Search

Your search keyword '"Laforce, Robert"' showing total 962 results
Start Over Author "Laforce, Robert"
962 results on '"Laforce, Robert"'

54. Association of low frequency variants with regional cortical grey matter volumes in genetic frontotemporal dementia: Results from GENFI

Author

Mirza, Saira S., primary, Pasternak, Maurice, additional, Patterson, Andrew D., additional, Tartaglia, Carmela, additional, Mitchell, Sara Berman, additional, Black, Sandra E., additional, Freedman, Morris, additional, Tang‐Wai, David F., additional, Rogaeva, Ekaterina, additional, Cash, David M, additional, Bocchetta, Martina, additional, van Swieten, John C., additional, Laforce, Robert, additional, Tagliavini, Fabrizio, additional, Borroni, Barbara, additional, Galimberti, Daniela, additional, Rowe, James B., additional, Graff, Caroline, additional, Finger, Elizabeth, additional, Sorbi, Sandro, additional, de Mendonça, Alexandre, additional, Butler, Christopher R., additional, Gerhard, Alexander, additional, Sanchez‐Valle, Raquel, additional, Moreno, Fermin, additional, Synofzik, Matthis, additional, Vandenberghe, Rik, additional, Ducharme, Simon, additional, Levin, Johannes, additional, Danek, Adrian, additional, Otto, Markus, additional, Santana, Isabel, additional, Rohrer, Jonathan D., additional, and Masellis, Mario, additional

Published
2023
Full Text
View/download PDF

55. Association of low‐frequency and rare variants with cognition in genetic frontotemporal dementia: Results from GENFI

Author

Mirza, Saira S., primary, Patterson, Andrew D., additional, Tartaglia, Carmela, additional, Mitchell, Sara Berman, additional, Black, Sandra E., additional, Freedman, Morris, additional, Tang‐Wai, David F., additional, Rogaeva, Ekaterina, additional, Cash, David M, additional, Bocchetta, Martina, additional, van Swieten, John C., additional, Laforce, Robert, additional, Tagliavini, Fabrizio, additional, Borroni, Barbara, additional, Galimberti, Daniela, additional, Rowe, James B., additional, Graff, Caroline, additional, Finger, Elizabeth, additional, Sorbi, Sandro, additional, de Mendonça, Alexandre, additional, Butler, Christopher R., additional, Gerhard, Alexander, additional, Sanchez‐Valle, Raquel, additional, Moreno, Fermin, additional, Synofzik, Matthis, additional, Vandenberghe, Rik, additional, Ducharme, Simon, additional, Levin, Johannes, additional, Danek, Adrian, additional, Otto, Markus, additional, Santana, Isabel, additional, Rohrer, Jonathan D., additional, and Masellis, Mario, additional

Published
2023
Full Text
View/download PDF

56. Developing a mass spectrometric assay to measure granulin peptides in CSF for progranulin‐associated frontotemporal dementia

Author

Swift, Imogen J, primary, Weiner, Sophia, additional, Sauer, Mathias, additional, Nilsson, Johanna, additional, van Swieten, John C., additional, Jiskoot, Lize C., additional, Seelaar, Harro, additional, Moreno, Fermin, additional, Sánchez‐Valle, Raquel, additional, Laforce, Robert, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, Carmela, additional, Rowe, James B., additional, Borroni, Barbara, additional, Finger, Elizabeth, additional, Synofzik, Matthis, additional, Galimberti, Daniela, additional, Vandenberghe, Rik, additional, de Mendonça, Alexandre, additional, Butler, Christopher, additional, Gerhard, Alexander, additional, Ducharme, Simon, additional, Ber, Isabelle Le, additional, Tiraboschi, Pietro, additional, Santana, Isabel, additional, Pasquier, Florence, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Brinkmalm, Ann, additional, Zetterberg, Henrik, additional, Rohrer, Jonathan D., additional, Esteve, Aitana Sogorb, additional, and Gobom, Johan, additional

Published
2023
Full Text
View/download PDF

57. Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study

Author

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

Published
2019
Full Text
View/download PDF

58. The Nonverbal Processing of Actions Is an Area of Relative Strength in the Semantic Variant of Primary Progressive Aphasia

Author

Auclair-Ouellet, Noemie, Fossard, Marion, Macoir, Joel, and Laforce, Robert, Jr.

Subjects
Aphasia, Cognition, Health
Abstract

Purpose: Better performance for actions compared to objects has been reported in the semantic variant of primary progressive aphasia (svPPA). This study investigated the influence of the assessment task (naming, semantic picture matching) over the dissociation between objects and actions. Method: Ten individuals with svPPA and 17 matched controls completed object and action naming tests, and object and action semantic picture matching tests. Performance was compared between the svPPA and control groups, within the svPPA group, and for each participant with svPPA versus the control group individually. Results: Compared to controls, participants with svPPA were impaired on object and action naming, and object and action semantic picture matching. As a group, participants with svPPA had an advantage for actions over objects and for semantic picture matching tests over naming tests. Eight participants had a better performance for actions compared to objects in naming, with three showing a significant difference. Nine participants had a better performance for actions compared to objects in semantic picture matching, with six showing a significant difference. For objects, semantic picture matching was better than naming in nine participants, with five showing a significant difference. For actions, semantic picture matching was better than naming in all 10 participants, with nine showing a significant difference. Conclusion: The nonverbal processing of actions, as assessed with a semantic picture matching test, is an area of relative strength in svPPA. Clinical implications for assessment planning and interpretation and theoretical implications for current models of semantic cognition are discussed., The semantic variant of primary progressive aphasia (svPPA; also known as semantic dementia) is a severe impairment of semantic cognition that affects various aspects of behavior, most strikingly language (Gomo-Tempini [...]

Published
2020
Full Text
View/download PDF

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

Author

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, 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, de Arriba, María, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M., Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Flanagana, Toby, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Ghidoni, Roberta, 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, van Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Padovani, Alessandro, Panman, Jessica, Papma, Janne, Pievani, Michela, Pijnenburg, Yolande, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rossi, Giacomina, Rosser, 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, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Rittman, Timothy, Borchert, Robin, Jones, Simon, van Swieten, John, Borroni, Barbara, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Tagliavini, Fabrizio, Frisoni, Giovanni B., Laforce, Robert, Jr., Finger, Elizabeth, Mendonça, Alexandre, Sorbi, Sandro, Rohrer, Jonathan D., and Rowe, James B.

Published
2019
Full Text
View/download PDF

61. The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia: The chronnectome fingerprint

Author

Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Luisa, Binetti, Giuliano, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, de Arriba, María, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M., Duro, Diana, Fenoglio, Chiara, Ferreira, Carlos, Ferreira, Catarina B., Flanagan, Toby, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gauthier, Serge, Ghidoni, Roberta, 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, van Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Panman, Jessica, Papma, Janne, Patzig, Maximilian, Pievani, Michela, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Tang-Wai, David, Thomas, David L., Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Zetterberg, Henrik, Zulaica, Miren, Premi, Enrico, Calhoun, Vince D., Diano, Matteo, Gazzina, Stefano, Cosseddu, Maura, Alberici, Antonella, Archetti, Silvana, Paternicò, Donata, Gasparotti, Roberto, van Swieten, John, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Robert, Jr., Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James, Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Butler, Chris, Ducharme, Simon, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Frisoni, Giovanni, Cappa, Stefano, Sorbi, Sandro, Padovani, Alessandro, Rohrer, Jonathan D., and Borroni, Barbara

Published
2019
Full Text
View/download PDF

62. Spatiotemporal analysis for detection of pre-symptomatic shape changes in neurodegenerative diseases: Initial application to the GENFI cohort

Author

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, Roberta, 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, Tartaglia, Carmela, Thonberg, Hakan, Tiraboschi, Pietro, Verdelho, Ana, Warren, Jason, Cury, Claire, Durrleman, Stanley, Cash, David M., Lorenzi, Marco, Nicholas, Jennifer M., Bocchetta, Martina, van Swieten, John C., Borroni, Barbara, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Graff, Caroline, Tagliavini, Fabrizio, Frisoni, Giovanni B., Laforce, Robert, Jr., Finger, Elizabeth, de Mendonça, Alexandre, Sorbi, Sandro, Ourselin, Sebastien, Rohrer, Jonathan D., and Modat, Marc

Published
2019
Full Text
View/download PDF

64. Parallel ICA of FDG-PET and PiB-PET in three conditions with underlying Alzheimer's pathology

Author

Laforce, Robert, Tosun, Duygu, Ghosh, Pia, Lehmann, Manja, Madison, Cindee M, Weiner, Michael W, Miller, Bruce L, Jagust, William J, and Rabinovici, Gil D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Dementia, Brain Disorders, Alzheimer's Disease, Clinical Research, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, Biomedical Imaging, Aging, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Alzheimer Disease, Amyloid beta-Peptides, Aniline Compounds, Benzothiazoles, Biomarkers, Brain, Data Interpretation, Statistical, Female, Fluorodeoxyglucose F18, Glucose, Humans, Image Interpretation, Computer-Assisted, Male, Middle Aged, Multimodal Imaging, Positron-Emission Tomography, Principal Component Analysis, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Thiazoles, Multivariate data analysis, Parallel ICA, Alzheimer's disease, Amyloid imaging, PiB-PET, FDG-PET, Functional connectivity, Networks, AD or AD-memory, Alzheimer's disease, AD-language or LPA, logopenic variant primary progressive aphasia, AUC, area under the curve, PCA or AD-visuospatial, posterior cortical atrophy, PCC, posterior cingulate cortex, PPC, posterior parietal cortex, Biological psychology, Clinical and health psychology
Abstract

The relationships between clinical phenotype, β-amyloid (Aβ) deposition and neurodegeneration in Alzheimer's disease (AD) are incompletely understood yet have important ramifications for future therapy. The goal of this study was to utilize multimodality positron emission tomography (PET) data from a clinically heterogeneous population of patients with probable AD in order to: (1) identify spatial patterns of Aβ deposition measured by ((11)C)-labeled Pittsburgh Compound B (PiB-PET) and glucose metabolism measured by FDG-PET that correlate with specific clinical presentation and (2) explore associations between spatial patterns of Aβ deposition and glucose metabolism across the AD population. We included all patients meeting the criteria for probable AD (NIA-AA) who had undergone MRI, PiB and FDG-PET at our center (N = 46, mean age 63.0 ± 7.7, Mini-Mental State Examination 22.0 ± 4.8). Patients were subclassified based on their cognitive profiles into an amnestic/dysexecutive group (AD-memory; n = 27), a language-predominant group (AD-language; n = 10) and a visuospatial-predominant group (AD-visuospatial; n = 9). All patients were required to have evidence of amyloid deposition on PiB-PET. To capture the spatial distribution of Aβ deposition and glucose metabolism, we employed parallel independent component analysis (pICA), a method that enables joint analyses of multimodal imaging data. The relationships between PET components and clinical group were examined using a Receiver Operator Characteristic approach, including age, gender, education and apolipoprotein E ε4 allele carrier status as covariates. Results of the first set of analyses independently examining the relationship between components from each modality and clinical group showed three significant components for FDG: a left inferior frontal and temporoparietal component associated with AD-language (area under the curve [AUC] 0.82, p = 0.011), and two components associated with AD-visuospatial (bilateral occipito-parieto-temporal [AUC 0.85, p = 0.009] and right posterior cingulate cortex [PCC]/precuneus and right lateral parietal [AUC 0.69, p = 0.045]). The AD-memory associated component included predominantly bilateral inferior frontal, cuneus and inferior temporal, and right inferior parietal hypometabolism but did not reach significance (AUC 0.65, p = 0.062). None of the PiB components correlated with clinical group. Joint analysis of PiB and FDG with pICA revealed a correlated component pair, in which increased frontal and decreased PCC/precuneus PiB correlated with decreased FDG in the frontal, occipital and temporal regions (partial r = 0.75, p

Published
2014

65. LMNB1‐duplication mediated nuclear architecture alteration and demyelination of cerebral white matter in a patient with ADLD.

Author

Roy, Vincent, Bienjonetti, Isabella, Brodeur, Alyssa, Dion‐Albert, Laurence, Touzel‐Deschênes, Lydia, Gould, Peter V., Saikali, Stephan, Laforce, Robert, and Gros‐Louis, François

Subjects
WHITE matter (Nerve tissue), DEMYELINATION, CENTRAL nervous system, AUTOPSY, FAMILIAL spastic paraplegia, NUCLEAR membranes, SPINAL cord, VOXEL-based morphometry
Published
2024
Full Text
View/download PDF

66. Characterizing the Clinical Features and Atrophy Patterns of MAPT-Related Frontotemporal Dementia With Disease Progression Modeling

Author

Young, Alexandra L., Bocchetta, Martina, Russell, Lucy L., Convery, Rhian S., Peakman, Georgia, Todd, Emily, Cash, David M., Greaves, Caroline V., van Swieten, John, Jiskoot, Lize, Seelaar, Harro, Moreno, Fermin, Sanchez-Valle, Raquel, Borroni, Barbara, Laforce, Robert, Jr, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alex, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Williams, Steven C.R., Alexander, Daniel C., Rohrer, Jonathan D., Rossor, Martin N., Fox, Nick C., Warren, Jason D., Woollacott, Ione, Shafei, Rachelle, Heller, Carolin, Swift, Imogen J, Moore, Katrina, Guerreiro, Rita, Bras, Jose, Thomas, David L., Nicholas, Jennifer, Mead, Simon, Meeter, Lieke, Panman, Jessica, Papma, Janne M., Poos, Jackie, van Minkelen, Rick, Pijnenburg, Yolande, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, de Arriba, María, Gorostidi, Ana, Zulaica, Miren, Villanua, Jorge, Díaz, Zigor, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargalló, Nuria, Premi, Enrico, Cosseddu, Maura, Gazzina, Stefano, Padovani, Alessandro, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Thonberg, Hakan, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnath, Hans Otto, Bender, Benjamin, Bruffaerts, Rose, Van Damme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B., Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Di Fede, Giuseppe, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Branco, Miguel Castelo, Leitão, Maria João, Pereira, Miguel Tábuas, Santiago, Beatriz, Gauthier, Serge, Neto, Pedro Rosa, Veldsman, Michele, Thompson, Paul, Prix, Catharina, Hoegen, Tobias, Mag.rer.nat, Elisabeth Wlasich, Loosli, Sandra, Schönecker, Sonja, Dr.hum.bio, Elisa Semler, Psych, Dipl., Anderl-Straub, Sarah, Psych, Dipl., Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, and Bessi, Valentina

Published
2021
Full Text
View/download PDF

67. Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort

Author

Samra, Kiran, primary, MacDougall, Amy M., additional, Bouzigues, Arabella, additional, Bocchetta, Martina, additional, Cash, David M., additional, Greaves, Caroline V., additional, Convery, Rhian S., additional, van Swieten, John C., additional, Jiskoot, Lize, additional, Seelaar, Harro, additional, Moreno, Fermin, additional, Sanchez-Valle, Raquel, additional, Laforce, Robert, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, Maria Carmela, additional, Rowe, James B., additional, Borroni, Barbara, additional, Finger, Elizabeth, additional, Synofzik, Matthis, additional, Galimberti, Daniela, additional, Vandenberghe, Rik, additional, de Mendonça, Alexandre, additional, Butler, Chris R., additional, Gerhard, Alex, additional, Ducharme, Simon, additional, Le Ber, Isabelle, additional, Tiraboschi, Pietro, additional, Santana, Isabel, additional, Pasquier, Florence, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Rohrer, Jonathan D., additional, Russell, Lucy L., additional, Nelson, Annabel, additional, Thomas, David L., additional, Todd, Emily, additional, Benotmane, Hanya, additional, Nicholas, Jennifer, additional, Shafei, Rachelle, additional, Timberlake, Carolyn, additional, Cope, Thomas, additional, Rittman, Timothy, additional, Benussi, Alberto, additional, Premi, Enrico, additional, Gasparotti, Roberto, additional, Archetti, Silvana, additional, Gazzina, Stefano, additional, Cantoni, Valentina, additional, Arighi, Andrea, additional, Fenoglio, Chiara, additional, Scarpini, Elio, additional, Fumagalli, Giorgio, additional, Borracci, Vittoria, additional, Rossi, Giacomina, additional, Giaccone, Giorgio, additional, Di Fede, Giuseppe, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Redaelli, Veronica, additional, Tang-Wai, David, additional, Rogaeva, Ekaterina, additional, Castelo-Branco, Miguel, additional, Freedman, Morris, additional, Keren, Ron, additional, Black, Sandra, additional, Mitchell, Sara, additional, Shoesmith, Christen, additional, Bartha, Robart, additional, Rademakers, Rosa, additional, Poos, Jackie, additional, Papma, Janne M., additional, Giannini, Lucia, additional, van Minkelen, Rick, additional, Pijnenburg, Yolande, additional, Nacmias, Benedetta, additional, Ferrari, Camilla, additional, Polito, Cristina, additional, Lombardi, Gemma, additional, Bessi, Valentina, additional, Veldsman, Michele, additional, Andersson, Christin, additional, Thonberg, Hakan, additional, Öijerstedt, Linn, additional, Jelic, Vesna, additional, Thompson, Paul, additional, Langheinrich, Tobias, additional, Lladó, Albert, additional, Antonell, Anna, additional, Olives, Jaume, additional, Balasa, Mircea, additional, Bargalló, Nuria, additional, Borrego-Ecija, Sergi, additional, Verdelho, Ana, additional, Maruta, Carolina, additional, Ferreira, Catarina B., additional, Miltenberger, Gabriel, additional, do Couto, Frederico Simões, additional, Gabilondo, Alazne, additional, Gorostidi, Ana, additional, Villanua, Jorge, additional, Cañada, Marta, additional, Tainta, Mikel, additional, Zulaica, Miren, additional, Barandiaran, Myriam, additional, Alves, Patricia, additional, Bender, Benjamin, additional, Wilke, Carlo, additional, Graf, Lisa, additional, Vogels, Annick, additional, Vandenbulcke, Mathieu, additional, Van Damme, Philip, additional, Bruffaerts, Rose, additional, Poesen, Koen, additional, Rosa-Neto, Pedro, additional, Gauthier, Serge, additional, Camuzat, Agnès, additional, Brice, Alexis, additional, Bertrand, Anne, additional, Funkiewiez, Aurélie, additional, Rinaldi, Daisy, additional, Saracino, Dario, additional, Colliot, Olivier, additional, Sayah, Sabrina, additional, Prix, Catharina, additional, Wlasich, Elisabeth, additional, Wagemann, Olivia, additional, Loosli, Sandra, additional, Schönecker, Sonja, additional, Hoegen, Tobias, additional, Lombardi, Jolina, additional, Anderl-Straub, Sarah, additional, Rollin, Adeline, additional, Kuchcinski, Gregory, additional, Bertoux, Maxime, additional, Lebouvier, Thibaud, additional, Deramecourt, Vincent, additional, Santiago, Beatriz, additional, Duro, Diana, additional, Leitão, Maria João, additional, Almeida, Maria Rosario, additional, Tábuas-Pereira, Miguel, additional, and Afonso, Sónia, additional

Published
2023
Full Text
View/download PDF

68. Patterns of gray matter atrophy in genetic frontotemporal dementia: results from the GENFI study

Author

Andersson, Christin, Archetti, Silvana, Arighi, Andrea, Benussi, Luisa, Black, Sandra, Cosseddu, Maura, Fallström, Marie, Ferreira, Carlos, Fenoglio, Chiara, Fox, Nick, 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, Scarpini, Elio, Tang-Wai, David, Tartaglia, Carmela, Thonberg, Hakan, Tiraboschi, Pietro, Verdelho, Ana, Warren, Jason, Cash, David M., Bocchetta, Martina, Thomas, David L., Dick, Katrina M., van Swieten, John C., Borroni, Barbara, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Graff, Caroline, Tagliavini, Fabrizio, Frisoni, Giovanni B., Laforce, Robert, Jr., Finger, Elizabeth, de Mendonça, Alexandre, Sorbi, Sandro, Rossor, Martin N., Ourselin, Sebastien, and Rohrer, Jonathan D.

Published
2018
Full Text
View/download PDF

69. Interrater reliability of the new criteria for behavioral variant frontotemporal dementia

Author

LaMarre, Amanda K, Rascovsky, Katya, Bostrom, Alan, Toofanian, Parnian, Wilkins, Sarah, Sha, Sharon J, Perry, David C, Miller, Zachary A, Naasan, Georges, Laforce, Robert Jr, Hagen, Jayne, Takada, Leonel T, Tartaglia, Maria Carmela, Kang, Gail, Galasko, Douglas, Salmon, David P, Farias, Sarah Tomaszewski, Kaur, Berneet, Olichney, John M, Quitania Park, Lovingly, Mendez, Mario F, Tsai, Po-Heng, Teng, Edmond, Dickerson, Bradford Clark, Domoto-Reilly, Kimiko, McGinnis, Scott, Miller, Bruce L, and Kramer, Joel H

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Rare Diseases, Alzheimer's Disease, Behavioral and Social Science, Frontotemporal Dementia (FTD), Alzheimer's Disease Related Dementias (ADRD), Dementia, Aphasia, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Acquired Cognitive Impairment, Mental Health, Neurological, Aged, Aged, 80 and over, Female, Frontotemporal Dementia, Humans, Male, Middle Aged, Neuropsychological Tests, Observer Variation, Physicians, Psychology, Single-Blind Method, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo evaluate the interrater reliability of the new International Behavioural Variant FTD Criteria Consortium (FTDC) criteria for behavioral variant frontotemporal dementia (bvFTD).MethodsTwenty standardized clinical case modules were developed for patients with a range of neurodegenerative diagnoses, including bvFTD, primary progressive aphasia (nonfluent, semantic, and logopenic variant), Alzheimer disease, and Lewy body dementia. Eighteen blinded raters reviewed the modules and 1) rated the presence or absence of core diagnostic features for the FTDC criteria, and 2) provided an overall diagnostic rating. Interrater reliability was determined by κ statistics for multiple raters with categorical ratings.ResultsThe mean κ value for diagnostic agreement was 0.81 for possible bvFTD and 0.82 for probable bvFTD ("almost perfect agreement"). Interrater reliability for 4 of the 6 core features had "substantial" agreement (behavioral disinhibition, perseverative/compulsive, sympathy/empathy, hyperorality; κ = 0.61-0.80), whereas 2 had "moderate" agreement (apathy/inertia, neuropsychological; κ = 0.41-0.6). Clinician years of experience did not significantly influence rater accuracy.ConclusionsThe FTDC criteria show promise for improving the diagnostic accuracy and reliability of clinicians and researchers. As disease-altering therapies are developed, accurate differential diagnosis between bvFTD and other neurodegenerative diseases will become increasingly important.

Published
2013

70. Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer’s disease

Author

Lehmann, Manja, Ghosh, Pia M, Madison, Cindee, Laforce, Robert, Corbetta-Rastelli, Chiara, Weiner, Michael W, Greicius, Michael D, Seeley, William W, Gorno-Tempini, Maria L, Rosen, Howard J, Miller, Bruce L, Jagust, William J, and Rabinovici, Gil D

Subjects
Biological Psychology, Psychology, Acquired Cognitive Impairment, Dementia, Aphasia, Aging, Neurodegenerative, Clinical Research, Eye Disease and Disorders of Vision, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, Alzheimer's Disease, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Amyloid, Female, Fluorodeoxyglucose F18, Glucose, Humans, Image Interpretation, Computer-Assisted, Male, Middle Aged, Neuropsychological Tests, Phenotype, Plaque, Amyloid, Positron-Emission Tomography, Radiopharmaceuticals, Alzheimer's disease, posterior cortical atrophy, logopenic variant of PPA, positron emission tomography, functional networks, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract

The factors driving clinical heterogeneity in Alzheimer's disease are not well understood. This study assessed the relationship between amyloid deposition, glucose metabolism and clinical phenotype in Alzheimer's disease, and investigated how these relate to the involvement of functional networks. The study included 17 patients with early-onset Alzheimer's disease (age at onset

Published
2013

71. Loss of brainstem white matter predicts onset and motor neuron symptoms in C9orf72 expansion carriers: a GENFI study

Author

Pérez-Millan, Agnès, Borrego-Écija, Sergi, van Swieten, John C., Jiskoot, Lize, Moreno, Fermin, 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, Alexander, Ducharme, Simon, Le Ber, Isabelle, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Tiraboschi, Pietro, Seelaar, Harro, Langheinrich, Tobias, Rohrer, Jonathan D., Sala-Llonch, Roser, Sánchez-Valle, Raquel, GENFI The Genetic FTD Initiative, Ullgren, Abbe, Rollin, Adeline, Camuzat, Agnès, Esteve, Aitana Sogorb, Gabilondo, Alazne, Lladó, Albert, Benussi, Alberto, Brice, Alexis, Gorostidi, Ana, Verdelho, Ana, Arighi, Andrea, Antonell, Anna, Bertrand, Anne, Engel, Annerose, Vogels, Annick, Bouzigues, Arabella, Funkiewiez, Aurélie, Nacmias, Benedetta, Bender, Benjamin, Ferrari, Camilla, Wilke, Carlo, Heller, Carolin, Maruta, Carolina, Greaves, Caroline V., Timberlake, Carolyn, Ferreira, Catarina B., Prix, Catharina, Fenoglio, Chiara, Shoesmith, Christen, Polito, Cristina, Rinaldi, Daisy, Saracino, Dario, Cash, David, Thomas, David L., Tang-Wai, David, Duro, Diana, Rogaeva, Ekaterina, Scarpini, Elio, Wlasich, Elisabeth, Buratti, Emanuele, Todd, Emily, Premi, Enrico, do Couto, Frederico Simões, Miltenberger, Gabriel, Lombardi, Gemma, Rossi, Giacomina, Fumagalli, Giorgio, Giaccone, Giorgio, Di Fede, Giuseppe, Kuchcinski, Gregory, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J., Poos, Jackie, M. Papma, Janne, Nicholas, Jennifer, Durães, João, Lombardi, Jolina, Juncà-Parella, Jordi, Sarto, Jordi, Villanua, Jorge, Samra, Kiran, Poesen, Koen, Öijerstedt, Linn, Graf, Lisa, Giannini, Lucia, Russell, Lucy L., Leitão, Maria João, Almeida, Maria Rosario, Serpente, Maria, Lima, Marisa, Cañada, Marta, Bocchetta, Martina, Polyakova, Maryna, Vandenbulcke, Mathieu, Bertoux, Maxime, Veldsman, Michele, Castelo-Branco, Miguel, Tábuas-Pereira, Miguel, Tainta, Mikel, Balasa, Mircea, Zulaica, Miren, Freedman, Morris, Barandiaran, Myriam, Bargalló, Nuria, Wagemann, Olivia, Colliot, Olivier, Caroppo, Paola, Alves, Patricia, Thompson, Paul, Rosa-Neto, Pedro, Van Damme, Philip, Shafei, Rachelle, Convery, Rhian S., van Minkelen, Rick, Bartha, Robart, Gasparotti, Roberto, Keren, Ron, Rademakers, Rosa, Bruffaerts, Rose, Sayah, Sabrina, Black, Sandra, Loosli, Sandra, Mitchell, Sara, Prioni, Sara, Anderl-Straub, Sarah, Gauthier, Serge, Afonso, Sónia, Schönecker, Sonja, Gazzina, Stefano, Lebouvier, Thibaud, Cope, Thomas, Rittman, Timothy, Hoegen, Tobias, Bessi, Valentina, Cantoni, Valentina, Redaelli, Veronica, Jelic, Vesna, Deramecourt, Vincent, Borracci, Vittoria, The Genetic FTD Initiative, GENFI, Almeida, Maria Rosario, Serpente, Maria, Lima, Marisa, Cañada, Marta, Bocchetta, Martina, Polyakova, Maryna, Vandenbulcke, Mathieu, Bertoux, Maxime, Veldsman, Michele, Castelo-Branco, Miguel, Tábuas-Pereira, Miguel, Tainta, Mikel, Balasa, Mircea, Zulaica, Miren, Freedman, Morris, Barandiaran, Myriam, Bargalló, Nuria, Wagemann, Olivia, Colliot, Olivier, Caroppo, Paola, Alves, Patricia, Thompson, Paul, Rosa-Neto, Pedro, Van Damme, Philip, Tiraboschi, Pietro, Shafei, Rachelle, Convery, Rhian S, van Minkelen, Rick, Bartha, Robart, Gasparotti, Roberto, Keren, Ron, Rademakers, Rosa, Bruffaerts, Rose, Sayah, Sabrina, Black, Sandra, Loosli, Sandra, Mitchell, Sara, Prioni, Sara, Anderl-Straub, Sarah, Gauthier, Serge, Afonso, Sónia, Schönecker, Sonja, Gazzina, Stefano, Lebouvier, Thibaud, Cope, Thomas, Rittman, Timothy, Hoegen, Tobias, Bessi, Valentina, Cantoni, Valentina, Redaelli, Veronica, Jelic, Vesna, Deramecourt, Vincent, Borracci, Vittoria, Ullgren, Abbe, Rollin, Adeline, Camuzat, Agnès, Esteve, Aitana Sogorb, Gabilondo, Alazne, Lladó, Albert, Benussi, Alberto, Brice, Alexis, Gorostidi, Ana, Verdelho, Ana, Arighi, Andrea, Antonell, Anna, Bertrand, Anne, Engel, Annerose, Vogels, Annick, Bouzigues, Arabella, Funkiewiez, Aurélie, Nacmias, Benedetta, Bender, Benjamin, Ferrari, Camilla, Wilke, Carlo, Heller, Carolin, Maruta, Carolina, Greaves, Caroline V, Timberlake, Carolyn, Ferreira, Catarina B, Prix, Catharina, Fenoglio, Chiara, Shoesmith, Christen, Polito, Cristina, Rinaldi, Daisy, Saracino, Dario, Cash, David, Thomas, David L, Tang-Wai, David, Duro, Diana, Rogaeva, Ekaterina, Scarpini, Elio, Wlasich, Elisabeth, Buratti, Emanuele, Todd, Emily, Premi, Enrico, do Couto, Frederico Simões, Miltenberger, Gabriel, Lombardi, Gemma, Rossi, Giacomina, Fumagalli, Giorgio, Giaccone, Giorgio, Di Fede, Giuseppe, Kuchcinski, Gregory, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Poos, Jackie, M Papma, Janne, Nicholas, Jennifer, Durães, João, Lombardi, Jolina, Juncà-Parella, Jordi, Sarto, Jordi, Villanua, Jorge, Samra, Kiran, Poesen, Koen, Öijerstedt, Linn, Graf, Lisa, Giannini, Lucia, Russell, Lucy L, and Leitão, Maria João

Subjects
diagnostic imaging [Brain Stem], pathology [Motor Neurons], diagnostic imaging [Motor Neuron Disease], diagnostic imaging [Frontotemporal Dementia], diagnostic imaging [White Matter], pathology [Brain Stem], Neurology, pathology [White Matter], pathology [Frontotemporal Dementia], Mutation, C9orf72, Humans, genetics [Motor Neuron Disease], ddc:610, Human medicine, Neurology (clinical), genetics [Frontotemporal Dementia], genetics [C9orf72 Protein], Brainstem, GENFI, Frontotemporal dementia
Abstract

Background and objectives The C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD) and/or motor neuron disease (MND). Corticospinal degeneration has been described in post-mortem neuropathological studies in these patients, especially in those with MND. We used MRI to analyze white matter (WM) volumes in presymptomatic and symptomatic C9orf72 expansion carriers and investigated whether its measure may be helpful in predicting the onset of symptoms. Methods We studied 102 presymptomatic C9orf72 mutation carriers, 52 symptomatic carriers: 42 suffering from FTD and 11 from MND, and 75 non-carriers from the Genetic Frontotemporal dementia Initiative (GENFI). All subjects underwent T1-MRI acquisition. We used FreeSurfer to estimate the volume proportion of WM in the brainstem regions (midbrain, pons, and medulla oblongata). We calculated group differences with ANOVA tests and performed linear and non-linear regressions to assess group-by-age interactions. Results A reduced WM ratio was found in all brainstem subregions in symptomatic carriers compared to both noncarriers and pre-symptomatic carriers. Within symptomatic carriers, MND patients presented a lower ratio in pons and medulla oblongata compared with FTD patients. No differences were found between presymptomatic carriers and non-carriers. Clinical severity was negatively associated with the WM ratio. C9orf72 carriers presented greater age-related WM loss than non-carriers, with MND patients showing significantly more atrophy in pons and medulla oblongata. Discussion We find consistent brainstem WM loss in C9orf72 symptomatic carriers with differences related to the clinical phenotype supporting the use of brainstem measures as neuroimaging biomarkers for disease tracking.

Published
2022

72. Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications

Author

Laforce, Robert and Rabinovici, Gil D

Subjects
Biomedical and Clinical Sciences, Health Sciences, Biomedical Imaging, Clinical Research, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Prevention, Aging, Acquired Cognitive Impairment, Dementia, Neurosciences, Neurodegenerative, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

In the past decade, positron emission tomography (PET) with carbon-11-labeled Pittsburgh Compound B (PIB) has revolutionized the neuroimaging of aging and dementia by enabling in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer's disease (AD). Studies suggest that PIB-PET is sensitive for AD pathology, can distinguish AD from non-AD dementia (for example, frontotemporal lobar degeneration), and can help determine whether mild cognitive impairment is due to AD. Although the short half-life of the carbon-11 radiolabel has thus far limited the use of PIB to research, a second generation of tracers labeled with fluorine-18 has made it possible for amyloid PET to enter the clinical era. In the present review, we summarize the literature on amyloid imaging in a range of neurodegenerative conditions. We focus on potential clinical applications of amyloid PET and its role in the differential diagnosis of dementia. We suggest that amyloid imaging will be particularly useful in the evaluation of mildly affected, clinically atypical or early age-at-onset patients, and illustrate this with case vignettes from our practice. We emphasize that amyloid imaging should supplement (not replace) a detailed clinical evaluation. We caution against screening asymptomatic individuals, and discuss the limited positive predictive value in older populations. Finally, we review limitations and unresolved questions related to this exciting new technique.

Published
2011

73. Clinical Assessment of Judgment in Adults and the Elderly: Development and Validation of the Three Domains of Judgment Test—Clinical Version (3DJT-CV)

Author

Bernard-Arevalo, Simon-Pierre, primary, Laforce, Robert Jr, additional, Khayat, Olivier, additional, Bouchard, Vital, additional, Bruneau, Marie-Andrée, additional, Brunelle, Sarah, additional, Caron, Stéphanie, additional, Chamelian, Laury, additional, Chénard, Marise, additional, Côté, Jean-François, additional, Crépeau-Gendron, Gabrielle, additional, Doré, Marie-Claire, additional, Fortin, Marie-Pierre, additional, Gagnon, Nadine, additional, Gagnon, Pierre R., additional, Giroux, Chloé, additional, Jean, Léonie, additional, Létourneau, Geneviève, additional, Marceau, Émilie, additional, Moreau, Vincent, additional, Morin, Michèle, additional, Ouellet, Christine, additional, Poulin, Stéphane, additional, Radermaker, Steve, additional, Rousseau, Katerine, additional, Touchette, Catherine, additional, and Dumais, Alexandre, additional

Published
2023
Full Text
View/download PDF

75. EFFECTS OF VASCULAR BURDEN ON COGNITION ARE MEDIATED BY ATROPHY, AMYLOID, AND GLUCOSE METABOLISM: A MULTI-CENTRE MIXED COHORT OF SMALL VESSEL DISEASE AND ALZHEIMER'S PATHOLOGY

Author

Ottoy, Julie, Ozzoude, Miracle, Zukotynski, Katherine, Adamo, Sabrina, Scott, Christopher, Gaudet, Vincent, Ramirez, Joel, Swardfager, Walter, Cogo-Moreira, Hugo, Lam, Benjamin, Bhan, Aparna, Mojiri, Parisa, Kang, Min Su, Rabin, Jennifer, Kiss, Alex, Strother, Stephen, Bocti, Christian, Borrie, Michael, Chertkow, Howard, Frayne, Richard, Hsiung, Robin, Laforce, Robert, Jr., Noseworthy, Michael D., Prato, Frank S., Sahlas, Demetrios J., Smith, Eric E., Kuo, Phillip H., Sossi, Vesna, Thiel, Alexander, Soucy, Jean-Paul, Tardif, Jean-Claude, Black, Sandra E., and Goubran, Maged

Published
2024
Full Text
View/download PDF

76. DTI changes of thalamic subregions in genetic frontotemporal dementia: findings from the GENFI cohort.

Author

Soskic, Sonja, Tregidgo, Henry F. J., Todd, Emily G., Bouzigues, Arabella, Cash, David M, Russell, Lucy L., Thomas, David L, Malone, Ian B, van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, Sanchez‐Valle, Raquel, Laforce, Robert, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, and Tartaglia, Carmela

Abstract

Background: Atrophy of thalamic subregions has been observed across the spectrum of frontotemporal dementia (FTD). To gain better insight into underlying tissue changes, we investigated how thalamic subregional fractional anisotropy (FA) and mean diffusivity (MD) derived from diffusion tensor imaging (DTI) are altered in genetic FTD. Method: We used our newly developed thalamus segmentation tool, which jointly combines structural and diffusion input MRI data, to segment thalami and extract thalamic subregional FA and MD values for 163 genetic mutation carriers and 126 non‐carriers with suitable 3T MRI data from the GENetic FTD Initiative (GENFI). Mutation carriers were divided according to their genetic diagnosis and CDR®+NACC FTLD global scores into presymptomatic/prodromal (≤0.5: 41 C9orf72, 59 GRN, 34 MAPT) and symptomatic (≥1: 8 C9orf72, 11 GRN, 10 MAPT) groups. Mean FA and MD values for thalamic subregions were obtained using diffusion tensors interpolated in the log domain and weighted by segmentation posterior probabilities. Thalamic subregional FA and MD values for presymptomatic and symptomatic mutation carriers within each genetic group were compared with non‐carriers using analysis of covariance with bootstrapping, where age, scanner type, and sex were covariates. We corrected for multiple comparisons and calculated percentage changes in adjusted FA and MD mean values for mutation carriers relative to non‐carriers. Result: The only significant change at the presymptomatic stage was found for C9orf72 expansion carriers, who showed FA reduction in the intralaminar subregion (5%) (Figure 1, Table 1). In symptomatic C9orf72 expansion carriers, FA was reduced in the laterodorsal (21%), lateral posterior (13%), anteroventral (13%) and intralaminar (11%) subregions. Symptomatic MAPT mutation carriers also showed FA reduction in the laterodorsal (15%) and anteroventral (11%) subregions. No significant FA reductions were found for GRN mutation carriers and no significant MD changes were observed for any group after correction for multiple comparisons. Conclusion: We detected FA reductions of thalamic subregions only for C9orf72 expansion carriers at the presymptomatic stage, and for C9orf72 and MAPT mutation carriers at the symptomatic stage. Combined with the lack of robust MD changes, our findings may warrant further assessment of thalamic microstructure with more advanced diffusion models. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

78. Examining empathy deficits across familial forms of frontotemporal dementia within the GENFI cohort

Author

Foster, Phoebe H, Russell, Lucy L, Moreno, Fermin, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Sanchez-Valle, Raquel, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Laforce, Robert, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Graff, Caroline, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Masellis, Mario, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Tartaglia, Carmela, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Rowe, James B, Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Peakman, Georgia, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R, Gerhard, Alex, Ducharme, Simon, Le Ber, Isabelle, Tagliavini, Fabrizio, Santana, Isabel, Pasquier, Florence, Convery, Rhian S, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D, Initiative, Genetic FTD, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Bouzigues, Arabella, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Greaves, Caroline V, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Bocchetta, Martina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Cash, David M, 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, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Rowe, James [0000-0001-7216-8679], Apollo - University of Cambridge Repository, Neurology, Amsterdam Neuroscience - Neurodegeneration, and Repositório da Universidade de Lisboa

Subjects
Empathic concern, Cognitive Neuroscience, Medizin, Empathy, Frontotemporal dementia, Interpersonal Reactivity Index, Perspective taking, C9orf72 Protein, Humans, Mutation, Progranulins, tau Proteins, Frontotemporal Dementia, Pick Disease of the Brain, Experimental and Cognitive Psychology, genetics [Progranulins], diagnosis [Frontotemporal Dementia], mental disorders, ddc:610, genetics [C9orf72 Protein], genetics [Frontotemporal Dementia], genetics [tau Proteins], Neuropsychology and Physiological Psychology
Abstract

© 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)., Background: Reduced empathy is a common symptom in frontotemporal dementia (FTD). Although empathy deficits have been extensively researched in sporadic cases, few studies have explored the differences in familial forms of FTD. Methods: Empathy was examined using a modified version of the Interpersonal Reactivity Index (mIRI) in 676 participants from the Genetic FTD Initiative: 216 mutation-negative controls, 192 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. Using global scores from the CDR® plus NACC FTLD, mutation carriers were divided into three groups, asymptomatic (0), very mildly symptomatic/prodromal (.5), or fully symptomatic (1 or more). The mIRI Total score, as well as the subscores of Empathic Concern (EC) and Perspective Taking (PT) were assessed. Linear regression models with bootstrapping were used to assess empathy ratings across genetic groups, as well as across phenotypes in the symptomatic carriers. Neural correlates of empathy deficits were examined using a voxel-based morphometry (VBM) analysis. Results: All fully symptomatic groups scored lower on the mIRI Total, EC, and PT when compared to controls and their asymptomatic or prodromal counterparts (all p < .001). Prodromal C9orf72 expansion carriers also scored significantly lower than controls on the mIRI Total score (p = .046). In the phenotype analysis, all groups (behavioural variant FTD, primary progressive aphasia and FTD with amyotrophic lateral sclerosis) scored significantly lower than controls (all p < .007). VBM revealed an overlapping neural correlate of the mIRI Total score across genetic groups in the orbitofrontal lobe but with additional involvement in the temporal lobe, insula and basal ganglia in both the GRN and MAPT groups, and uniquely more posterior regions such as the parietal lobe and thalamus in the GRN group, and medial temporal structures in the MAPT group. Conclusions: Significant empathy deficits present in genetic FTD, particularly in symptomatic individuals and those with a bvFTD phenotype, while prodromal deficits are only seen using the mIRI in C9orf72 expansion carriers., 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. 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). 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). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510. RC/CG are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal (RCN 290173). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004-517). MB's work is 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. JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organisation for Scientific Research grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). RS-V is supported by an Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2), and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. JBR has received funding from the Wellcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). EF has received funding from a CIHR grant #327387. DG received support from the EU Joint Programme – Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. MO has received funding from BMBF (FTLDc).

Published
2022

79. Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Author

Premi, Enrico, primary, Pengo, Marta, additional, Mattioli, Irene, additional, Cantoni, Valentina, additional, Dukart, Juergen, additional, Gasparotti, Roberto, additional, Buratti, Emanuele, additional, Padovani, Alessandro, additional, Bocchetta, Martina, additional, Todd, Emily G., additional, Bouzigues, Arabella, additional, Cash, David M., additional, Convery, Rhian S., additional, Russell, Lucy L., additional, Foster, Phoebe, additional, Thomas, David L., additional, van Swieten, John C., additional, Jiskoot, Lize C., additional, Seelaar, Harro, additional, Galimberti, Daniela, additional, Sanchez-Valle, Raquel, additional, Laforce, Robert, additional, Moreno, Fermin, additional, Synofzik, Matthis, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, Maria Carmela, additional, Rowe, James B., additional, Tsvetanov, Kamen A., additional, Vandenberghe, Rik, additional, Finger, Elizabeth, additional, Tiraboschi, Pietro, additional, de Mendonça, Alexandre, additional, Santana, Isabel, additional, Butler, Chris R., additional, Ducharme, Simon, additional, Gerhard, Alexander, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Le Ber, Isabelle, additional, Pasquier, Florence, additional, Rohrer, Jonathan D., additional, Borroni, Barbara, additional, Esteve, Aitana Sogorb, additional, Heller, Carolin, additional, Greaves, Caroline V., additional, Zetterberg, Henrik, additional, Swift, Imogen J., additional, Samra, Kiran, additional, Shafei, Rachelle, additional, Timberlake, Carolyn, additional, Cope, Thomas, additional, Rittman, Timothy, additional, Arighi, Andrea, additional, Fenoglio, Chiara, additional, Scarpini, Elio, additional, Fumagalli, Giorgio, additional, Borracci, Vittoria, additional, Rossi, Giacomina, additional, Giaccone, Giorgio, additional, Di Fede, Giuseppe, additional, Caroppo, Paola, additional, Prioni, Sara, additional, Redaelli, Veronica, additional, Tang-Wai, David, additional, Rogaeva, Ekaterina, additional, Castelo-Branco, Miguel, additional, Freedman, Morris, additional, Keren, Ron, additional, Black, Sandra, additional, Mitchell, Sara, additional, Shoesmith, Christen, additional, Bartha, Robart, additional, Rademakers, Rosa, additional, Poos, Jackie, additional, Papma, Janne M., additional, Giannini, Lucia, additional, van Minkelen, Rick, additional, Pijnenburg, Yolande, additional, Nacmias, Benedetta, additional, Ferrari, Camilla, additional, Polito, Cristina, additional, Lombardi, Gemma, additional, Bessi, Valentina, additional, Veldsman, Michele, additional, Andersson, Christin, additional, Thonberg, Hakan, additional, Öijerstedt, Linn, additional, Jelic, Vesna, additional, Thompson, Paul, additional, Langheinrich, Tobias, additional, Lladó, Albert, additional, Antonell, Anna, additional, Olives, Jaume, additional, Balasa, Mircea, additional, Bargalló, Nuria, additional, Borrego-Ecija, Sergi, additional, Verdelho, Ana, additional, Maruta, Carolina, additional, Ferreira, Catarina B., additional, Miltenberger, Gabriel, additional, do Couto, Frederico Simões, additional, Gabilondo, Alazne, additional, Gorostidi, Ana, additional, Villanua, Jorge, additional, Cañada, Marta, additional, Tainta, Mikel, additional, Zulaica, Miren, additional, Barandiaran, Myriam, additional, Alves, Patricia, additional, Bender, Benjamin, additional, Wilke, Carlo, additional, Graf, Lisa, additional, Vogels, Annick, additional, Vandenbulcke, Mathieu, additional, Van Damme, Philip, additional, Bruffaerts, Rose, additional, Poesen, Koen, additional, Rosa-Neto, Pedro, additional, Gauthier, Serge, additional, Camuzat, Agnès, additional, Brice, Alexis, additional, Bertrand, Anne, additional, Funkiewiez, Aurélie, additional, Rinaldi, Daisy, additional, Saracino, Dario, additional, Colliot, Olivier, additional, Sayah, Sabrina, additional, Prix, Catharina, additional, Wlasich, Elisabeth, additional, Wagemann, Olivia, additional, Loosli, Sandra, additional, Schönecker, Sonja, additional, Hoegen, Tobias, additional, Lombardi, Jolina, additional, Anderl-Straub, Sarah, additional, Rollin, Adeline, additional, Kuchcinski, Gregory, additional, Bertoux, Maxime, additional, Lebouvier, Thibaud, additional, Deramecourt, Vincent, additional, Santiago, Beatriz, additional, Duro, Diana, additional, Leitão, Maria João, additional, Almeida, Maria Rosario, additional, Tábuas-Pereira, Miguel, additional, and Afonso, Sónia, additional

Published
2023
Full Text
View/download PDF

80. Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA‐H)

Author

Dawes, Piers, primary, Reeves, David, additional, Yeung, Wai Kent, additional, Holland, Fiona, additional, Charalambous, Anna Pavlina, additional, Côté, Mathieu, additional, David, Renaud, additional, Helmer, Catherine, additional, Laforce, Robert, additional, Martins, Ralph N., additional, Politis, Antonis, additional, Pye, Annie, additional, Russell, Gregor, additional, Sheikh, Saima, additional, Sirois, Marie‐Josée, additional, Sohrabi, Hamid R., additional, Thodi, Chyrssoula, additional, Gallant, Kathleen, additional, Nasreddine, Ziad, additional, and Leroi, Iracema, additional

Published
2023
Full Text
View/download PDF

81. Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H)

Author

Dawes, Piers, Reeves, David, Yeung, Wai Kent, Holland, Fiona, Charalambous, Anna Pavlina, Côté, Mathieu, David, Renaud, Helmer, Catherine, Laforce, Robert, Martins, Ralph N., Politis, Antonis, Pye, Annie, Russell, Gregor, Sheikh, Saima, Sirois, Marie-Josée, Sohrabi, Hamid R., Thodi, Chyrssoula, Gallant, Kathleen, Nasreddine, Ziad, Leroi, Iracema, Dawes, Piers, Reeves, David, Yeung, Wai Kent, Holland, Fiona, Charalambous, Anna Pavlina, Côté, Mathieu, David, Renaud, Helmer, Catherine, Laforce, Robert, Martins, Ralph N., Politis, Antonis, Pye, Annie, Russell, Gregor, Sheikh, Saima, Sirois, Marie-Josée, Sohrabi, Hamid R., Thodi, Chyrssoula, Gallant, Kathleen, Nasreddine, Ziad, and Leroi, Iracema

Abstract

Background: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. Methods: We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. Results: One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2–4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952–0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test–retest reliability was 0.92 (95%CI 0.78–0.97). Conclusion: The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.

Published
2023

82. Motor symptoms in genetic frontotemporal dementia:developing a new module for clinical rating scales

Author

MacDougall, Amy M., Samra, Kiran, Peakman, Georgia, Bouzigues, Arabella, Bocchetta, Martina, Cash, David, Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize, Seelaar, Harro, Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Russell, Lucy L., Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, MacDougall, Amy M., Samra, Kiran, Peakman, Georgia, Bouzigues, Arabella, Bocchetta, Martina, Cash, David, Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize, Seelaar, Harro, Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Russell, Lucy L., Poos, Jackie, Papma, Janne M., Giannini, Lucia, and van Minkelen, Rick

Abstract

Objective: To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). Methods: Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-negative controls. A standardised clinical questionnaire was used to assess eight motor symptoms (dysarthria, dysphagia, tremor, slowness, weakness, gait disorder, falls and functional difficulties using hands). Frequency and severity of each motor symptom was assessed, and a principal component analysis (PCA) was performed to identify how the different motor symptoms loaded together. Finally, addition of a motor component to the CDR® plus NACC FTLD was investigated (CDR® plus NACC FTLD-M). Results: 24.3% of mutation carriers had motor symptoms (31.7% C9orf72, 18.8% GRN, 19.3% MAPT) compared to 6.8% of controls. Slowness and gait disorder were the commonest in all genetic groups while tremor and falls were the least frequent. Symptom severity scores were similar to equivalent physical motor examination scores. PCA revealed that all motor symptoms loaded together so a single additional motor component was added to the CDR® plus NACC FTLD to form the CDR® plus NACC FTLD-M. Individual global scores were more severe with the CDR® plus NACC FTLD-M, and no patients with a clinically diagnosed motor disorder (ALS/FTD-ALS or parkinsonism) were classified anymore as asymptomatic (unlike the CDR® plus NACC FTLD alone). Conclusions: Motor features are present in mutation carriers at all disease stages across all three genetic groups. Inclusion of motor symptoms in a rating scale that can be used in future clinical trials will not only ensure a more accurate severity measure is recorded but that a wider spectrum of FTD phenotypes can be included in the same trial.

Published
2023

83. Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort

Author

Samra, Kiran, MacDougall, Amy M., Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize, Seelaar, Harro, 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, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Russell, Lucy L., Samra, Kiran, MacDougall, Amy M., Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize, Seelaar, Harro, 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, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., and Russell, Lucy L.

Abstract

Objective: To identify whether language impairment exists presymptomatically in genetic frontotemporal dementia (FTD), and if so, the key differences between the main genetic mutation groups. Methods: 682 participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 290 asymptomatic and 82 prodromal mutation carriers (with C9orf72, GRN, and MAPT mutations) as well as 310 mutation-negative controls. Language was assessed using items from the Progressive Aphasia Severity Scale, as well as the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency task. Participants also underwent a 3 T volumetric T1-weighted MRI from which regional brain volumes within the language network were derived and compared between the groups. Results: 3% of asymptomatic (4% C9orf72, 4% GRN, 2% MAPT) and 48% of prodromal (46% C9orf72, 42% GRN, 64% MAPT) mutation carriers had impairment in at least one language symptom compared with 13% of controls. In prodromal mutation carriers significantly impaired word retrieval was seen in all three genetic groups whilst significantly impaired grammar/syntax and decreased fluency was seen only in C9orf72 and GRN mutation carriers, and impaired articulation only in the C9orf72 group. Prodromal MAPT mutation carriers had significant impairment on the category fluency task and the BNT whilst prodromal C9orf72 mutation carriers were impaired on the category fluency task only. Atrophy in the dominant perisylvian language regions differed between groups, with earlier, more widespread volume loss in C9orf72, and later focal atrophy in the temporal lobe in MAPT mutation carriers. Conclusions: Language deficits exist in the prodromal but not asymptomatic stages of genetic FTD across all three genetic groups. Improved understanding of the language phenotype prior to phenoconversion to fully symptomatic FTD will help develop outcome measures for future presymptomatic trials.

Published
2023

84. Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia:Findings from the GENetic Frontotemporal dementia Initiative cohort

Author

Bocchetta, Martina, Todd, Emily G., Bouzigues, Arabella, Cash, David M., Nicholas, Jennifer M., Convery, Rhian S., Russell, Lucy L., Thomas, David L., Malone, Ian B., Iglesias, Juan Eugenio, Van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Robert, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, De Mendonca, Alexandre, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D., Bocchetta, Martina, Todd, Emily G., Bouzigues, Arabella, Cash, David M., Nicholas, Jennifer M., Convery, Rhian S., Russell, Lucy L., Thomas, David L., Malone, Ian B., Iglesias, Juan Eugenio, Van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Borroni, Barbara, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Robert, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, De Mendonca, Alexandre, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, and Rohrer, Jonathan D.

Abstract

Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative. Three hundred eighty-seven mutation carriers were included (160 GRN, 160 C9orf72, 67 MAPT), together with 240 non-carrier cognitively normal controls. Cortical and subcortical grey matter volumes were generated using automated parcellation methods on volumetric 3T T1-weighted MRI scans, while white matter characteristics were estimated using diffusion tensor imaging. Mutation carriers were divided into two disease stages based on their global CDR®+NACC-FTLD score: presymptomatic (0 or 0.5) and fully symptomatic (1 or greater). The w-scores in each grey matter volumes and white matter diffusion measures were computed to quantify the degree of abnormality compared to controls for each presymptomatic carrier, adjusting for their age, sex, total intracranial volume, and scanner type. Presymptomatic carriers were classified as 'normal' or 'abnormal' based on whether their grey matter volume and white matter diffusion measure w-scores were above or below the cut point corresponding to the 10th percentile of the controls. We then compared the change in disease severity between baseline and one year later in both the 'normal' and 'abnormal' groups within each genetic subtype, as measured by the CDR®+NACC-FTLD sum-of-boxes score and revised Cambridge Behavioural Inventory total score. Overall, presymptomatic carriers with normal regional w-scores at baseline did not progress clinically as much as those with abnormal regional w-scores. Having abnormal grey or white matter measures at baseline was associated with a statistically significant increase in the CDR®+NACC-FTLD of up to 4 points in C9orf72 expansion carriers, and 5 poi

Published
2023

85. Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort:Comparison with sporadic primary progressive aphasia

Author

Samra, Kiran, MacDougall, Amy M., Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., Hardy, Chris, Van Swieten, John C., Seelaar, Harro, 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, Alexander, Ducharme, Simon, Le Ber, Isabelle, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Warren, Jason D., Rohrer, Jonathan D., Russell, Lucy L., Samra, Kiran, MacDougall, Amy M., Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., Hardy, Chris, Van Swieten, John C., Seelaar, Harro, 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, Alexander, Ducharme, Simon, Le Ber, Isabelle, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Warren, Jason D., Rohrer, Jonathan D., and Russell, Lucy L.

Abstract

Primary progressive aphasia is most commonly a sporadic disorder, but in some cases, it can be genetic. This study aimed to understand the clinical, cognitive and imaging phenotype of the genetic forms of primary progressive aphasia in comparison to the canonical nonfluent, semantic and logopenic subtypes seen in sporadic disease. Participants with genetic primary progressive aphasia were recruited from the international multicentre GENetic Frontotemporal dementia Initiative study and compared with healthy controls as well as a cohort of people with sporadic primary progressive aphasia. Symptoms were assessed using the GENetic Frontotemporal dementia Initiative language, behavioural, neuropsychiatric and motor scales. Participants also underwent a cognitive assessment and 3T volumetric T1-weighted MRI. One C9orf72 (2%), 1 MAPT (6%) and 17 GRN (44%) symptomatic mutation carriers had a diagnosis of primary progressive aphasia. In the GRN cohort, 47% had a diagnosis of nonfluent variant primary progressive aphasia, and 53% had a primary progressive aphasia syndrome that did not fit diagnostic criteria for any of the three subtypes, called primary progressive aphasia-not otherwise specified here. The phenotype of the genetic nonfluent variant primary progressive aphasia group largely overlapped with that of sporadic nonfluent variant primary progressive aphasia, although the presence of an associated atypical parkinsonian syndrome was characteristic of sporadic and not genetic disease. The primary progressive aphasia-not otherwise specified group however was distinct from the sporadic subtypes with impaired grammar/syntax in the presence of relatively intact articulation, alongside other linguistic deficits. The pattern of atrophy seen on MRI in the genetic nonfluent variant primary progressive aphasia group overlapped with that of the sporadic nonfluent variant primary progressive aphasia cohort, although with more posterior cortical involvement, whilst the primary

Published
2023

86. Neuropsychiatric symptoms in genetic frontotemporal dementia:developing a new module for Clinical Rating Scales

Author

Samra, Kiran, Macdougall, Amy, Peakman, Georgia, Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Moreno, Fermin, Sánchez-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 Mendonca, Alexandre, Butler, Christopher R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Russell, Lucy L., Samra, Kiran, Macdougall, Amy, Peakman, Georgia, Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Moreno, Fermin, Sánchez-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 Mendonca, Alexandre, Butler, Christopher R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., and Russell, Lucy L.

Abstract

BACKGROUND: Current clinical rating scales in frontotemporal dementia (FTD) often do not incorporate neuropsychiatric features and may therefore inadequately measure disease stage. METHODS: 832 participants from the Genetic FTD Initiative (GENFI) were recruited: 522 mutation carriers and 310 mutation-negative controls. The standardised GENFI clinical questionnaire assessed the frequency and severity of 14 neuropsychiatric symptoms: visual, auditory, and tactile hallucinations, delusions, depression, anxiety, irritability/lability, agitation/aggression, euphoria/elation, aberrant motor behaviour, hypersexuality, hyperreligiosity, impaired sleep, and altered sense of humour. A principal component analysis (PCA) was performed to identify key groupings of neuropsychiatric and behavioural items in order to create a new neuropsychiatric module that could be used as an addition to the Clinical Dementia Rating (CDR) plus National Alzheimer's Coordinating Center Behaviour and Language Domains (NACC FTLD) rating scale. RESULTS: Overall, 46.4% of mutation carriers had neuropsychiatric symptoms (51.6% C9orf72, 40.8% GRN, 46.6% MAPT) compared with 24.5% of controls. Anxiety and depression were the most common in all genetic groups but fluctuated longitudinally and loaded separately in the PCA. Hallucinations and delusions loaded together, with the remaining neuropsychiatric symptoms loading with the core behavioural features of FTD. These results suggest using a single 'psychosis' neuropsychiatric module consisting of hallucinations and delusions. Adding this to the CDR plus NACC FTLD, called the CDR plus NACC FTLD-N, leads to a number of participants being scored more severely, including those who were previously considered asymptomatic now being scored as prodromal. CONCLUSIONS: Neuropsychiatric symptoms occur in mutation carriers at all disease stages across all three genetic groups. However, only psychosis features provided additional staging benefit to the CDR plus NACC

Published
2023

87. Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

Author

Bussy, Aurélie, Levy, Jake P., Best, Tristin, Patel, Raihaan, Cupo, Lani, Van Langenhove, Tim, Nielsen, Jørgen E., Pijnenburg, Yolande, Waldö, Maria Landqvist, Remes, Anne M., Schroeter, Matthias L., Santana, Isabel, Pasquier, Florence, Otto, Markus, Danek, Adrian, Levin, Johannes, Le Ber, Isabelle, Vandenberghe, Rik, Synofzik, Matthis, Moreno, Fermin, de Mendonça, Alexandre, Sanchez-Valle, Raquel, Laforce, Robert, Langheinrich, Tobias, Gerhard, Alexander, Graff, Caroline, Butler, Chris R., Sorbi, Sandro, Jiskoot, Lize, Seelaar, Harro, van Swieten, John C., Finger, Elizabeth, Tartaglia, Maria Carmela, Masellis, Mario, Tiraboschi, Pietro, Galimberti, Daniela, Borroni, Barbara, Rowe, James B., Bocchetta, Martina, Rohrer, Jonathan D., Devenyi, Gabriel A., Chakravarty, M. Mallar, Ducharme, Simon, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Bussy, Aurélie, Levy, Jake P., Best, Tristin, Patel, Raihaan, Cupo, Lani, Van Langenhove, Tim, Nielsen, Jørgen E., Pijnenburg, Yolande, Waldö, Maria Landqvist, Remes, Anne M., Schroeter, Matthias L., Santana, Isabel, Pasquier, Florence, Otto, Markus, Danek, Adrian, Levin, Johannes, Le Ber, Isabelle, Vandenberghe, Rik, Synofzik, Matthis, Moreno, Fermin, de Mendonça, Alexandre, Sanchez-Valle, Raquel, Laforce, Robert, Langheinrich, Tobias, Gerhard, Alexander, Graff, Caroline, Butler, Chris R., Sorbi, Sandro, Jiskoot, Lize, Seelaar, Harro, van Swieten, John C., Finger, Elizabeth, Tartaglia, Maria Carmela, Masellis, Mario, Tiraboschi, Pietro, Galimberti, Daniela, Borroni, Barbara, Rowe, James B., Bocchetta, Martina, Rohrer, Jonathan D., Devenyi, Gabriel A., Chakravarty, M. Mallar, Ducharme, Simon, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Poos, Jackie, Papma, Janne M., Giannini, Lucia, and van Minkelen, Rick

Abstract

Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.

Published
2023

88. Early neurotransmitters changes in prodromal frontotemporal dementia:A GENFI study

Author

Premi, Enrico, Pengo, Marta, Mattioli, Irene, Cantoni, Valentina, Dukart, Juergen, Gasparotti, Roberto, Buratti, Emanuele, Padovani, Alessandro, Bocchetta, Martina, Todd, Emily G., Bouzigues, Arabella, Cash, David M., Convery, Rhian S., Russell, Lucy L., Thomas, David L., van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Robert, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Tsvetanov, Kamen A., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D., Borroni, Barbara, Premi, Enrico, Pengo, Marta, Mattioli, Irene, Cantoni, Valentina, Dukart, Juergen, Gasparotti, Roberto, Buratti, Emanuele, Padovani, Alessandro, Bocchetta, Martina, Todd, Emily G., Bouzigues, Arabella, Cash, David M., Convery, Rhian S., Russell, Lucy L., Thomas, David L., van Swieten, John C., Jiskoot, Lize C., Seelaar, Harro, Galimberti, Daniela, Sanchez-Valle, Raquel, Laforce, Robert, Moreno, Fermin, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Tsvetanov, Kamen A., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Butler, Chris R., Ducharme, Simon, Gerhard, Alexander, Danek, Adrian, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D., and Borroni, Barbara

Abstract

Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches. Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission. We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR® plus NACC FTLD = 0.5) and in symptomatic (CDR® plus NACC FTLD≥1) FTD. Results: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways; in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p < 0.05, Family Wise Error corrected). In symptomatic FTD, a widespread involvement of dopamine, serotonin, glutamate and acetylcholine pathways across all genetic subtypes was found. Social cognition scores, loss of empathy and poor response to emotional cues were found to correlate with the strength of GMV colocalization of dopamine and serotonin pathways (all p < 0.01). Conclusions: This study, indirectly assessing neurotransmitter deficits in monogenic FTD, provides novel insight into disease mechanisms and might suggest potential therapeutic targets to counteract disease-related symptoms.

Published
2023

89. Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia

Author

Whiteside, David J., Malpetti, Maura, Jones, P. Simon, Ghosh, Boyd C.P., Coyle-Gilchrist, Ian, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Ber, Isabelle Le, Gerhard, Alexander, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, Bouzigues, Arabella, Russell, Lucy L., Rohrer, Jonathan D., Rowe, James B., Rittman, Timothy, Whiteside, David J., Malpetti, Maura, Jones, P. Simon, Ghosh, Boyd C.P., Coyle-Gilchrist, Ian, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Ber, Isabelle Le, Gerhard, Alexander, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, Bouzigues, Arabella, Russell, Lucy L., Rohrer, Jonathan D., Rowe, James B., and Rittman, Timothy

Abstract

Introduction: We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). Methods: For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. Results: We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. Discussion: Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. Highlights: We investigated brain network predictors of dementia symptom onset Frontotemporal dementia results in characteristic dynamic network patterns Alterations in network dynamics are associated with neuropsychological impairment Network dynamic changes predict symptomatic conversion in presymptomatic carriers Network dynamic changes are associated with longitudinal cognitive decline.

Published
2023

92. Language impairment in the genetic forms of behavioural variant frontotemporal dementia

Author

On Behalf of the Genetic FTD Initiative (GENFI), Samra, Kiran, MacDougall, Amy M., Bouzigues, Arabella, Bocchetta, Martina, Cash, David M., Greaves, Caroline V., Convery, Rhian S., van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, 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, Christopher R., Gerhard, Alexander, Ducharme, Simon, Le Ber, Isabelle, Tiraboschi, Pietro, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Russell, Lucy L., Nelson, Annabel, Thomas, David L., Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Maruta, Carolina, do Couto, Frederico Simões, and Veritati - Repositório Institucional da Universidade Católica Portuguesa

Subjects
Progranulin, C9orf72, Genetics, Tau, Frontotemporal dementia, Language
Abstract

Background: Behavioural variant fronto-temporal dementia (bvFTD) is characterised by a progressive change in personality in association with atrophy of the frontal and temporal lobes. Whilst language impairment has been described in people with bvFTD, little is currently known about the extent or type of linguistic difficulties that occur, particularly in the genetic forms. Methods: Participants with genetic bvFTD along with healthy controls were recruited from the international multicentre Genetic FTD Initiative (GENFI). Linguistic symptoms were assessed using items from the Progressive Aphasia Severity Scale (PASS). Additionally, participants undertook the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency test. Participants underwent a 3T volumetric T1-weighted MRI, with language network regional brain volumes measured and compared between the genetic groups and controls. Results: 76% of the genetic bvFTD cohort had impairment in at least one language symptom: 83% C9orf72, 80% MAPT and 56% GRN mutation carriers. All three genetic groups had significantly impaired functional communication, decreased fluency, and impaired sentence comprehension. C9orf72 mutation carriers also had significantly impaired articulation and word retrieval as well as dysgraphia whilst the MAPT mutation group also had impaired word retrieval and single word comprehension. All three groups had difficulties with naming, semantic knowledge and verbal fluency. Atrophy in key left perisylvian language regions differed between the groups, with generalised involvement in the C9orf72 group and more focal temporal and insula involvement in the other groups. Correlates of language symptoms and test scores also differed between the groups. Conclusions: Language deficits exist in a substantial proportion of people with familial bvFTD across all three genetic groups. Significant atrophy is seen in the dominant perisylvian language areas and correlates with language impairments within each of the genetic groups. Improved understanding of the language phenotype in the main genetic bvFTD subtypes will be helpful in future studies, particularly in clinical trials where accurate stratification and monitoring of disease progression is required.

Published
2023

93. An Automated Toolbox to Predict Single Subject Atrophy in Presymptomatic Granulin Mutation Carriers

Author

Premi, Enrico, Costa, Tommaso, Moreno, Fermin, Panman, Jessica, Papma, Janne, Pievani, Michela, Pijnenburg, Yolande, Polito, Cristina, Prioni, Sara, Prix, Catharina, Rademakers As London Ontario Geneticist, Rosa, Redaelli, Veronica, Rittman, Tim, Santana, Isabel, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Laforce, Robert, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, L Thomas, David, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Ducharme, Simon, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Graff, Caroline, Galimberti, Daniela, Masellis, Mario, Tartaglia, Carmela, Rowe, James B, Finger, Elizabeth, Gazzina, Stefano, Tagliavini, Fabrizio, de Mendonça, Alexandre, Vandenberghe, Rik, Gerhard, Alexander, Butler, Chris R, Danek, Adrian, Synofzik, Matthis, Levin, Johannes, Otto, Markus, Ghidoni, Roberta, Benussi, Alberto, Frisoni, Giovanni B, Sorbi, Sandro, Peakman, Georgia, Todd, Emily, Bocchetta, Martina, Rohrer, Johnathan D, Borroni, Barbara, Members, GENFI Consortium, Afonso, Sónia, Rosario Almeida, Maria, Cauda, Franco, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Luisa, Gasparotti, Roberto, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Archetti, Silvana, Cope, Thomas, de Arriba, María, Di Fede, Giuseppe, Díaz, Zigor, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, B Ferreira, Catarina, Fox, Nick, Freedman, Morris, Alberici, Antonella, Fumagalli, Giorgio, Gabilondo, Alazne, Gauthier, Serge, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, van Swieten, John C, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans Otto, Keren, Ron, Langheinrich, Tobias, João Leitão, Maria, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Sanchez-Valle, Raquel, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, GENFI Consortium Members, Neurology, Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository

Subjects
genetics [Granulins], Frontotemporal dementia, granulin, magnetic resonance imaging, mutation, preclinical, presymptomatic, Atrophy, Brain, Granulins, Humans, Magnetic Resonance Imaging, Mutation, Progranulins, Frontotemporal Dementia, Medizin, genetics [Mutation], diagnostic imaging [Frontotemporal Dementia], frontotemporal dementia, genetics [Progranulins], methods [Magnetic Resonance Imaging], SDG 3 - Good Health and Well-being, pathology [Brain], Settore BIO/13 - Biologia Applicata, ddc:610, diagnostic imaging [Brain], genetics [Frontotemporal Dementia], pathology [Atrophy], Frontotemporal dementia, granulin, magnetic resonance imaging, mutation, preclinical, presymptomatic, General Neuroscience, General Medicine, Psychiatry and Mental health, Clinical Psychology, pathology [Frontotemporal Dementia], Geriatrics and Gerontology
Abstract

Background:Magnetic resonance imaging (MRI) measures may be used as outcome markers in frontotemporal dementia (FTD). Objectives:To predict MRI cortical thickness (CT) at follow-up at the single subject level, using brain MRI acquired at baseline in preclinical FTD. Methods:84 presymptomatic subjects carrying Granulin mutations underwent MRI scans at baseline and at follow-up (31.2±16.5 months). Multivariate nonlinear mixed-effects model was used for estimating individualized CT at follow-up based on baseline MRI data. The automated user-friendly preGRN-MRI script was coded. Results:Prediction accuracy was high for each considered brain region (i.e., prefrontal region, real CT at follow-up versus predicted CT at follow-up, mean error ≤1.87%). The sample size required to detect a reduction in decline in a 1-year clinical trial was equal to 52 subjects (power = 0.80, alpha = 0.05). Conclusion:The preGRN-MRI tool, using baseline MRI measures, was able to predict the expected MRI atrophy at follow-up in presymptomatic subjects carrying GRN mutations with good performances. This tool could be useful in clinical trials, where deviation of CT from the predicted model may be considered an effect of the intervention itself. Swedish Frontotemporal Dementia Initiative Schörling Foundation; Swedish Research Council: JPND Prefrontals, 2015-02926 ,2018-02754; Swedish Alzheimer foundation; Swedish Brain Foundation; Karolinska Institutet Doctoral Funding; KI StratNeuro; Swedish Dementia foundation and Stockholm County Council ALF/Region Stockholm.

Published
2022

94. Data‐driven staging of genetic frontotemporal dementia using multi‐modal <scp>MRI</scp>

Author

McCarthy, Jillian, Borroni, Barbara, Tartaglia, Maria Carmela, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne, Peakman, Georgia, Piaceri, Irene, Finger, Elizabeth, Pievani, Michela, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Vandenberghe, Rik, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas-Pereira, Miguel, de Mendonça, Alexandre, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Vandamme, Philip, Tagliavini, Fabrizio, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Santana, Isabel, Butler, Chris, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Sanchez-Valle, Raquel, Otto, Markus, Frisoni, Giovanni B, Ghidoni, Roberta, Sorbi, Sandro, Jiskoot, Lize C, Seelaar, Harro, van Swieten, John C, Rohrer, Jonathan D, Iturria-Medina, Yasser, Ducharme, Simon, Moreno, Fermin, Initiative, GENetic Frontotemporal Dementia, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Laforce, Robert, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Graff, Caroline, Bras, Jose, Bruffaerts, Rose, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, Cosseddu, Maura, Synofzik, Matthis, de Arriba, María, Di Fede, Giuseppe, Díaz, Zigor, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Carlos, Ferreira, Catarina B, Flanagan, Toby, Galimberti, Daniela, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Rowe, James B, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans Otto, Keren, Ron, Langheinrich, Tobias, Leitão, Maria João, Lladó, Albert, Masellis, Mario, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina M, Nacmias, Benedetta, Repositório da Universidade de Lisboa, Neurology, Amsterdam Neuroscience - Neurodegeneration, McCarthy, Jillian [0000-0002-9285-0023], Borroni, Barbara [0000-0001-9340-9814], Apollo - University of Cambridge Repository, GENetic Frontotemporal Dementia Initiative (GENFI), Clinical Genetics, and Clinical Psychology

Subjects
disease progression, frontotemporal dementia, magnetic resonance imaging, unsupervised machine learning, BIOMARKER, Heterozygote, Medizin, Neuroimaging, diagnostic imaging [Frontotemporal Dementia], Magnetic resonance imaging, SDG 3 - Good Health and Well-being, HARMONIZATION, Settore BIO/13 - Biologia Applicata, NEUROFILAMENT LIGHT-CHAIN, BEHAVIORAL VARIANT, CRITERIA, Humans, Radiology, Nuclear Medicine and imaging, ddc:610, Cross-Sectional Studies, Language, Magnetic Resonance Imaging, Frontotemporal Dementia, genetics [Frontotemporal Dementia], Unsupervised machine learning, Disease progression, Science & Technology, Radiological and Ultrasound Technology, Radiology, Nuclear Medicine & Medical Imaging, Neurosciences, DEGENERATION, DIFFUSION, psychology [Frontotemporal Dementia], Neurology, GRAY-MATTER ATROPHY, Neurosciences & Neurology, Neurology (clinical), Anatomy, Life Sciences & Biomedicine, GENFI, CLINICAL-TRIALS, Frontotemporal dementia
Abstract

Funder: Fondation Brain Canada; Id: http://dx.doi.org/10.13039/100009408, Funder: Fonds de Recherche du Québec ‐ Santé; Id: http://dx.doi.org/10.13039/501100000156, Funder: Health Canada; Id: http://dx.doi.org/10.13039/501100000008, Funder: Brain Canada Foundation; Id: http://dx.doi.org/10.13039/100009408, Frontotemporal dementia in genetic forms is highly heterogeneous and begins many years to prior symptom onset, complicating disease understanding and treatment development. Unifying methods to stage the disease during both the presymptomatic and symptomatic phases are needed for the development of clinical trials outcomes. Here we used the contrastive trajectory inference (cTI), an unsupervised machine learning algorithm that analyzes temporal patterns in high-dimensional large-scale population datasets to obtain individual scores of disease stage. We used cross-sectional MRI data (gray matter density, T1/T2 ratio as a proxy for myelin content, resting-state functional amplitude, gray matter fractional anisotropy, and mean diffusivity) from 383 gene carriers (269 presymptomatic and 115 symptomatic) and a control group of 253 noncarriers in the Genetic Frontotemporal Dementia Initiative. We compared the cTI-obtained disease scores to the estimated years to onset (age-mean age of onset in relatives), clinical, and neuropsychological test scores. The cTI based disease scores were correlated with all clinical and neuropsychological tests (measuring behavioral symptoms, attention, memory, language, and executive functions), with the highest contribution coming from mean diffusivity. Mean cTI scores were higher in the presymptomatic carriers than controls, indicating that the method may capture subtle pre-dementia cerebral changes, although this change was not replicated in a subset of subjects with complete data. This study provides a proof of concept that cTI can identify data-driven disease stages in a heterogeneous sample combining different mutations and disease stages of genetic FTD using only MRI metrics.

Published
2022

95. Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Author

Tavares, Tamara P., Mitchell, Derek G.V., Coleman, Kristy, Shoesmith, Christen, Bartha, Robert, Cash, David M., Moore, Katrina M., van Swieten, John, Borroni, Barbara, Galimberti, Daniela, Tartaglia, Maria Carmela, Rowe, James, Graff, Caroline, Tagliavini, Fabrizio, Frisoni, Giovanni, Cappa, Stefano, Laforce, Robert, Jr, de Mendonça, Alexandre, Sorbi, Sandro, Wallstrom, Garrick, Masellis, Mario, Rohrer, Jonathan D., and Finger, Elizabeth C.

Published
2019
Full Text
View/download PDF

96. The Use of Random Forests to Classify Amyloid Brain PET

Author

Zukotynski, Katherine, Gaudet, Vincent, Kuo, Phillip H., Adamo, Sabrina, Goubran, Maged, Scott, Christopher, Bocti, Christian, Borrie, Michael, Chertkow, Howard, Frayne, Richard, Hsiung, Robin, Laforce, Robert, Jr, Noseworthy, Michael D., Prato, Frank S., Sahlas, Demetrios J., Smith, Eric E., Sossi, Vesna, Thiel, Alexander, Soucy, Jean-Paul, Tardif, Jean-Claude, and Black, Sandra E.

Published
2019
Full Text
View/download PDF

98. 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

99. Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales

Author

Samra, Kiran, primary, Macdougall, Amy, additional, Peakman, Georgia, additional, Bouzigues, Arabella, additional, Bocchetta, Martina, additional, Cash, David M, additional, Greaves, Caroline V, additional, Convery, Rhian S, additional, van Swieten, John C, additional, Jiskoot, Lize C, additional, Seelaar, Harro, additional, Moreno, Fermin, additional, Sánchez-Valle, Raquel, additional, Laforce, Robert, additional, Graff, Caroline, additional, Masellis, Mario, additional, Tartaglia, Maria Carmela, additional, Rowe, James B, additional, Borroni, Barbara, additional, Finger, Elizabeth, additional, Synofzik, Matthis, additional, Galimberti, Daniela, additional, Vandenberghe, Rik, additional, de Mendonca, Alexandre, additional, Butler, Christopher R, additional, Gerhard, Alexander, additional, Ducharme, Simon, additional, Le Ber, Isabelle, additional, Tiraboschi, Pietro, additional, Santana, Isabel, additional, Pasquier, Florence, additional, Levin, Johannes, additional, Otto, Markus, additional, Sorbi, Sandro, additional, Rohrer, Jonathan D, additional, and Russell, Lucy L, additional

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results