23 results on '"Jiskoot, Lize"'
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2. Language impairment in the genetic forms of behavioural variant frontotemporal dementia
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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., and Russell, Lucy L.
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- 2023
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3. Loss of brainstem white matter predicts onset and motor neuron symptoms in C9orf72 expansion carriers: a GENFI study
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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, and Sánchez-Valle, Raquel
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- 2023
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4. Motor symptoms in genetic frontotemporal dementia: developing a new module for clinical rating scales
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Samra, Kiran, MacDougall, Amy M., Peakman, Georgia, 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, 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., and Russell, Lucy L.
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- 2023
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5. Anomia is present pre-symptomatically in frontotemporal dementia due to MAPT mutations
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Bouzigues, Arabella, Russell, Lucy L., Peakman, Georgia, Bocchetta, Martina, Greaves, Caroline V., Convery, Rhian S., Todd, Emily, Rowe, James B., Borroni, Barbara, Galimberti, Daniela, Tiraboschi, Pietro, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Sorbi, Sandro, Butler, Chris R., Graff, Caroline, Gerhard, Alexander, Langheinrich, Tobias, Laforce, Robert, Sanchez-Valle, Raquel, de Mendonça, Alexandre, Moreno, Fermin, Synofzik, Matthis, Vandenberghe, Rik, Ducharme, Simon, Le Ber, Isabelle, Levin, Johannes, Danek, Adrian, Otto, Markus, Pasquier, Florence, Santana, Isabel, and Rohrer, Jonathan D.
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- 2022
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6. Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia.
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Samra, Kiran, Peakman, Georgia, MacDougall, Amy M., Bouzigues, Arabella, 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, and Galimberti, Daniela
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FRONTOTEMPORAL dementia ,ALZHEIMER'S disease ,RECEIVER operating characteristic curves ,PHENOTYPES ,VERBAL behavior - Abstract
INTRODUCTION: We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS: Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD‐NM scale. This was assessed in 522 mutation carriers and 310 mutation‐negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS: The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION: Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights: The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD‐NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS).No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD‐NM rating scale.Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains.A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Loss of brainstem white matter predicts onset and motor neuron symptoms in C9orf72 expansion carriers: a GENFI study
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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
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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.
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- 2022
8. Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales
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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., Rademakers, Rosa, Bruffaerts, Rose, Genetic FTD Initiative (GENFI), Neurology, Genetic FTD Initiative (GENFI), Samra, Kiran [0000-0002-3105-7099], Peakman, Georgia [0000-0002-3319-138X], Bocchetta, Martina [0000-0003-1814-5024], Convery, Rhian S [0000-0002-9477-1812], van Swieten, John C [0000-0001-6278-6844], Jiskoot, Lize C [0000-0002-1120-1858], Seelaar, Harro [0000-0003-1989-7527], Rowe, James B [0000-0001-7216-8679], Borroni, Barbara [0000-0001-9340-9814], Finger, Elizabeth [0000-0003-4461-7427], Synofzik, Matthis [0000-0002-2280-7273], Galimberti, Daniela [0000-0002-9284-5953], Gerhard, Alexander [0000-0002-8071-6062], Ducharme, Simon [0000-0002-7309-1113], Le Ber, Isabelle [0000-0002-2508-5181], Tiraboschi, Pietro [0000-0002-2171-1720], Sorbi, Sandro [0000-0002-0380-6670], Rohrer, Jonathan D [0000-0002-6155-8417], Apollo - University of Cambridge Repository, Miltenberger, Gabriel, Couto, Frederico Simões do, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Damme, Philip Van, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, 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, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Fede, Giuseppe Di, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, Minkelen, Rick van, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, and Repositório da Universidade de Lisboa
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genetics [Hallucinations] ,GENETICS ,Hallucinations ,Clinical Neurology ,Medizin ,C9ORF72 ,PROGRESSION ,Anxiety ,DIAGNOSIS ,PHENOTYPE ,AMYOTROPHIC-LATERAL-SCLEROSIS ,diagnosis [Frontotemporal Dementia] ,SDG 3 - Good Health and Well-being ,CRITERIA ,Humans ,ddc:610 ,MUTATION ,genetics [Frontotemporal Dementia] ,Psychiatry ,NEUROPSYCHIATRY ,Science & Technology ,PSYCHIATRIC-SYMPTOMS ,FRONTOTEMPORAL DEMENTIA ,Mental Status and Dementia Tests ,HEXANUCLEOTIDE REPEAT EXPANSION ,PREVALENCE ,Psychiatry and Mental health ,Psychotic Disorders ,Frontotemporal Dementia ,Surgery ,Neurosciences & Neurology ,Human medicine ,Neurology (clinical) ,Life Sciences & Biomedicine - Abstract
Peer reviewed: True, Acknowledgements: We thank the research participants and their families for their contribution to the study. Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510., Funder: Bluefield Project, Funder: National Institute for Health Research Cambridge Biomedical Research Centre, 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 FTLD. Inclusion of these features brings us closer to optimising the rating scale for use in trials.
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- 2023
9. Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort
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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, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, Arriba, María de, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Cerveau, Institut du, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, João Leitão, Maria, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick van, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Damme, Philip Van, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, GENetic Frontotemporal dementia Initiative (GENFI), Bruffaerts, Rose, Bocchetta, Martina [0000-0003-1814-5024], Cash, David M [0000-0001-7833-616X], Seelaar, Harro [0000-0003-1989-7527], Jiskoot, Lize C [0000-0002-1120-1858], Sanchez-Valle, Raquel [0000-0001-7750-896X], Graff, Caroline [0000-0002-9949-2951], Borroni, Barbara [0000-0001-9340-9814], Synofzik, Matthis [0000-0002-2280-7273], Vandenberghe, Rik [0000-0001-6237-2502], Gerhard, Alexander [0000-0002-8071-6062], Ducharme, Simon [0000-0002-7309-1113], Pasquier, Florence [0000-0001-9880-9788], Apollo - University of Cambridge Repository, Neurology, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, du Cerveau, Institut, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Damme, Philip Van, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Fede, Giuseppe Di, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, João Leitão, Maria, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, and Mead, Simon
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Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Neurology ,SDG 3 - Good Health and Well-being ,Medizin ,MAPT ,primary progressive aphasia ,ddc:610 ,c9orf72 ,GRN ,Biological Psychiatry - Abstract
Funder: Alzheimer's Research UK, Funder: Bluefield Project, Funder: Royal National Institute, Funder: Weston Brain Institute and Ontario Brain Institute, Funder: Alzheimer Nederland and the Bluefield, Funder: Alzheimer's Society, Funder: Dementia Research Centre, Funder: Medical Research Council, Funder: National Institute for Health Research University College London/Hospitals Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre Clinical Research Facility, Funder: Alzheimer Foundation, Funder: Alzheimer's Society and Alzheimer's Research UK, Funder: Association for Frontotemporal Dementias Research Grant 2009, Funder: Brain Research UK, Funder: Dementia Research Institute Ltd, Funder: The Wolfson Foundation, Funder: UK Dementia Research Institute, Funder: UK Dementia Research Institute Ltd, Funder: Deaf People Dunhill Medical Trust Pauline Ashley Fellowship, Funder: Frontotemporal Dementia Research Studentships, Funder: Germany’s Federal Ministry of Education and Research, Funder: Miriam Marks Brain Research UK Senior Fellowship, Funder: Tau Consortium and the Center for Networked Biomedical Research, Funder: Mady Browaeys Fund for Research into Frontotemporal Dementia, Funder: Brain Foundation and Stockholm County Council ALF, Funder: Deutsche Forschungsgemeinschaft German Research Foundation under Germany’s Excellence Strategy, Funder: Alzheimer’s Research UK, Funder: Memory of David Blechner, Funder: Swedish FTD Inititative-Schörling Foundation, 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 3 T 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 progressive aphasia-not otherwise specified group was strikingly asymmetrical with involvement particularly of the insula and dorsolateral prefrontal cortex but also atrophy of the orbitofrontal cortex and the medial temporal lobes. Whilst there are overlapping symptoms between genetic and sporadic primary progressive aphasia syndromes, there are also distinct features. Future iterations of the primary progressive aphasia consensus criteria should encompass such information with further research needed to understand the earliest features of these disorders, particularly during the prodromal period of genetic disease.
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- 2023
10. Neurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers
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Finger, Elizabeth, Malik, Rubina, Bocchetta, Martina, Coleman, Kristy, Graff, Caroline, Borroni, Barbara, Masellis, Mario, Laforce, Robert, Greaves, Caroline V., Russell, Lucy L., Convery, Rhian S., Bouzigues, Arabella, Cash, David M., Otto, Markus, Synofzik, Matthis, Rowe, James B., Galimberti, Daniela, Tiraboschi, Pietro, Bartha, Robert, Shoesmith, Christen, Tartaglia, Maria Carmela, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize C., Sorbi, Sandro, Butler, Chris R., Gerhard, Alexander, Sanchez-Valle, Raquel, De Mendonça, Alexandre, Moreno, Fermin, Vandenberghe, Rik, Le Ber, Isabelle, Levin, Johannes, Pasquier, Florence, Santana, Isabel, Rohrer, Jonathan D., Ducharme, Simon, Esteve, Aitana Sogorb, Heller, Carolin, Thomas, David L., Todd, Emily G., Nicholas, Jennifer, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J., Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Rademakers, Rosa, Poos, Jackie, Papma, Janne M., Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B., Miltenberger-Miltenyi, Gabriel, Simões Do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Genetic FTD Initiative, GENFI, the Genetic FTD Initiative (GENFI), Repositório da Universidade de Lisboa, Bocchetta, Martina [0000-0003-1814-5024], Graff, Caroline [0000-0002-9949-2951], Borroni, Barbara [0000-0001-9340-9814], Cash, David M [0000-0001-7833-616X], Synofzik, Matthis [0000-0002-2280-7273], Seelaar, Harro [0000-0003-1989-7527], Jiskoot, Lize C [0000-0002-8120-7366], Gerhard, Alexander [0000-0002-8071-6062], Sanchez-Valle, Raquel [0000-0001-7750-896X], Vandenberghe, Rik [0000-0001-6237-2502], Pasquier, Florence [0000-0001-9880-9788], Ducharme, Simon [0000-0002-7309-1113], Apollo - University of Cambridge Repository, Neurology, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Esteve, Aitana Sogorb, Heller, Carolin, Thomas, David L, Todd, Emily G, Nicholas, Jennifer, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, and Borrego-Ecija, Sergi
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Adult ,C9orf72 Protein ,neurodevelopment ,Nocturnal pulsed oximetry ,Medizin ,Brain ,Neurodegenerative Diseases ,tau Proteins ,Amyotrophic lateral sclerosis ,frontotemporal dementia ,Phrenic nerve ,Young Adult ,Progranulins ,Pick Disease of the Brain ,Respiratory tests ,Mutation ,C9orf72 ,MAPT ,Humans ,ddc:610 ,Neurology (clinical) ,Human medicine ,GRN ,Respiratory function - Abstract
© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved., While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age. Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years. The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period., This project was supported by Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and by Canadian Institutes of Health Research operating grants (327387; 452843; 70797). The Dementia Research Centre is supported by Alzheimer’s Research UK, Alzheimer’s Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the National Institute for Health Research (NIHR) Queen Square Dementia Biomedical Research Unit and the University College London Hospitals Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC), 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. This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), the Alzheimer’s Society grant (AS-PG-16-007), the Bluefield Project and the EU Joint Programme – Neurodegenerative Disease Research (GENFI-PROX grant 2019-02248). M.B. is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a- 004-517). M.B.’s work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd., funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). J.B.R. is funded by the Wellcome Trust (103838) and the National Institute for Health Research Cambridge Biomedical Research Centre. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). It is also funded by the Ministry of Health, Italy (S.S.). R.V.’s work is supported by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie. R.S.-V.’s work is supported by Instituto de Salud Carlos III (grant number 20/00448), cofunded by the EU. ANR-PRTS PrevdemALS study funding (I.L.B.). Several authors of this publication (J.C.vS., M.S., A.D., M.O., R.V., I.L.B., J.D.R.) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) - Project ID No 739510.
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- 2023
11. Language impairment in the genetic forms of behavioural variant frontotemporal dementia
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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
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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.
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- 2023
12. A modified Camel and Cactus Test detects presymptomatic semantic impairment in genetic frontotemporal dementia within the GENFI cohort
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Moore, Katrina, Convery, Rhian, Bocchetta, Martina, Neason, Mollie, Cash, David M., Greaves, Caroline, Russell, Lucy L., Clarke, Mica T. M., Peakman, Georgia, van Swieten, John, Jiskoot, Lize, Moreno, Fermin, Barandiaran, Myriam, Sanchez-Valle, Raquel, Borroni, Barbara, Laforce, Robert, Dore, Marie-Claire, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Finger, Elizabeth, Synofzik, Matthis, Karnath, Hans-Otto, Vandenberghe, Rik, de Mendonca, Alexandre, Maruta, Carolina, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alex, Levin, Johannes, Danek, Adrian, Otto, Markus, Warren, Jason D., Rohrer, Jonathan D., Rossor, Martin N., Fox, Nick C., Woollacott, Ione O. C., Shafei, Rachelle, Heller, Carolin, Guerreiro, Rita, Bras, Jose, Thomas, David L., Nicholas, Jennifer, Mead, Simon, Meeter, Lieke, Panman, Jessica, Papma, Janne, van Minkelen, Rick, Pijnenburg, Yolande, Indakoetxea, Begona, Gabilondo, Alazne, Tainta, Mikel, de Arriba, Maria, Gorostidi, Ana, Zulaica, Miren, Villanua, Jorge, Diaz, Zigor, Borrego-Ecija, Sergi, Olives, Jaume, Llado, 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-Wa, David, Oijerstedt, 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, Bender, Benjamin, Bruffaerts, Rose, Van Damme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B., Miltenberger, Gabriel, Verdelho, Ana, Afonso, Sonia, Taipa, Ricardo, Caroppo, Paola, Di Fede, Giuseppe, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitao, Maria Joao, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Veldsman, Michele, Flanagan, Toby, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Semler, Elisa, Anderl-Straub, Sarah, Neurology, Clinical Psychology, Clinical Genetics, Moore, Katrina [0000-0002-4458-8390], Convery, Rhian [0000-0002-9477-1812], Bocchetta, Martina [0000-0003-1814-5024], Neason, Mollie [0000-0001-9419-7171], Greaves, Caroline [0000-0002-6446-1960], Russell, Lucy L [0000-0001-5023-5893], Clarke, Mica TM [0000-0003-0570-4296], Peakman, Georgia [0000-0002-3319-138X], Galimberti, Daniela [0000-0002-9284-5953], Otto, Markus [0000-0003-4273-4267], Rohrer, Jonathan D [0000-0002-6155-8417], and Apollo - University of Cambridge Repository
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Oncology ,Cactaceae ,medicine.medical_specialty ,Camelus ,Semantic dementia ,Temporal lobe ,Atrophy ,Progranulins ,ddc:150 ,complications [Frontotemporal Dementia] ,C9orf72 ,Internal medicine ,Developmental and Educational Psychology ,medicine ,MAPT ,progranulin ,Semantic memory ,Animals ,Humans ,genetics ,genetics [Frontotemporal Dementia] ,semantic knowledge ,C9orf72 Protein ,Cognition ,medicine.disease ,Semantics ,Neuropsychology and Physiological Psychology ,Frontal lobe ,Frontotemporal Dementia ,Psychology ,Frontotemporal dementia - Abstract
Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes MAPT, C9orf72, and GRN. We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 MAPT mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 GRN mutation carriers (33 symptomatic, 132 presymptomatic), and 164 C9orf72 mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = −0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: MAPT mean 22.3 (standard deviation 8.0), GRN 24.4 (7.2), C9orf72 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late MAPT and late C9orf72 mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic MAPT mutation group (rho > 0.80). In the C9orf72 group, mCCT score correlated with both bilateral temporal lobe volume (rho > 0.31) and bilateral frontal lobe volume (rho > 0.29), whilst in the GRN group mCCT score correlated only with left frontal lobe volume (rho = 0.48). This study provides evidence for presymptomatic impaired semantic knowledge in genetic FTD. The different neuroanatomical associations of the mCCT score may represent distinct cognitive processes causing deficits in different groups: loss of core semantic knowledge associated with temporal lobe atrophy (particularly in the MAPT group), and impaired executive control of semantic information associated with frontal lobe atrophy. Further studies will be helpful to address the longitudinal change in mCCT performance and the exact time at which presymptomatic impairment occurs.
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- 2022
13. Comparison of clinical rating scales in genetic frontotemporal dementia within the GENFI cohort
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Peakman, Georgia, Russell, Lucy L., Convery, Rhian S., Nicholas, Jennifer M., van Swieten, John C., Jiskoot, Lize C., Moreno, Fermin, Sanchez-Valle, Raquel, Laforce, Robert, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James B., Borroni, Barbara, Finger, Elizabeth, Synofzik, Matthis, Galimberti, Daniela, Vandenberghe, Rik, de Mendonça, Alexandre, Butler, Chris R., Gerhard, Alex, Ducharme, Simon, Le Ber, Isabelle, Tagliavini, Fabrizio, Santana, Isabel, Pasquier, Florence, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Rohrer, Jonathan D., Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans-Otto, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M., Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Thomas, David L., Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Neurology, Amsterdam Neuroscience - Neurodegeneration, University College of London [London] (UCL), London School of Hygiene and Tropical Medicine (LSHTM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Donostia International Physics Center - DIPC (SPAIN), Donostia International Physics Center (DIPC), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU)-University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centre Hospitalier Université Laval [Quebec] (CHUL), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Karolinska Institutet [Stockholm], University of Toronto, University of Cambridge [UK] (CAM), University of Brescia, University of Western Ontario (UWO), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Lusófona University [Lisbon], University of Oxford, University of Manchester [Manchester], McGill University = Université McGill [Montréal, Canada], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Coimbra [Portugal] (UC), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ludwig-Maximilians-Universität München (LMU), University of Ulm (UUlm), Università degli Studi di Firenze = University of Florence (UniFI), HAL-SU, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Oxford [Oxford], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Peakman, Georgia [0000-0002-3319-138X], Convery, Rhian S [0000-0002-9477-1812], Van Swieten, John C [0000-0001-6278-6844], Jiskoot, Lize C [0000-0002-1120-1858], Rowe, James B [0000-0001-7216-8679], Borroni, Barbara [0000-0001-9340-9814], Finger, Elizabeth [0000-0003-4461-7427], Galimberti, Daniela [0000-0002-9284-5953], Gerhard, Alex [0000-0002-8071-6062], Ducharme, Simon [0000-0002-7309-1113], Le Ber, Isabelle [0000-0002-2508-5181], Danek, Adrian [0000-0001-8857-5383], Otto, Markus [0000-0002-6647-5944], Sorbi, Sandro [0000-0002-0380-6670], Rohrer, Jonathan D [0000-0002-6155-8417], Apollo - University of Cambridge Repository, and Genetic FTD Initiative (GENFI)
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Oncology ,Medizin ,LANGUAGE ,Disease ,Genetic FTD Initiative (GENFI) ,Cohort Studies ,0302 clinical medicine ,diagnosis [Frontotemporal Dementia] ,ddc:150 ,C9orf72 ,CRITERIA ,030212 general & internal medicine ,frontotemporal dementia ,C9orf72 Protein ,Cross-Sectional Studies ,Disease Progression ,Frontotemporal Dementia ,Humans ,Mutation ,tau Proteins ,Mental Status and Dementia Tests ,VERSION ,11 Medical and Health Sciences ,Psychiatry ,UTILITY ,DDC 150 / Psychology ,biology ,FTD ,17 Psychology and Cognitive Sciences ,Psychiatry and Mental health ,Mutation (genetic algorithm) ,Cohort ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,medicine.symptom ,FTLD ,Life Sciences & Biomedicine ,Alzheimer’s disease ,Frontotemporal dementia ,medicine.medical_specialty ,Clinical Dementia Rating ,Tau protein ,Clinical Neurology ,Alzheimerkrankheit ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,DIAGNOSIS ,Asymptomatic ,VALIDATION ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,mental disorders ,medicine ,ddc:610 ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neurodegeneration ,Science & Technology ,Neurology & Neurosurgery ,[SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE] ,business.industry ,MUTATIONS ,medicine.disease ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,biology.protein ,[SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE] ,Surgery ,Neurology (clinical) ,Neurosciences & Neurology ,business ,030217 neurology & neurosurgery - Abstract
BackgroundTherapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD.MethodsThe CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-associated protein tau (MAPT), 187 GRN, 193 C9orf72) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72) and 145 non-carriers had available longitudinal data at a follow-up time point.ResultsCross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p, publishedVersion
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- 2022
14. Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia
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Heller, Carolin, Foiani, Martha S, Shafei, Rachelle, Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Caroppo, Paola, Fede, Giuseppe Di, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Van Swieten, John C, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Moreno, Fermin, Veldsman, Michele, Flanagan, Toby, Prix, Catharina, Hoegen, Tobias, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Semler, Elisa, Anderl-Straub, Sarah, Benussi, Luisa, Sanchez-Valle, Raquel, Binetti, Giuliano, Ghidoni, Roberta, Pievani, Michela, Lombardi, Gemma, Nacmias, Benedetta, Ferrari, Camilla, Bessi, Valentina, Borroni, Barbara, Laforce, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Moore, Katrina, Rowe, James B, Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonca, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Christopher R, Gerhard, Alex, Convery, Rhian, Levin, Johannes, Danek, Adrian, Frisoni, Giovanni, Sorbi, Sandro, Otto, Markus, Heslegrave, Amanda J, Zetterberg, Henrik, Rohrer, Jonathan D, GENFI, Rossor, Martin N, Bocchetta, Martina, Warren, Jason D, Fox, Nick C, Guerreiro, Rita, Bras, Jose, Nicholas, Jennifer, Mead, Simon, Jiskoot, Lize, Meeter, Lieke, Panman, Jessica, Papma, Janne, Neason, Mollie, Minkelen, Rick van, Pijnenburg, Yolanda, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Arriba, Maria de, Gorostidi, Ana, Zulaica, Miren, Villanua, Jorge, Cash, David M, Diaz, Zigor, Borrego-Ecija, Sergi, Olives, Jaume, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargallo, Nuria, Premi, Enrico, Cosseddu, Maura, Gazzina, Stefano, Thomas, David, Padovani, Alessandro, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Öijerstedt, Linn, Greaves, Caroline V, Andersson, Christin, Jelic, Vesna, Thonberg, Hakan, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Woollacott, Ione Oc, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans-Otto, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B, Amsterdam Neuroscience - Neurodegeneration, Neurology, Heller, Carolin [0000-0002-1934-6162], Foiani, Martha S [0000-0003-4157-2606], Moore, Katrina [0000-0002-4458-8390], Convery, Rhian [0000-0002-9477-1812], Bocchetta, Martina [0000-0003-1814-5024], Neason, Mollie [0000-0001-9419-7171], Thomas, David [0000-0003-1491-1641], Greaves, Caroline V [0000-0002-6446-1960], Woollacott, Ione Oc [0000-0003-1166-6417], Shafei, Rachelle [0000-0002-4760-8684], Van Swieten, John C [0000-0001-6278-6844], Borroni, Barbara [0000-0001-9340-9814], Rowe, James B [0000-0001-7216-8679], Finger, Elizabeth [0000-0003-4461-7427], Otto, Markus [0000-0002-6647-5944], Rohrer, Jonathan D [0000-0002-6155-8417], Apollo - University of Cambridge Repository, Repositório da Universidade de Lisboa, and Woollacott, Ione OC [0000-0003-1166-6417]
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blood [Frontotemporal Dementia] ,Male ,blood [Neurofilament Proteins] ,Gastroenterology ,genetics [Progranulins] ,Progranulins ,0302 clinical medicine ,Neurofilament Proteins ,C9orf72 ,blood [Glial Fibrillary Acidic Protein] ,genetics [Frontotemporal Dementia] ,0303 health sciences ,blood [Biomarkers] ,Glial fibrillary acidic protein ,biology ,Middle Aged ,Astrogliosis ,Psychiatry and Mental health ,Frontotemporal Dementia ,Biomarker (medicine) ,Female ,Frontotemporal dementia ,Adult ,medicine.medical_specialty ,genetics [Mutation] ,tau Proteins ,03 medical and health sciences ,Atrophy ,Internal medicine ,Glial Fibrillary Acidic Protein ,medicine ,Humans ,ddc:610 ,Neurodegeneration ,genetics [C9orf72 Protein] ,Pathological ,Aged ,030304 developmental biology ,C9orf72 Protein ,business.industry ,Case-control study ,medicine.disease ,genetics [tau Proteins] ,Case-Control Studies ,Mutation ,biology.protein ,Surgery ,Neurology (clinical) ,business ,GENFI ,Biomarkers ,030217 neurology & neurosurgery - Abstract
© Author(s) (or their employer(s)). No commercial re-use. See rights and permissions. Published by BMJ., Background: There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to be explored as potential biomarker. Methods: Plasma GFAP and neurofilament light chain (NfL) concentration were measured in 469 individuals enrolled in the Genetic FTD Initiative: 114 C9orf72 expansion carriers (74 presymptomatic, 40 symptomatic), 119 GRN mutation carriers (88 presymptomatic, 31 symptomatic), 53 MAPT mutation carriers (34 presymptomatic, 19 symptomatic) and 183 non-carrier controls. Biomarker measures were compared between groups using linear regression models adjusted for age and sex with family membership included as random effect. Participants underwent standardised clinical assessments including the Mini-Mental State Examination (MMSE), Frontotemporal Lobar Degeneration-Clinical Dementia Rating scale and MRI. Spearman's correlation coefficient was used to investigate the relationship of plasma GFAP to clinical and imaging measures. Results: Plasma GFAP concentration was significantly increased in symptomatic GRN mutation carriers (adjusted mean difference from controls 192.3 pg/mL, 95% CI 126.5 to 445.6), but not in those with C9orf72 expansions (9.0, -61.3 to 54.6), MAPT mutations (12.7, -33.3 to 90.4) or the presymptomatic groups. GFAP concentration was significantly positively correlated with age in both controls and the majority of the disease groups, as well as with NfL concentration. In the presymptomatic period, higher GFAP concentrations were correlated with a lower cognitive score (MMSE) and lower brain volume, while in the symptomatic period, higher concentrations were associated with faster rates of atrophy in the temporal lobe. Conclusions: Raised GFAP concentrations appear to be unique to GRN-related FTD, with levels potentially increasing just prior to symptom onset, suggesting that GFAP may be an important marker of proximity to onset, and helpful for forthcoming therapeutic prevention trials., The GENFI study has been supported by the Medical Research Council UK (MR/M023664/1), the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, as well as other individual funding to investigators. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, Alzheimer’s Research UK, the Brain Research Trust and the Wolfson Foundation as well as an Alzheimer's Society grant (AS-PG-16-007). The biomarker measurements were funded in part by the UK Dementia Research Institute at UCL and by a Wellcome Trust Multi-User Equipment Grant. KM has received funding from an Alzheimer’s Society PhD studentship. IOCW is supported by a MRC Clinical Research Training Fellowship (MR/M018288/1). RS-V is supported by an Alzheimer's Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2). JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontemporal Dementias Research Grant 2009, The Netherlands Organization for Scientific Research (NWO) grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield project. CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Initiative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. DG received support from the EU Joint Programme—Neurodegenerative Disease Research (JPND) and the Italian Ministry of Health (PreFrontALS) grant 733051042. RS-V has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). JBR has received funding from the Wellcome Trust (103838) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. MO has received funding from BMBF (FTLDc). MM has received funding from a Canadian Institutes of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. EF has received funding from a CIHR grant #327387. HZ is a Wallenberg Academy Fellow. JR is a MRC Clinician Scientist (MR/M008525/1) and has received funding from the NIHR Rare Diseases Translational Research Collaboration (BRC149/NS/MH), the Bluefield Project and the Association for Frontotemporal Degeneration.
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- 2020
15. Faster Cortical Thinning and Surface Area Loss in Presymptomatic and Symptomatic C9orf72 Repeat Expansion Adult Carriers
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Le Blanc, Gabriella, Jetté Pomerleau, Vincent, Graff, Caroline, Rittman, Tim, Rogaeva, Ekaterina, Rosa‐Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Masellis, Mario, Tábuas‐Pereira, Miguel, Tainta, Mikel, Tang‐Wai, David, Thomas, David L, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Tartaglia, Maria C., Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Zetterberg, Henrik, Zulaica, Miren, Rowe, James B., Vandenberghe, Rik, Finger, Elizabeth, Tagliavini, Fabrizio, Mendonça, Alexandre, Santana, Isabel, Butler, Chris, McCarthy, Jillian, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Frisoni, Giovanni, Sorbi, Sandro, Rohrer, Jonathan D., Ducharme, Simon, Almeida, Maria Rosario, Anderl‐Straub, Sarah, Borroni, Barbara, Andersson, Christin, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Luisa, Binetti, Giuliano, Swieten, John, Black, Sandra, Bocchetta, Martina, Borrego, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo‐Branco, Miguel, Convery, Rhian, Cope, Thomas, Galimberti, Daniela, Arriba, María, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M, Duro, Diana, Fenoglio, Chiara, Ferreira, Carlos, Ferreira, Catarina B., Flanagan, Toby, Fox, Nick, Sanchez‐Valle, Raquel, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gauthier, Serge, Ghidoni, Roberta, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, LaForce, Robert, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans‐Otto, Keren, Ron, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Moreno, Fermin, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Synofzik, Matthis, Olives, Jaume, Panman, Jessica, Papma, Janne, Patzig, Maximilian, Pievani, Michela, Pijnenburg, Yolande, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Neurology, Ducharme, Simon [0000-0002-7309-1113], and Apollo - University of Cambridge Repository
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,diagnostic imaging [Frontotemporal Dementia] ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Atrophy ,C9orf72 ,Internal medicine ,diagnostic imaging [Cerebral Cortex] ,medicine ,Humans ,ddc:610 ,Young adult ,genetics [C9orf72 Protein] ,genetics [Frontotemporal Dementia] ,Aged ,Aged, 80 and over ,Cerebral Cortex ,DNA Repeat Expansion ,medicine.diagnostic_test ,C9orf72 Protein ,business.industry ,Magnetic resonance imaging ,diagnostic imaging [Atrophy] ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Cerebral cortex ,Frontotemporal Dementia ,Cardiology ,Female ,Neurology (clinical) ,Trinucleotide repeat expansion ,business ,Asymptomatic carrier ,030217 neurology & neurosurgery ,Frontotemporal dementia ,genetics [Atrophy] - Abstract
Objective C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD). We examined aging trajectories of cortical thickness (CTh) and surface area in C9orf72 expansion adult carriers compared to healthy controls to characterize preclinical cerebral changes leading to symptoms. Methods Data were obtained from the Genetic Frontotemporal Dementia Initiative. T1-weighted magnetic resonance imaging scans were processed with CIVET 2.1 to extract vertex-wide CTh and cortical surface area (CSA). Symptomatic and presymptomatic subjects were compared to age-matched controls using mixed-effects models, controlling for demographic variables. Aging trajectories were compared between carriers and noncarriers by testing the "age by genetic status" interaction. False discovery rate corrections were applied to all vertex-wide analyses. Results The sample included 640 scans from 386 subjects, including 54 symptomatic C9orf72 carriers (72.2% behavioral variant FTD), 83 asymptomatic carriers, and 249 controls (age range = 18-86 years). Symptomatic carriers showed fairly symmetric reduction in CTh/CSA in most of the frontal lobes, in addition to large temporoparietal areas. Presymptomatic subjects had reduced CTh/CSA in more restricted areas of the medial frontoparietal lobes, in addition to scattered lateral frontal, parietal, and temporal areas. These differences were explained by faster cortical thinning linearly throughout adulthood in a similar anatomical distribution, with differences emerging in the early 30s. CSA reduction was also faster in mutation carriers predominantly in the ventrofrontal regions. Interpretation C9orf72 mutation carriers have faster cortical thinning and surface loss throughout adulthood in regions that show atrophy in symptomatic subjects. This suggests that the pathogenic effects of the mutation lead to structural cerebral changes decades prior to symptoms. ANN NEUROL 2020 ANN NEUROL 2020;88:113-122.
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- 2020
16. Stratifying the Presymptomatic Phase of Genetic Frontotemporal Dementia by Serum NfL and pNfH: A Longitudinal Multicentre Study
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Wilke, Carlo, Reich, Selina, Swieten, John C., Borroni, Barbara, Sanchez‐Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria C., Finger, Elizabeth, Vandenberghe, Rik, Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Sorbi, Sandro, Bocchetta, Martina, Todd, Emily, Kuhle, Jens, Barro, Christian, Afonso, Sónia, Almeida, Maria Rosario, Anderl‐Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Borrego‐Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo‐Branco, Miguel, Convery, Rhian, Cope, Thomas, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans‐Otto, Keren, Ron, Langheinrich, Tobias, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M., Peakman, Georgia, Pievani, Michela, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Rosa‐Neto, Pedro, Rossi, Giacomina, Rosser, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas‐Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang‐Wai, David, Thomas, David L., Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Rohrer, Jonathan D., Synofzik, Matthis, Repositório da Universidade de Lisboa, Neurology, and Clinical Genetics
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blood [Frontotemporal Dementia] ,Male ,Oncology ,Medizin ,blood [Neurofilament Proteins] ,Disease ,Cohort Studies ,0302 clinical medicine ,Settore BIO/13 - Biologia Applicata ,Neurofilament Proteins ,C9orf72 ,CRITERIA ,Longitudinal Studies ,Stage (cooking) ,0303 health sciences ,blood [Biomarkers] ,FTD ,Middle Aged ,3. Good health ,Neurology ,Frontotemporal Dementia ,Cohort ,Biomarker (medicine) ,Female ,Life Sciences & Biomedicine ,Frontotemporal dementia ,Treatment response ,medicine.medical_specialty ,Clinical Neurology ,C9ORF72 ,IMMUNOASSAY ,03 medical and health sciences ,Atrophy ,Internal medicine ,NEUROFILAMENT LIGHT-CHAIN ,medicine ,Humans ,ddc:610 ,Aged ,030304 developmental biology ,Science & Technology ,HEXANUCLEOTIDE REPEAT ,MUTATIONS ,business.industry ,DISEASE PROGRESSION ,Neurosciences ,medicine.disease ,Biomarkers ,Neurosciences & Neurology ,Neurology (clinical) ,TAU ,business ,030217 neurology & neurosurgery - Abstract
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Objective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: the conversion stage. Methods: We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single-molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation-negative within-family controls. Results: In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra-individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage-dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity-to-onset. We estimate stage-dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Interpretation: Blood NfL and pNfH provide dynamic stage-dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD., W. and M.S. are members of the European Reference Network for Rare Neurological Diseases Project ID No. 739510. This work was supported by the Horizon 2020 research and innovation program (grant 779257 Solve-RD to M.S.), the National Ataxia Foundation (grant to C.W. and M.S.), the Wilhelm Vaillant Stiftung (grant to C.W.), the EU Joint Programme – Neurodegenerative Disease Research (JPND) “GENFI-prox” through participating national funding agencies (by DLR/BMBF to M.S., J.D.R., B.B., C.G., and M.O.), and the European Union's Horizon 2020 research and innovation programme under grant agreement No. 643417. J.C.S. and H.S. received funding by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813 and 733050103) in the Netherlands and the Bluefield Project to Cure Frontotemporal Dementia. J.B.R. was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and the Medical Research Council (SUAG/051 G101400). C.B. is supported by a postdoctoral fellowship from the Swiss National Science Foundation (P400PM_191077). J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248).
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- 2021
17. The inner fluctuations of the brain in presymptomatic Frontotemporal Dementia: The chronnectome fingerprint
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Premi, Enrico, Calhoun, Vince D, Galimberti, Daniela, Panman, Jessica, Papma, Janne, Patzig, Maximilian, Pievani, Michela, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Sanchez-Valle, Raquel, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Scarpini, Elio, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas-Pereira, Miguel, Tainta, Mikel, Laforce, Robert, Tang-Wai, David, Thomas, David L, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Moreno, Fermin, Warren, Jason, Wilke, Carlo, Zetterberg, Henrik, Zulaica, Miren, Synofzik, Matthis, Graff, Caroline, Masellis, Mario, Tartaglia, Maria Carmela, Rowe, James, Vandenberghe, Rik, Diano, Matteo, Finger, Elizabeth, Tagliavini, Fabrizio, de Mendonça, Alexandre, Santana, Isabel, Butler, Chris, Ducharme, Simon, Gerhard, Alex, Danek, Adrian, Levin, Johannes, Otto, Markus, Gazzina, Stefano, Frisoni, Giovanni, Cappa, Stefano, Sorbi, Sandro, Padovani, Alessandro, Rohrer, Jonathan D, Borroni, Barbara, Genetic FTD Initiative, GENFI, Almeida, Maria Rosario, Anderl-Straub, Sarah, Andersson, Christin, Cosseddu, Maura, Antonell, Anna, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Luisa, Binetti, Giuliano, Black, Sandra, Alberici, Antonella, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, de Arriba, María, Archetti, Silvana, Di Fede, Giuseppe, Díaz, Zigor, Dick, Katrina M, Duro, Diana, Fenoglio, Chiara, Ferreira, Carlos, Ferreira, Catarina B, Flanagan, Toby, Fox, Nick, Freedman, Morris, Paternicò, Donata, Fumagalli, Giorgio, Gabilondo, Alazne, Gauthier, Serge, Ghidoni, Roberta, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Gasparotti, Roberto, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans-Otto, Keren, Ron, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, van Swieten, John, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Rowe, James [0000-0001-7216-8679], Apollo - University of Cambridge Repository, Neurology, National Institutes of Health (US), National Science Foundation (US), Wellcome Trust, and Repositório da Universidade de Lisboa
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Male ,Time Factors ,MOTION ,Gene mutation ,physiopathology [Frontotemporal Dementia] ,methods [Connectome] ,0302 clinical medicine ,C9orf72 ,physiopathology [Nerve Net] ,BEHAVIORAL VARIANT ,Medicine ,genetics [Frontotemporal Dementia] ,11 Medical and Health Sciences ,dult Connectome/*methods Female Frontotemporal Dementia/diagnostic imaging/genetics/*physiopathology Heterozygote Humans Magnetic Resonance Imaging Male Middle Aged Nerve Net/diagnostic imaging/*physiopathology *Prodromal Symptoms Time Factors C9orf72 Chronnectome Dynamic brain functional connectivity Frontotemporal dementia Granulin Microtuble associate protein tau Mutation resting-state fMRI ,medicine.diagnostic_test ,Radiology, Nuclear Medicine & Medical Imaging ,05 social sciences ,Genetic FTD Initiative, GENFI ,Middle Aged ,Magnetic Resonance Imaging ,Demência Frontotemporal ,17 Psychology and Cognitive Sciences ,DYNAMIC FUNCTIONAL CONNECTIVITY ,Chronnectome ,Dynamic brain functional connectivity ,Frontotemporal dementia ,Granulin ,Microtuble associate protein tau ,Mutation ,resting-state fMRI ,Adult ,Connectome ,Female ,Frontotemporal Dementia ,Heterozygote ,Humans ,Nerve Net ,Prodromal Symptoms ,Neurology ,SENSITIVITY ,Life Sciences & Biomedicine ,Cognitive Neuroscience ,Neuroimaging ,FREQUENCY ,diagnostic imaging [Frontotemporal Dementia] ,Article ,050105 experimental psychology ,03 medical and health sciences ,mental disorders ,0501 psychology and cognitive sciences ,LOBAR DEGENERATION ,ddc:610 ,Dynamic functional connectivity ,RESTING-STATE NETWORKS ,Neurology & Neurosurgery ,Science & Technology ,Resting state fMRI ,SUBJECT ,diagnostic imaging [Nerve Net] ,business.industry ,Neurosciences ,medicine.disease ,FMRI DATA ,PATTERNS ,Neurosciences & Neurology ,business ,Functional magnetic resonance imaging ,Neuroscience ,030217 neurology & neurosurgery - Abstract
© 2019 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), Frontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varying patterns of connectivity) to evaluate measures of dynamic connectivity in 472 at-risk FTD subjects from the Genetic Frontotemporal dementia research Initiative (GENFI) cohort. We considered 249 subjects with FTD-related pathogenetic mutations and 223 mutation non-carriers (HC). Dynamic connectivity was evaluated using independent component analysis and sliding-time window correlation to rs-fMRI data, and meta-state measures of global brain flexibility were extracted. Results show that presymptomatic FTD exhibits diminished dynamic fluidity, visiting less meta-states, shifting less often across them, and travelling through a narrowed meta-state distance, as compared to HC. Dynamic connectivity changes characterize preclinical FTD, arguing for the desynchronization of the inner fluctuations of the brain. These changes antedate clinical symptoms, and might represent an early signature of FTD to be used as a biomarker in clinical trials., This work was supported in part by grants from the NIH (R01REB020407, P20GM103472), NSF grant 1539067 and the Well- come Trust grant (JBR 103838).
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- 2019
18. The Revised Self-Monitoring Scale detects early impairment of social cognition in genetic frontotemporal dementia within the GENFI cohort
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Franklin, Hannah D, Russell, Lucy L, Jiskoot, Lize, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nelson, Annabel, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Moreno, Fermin, Padovani, Alessandro, Panman, Jessica, Papma, Janne M, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Sanchez-Valle, Raquel, Rinaldi, Daisy, Rittman, Tim, Rogaeva, Ekaterina, Rollin, Adeline, Rosa-Neto, Pedro, Rossi, Giacomina, Rossor, Martin, Santiago, Beatriz, Saracino, Dario, Sayah, Sabrina, Borroni, Barbara, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Swift, Imogen, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Laforce, Robert, Tang-Wai, David, Thomas, David L, Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Todd, Emily, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Masellis, Mario, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Tartaglia, Maria Carmela, Graff, Caroline, Galimberti, Daniela, Rowe, James B, Peakman, Georgia, Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris, Gerhard, Alex, Levin, Johannes, Greaves, Caroline V, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Le Ber, Isabelle, Pasquier, Florence, Rohrer, Jonathan D, Genetic FTD Initiative, GENFI, Afonso, Sónia, Almeida, Maria Rosario, Anderl-Straub, Sarah, Bocchetta, Martina, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Nicholas, Jennifer, Bertoux, Maxime, Bertrand, Anne, Bessi, Valentina, Black, Sandra, Borrego-Ecija, Sergi, Bras, Jose, Brice, Alexis, Bruffaerts, Rose, Camuzat, Agnès, Cañada, Marta, Poos, Jackie, Cantoni, Valentina, Caroppo, Paola, Castelo-Branco, Miguel, Colliot, Olivier, Cope, Thomas, Deramecourt, Vincent, de Arriba, María, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Convery, Rhian S, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B, Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Funkiewiez, Aurélie, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Cash, David M, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Karnath, Hans Otto, van Swieten, John, Keren, Ron, Kuchcinski, Gregory, Langheinrich, Tobias, Lebouvier, Thibaud, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Rohrer, Jonathan D. [0000-0002-6155-8417], Apollo - University of Cambridge Repository, Bocchetta, Martina [0000-0003-1814-5024], Rowe, James B [0000-0001-7216-8679], Rohrer, Jonathan D [0000-0002-6155-8417], Neurology, Clinical Psychology, Clinical Genetics, and Repositório da Universidade de Lisboa
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Social Cognition ,Neurology ,Medizin ,RSMS ,PROGRESSION ,Audiology ,genetics [Progranulins] ,0302 clinical medicine ,Progranulins ,Familial ,C9orf72 ,MAPT ,Medicine ,CDR® plus NACC FTLD ,VBM ,genetics [Frontotemporal Dementia] ,11 Medical and Health Sciences ,Socioemotional selectivity theory ,05 social sciences ,Prodromal Stage ,Genetic FTD Initiative, GENFI ,Frontotemporal dementia ,GRN ,C9orf72 Protein ,Humans ,Magnetic Resonance Imaging ,Mutation ,tau Proteins ,Frontotemporal Dementia ,ORBITOFRONTAL CORTEX ,Life Sciences & Biomedicine ,RC321-571 ,medicine.medical_specialty ,Cognitive Neuroscience ,Clinical Neurology ,Neurosciences. Biological psychiatry. Neuropsychiatry ,genetics [Mutation] ,diagnostic imaging [Frontotemporal Dementia] ,050105 experimental psychology ,Temporal lobe ,03 medical and health sciences ,mental disorders ,0501 psychology and cognitive sciences ,ddc:610 ,RC346-429 ,genetics [C9orf72 Protein] ,Science & Technology ,CDR (R) plus NACC FTLD ,business.industry ,Research ,Neurosciences ,medicine.disease ,DYSFUNCTION ,genetics [tau Proteins] ,Orbitofrontal cortex ,Neurology. Diseases of the nervous system ,Neurosciences & Neurology ,Neurology (clinical) ,business ,Insula ,030217 neurology & neurosurgery - Abstract
© The Author(s). 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data., Background: Although social cognitive dysfunction is a major feature of frontotemporal dementia (FTD), it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts. Methods: We used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional sensitivity in 730 participants from the genetic FTD initiative (GENFI) observational study: 269 mutation-negative healthy controls, 193 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. All participants underwent the standardised GENFI clinical assessment including the 'CDR® plus NACC FTLD' scale and RSMS. The RSMS total score and its two subscores, socioemotional expressiveness (EX score) and modification of self-presentation (SP score) were measured. Volumetric T1-weighted magnetic resonance imaging was available from 377 mutation carriers for voxel-based morphometry (VBM) analysis. Results: The RSMS was decreased in symptomatic mutation carriers in all genetic groups but at a prodromal stage only in the C9orf72 (for the total score and both subscores) and GRN (for the modification of self-presentation subscore) groups. RSMS score correlated with disease severity in all groups. The VBM analysis implicated an overlapping network of regions including the orbitofrontal cortex, insula, temporal pole, medial temporal lobe and striatum. Conclusions: The RSMS indexes socioemotional impairment at an early stage of genetic FTD and may be a suitable outcome measure in forthcoming trials., The Dementia Research Centre is supported by Alzheimer’s Research UK, Brain Research Trust and The Wolfson Foundation. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility as well as an Alzheimer’s Society grant [AS-PG-16-007]. This work was also supported by the MRC UK GENFI grant [MR/M023664/1], the Italian Ministry of Health (CoEN015 and Ricerca Corrente) and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant, The Bluefield Project and the JPND GENFI-PROX grant [2019-02248]. JDR is supported by an MRC Clinician Scientist Fellowship [MR/M008525/1] and has received funding from the NIHR Rare Disease Translational Research Collaboration [BRC149/NS/MH], the Bluefield Project and the Association for Frontotemporal Degeneration. MB is supported by a Fellowship award from the Alzheimer’s Society, UK [AS-JF-19a-004-517]. JBR is supported by the Wellcome Trust [103838], the Medical Research Council and NIHR Cambridge Biomedical Research Centre. This work was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology [EXC 2145 SyNergy – ID 390857198]. Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.
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- 2021
19. Impairment of episodic memory in genetic frontotemporal dementia
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Poos, Jackie M, Russell, Lucy L, Pijnenburg, Yolande A L, Bender, Benjamin, Bruffaerts, Rose, Vandamme, Philip, Vandenbulcke, Mathieu, Ferreira, Catarina B, Miltenberger, Gabriel, Maruta, Carolina, Verdelho, Ana, Afonso, Sónia, Taipa, Ricardo, Borroni, Barbara, Caroppo, Paola, Di Fede, Giuseppe, Giaccone, Giorgio, Prioni, Sara, Redaelli, Veronica, Rossi, Giacomina, Tiraboschi, Pietro, Duro, Diana, Almeida, Maria Rosario, Castelo-Branco, Miguel, Sanchez-Valle, Raquel, Leitão, Maria João, Tabuas-Pereira, Miguel, Santiago, Beatriz, Gauthier, Serge, Rosa-Neto, Pedro, Veldsman, Michele, Thompson, Paul, Langheinrich, Tobias, Prix, Catharina, Hoegen, Tobias, Moreno, Fermin, Wlasich, Elisabeth, Loosli, Sandra, Schonecker, Sonja, Anderl-Straub, Sarah, Lombardi, Jolina, Bargalló, Nuria, Benussi, Alberto, Cantoni, Valentina, Bertoux, Maxime, Bertrand, Anne, Laforce, Robert, Brice, Alexis, Camuzat, Agnès, Colliot, Olivier, Sayah, Sabrina, Funkiewiez, Aurélie, Rinaldi, Daisy, Lombardi, Gemma, Nacmias, Benedetta, Saracino, Dario, Bessi, Valentina, Graff, Caroline, Ferrari, Camilla, Cañada, Marta, Deramecourt, Vincent, Kuchcinski, Gregory, Lebouvier, Thibaud, Ourselin, Sebastien, Polito, Cristina, Rollin, Adeline, Synofzik, Matthias, Galimberti, Daniela, Rowe, James B, Masellis, Mario, Peakman, Georgia, Tartaglia, Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Medonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R, Santana, Isabel, Ber, Isabelle Le, Gerhard, Alex, Ducharme, Simon, Bocchetta, Martina, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, van Swieten, John C, Rohrer, Jonathan D, Genetic FTD Initiative, GENF, Rossor, Martin N, Fox, Nick C, Greaves, Caroline V, Warren, Jason D, Moore, Katrina, Convery, Rhian, Swift, Imogen J, Shafei, Rachelle, Heller, Carolin, Todd, Emily, Bouzigues, Arabella, Cash, David, Woollacott, Ione, Jiskoot, Lize C, Zetterberg, Henrik, Nelson, Annabel, Nicholas, Jennifer, Guerreiro, Rita, Bras, Jose, Thomas, David L, Mead, Simon, Meeter, Lieke, Panman, Jessica, van Minkelen, Rick, van der Ende, Emma L, Barandiaran, Myriam, Indakoetxea, Begoña, Gabilondo, Alazne, Tainta, Mikel, Gorostidi, Ana, Zulaica, Miren, Díez, Alina, Villanua, Jorge, Borrego-Ecija, Sergi, Jaume, Olives, Seelaar, Harro, Lladó, Albert, Balasa, Mircea, Antonell, Anna, Bargallo, Nuria, Premi, Enrico, Gazzina, Stefano, Gasparotti, Roberto, Archetti, Silvana, Black, Sandra, Mitchell, Sara, Papma, Janne M, Rogaeva, Ekaterina, Freedman, Morris, Keren, Ron, Tang-Wai, David, Thonberg, Hakan, Öijerstedt, Linn, Andersson, Christin, Jelic, Vesna, Arighi, Andrea, Fenoglio, Chiara, van den Berg, Esther, Scarpini, Elio, Fumagalli, Giorgio, Cope, Thomas, Timberlake, Carolyn, Rittman, Timothy, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Wilke, Carlo, Karnarth, Hans-Otto, Apollo - University of Cambridge Repository, Repositório da Universidade de Lisboa, Rowe, James [0000-0001-7216-8679], Rowe, James B [0000-0001-7216-8679], Neurology, Amsterdam Neuroscience - Neurodegeneration, Genetic FTD Initiative, GENFI, Radiology & Nuclear Medicine, Neurosurgery, Clinical Psychology, and Clinical Genetics
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cognition ,Medizin ,neuropsychology ,Audiology ,frontotemporal dementia ,DISEASE ,0302 clinical medicine ,COGNITIVE & BEHAVIORAL ASSESSMENT ,C9orf72 ,BEHAVIORAL VARIANT ,CRITERIA ,voxel‐based morphometry ,ALZHEIMERS ,Episodic memory ,0303 health sciences ,episodic memory ,CARRIERS ,frontal lobe ,Psychiatry and Mental health ,Frontal lobe ,Life Sciences & Biomedicine ,Frontotemporal dementia ,temporal lobe ,Cognition ,Executive function ,Genetic disorders ,Neuropsychology ,Temporal lobe ,Voxel-based morphometry ,medicine.medical_specialty ,Clinical Neurology ,DIAGNOSIS ,RESEARCH ARTICLE ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,Memory impairment ,voxel-based morphometry ,genetic disorders ,ddc:610 ,PROGRANULIN ,RC346-429 ,030304 developmental biology ,0604 Genetics ,Science & Technology ,Recall ,business.industry ,RC952-954.6 ,Neurosciences ,PROFILES ,medicine.disease ,executive function ,Geriatrics ,VOLUME ,Genetic FTD Initiative, GENF ,Neurology (clinical) ,Neurology. Diseases of the nervous system ,Neurosciences & Neurology ,business ,1109 Neurosciences ,030217 neurology & neurosurgery - Abstract
© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT). Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule-associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel-based morphometry to investigate the underlying neural substrates of the FCSRT. Results: All symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers. Discussion: The FCSRT detects presymptomatic deficits in C9orf72- and MAPT-associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD., The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK. J. D. Rohrer is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1); the Bluefield Project; the JPND GENFI-PROX grant (2019-02248); the Dioraphte Foundation (grant numbers 09-02-00); the Association for Frontotemporal Dementias Research Grant 2009; The Netherlands Organization for Scientific Research (NWO; grant HCMI 056-13-018); ZonMw Memorabel (Deltaplan Dementie, project numbers 733 050 103 and 733 050 813); JPND PreFrontAls consortium (project number 733051042). J. M. Poos is supported by a Fellowship award from Alzheimer Nederland (WE.15-2019.02). This work was conducted using the MRC Dementias Platform UK (MR/L023784/1 and MR/009076/1). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.
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- 2021
20. Social cognition impairment in genetic frontotemporal dementia within the GENFI cohort
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Russell, Lucy L, Greaves, Caroline V, Bocchetta, Martina, Nicholas, Jennifer, Convery, Rhian S, Moore, Katrina, Cash, David M, van Swieten, John, Jiskoot, Lize, Moreno, Fermin, Sanchez-Valle, Raquel, Borroni, Barbara, Laforce, Robert, Masellis, Mario, Tartaglia, Maria Carmela, Graff, Caroline, Rotondo, Emanuela, 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, Warren, Jason D, Rohrer, Jonathan D, Genetic FTD Initiative, GENFI, Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository
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Social Cognition ,Progranulin ,C9orf72 Protein ,Emotion processing ,Magnetic Resonance Imaging ,Progranulins ,Theory of mind ,Frontotemporal Dementia ,C9orf72 ,Mutation ,mental disorders ,MAPT ,Humans ,Facial emotion recognition ,Faux pas - Abstract
A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and Faux Pas (FP) recognition tests were used to study social cognition within the Genetic Frontotemporal Dementia Initiative (GENFI), a large familial FTD cohort of C9orf72, GRN, and MAPT mutation carriers. 627 participants undertook at least one of the tasks, and were separated into mutation-negative healthy controls, presymptomatic mutation carriers (split into early and late groups) and symptomatic mutation carriers. Groups were compared using a linear regression model with bootstrapping, adjusting for age, sex, education, and for the FP recognition test, language. Neural correlates of social cognition deficits were explored using a voxel-based morphometry (VBM) study. All three of the symptomatic genetic groups were impaired on both tasks with no significant difference between them. However, prior to onset, only the late presymptomatic C9orf72 mutation carriers on the FER test were impaired compared to the control group, with a subanalysis showing differences particularly in fear and sadness. The VBM analysis revealed that impaired social cognition was mainly associated with a left hemisphere predominant network of regions involving particularly the striatum, orbitofrontal cortex and insula, and to a lesser extent the inferomedial temporal lobe and other areas of the frontal lobe. In conclusion, theory of mind and emotion processing abilities are impaired in familial FTD, with early changes occurring prior to symptom onset in C9orf72 presymptomatic mutation carriers. Future work should investigate how performance changes over time, in order to gain a clearer insight into social cognitive impairment over the course of the disease.
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- 2020
21. Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort.
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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, and Synofzik, Matthis
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FRONTOTEMPORAL dementia , *DOMINANT language , *LANGUAGE ability testing , *TEMPORAL lobe , *LINGUISTICS , *SYNTAX (Grammar) , *GAIN-of-function mutations - Abstract
To identify whether language impairment exists presymptomatically in genetic frontotemporal dementia (FTD), and if so, the key differences between the main genetic mutation groups. 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. 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. 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. • Language deficits occur in prodromal frontotemporal dementia. • Differential patterns of language symptoms are seen in different genetic groups. • Language assessment may be important as a measure of staging in frontotemporal dementia. [ABSTRACT FROM AUTHOR]
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- 2023
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22. A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers
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Yolande A.L. Pijnenburg, Alessandro Padovani, Lieke H.H. Meeter, Rita Guerreiro, Mathieu Vandenbulcke, Rose Bruffaerts, Sonja Schönecker, Sofia Bergström, Florence Pasquier, Mikel Tainta, Beatriz Santiago, Roberto Gasparotti, Maria Rosário Almeida, Núria Bargalló, Abbe Ullgren, Martina Bocchetta, James B. Rowe, Pietro Tiraboschi, Robart Bartha, Rachelle Shafei, Benjamin Bender, Anna Månberg, Enrico Premi, Sergi Borrego-Écija, Sandro Sorbi, Christopher C Butler, Rick van Minkelen, Alberto Benussi, Marta Cañada, Carlo Wilke, Christin Andersson, Caroline Graff, Isabel Santana, Elisa Semler, Valentina Bessi, Miren Zulaica, Benedetta Nacmias, Tobias Langheinrich, Christen Shoesmith, Philip Van Damme, Camilla Ferrari, Martin Rosser, Pedro Rosa-Neto, Alexandre de Mendonça, Jennifer M. Nicholas, Catharina Prix, Sebastien Ourselin, Michele Veldsman, Jessica L. Panman, Håkan Thonberg, Jennie Olofsson, Paul M. Thompson, Ana Gorostidi, Andrea Arighi, Raquel Sánchez-Valle, Anna Antonell, Vesna Jelic, Ana Verdelho, Sara Mitchell, Janne M. Papma, Alina Díez, Giuliano Binetti, Rhian S Convery, Silvana Archetti, Ekaterina Rogaeva, Michela Pievani, C. Ferreira, Hans-Otto Karnath, Veronica Redaelli, Giuseppe Di Fede, Giovanni B. Frisoni, Carolina Maruta, Giacomina Rossi, Jaume Olives, Simon Ducharme, Roberta Ghidoni, Alexander Gerhard, Ron Keren, Johannes Levin, Sandra V. Loosli, Jose Bras, Isabelle Le Ber, Emily Todd, Robert Laforce, Sónia Afonso, Matthis Synofzik, Alazne Gabilondo, Elizabeth Finger, Thomas E. Cope, Paola Caroppo, Jorge Villanua, Diana Duro, Georgia Peakman, Giorgio G. Fumagalli, Serge Gauthier, Mario Masellis, Markus Otto, Caroline V. Greaves, Carolyn Timberlake, Harro Seelaar, Ione O.C. Woollacott, Sara Prioni, Jason D. Warren, Cristina Polito, Miguel Tábuas-Pereira, David F. Tang-Wai, Carmela Tartaglia, Linn Öijerstedt, Luisa Benussi, Barbara Borroni, Ricardo Taipa, Albert Lladó, Mircea Balasa, Rosa Rademakers, Lize C. Jiskoot, Miguel Castelo-Branco, Julia Remnestål, Fabrizio Tagliavini, Giorgio Giaccone, Maria João Leitão, Henrik Zetterberg, Valentina Cantoni, Daniela Galimberti, Sarah Anderl-Straub, Simon Mead, Myriam Barandiaran, Adrian Danek, Timothy Rittman, Chiara Fenoglio, Katrina M. Moore, David M. Cash, Rik Vandenberghe, Peter Nilsson, Elisabeth Wlasich, John C. van Swieten, Morris Freedman, Sandra E. Black, Carolin Heller, Stefano Gazzina, Gabriel Miltenberger, Fermin Moreno, Nick C. Fox, David L. Thomas, Jonathan D. Rohrer, Begoña Indakoetxea, Tobias Hoegen, Gemma Lombardi, Elio Scarpini, Bergström, Sofia [0000-0003-2910-4754], Apollo - University of Cambridge Repository, Neurology, Amsterdam Neuroscience - Neurodegeneration, Genetic Frontotemporal Dementia Initiative (GENFI), Jiskoot, Lize (Beitragende*r), Rowe, James B. (Beitragende*r), de Mendonça, Alexandre (Beitragende*r), Tagliavini, Fabrizio (Beitragende*r), Santana, Isabel (Beitragende*r), Le Ber, Isabelle (Beitragende*r), Levin, Johannes (Beitragende*r), Danek, Adrian (Beitragende*r), Otto, Markus (Beitragende*r), Frisoni, Giovanni (Beitragende*r), Ghidoni, Roberta (Beitragende*r), Sorbi, Sandro (Beitragende*r), Pasquier, Florence (Beitragende*r), Jelic, Vesna (Beitragende*r), Andersson, Christin (Beitragende*r), Afonso, Sónia (Beitragende*r), Almeida, Maria Rosario (Beitragende*r), Anderl-Straub, Sarah (Beitragende*r), Antonell, Anna (Beitragende*r), Archetti, Silvana (Beitragende*r), Arighi, Andrea (Beitragende*r), Balasa, Mircea (Beitragende*r), Barandiaran, Myriam (Beitragende*r), Bargalló, Nuria (Beitragende*r), Bartha, Robart (Beitragende*r), Bender, Benjamin (Beitragende*r), Benussi, Alberto (Beitragende*r), Benussi, Luisa (Beitragende*r), Bessi, Valentina (Beitragende*r), Binetti, Giuliano (Beitragende*r), Black, Sandra (Beitragende*r), Bocchetta, Martina (Beitragende*r), Borrego-Ecija, Sergi (Beitragende*r), Bras, Jose (Beitragende*r), Bruffaerts, Rose (Beitragende*r), Cañada, Marta (Beitragende*r), Cantoni, Valentina (Beitragende*r), Caroppo, Paola (Beitragende*r), Cash, David (Beitragende*r), Castelo-Branco, Miguel (Beitragende*r), Convery, Rhian (Beitragende*r), Cope, Thomas (Beitragende*r), Di Fede, Giuseppe (Beitragende*r), Díez, Alina (Beitragende*r), Duro, Diana (Beitragende*r), Fenoglio, Chiara (Beitragende*r), Ferrari, Camilla (Beitragende*r), Ferreira, Catarina B. (Beitragende*r), Fox, Nick (Beitragende*r), Freedman, Morris (Beitragende*r), Fumagalli, Giorgio (Beitragende*r), Gabilondo, Alazne (Beitragende*r), Gasparotti, Roberto (Beitragende*r), Gauthier, Serge (Beitragende*r), Gazzina, Stefano (Beitragende*r), Giaccone, Giorgio (Beitragende*r), Gorostidi, Ana (Beitragende*r), Greaves, Caroline (Beitragende*r), Guerreiro, Rita (Beitragende*r), Heller, Carolin (Beitragende*r), Hoegen, Tobias (Beitragende*r), Indakoetxea, Begoña (Beitragende*r), Karnath, Hans-Otto (Beitragende*r), Keren, Ron (Beitragende*r), Langheinrich, Tobias (Beitragende*r), Leitão, Maria João (Beitragende*r), Lladó, Albert (Beitragende*r), Lombardi, Gemma (Beitragende*r), Loosli, Sandra (Beitragende*r), Maruta, Carolina (Beitragende*r), Mead, Simon (Beitragende*r), Meeter, Lieke (Beitragende*r), Miltenberger, Gabriel (Beitragende*r), van Minkelen, Rick (Beitragende*r), Mitchell, Sara (Beitragende*r), Moore, Katrina (Beitragende*r), Nacmias, Benedetta (Beitragende*r), Nicholas, Jennifer (Beitragende*r), Olives, Jaume (Beitragende*r), Ourselin, Sebastien (Beitragende*r), Padovani, Alessandro (Beitragende*r), Panman, Jessica (Beitragende*r), Papma, Janne M. (Beitragende*r), Peakman, Georgia (Beitragende*r), Pievani, Michela (Beitragende*r), Pijnenburg, Yolande (Beitragende*r), Polito, Cristina (Beitragende*r), Premi, Enrico (Beitragende*r), Prioni, Sara (Beitragende*r), Prix, Catharina (Beitragende*r), Rademakers, Rosa (Beitragende*r), Redaelli, Veronica (Beitragende*r), Rittman, Tim (Beitragende*r), Rogaeva, Ekaterina (Beitragende*r), Rosa-Neto, Pedro (Beitragende*r), Rossi, Giacomina (Beitragende*r), Rosser, Martin (Beitragende*r), Santiago, Beatriz (Beitragende*r), Scarpini, Elio (Beitragende*r), Schönecker, Sonja (Beitragende*r), Semler, Elisa (Beitragende*r), Shafei, Rachelle (Beitragende*r), Shoesmith, Christen (Beitragende*r), Tábuas-Pereira, Miguel (Beitragende*r), Tainta, Mikel (Beitragende*r), Taipa, Ricardo (Beitragende*r), Tang-Wai, David (Beitragende*r), Thomas, David L. (Beitragende*r), Thompson, Paul (Beitragende*r), Thonberg, Håkan (Beitragende*r), Timberlake, Carolyn (Beitragende*r), Tiraboschi, Pietro (Beitragende*r), Todd, Emily (Beitragende*r), Van Damme, Philip (Beitragende*r), Vandenbulcke, Mathieu (Beitragende*r), Veldsman, Michele (Beitragende*r), Verdelho, Ana (Beitragende*r), Villanua, Jorge (Beitragende*r), Warren, Jason (Beitragende*r), Wilke, Carlo (Beitragende*r), Woollacott, Ione (Beitragende*r), Wlasich, Elisabeth (Beitragende*r), Zetterberg, Henrik (Beitragende*r), and Zulaica, Miren (Beitragende*r)
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medicine.medical_specialty ,Neurology ,NEFM ,Medizin ,genetics [Mutation] ,LASSO ,Biology ,Aquaporin 4 (AQP4) ,Neurosecretory protein VGF (VGF) ,DISEASE ,genetics [Progranulins] ,Cellular and Molecular Neuroscience ,Progranulins ,CEREBROSPINAL-FLUID ,C9orf72 ,ddc:570 ,medicine ,CRITERIA ,Humans ,Neuronal pentraxin 2 (NPTX2) ,RC346-429 ,genetics [Frontotemporal Dementia] ,Molecular Biology ,Pathological ,Genetics ,Science & Technology ,Neurosciences ,RC952-954.6 ,Brain ,Neurofilament medium polypeptide (NEFM) ,medicine.disease ,Molecular medicine ,Cerebrospinal fluid ,Aquaporin 4 ,Geriatrics ,Suspension bead array ,Frontotemporal Dementia ,Mutation ,Mutation (genetic algorithm) ,Neurosciences & Neurology ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,Life Sciences & Biomedicine ,Random forest ,Biomarkers ,Research Article ,Frontotemporal dementia - Abstract
Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Supplementary Information: Additional file 1 of A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study; Additional file 2 of A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study; both files are available online at https://doi.org/10.1186/s13024-021-00499-4 Copyright © The Author(s) 2021. Background: A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers. Methods: A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest. Results: When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN). Conclusion: In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD. This study has received support from the Swedish FTD initiative funded by the Schörling Family Foundation. This work was also funded by KTH Center for Applied Precision Medicine (KCAP) funded by the Erling-Persson Family Foundation, grants from Vetenskapsrådet Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, Swedish Alzheimer Foundation, Swedish Brain Foundation, Åhlén foundation, Demensfonden, Stohnes foundation, Gamla Tjänarinnor and Stockholm County Council ALF. Furthermore, support was received by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX grant (2019-02248), the Dioraphte Foundation [grant numbers 09-02-00]; the Association for Frontotemporal Dementias Research Grant 2009; The Netherlands Organization for Scientific Research (NWO) (grant HCMI 056-13-018); ZonMw Memorabel (Deltaplan Dementie), (project numbers 733 050 103 and 733 050 813); JPND PreFrontAls consortium (project number 733051042). 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). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510. M.S. was supported by the JPND grant “GENFI-prox” (by DLR/BMBF to M. S, joint with JDR., J.vS., M.O., B.B. and C.G.). Open Access funding provided by Royal Institute of Technology.
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- 2021
23. Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia
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Elise G.P. Dopper, Desheng Xu, Christopher C Butler, Alexandre de Mendonça, James B. Rowe, Isabel Santana, Fabrizio Tagliavini, Barbara Borroni, Lize C. Jiskoot, Robert Laforce, Jessica L. Panman, Jackie M. Poos, Yolande A.L. Pijnenburg, Lieke H.H. Meeter, Emma L. van der Ende, Harro Seelaar, Georgia Peakman, Alexander Gerhard, Daniela Galimberti, Jonathan D. Rohrer, Simon Ducharme, Janne M. Papma, Mollie Neason, Charlotte E. Teunissen, Rik Vandenberghe, Meifang Xiao, Elizabeth Finger, Maria Carmela Tartaglia, Adrian Danek, Raquel Sánchez-Valle, Johannes Levin, Markus Otto, Paul F. Worley, Fermin Moreno, Carolin Heller, David M. Cash, Katrina M. Moore, Martina Bocchetta, Rhian S Convery, Caroline Graff, Matthis Synofzik, John C. van Swieten, Mario Masellis, Neurology, van der Ende, Emma L [0000-0003-2570-8796], Poos, Jackie M [0000-0001-8843-7247], Jiskoot, Lize C [0000-0002-1120-1858], Heller, Carolin [0000-0002-1934-6162], Convery, Rhian [0000-0002-9477-1812], Bocchetta, Martina [0000-0003-1814-5024], Finger, Elizabeth [0000-0003-4461-7427], Rowe, James B [0000-0001-7216-8679], Otto, Markus [0000-0002-6647-5944], Borroni, Barbara [0000-0001-9340-9814], van Swieten, John C [0000-0001-6278-6844], Apollo - University of Cambridge Repository, Laboratory Medicine, Amsterdam Neuroscience - Neurodegeneration, and Amsterdam Reproduction & Development (AR&D)
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Oncology ,Male ,VARIANT ,Medizin ,cerebrospinal fluid [Frontotemporal Dementia] ,NARP ,0302 clinical medicine ,Cerebrospinal fluid ,diagnosis [Frontotemporal Dementia] ,Neurofilament Proteins ,C9orf72 ,CRITERIA ,Verbal fluency test ,genetics [Frontotemporal Dementia] ,Psychiatry ,0303 health sciences ,biology ,Middle Aged ,3. Good health ,ALZHEIMERS-DISEASE ,Psychiatry and Mental health ,C-Reactive Protein ,medicine.anatomical_structure ,cerebrospinal fluid [Biomarkers] ,Frontotemporal Dementia ,Disease Progression ,Biomarker (medicine) ,Female ,Life Sciences & Biomedicine ,Frontotemporal dementia ,Adult ,medicine.medical_specialty ,Heterozygote ,Clinical Dementia Rating ,Clinical Neurology ,Nerve Tissue Proteins ,Grey matter ,cerebrospinal fluid [C-Reactive Protein] ,03 medical and health sciences ,CEREBROSPINAL-FLUID ,Internal medicine ,medicine ,Humans ,ddc:610 ,Neurodegeneration ,030304 developmental biology ,Aged ,Science & Technology ,Pentraxins ,business.industry ,cerebrospinal fluid [Nerve Tissue Proteins] ,medicine.disease ,DYSFUNCTION ,cerebrospinal fluid [Neurofilament Proteins] ,biology.protein ,Surgery ,Neurosciences & Neurology ,Neurology (clinical) ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
IntroductionSynapse dysfunction is emerging as an early pathological event in frontotemporal dementia (FTD), however biomarkers are lacking. We aimed to investigate the value of cerebrospinal fluid (CSF) neuronal pentraxins (NPTXs), a family of proteins involved in homeostatic synapse plasticity, as novel biomarkers in genetic FTD.MethodsWe included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN, C9orf72 or MAPT, and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses.ResultsSymptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301–872)) than presymptomatic carriers (1003 pg/mL (624–1358), pDiscussionWe conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.
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- 2020
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