Elio, additional, Fumagalli, Giorgio G, additional, Mackenzie, Ian R, additional, Hsiung, Ging-Yuek R, additional, Sengdy, Pheth, additional, Boxer, Adam L, additional, Rosen, Howie, additional, Taylor, Joanne B, additional, Synofzik, Matthis, additional, Wilke, Carlo, additional, Sulzer, Patricia, additional, Hodges, John R, additional, Halliday, Glenda, additional, Kwok, John, additional, Sanchez-Valle, Raquel, additional, Lladó, Albert, additional, Borrego-Ecija, Sergi, additional, Santana, Isabel, additional, Almeida, Maria Rosário, additional, Tábuas-Pereira, Miguel, additional, Moreno, Fermin, additional, Barandiaran, Myriam, additional, Indakoetxea, Begoña, additional, Levin, Johannes, additional, Danek, Adrian, additional, Rowe, James B, additional, Cope, Thomas E, additional, Otto, Markus, additional, Anderl-Straub, Sarah, additional, de Mendonça, Alexandre, additional, Maruta, Carolina, additional, Masellis, Mario, additional, Black, Sandra E, additional, Couratier, Philippe, additional, Lautrette, Geraldine, additional, Huey, Edward D, additional, Sorbi, Sandro, additional, Nacmias, Benedetta, additional, Laforce, Robert, additional, Tremblay, Marie-Pier L, additional, Vandenberghe, Rik, additional, Damme, Philip Van, additional, Rogalski, Emily J, additional, Weintraub, Sandra, additional, Gerhard, Alexander, additional, Onyike, Chiadi U, additional, Ducharme, Simon, additional, Papageorgiou, Sokratis G, additional, Ng, Adeline Su Lyn, additional, Brodtmann, Amy, additional, Finger, Elizabeth, additional, Guerreiro, Rita, additional, Bras, Jose, additional, Rohrer, Jonathan D, additional, Heller, Carolin, additional, Convery, Rhian S, additional, Woollacott, Ione OC, additional, Shafei, Rachelle M, additional, Graff-Radford, Jonathan, additional, Jones, David T, additional, Dheel, Christina M, additional, Savica, Rodolfo, additional, Lapid, Maria I, additional, Baker, Matt, additional, Fields, Julie A, additional, Gavrilova, Ralitza, additional, Domoto-Reilly, Kimiko, additional, Poos, Jackie M, additional, Van der Ende, Emma L, additional, Panman, Jessica L, additional, Donker Kaat, Laura, additional, Seelaar, Harro, additional, Richardson, Anna, additional, Frisoni, Giovanni, additional, Mega, Anna, additional, Fostinelli, Silvia, additional, Chiang, Huei-Hsin, additional, Alberici, Antonella, additional, Arighi, Andrea, additional, Fenoglio, Chiara, additional, Heuer, Hilary, additional, Miller, Bruce, additional, Karydas, Anna, additional, Fong, Jamie, additional, João Leitão, Maria, additional, Santiago, Beatriz, additional, Duro, Diana, additional, Ferreira, Carlos, additional, Gabilondo, Alazne, additional, De Arriba, Maria, additional, Tainta, Mikel, additional, Zulaica, Miren, additional, Ferreira, Catarina, additional, Semler, Elisa, additional, Ludolph, Albert, additional, Landwehrmeyer, Bernhard, additional, Volk, Alexander E, additional, Miltenberger, Gabriel, additional, Verdelho, Ana, additional, Afonso, Sónia, additional, Tartaglia, Maria Carmela, additional, Freedman, Morris, additional, Rogaeva, Ekaterina, additional, Ferrari, Camilla, additional, Piaceri, Irene, additional, Bessi, Valentina, additional, Lombardi, Gemma, additional, St-Onge, Frédéric, additional, Doré, Marie-Claire, additional, Bruffaerts, Rose, additional, Vandenbulcke, Mathieu, additional, Van den Stock, Jan, additional, Mesulam, M Marsel, additional, Bigio, Eileen, additional, Koros, Christos, additional, Papatriantafyllou, John, additional, Kroupis, Christos, additional, Stefanis, Leonidas, additional, Shoesmith, Christien, additional, Robertson, Erik, additional, Coppola, Giovanni, additional, Da Silva Ramos, Eliana Marisa, additional, and Geschwind, Daniel, additional
Published: 2020
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94. White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort

Author: Sudre, Carole H., Bocchetta, Martina, Cash, David, Thomas, David L., Woollacott, Ione, Dick, Katrina M., van Swieten, John, Borroni, Barbara, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Graff, Caroline, Tagliavini, Fabrizio, Frisoni, Giovanni, Laforce, Robert, Finger, Elizabeth, De Mendonça, Alexandre, Sorbi, Sandro, Ourselin, Sébastien, Cardoso, M. Jorge, Rohrer, Jonathan D., Andersson, Christin, Archetti, Silvana, Arighi, Andrea, Benussi, Luisa, Binetti, Giuliano, Black, Sandra, Cosseddu, Maura, Fallström, Marie, Ferreira, Carlos, Fenoglio, Chiara, Fox, Nick C., Freedman, Morris, Fumagalli, Giorgio, Gazzina, Stefano, Ghidoni, Roberta, Grisoli, Marina, Jelic, Vesna, Jiskoot, Lize, Keren, Ron, Lombardi, Gemma, Maruta, Carolina, Mead, Simon, Meeter, Lieke, van Minkelen, Rick, Nacmias, Benedetta, Öijerstedt, Linn, Padovani, Alessandro, Panman, Jessica, Pievani, Michela, Polito, Cristina, Premi, Enrico, Prioni, Sara, Rademakers, Rosa, Redaelli, Veronica, Rogaeva, Ekaterina, Rossi, Giacomina, Rossor, Martin N., Scarpini, Elio, Tang-Wai, David, Thonberg, Hakan, Tiraboschi, Pietro, Verdelho, Ana, Warren, Jason D., and Repositório da Universidade de Lisboa
Subjects: TIV, Total Intracranial volume, FTD, Frontotemporal dementia, CI, Confidence interval, PS, Presymptomatic, mental disorders, lcsh:R858-859.7, IQR, Inter Quartile Range, S, Symptomatic, lcsh:Computer applications to medicine. Medical informatics, WMH, White matter hyperintensity, behavioral disciplines and activities, lcsh:Neurology. Diseases of the nervous system, lcsh:RC346-429
Abstract: © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/)., Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members. An automatic detection and quantification algorithm was developed for determining load, location and appearance of WMH. Significant differences were seen only in the symptomatic GRN group compared with the other groups with no differences in the MAPT or C9orf72 groups: increased global load of WMH was seen, with WMH located in the frontal and occipital lobes more so than the parietal lobes, and nearer to the ventricles rather than juxtacortical. Although no differences were seen in the presymptomatic group as a whole, in the GRN cohort only there was an association of increased WMH volume with expected years from symptom onset. The appearance of the WMH was also different in the GRN group compared with the other groups, with the lesions in the GRN group being more similar to each other. The presence of WMH in those with progranulin deficiency may be related to the known role of progranulin in neuroinflammation, although other roles are also proposed including an effect on blood-brain barrier permeability and the cerebral vasculature. Future studies will be useful to investigate the longitudinal evolution of WMH and their potential use as a biomarker as well as post-mortem studies investigating the histopathological nature of the lesions., This work was funded by the UK Medical Research Council, the Italian Ministry of Health, and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant (CoEN015). The Dementia Research Centre is supported by Alzheimer's Research UK, Brain Research Trust, and The Wolfson Foundation. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit and the NIHR UCL/H Biomedical Research Centre. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). KD is supported by an Alzheimer's Society PhD Studentship (AS-PhD-2015-005). JBR is supported by the Wellcome Trust (103838) and the NIHR Cambridge Biomedical Research Centre. MM is supported by the Canadian Institutes of Health Research and the Ontario Research Fund. RL is supported by Réseau de médecine génétique appliquée, Fonds de recherche du Québec—Santé (FRQS). FT is supported by the Italian Ministry of Health. DG is supported by the Fondazione Monzino and Italian Ministry of Health, Ricerca Corrente. SS is supported by Cassa di Risparmio di Firenze (CRF 2013/0199) and the Ministry of Health RF-2010-2319722. SO is supported by the Engineering and Physical Sciences Research Council (EP/H046410/1, EP/J020990/1, EP/K005278), the Medical Research Council (MR/J01107X/1), the EU-FP7 project VPH-DARE@IT (FP7-ICT-2011-9-601055), and the National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative BW.mn.BRC10269). JvS is supported by The Netherlands Organisation for Health Research and Development Memorable grant (733050103) and Netherlands Alzheimer Foundation Memorable grant (733050103).
Published: 2017

95. Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia

Author: Rittman, Timothy, Borchert, Robin, Frisoni, Giovanni B, Rosser, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Laforce, Robert, Tang-Wai, David, Thomas, David L, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Finger, Elizabeth, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Mendonça, Alexandre, Sorbi, Sandro, Rohrer, Jonathan D, Rowe, James B, Initiative, Genetic Frontotemporal Dementia, Afonso, Sónia, Almeida, Maria Rosario, Jones, Simon, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, van Swieten, John, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Borroni, Barbara, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, Cosseddu, Maura, de Arriba, María, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M, Duro, Diana, Fenoglio, Chiara, Galimberti, Daniela, Ferrari, Camilla, Ferreira, Catarina B, Flanagana, Toby, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Masellis, Mario, Ghidoni, Roberta, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Tartaglia, Maria Carmela, Karnath, Hans-Otto, Keren, Ron, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Graff, Caroline, van Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Padovani, Alessandro, Panman, Jessica, Papma, Janne, Tagliavini, Fabrizio, Pievani, Michela, Pijnenburg, Yolande, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rossi, Giacomina, Rittman, Timothy [0000-0003-1063-6937], Jones, Simon [0000-0001-9695-0702], Rowe, James [0000-0001-7216-8679], Apollo - University of Cambridge Repository, and Repositório da Universidade de Lisboa
Subjects: Adult, Male, Heterozygote, Tau Proteins/genetics, pathology [Nerve Net], C9orf72 Protein/genetics, MAPT protein, human, Neuroimaging, tau Proteins, Brain/diagnostic imaging/pathology/physiopathology, physiopathology [Brain], Article, ddc:616.89, Frontotemporal Dementia/genetics/pathology/psychology, Cognition, pathology [Brain], physiopathology [Nerve Net], Genetics, Humans, ddc:610, diagnostic imaging [Brain], genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], Aged, Connectivity, C9orf72 Protein, diagnostic imaging [Nerve Net], Brain, Organ Size, Middle Aged, Magnetic Resonance Imaging, psychology [Frontotemporal Dementia], Frontotemporal dementia, Functional imaging, genetics [tau Proteins], FOS: Biological sciences, Frontotemporal Dementia, pathology [Frontotemporal Dementia], Female, C9orf72 protein, human, Atrophy, Nerve Net, Nerve Net/diagnostic imaging/pathology/physiopathology
Abstract: © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically., This work was funded by the UK Medical Research Council, the Italian Ministry of Health, and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant [grant number CoEN015]. JBR was supported by the Wellcome Trust [grant number 103838]. JBR, RB, TR, and SJ were supported by the NIHR Cambridge Biomedical Research Centre and Medical Research Council [grant number G1100464]. The Dementia Research Centre at UCL is supported by Alzheimer's Research UK, Brain Research Trust, and The Wolfson Foundation, NIHR Queen Square Dementia Biomedical Research Unit, NIHR UCL/H Biomedical Research Centre and Dementia Platforms UK. JDR is supported by an MRC Clinician Scientist Fellowship [grant number MR/M008525/1] and has received funding from the NIHR Rare Disease Translational Research Collaboration [grant number BRC149/NS/MH]. MM is supported by the Canadian Institutes of Health Research, Department of Medicine at Sunnybrook Health Sciences Centre and the University of Toronto, and the Sunnybrook Research Institute. RL is supported by Réseau de médecine génétique appliquée, Fonds de recherche du Québec—Santé [grant number FRQS]. FT is supported by the Italian Ministry of Health. DG is supported by the Fondazione Monzino and Italian Ministry of Health, Ricerca Corrente. SS is supported by Cassa di Risparmio di Firenze [grant number CRF 2013/0199] and the Ministry of Health [grant number RF-2010-2319722]. JvS is supported by The Netherlands Organisation for Health Research and Development Memorable grant [grant number 733050103] and Netherlands Alzheimer Foundation Memorable grant [grant number 733050103].
Published: 2019
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96. Behavioural disorders in Alzheimer's disease: the descriptive and predictive role of brain 18F‐fluorodesoxyglucose‐positron emission tomography.

Author: Cappelletto, Pietro, Polito, Cristina, Berti, Valentina, Lombardi, Gemma, Lucidi, Giulia, Bessi, Valentina, Sorbi, Sandro, and Ferrari, Camilla
Subjects: BRAIN metabolism, ALZHEIMER'S disease, TEMPORAL lobe, AGITATION (Psychology), RETROSPECTIVE studies, FACIAL expression, BEHAVIOR disorders, RADIOPHARMACEUTICALS, DEMENTIA, AGGRESSION (Psychology), DEOXY sugars, LONGITUDINAL method
Abstract: Background: Alzheimer's disease (AD) has a high incidence in the elderly. Besides cognitive disorders, patients may also develop behavioural and psychological symptoms of dementia (BPSD), which can be particularly disabling for patients and families. BPSD encompass a wide range of symptoms, among which psychotic symptoms and disruptive behaviours often prompt the first related hospitalization and request for family support. The aetiological mechanism of BPSD has not yet been clarified, and no predictive or risk factors have been identified. The main objectives of our study are to describe the frequency of aggression/agitation and psychotic symptoms, defined 'positive BPSD', in a cohort of 60 AD patients, identify areas of the brain involved in behavioural symptomatology through brain 18F‐fluorodesoxyglucose‐positron emission tomography (FDG‐PET), and investigate a potential predictive role of brain FDG‐PET in BPSD development. Methods: A cohort of 60 AD patients was retrospectively enrolled and regularly followed for at least 3 years. Each subject underwent brain FDG‐PET at the time of diagnosis. Patients were divided into three groups based on the presence of behavioural disturbances: present, absent, and developed later. Results: Of the 60 AD patients in the cohort, 52% had positive BPSD: 17 at baseline and 14 during the 3‐year follow‐up. FDG‐PET identified an association between hypometabolism in the bilateral temporal lobes and the presence of BPSD, and showed initial hypometabolism in the postero‐temporal lobes 3 years before symptom onset. Conclusions: Positive BPSD are frequently manifested in AD. Our study identified the temporal lobes as the neurobiological substrate of positive BPSD and FDG‐PET as a potential instument to predict their developement. Temporal lobes are involved in processing facial expression and recognizing emotions; an impairment of these functions could cause delusions and agitated/aggressive behaviour. To confirm the potential predictive role of FDG‐PET in the onset of BPSD in AD, further studies are needed. [ABSTRACT FROM AUTHOR]
Published: 2021
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97. A case of limbic encephalitis evolving into a frontotemporal dementia‐like picture

Author: Lombardi, Gemma, primary, Matà, Sabrina, additional, Berti, Valentina, additional, Padiglioni, Sonia, additional, Ginestroni, Andrea, additional, Piaceri, Irene, additional, Bagnoli, Silvia, additional, Nacmias, Benedetta, additional, De Cristofaro, Maria Teresa, additional, Pupi, Alberto, additional, and Sorbi, Sandro, additional
Published: 2019
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98. High Frequency of Crossed Aphasia in Dextral in an Italian Cohort of Patients with Logopenic Primary Progressive Aphasia

Author: Ferrari, Camilla, primary, Polito, Cristina, additional, Berti, Valentina, additional, Lombardi, Gemma, additional, Lucidi, Giulia, additional, Bessi, Valentina, additional, Bagnoli, Silvia, additional, Piaceri, Irene, additional, Nacmias, Benedetta, additional, and Sorbi, Sandro, additional
Published: 2019
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99. Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study

Author: van der Ende, Emma L, primary, Meeter, Lieke H, additional, Poos, Jackie M, additional, Panman, Jessica L, additional, Jiskoot, Lize C, additional, Dopper, Elise G P, additional, Papma, Janne M, additional, de Jong, Frank Jan, additional, Verberk, Inge M W, additional, Teunissen, Charlotte, additional, Rizopoulos, Dimitris, additional, Heller, Carolin, additional, Convery, Rhian S, additional, Moore, Katrina M, additional, Bocchetta, Martina, additional, Neason, Mollie, additional, Cash, David M, additional, Borroni, Barbara, additional, Galimberti, Daniela, additional, Sanchez-Valle, Raquel, additional, Laforce, Robert, additional, Moreno, Fermin, additional, Synofzik, Matthis, additional, Graff, Caroline, additional, Masellis, Mario, additional, Carmela Tartaglia, Maria, additional, Rowe, James B, additional, Vandenberghe, Rik, additional, Finger, Elizabeth, additional, Tagliavini, Fabrizio, additional, de Mendonça, Alexandre, additional, Santana, Isabel, additional, Butler, Chris, additional, Ducharme, Simon, additional, Gerhard, Alex, additional, Danek, Adrian, additional, Levin, Johannes, additional, Otto, Markus, additional, Frisoni, Giovanni B, additional, Cappa, Stefano, additional, Pijnenburg, Yolande A L, additional, Rohrer, Jonathan D, additional, van Swieten, John C, additional, Rossor, Martin N., additional, Warren, Jason D., additional, Fox, Nick C., additional, Woollacott, Ione O.C., additional, Shafei, Rachelle, additional, Greaves, Caroline, additional, Guerreiro, Rita, additional, Bras, Jose, additional, Thomas, David L., additional, Nicholas, Jennifer, additional, Mead, Simon, additional, van Minkelen, Rick, additional, Barandiaran, Myriam, additional, Indakoetxea, Begoña, additional, Gabilondo, Alazne, additional, Tainta, Mikel, additional, de Arriba, Maria, additional, Gorostidi, Ana, additional, Zulaica, Miren, additional, Villanua, Jorge, additional, Diaz, Zigor, additional, Borrego-Ecija, Sergi, additional, Olives, Jaume, additional, Lladó, Albert, additional, Balasa, Mircea, additional, Antonell, Anna, additional, Bargallo, Nuria, additional, Premi, Enrico, additional, Cosseddu, Maura, additional, Gazzina, Stefano, additional, Padovani, Alessandro, additional, Gasparotti, Roberto, additional, Archetti, Silvana, additional, Black, Sandra, additional, Mitchell, Sara, additional, Rogaeva, Ekaterina, additional, Freedman, Morris, additional, Keren, Ron, additional, Tang-Wai, David, additional, Öijerstedt, Linn, additional, Andersson, Christin, additional, Jelic, Vesna, additional, Thonberg, Hakan, additional, Arighi, Andrea, additional, Fenoglio, Chiara, additional, Scarpini, Elio, additional, Fumagalli, Giorgio, additional, Cope, Thomas, additional, Timberlake, Carolyn, additional, Rittman, Timothy, additional, Shoesmith, Christen, additional, Bartha, Robart, additional, Rademakers, Rosa, additional, Wilke, Carlo, additional, Karnath, Hans-Otto, additional, Bender, Benjamin, additional, Bruffaerts, Rose, additional, Vandamme, Philip, additional, Vandenbulcke, Mathieu, additional, Ferreira, Catarina B., additional, Miltenberger, Gabriel, additional, Maruta, Carolina, additional, Verdelho, Ana, additional, Afonso, Sónia, additional, Taipa, Ricardo, additional, Caroppo, Paola, additional, Di Fede, Giuseppe, additional, Giaccone, Giorgio, additional, Prioni, Sara, additional, Redaelli, Veronica, additional, Rossi, Giacomina, additional, Tiraboschi, Pietro, additional, Duro, Diana, additional, Rosario Almeida, Maria, additional, Castelo-Branco, Miguel, additional, João Leitão, Maria, additional, Tabuas-Pereira, Miguel, additional, Santiago, Beatriz, additional, Gauthier, Serge, additional, Schonecker, Sonja, additional, Semler, Elisa, additional, Anderl-Straub, Sarah, additional, Benussi, Luisa, additional, Binetti, Giuliano, additional, Ghidoni, Roberta, additional, Pievani, Michela, additional, Lombardi, Gemma, additional, Nacmias, Benedetta, additional, Ferrari, Camilla, additional, and Bessi, Valentina, additional
Published: 2019
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100. Clinical and neuroimaging profiles to identify C9orf72 ‐FTD patients and serum Neurofilament to monitor the progression and the severity of the disease

Author: Lucidi, Giulia, primary, Berti, Valentina, additional, Piaceri, Irene, additional, Ginestroni, Andrea, additional, Lombardi, Gemma, additional, Ferrari, Camilla, additional, Polito, Cristina, additional, Bessi, Valentina, additional, Pupi, Alberto, additional, Nacmias, Benedetta, additional, Sorbi, Sandro, additional, and Bagnoli, Silvia, additional
Published: 2019
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230 results on '"Lombardi, Gemma"'

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