Search

Your search keyword '"Miltenberger, G"' showing total 23 results
Start Over Author "Miltenberger, G"
23 results on '"Miltenberger, G"'

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

Author

Bussy, A., Levy, J., Best, T., Patel, R., Cupo, L., Van Langenhove, T., Nielsen, J., Pijnenburg, Y., Waldö, M., Remes, A., Schroeter, M., Santana, I., Pasquier, F., Otto, M., Danek, A., Levin, J., Le Ber, I., Vandenberghe, R., Synofzik, M., Moreno, F., de Mendonça, A., Sanchez‐Valle, R., Laforce, R., Langheinrich, T., Gerhard, A., Graff, C., Butler, C., Sorbi, S., Jiskoot, L., Seelaar, H., van Swieten, J., Finger, E., Tartaglia, M., Masellis, M., Tiraboschi, P., Galimberti, D., Borroni, B., Rowe, J., Bocchetta, M., Rohrer, J., Devenyi, G., Chakravarty, M., Ducharme, S., Esteve, A., Nelson, A., Bouzigues, A., Heller, C., Greaves, C., Cash, D., Thomas, D., Todd, E., Benotmane, H., Zetterberg, H., Swift, I., Nicholas, J., Samra, K., Russell, L., Shafei, R., Convery, R., Timberlake, C., Cope, T., Rittman, T., Benussi, A., Premi, E., Gasparotti, R., Archetti, S., Gazzina, S., Cantoni, V., Arighi, A., Fenoglio, C., Scarpini, E., Fumagalli, G., Borracci, V., Rossi, G., Giaccone, G., Di Fede, G., Caroppo, P., Prioni, S., Redaelli, V., Tang‐Wai, D., Rogaeva, E., Castelo‐Branco, M., Freedman, M., Keren, R., Black, S., Mitchell, S., Shoesmith, C., Bartha, R., Rademakers, R., Poos, J., Papma, J., Giannini, L., van Minkelen, R., Nacmias, B., Ferrari, C., Polito, C., Lombardi, G., Bessi, V., Veldsman, M., Andersson, C., Thonberg, H., Öijerstedt, L., Jelic, V., Thompson, P., Lladó, A., Antonell, A., Olives, J., Balasa, M., Bargalló, N., Borrego‐Ecija, S., Verdelho, A., Maruta, C., Ferreira, C., Miltenberger, G., do Couto, F., Gabilondo, A., Gorostidi, A., Villanua, J., Cañada, M., Tainta, M., Zulaica, M., Barandiaran, M., Alves, P., Bender, B., Wilke, C., Graf, L., Vogels, A., Vandenbulcke, M., Van Damme, P., Bruffaerts, R., Poesen, K., Rosa‐Neto, P., Gauthier, S., Camuzat, A., Brice, A., Bertrand, A., Funkiewiez, A., Rinaldi, D., Saracino, D., Colliot, O., Sayah, S., Prix, C., Wlasich, E., Wagemann, O., Loosli, S., Schönecker, S., Hoegen, T., Lombardi, J., Anderl‐Straub, S., Rollin, A., Kuchcinski, G., Bertoux, M., Lebouvier, T., Deramecourt, V., Santiago, B., Duro, D., Leitão, M., Almeida, M., Tábuas‐Pereira, M., Afonso, S., Engel, A., Polyakova, M., Erasmus MC other, Neurology, Radiology & Nuclear Medicine, Clinical Genetics, GENetic Frontotemporal dementia Initiative (GENFI), Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, 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, Engel, Annerose, Polyakova, Maryna, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Russell, Lucy L, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Bussy, Aurélie [0000-0001-6695-9941], Nielsen, Jørgen E [0000-0003-0453-5582], Borroni, Barbara [0000-0001-9340-9814], Bocchetta, Martina [0000-0003-1814-5024], Devenyi, Gabriel A [0000-0002-7766-1187], Apollo - University of Cambridge Repository, and Amsterdam Neuroscience - Neurodegeneration

Subjects
C9orf72 Protein, Radiological and Ultrasound Technology, Medizin, frontotemporal dementia, Neurology, Frontotemporal Dementia, Cerebellum, Humans, magnetic resonance imaging, genetics, neuropsychiatry, Radiology, Nuclear Medicine and imaging, Human medicine, ddc:610, Neurology (clinical), Atrophy, Anatomy, genetics [Frontotemporal Dementia], genetics [C9orf72 Protein]
Abstract

Funder: Alzheimer Society of Canada; Id: http://dx.doi.org/10.13039/501100000143, Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479, Funder: Fonds de Recherche du Québec ‐ Santé, Funder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024, Funder: NIHR Rare Diseases Translational Research Collaboration, Funder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659, Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.

Published
2023
Full Text
View/download PDF

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

Author

Samra, K, MacDougall, AM, Peakman, G, Bouzigues, A, Bocchetta, M, Cash, DM, Greaves, CV, Convery, RS, van Swieten, JC, Jiskoot, L, Seelaar, H, Butler, CR, Fenoglio, C, Rohrer, JD, Gerhard, A, Ducharme, S, Le Ber, I, Tiraboschi, P, Santana, I, Pasquier, F, Levin, J, Shoesmith, C, Otto, M, Russell, LL, Nelson, A, Cash, D, Thomas, DL, Todd, E, Ferrari, C, Benotmane, H, Timberlake, C, Gabilondo, A, Cope, T, Rittman, T, Benussi, A, Premi, E, Gasparotti, R, Thompson, P, Archetti, S, Fumagalli, G, do Couto, FS, Borracci, V, Polito, C, Rossi, G, Giaccone, G, Di Fede, G, Caroppo, P, Ferreira, CB, Prioni, S, Langheinrich, T, Redaelli, V, Lladó, A, Bartha, R, Tang-Wai, D, Rogaeva, E, Castelo-Branco, M, Freedman, M, Keren, R, Black, S, Mitchell, S, Miltenberger, G, Rademakers, R, Poos, J, Papma, JM, Giannini, L, van Minkelen, R, Pijnenburg, Y, Gauthier, S, Nacmias, B, Lombardi, G, Bessi, V, Veldsman, M, Andersson, C, Thonberg, H, Öijerstedt, L, Prix, C, Jelic, V, Antonell, A, Graff, C, Olives, J, Balasa, M, Bargalló, N, Borrego-Ecija, S, Verdelho, A, Kuchcinski, G, Maruta, C, Gorostidi, A, Laforce, R, Villanua, J, Wlasich, E, Cañada, M, Tainta, M, Zulaica, M, Barandiaran, M, Moreno, F, Alves, P, Bender, B, Bertoux, M, Wilke, C, Lebouvier, T, Camuzat, A, Graf, L, Vogels, A, Vandenbulcke, M, Van Damme, P, Bruffaerts, R, Poesen, K, Rosa-Neto, P, Sanchez-Valle, R, Brice, A, Bertrand, A, Funkiewiez, A, Rinaldi, D, Saracino, D, Colliot, O, Sorbi, S, Sayah, S, Wagemann, O, Loosli, S, Schönecker, S, Hoegen, T, Lombardi, J, Anderl-Straub, S, Nicholas, J, Rollin, A, Deramecourt, V, Arighi, A, Santiago, B, Duro, D, Leitão, MJ, Almeida, MR, Tábuas-Pereira, M, Gazzina, S, Afonso, S, Masellis, M, Tartaglia, C, Shafei, R, Rowe, JB, Borroni, B, Finger, E, Synofzik, M, Galimberti, D, Vandenberghe, R, de Mendonça, A, Cantoni, V, Genetic FTD Initiative (GENFI), Samra, Kiran [0000-0002-3105-7099], Apollo - University of Cambridge Repository, 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, Nelson, Annabel, Bocchetta, Martina, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, 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, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, 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, and Verdelho, Ana

Subjects
Progranulin, Clinical Neurology, C9ORF72, tau Proteins, AMYOTROPHIC-LATERAL-SCLEROSIS, diagnosis [Frontotemporal Dementia], C9orf72, Tremor, Genetics, Humans, ddc:610, genetics [Frontotemporal Dementia], genetics [C9orf72 Protein], MUTATION, Science & Technology, C9orf72 Protein, HERITABILITY, Amyotrophic Lateral Sclerosis, PROGRESSIVE SUPRANUCLEAR PALSY, COGNITIVE IMPAIRMENT, REPEAT EXPANSION, genetics [tau Proteins], Motor, PATHOLOGICAL FEATURES, Neurology, FOS: Biological sciences, Frontotemporal Dementia, Mutation, Human medicine, Neurosciences & Neurology, Neurology (clinical), Tau, TAU, Life Sciences & Biomedicine, Frontotemporal dementia, PARKINSONISM
Abstract

Funder: CIBERNED, Funder: Canadian Institutes of Health Research; doi: http://dx.doi.org/10.13039/501100000024, Funder: Lemaire Family Foundation, Funder: Swedish Frontotemporal Dementia Initiative, Funder: Italian Ministry of Health, Funder: Weston Brain Institute; doi: http://dx.doi.org/10.13039/100012479, Funder: Mady Browaaeys Fund, Funder: Miriam Marks Brain Research UK, Funder: Bluefield Project, OBJECTIVE: To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). METHODS: Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-negative controls. A standardised clinical questionnaire was used to assess eight motor symptoms (dysarthria, dysphagia, tremor, slowness, weakness, gait disorder, falls and functional difficulties using hands). Frequency and severity of each motor symptom was assessed, and a principal component analysis (PCA) was performed to identify how the different motor symptoms loaded together. Finally, addition of a motor component to the CDR® plus NACC FTLD was investigated (CDR® plus NACC FTLD-M). RESULTS: 24.3% of mutation carriers had motor symptoms (31.7% C9orf72, 18.8% GRN, 19.3% MAPT) compared to 6.8% of controls. Slowness and gait disorder were the commonest in all genetic groups while tremor and falls were the least frequent. Symptom severity scores were similar to equivalent physical motor examination scores. PCA revealed that all motor symptoms loaded together so a single additional motor component was added to the CDR® plus NACC FTLD to form the CDR® plus NACC FTLD-M. Individual global scores were more severe with the CDR® plus NACC FTLD-M, and no patients with a clinically diagnosed motor disorder (ALS/FTD-ALS or parkinsonism) were classified anymore as asymptomatic (unlike the CDR® plus NACC FTLD alone). CONCLUSIONS: Motor features are present in mutation carriers at all disease stages across all three genetic groups. Inclusion of motor symptoms in a rating scale that can be used in future clinical trials will not only ensure a more accurate severity measure is recorded but that a wider spectrum of FTD phenotypes can be included in the same trial.

Published
2022
Full Text
View/download PDF

3. Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia

Author

Panman, J. L., Venkatraghavan, V., Van Der Ende, E. L., Steketee, R. M. E., Jiskoot, L. C., Poos, J. M., Dopper, E. G. P., Meeter, L. H. H., Kaat, L. D., Rombouts, S. A. R. B., Vernooij, M. W., Kievit, A. J. A., Premi, E., Cosseddu, M., Bonomi, E., Olives, J., Rohrer, J. D., Sanchez-Valle, R., Borroni, B., Bron, E. E., Van Swieten, J. C., Papma, J. M., Klein, S., Afonso, S., Almeida, M. R., Anderl-Straub, S., Andersson, C., Antonell, A., Archetti, S., Arighi, A., Balasa, M., Barandiaran, M., Bargallo, N., Bartha, R., Bender, B., Black, S., Butler, C., Bocchetta, M., Borrego-Ecija, S., Bras, J., Bruffaerts, R., Caroppo, P., Cash, D., Castelo-Branco, M., Convery, R., Cope, T., Danek, A., De Arriba, M., De Mendonca, A., Di Fede, G., Diaz, Z., Ducharme, S., Duro, D., Fenoglio, C., Ferreira, C. B., Finger, E., Flanagan, T., Fox, N., Freedman, M., Fumagalli, G., Gabilondo, A., Galimberti, D., Gasparotti, R., Gauthier, S., Gazzina, S., Gerhard, A., Giaccone, G., Gorostidi, A., Graff, C., Greaves, C., Guerreiro, R., Heller, C., Hoegen, T., Indakoetxea, B., Jelic, V., Karnath, H. -O., Keren, R., Laforce, R., Leitao, M. J., Levin, J., Llado, A., Loosli, S., Maruta, C., Masellis, M., Mead, S., Miltenberger, G., Van Minkelenm Sara Mitchell, R., Moore, K., Moreno, F., Nicholas, J., Oijerstedt, L., Otto, M., Ourselin, S., Padovani, A., Peakman, G., Pijnenburg, Y., Polito, C., Prioni, S., Prix, C., Rademakers, R., Redaelli, V., Rittman, T., Rogaeva, E., Rosa-Neto, P., Rossi, G., Rosser, M., Rowe, J., Santana, I., Santiago, B., Scarpini, E., Schonecker, S., Shafei, E. S. R., Shoesmith, C., Synofzik, M., Tabuas-Pereira, M., Tagliavini, F., Tartaglia, C., Tainta, M., Taipa, R., Tang-Wai, D., Thomas, D. L., Thonberg, H., Timberlake, C., Tiraboschi, P., Todd, E., Vandamme, P., Vandenberghe, R., Vandenbulcke, M., Veldsman, M., Verdelho, A., Villanua, J., Warren, J., Wilkeione, C., Elisabeth, W., Henrik, W., Zulaica, Z. M., Neurology, Physics and medical technology, Radiology & Nuclear Medicine, Clinical Genetics, and Medical Research Council

Subjects
Male, Oncology, Disease, Neuropsychological Tests, GENFI consortium investigators, Primary progressive aphasia, Cognition, Progranulins, 0302 clinical medicine, Neurofilament Proteins, BEHAVIORAL VARIANT, HETEROGENEITY, Gray Matter, 11 Medical and Health Sciences, Language, Psychiatry, 0303 health sciences, Brain, Middle Aged, Magnetic Resonance Imaging, White Matter, 17 Psychology and Cognitive Sciences, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Phenotype, medicine.anatomical_structure, Frontotemporal Dementia, Disease Progression, Biomarker (medicine), Female, Life Sciences & Biomedicine, Frontotemporal dementia, medicine.medical_specialty, Clinical Neurology, EVENT-BASED MODEL, Grey matter, Lateralization of brain function, White matter, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, NEUROFILAMENT LIGHT-CHAIN, medicine, Humans, LOBAR DEGENERATION, PROGRANULIN, Aged, 030304 developmental biology, Science & Technology, Neurology & Neurosurgery, business.industry, DISEASE PROGRESSION, medicine.disease, Mutation, WHITE-MATTER INTEGRITY, Surgery, Neurosciences & Neurology, Neurology (clinical), business, GENFI, Biomarkers, 030217 neurology & neurosurgery, Progressive disease
Abstract

ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.

Published
2021
Full Text
View/download PDF

4. Abnormal pain perception is associated with thalamo-cortico-striatal atrophy in C9orf72 expansion carriers in the GENFI cohort

Author

Convery, Rhian S, Bocchetta, Martina, Masellis, Mario, Afonso, S., Taipa, R., Caroppo, P., Di Fede, G., Giaccone, G., Prioni, S., Redaelli, V., Rossi, G., Tiraboschi, P., Duro, D., Tartaglia, Maria Carmela, Almeida, M. R., Branco, M. C., Leitão, M. J., Tabuas-Pereira, M., Santiago, B., Gauthier, S., Rosa-Neto, P., Veldsman, M., Flanagan, T., Prix, C., Graff, Caroline, Hoegen, T., Wlasich, E., Loosli, S., Schonecker, S., Semler, E., Anderl-Straub, S., Galimberti, Daniela, Rowe, James B, Finger, Elizabeth, Synofzik, Matthis, Vandenberghe, Rik, de Mendonca, Alexandre, Tagliavini, Fabrizio, Greaves, Caroline V, Santana, Isabel, Ducharme, Simon, Butler, Christopher, Gerhard, Alex, Levin, Johannes, Danek, Adrian, Otto, Markus, Warren, Jason D, Rohrer, Jonathan D, Initiative, Genetic FTD, Moore, Katrina M, Rossor, M. N., Fox, N. C., Woollacott, I. O. C., Shafei, R., Heller, C., Peakman, G., Swift, I., Todd, E., Guerreiro, R., Bras, J., Cash, David M, Thomas, D. L., Nicholas, J., Mead, S., Jiskoot, L., Meeter, L., Panman, J., Papma, J., van Minkelen, R., Pijnenburg, Y., Barandiara, M., Van Swieten, John, Indakoetxea, B., Gabilondo, A., Tainta, M., de Arriba, M., Gorostidi, A., Zulaica, M., Villanua, J., Diaz, Z., Borrego-Ecija, S., Olives, J., Moreno, Fermin, Lladó, A., Balasa, M., Antonell, A., Bargallo, N., Premi, E., Cosseddu, M., Gazzina, S., Padovani, A., Gasparotti, R., Archetti, S., Sánchez-Valle, Raquel, Black, S., Mitchell, S., Rogaeva, E., Freedman, M., Keren, R., Tang-Wai, D., Öijerstedt, L., Andersson, C., Jelic, V., Thonberg, H., Borroni, Barbara, Arighi, A., Fenoglio, C., Scarpini, E., Fumagalli, G., Cope, T., Timberlake, C., Rittman, T., Shoesmith, C., Bartha, R., Rademakers, R., Laforce, Robert, Wilke, C., Karnarth, H-O, Bender, B., Bruffaerts, R., Vandamme, P., Vandenbulcke, M., Ferreira, C. B., Miltenberger, G., Maruta, C., Verdelho, A., Convery, Rhian S [0000-0002-9477-1812], Bocchetta, Martina [0000-0003-1814-5024], Greaves, Caroline V [0000-0002-6446-1960], Moore, Katrina M [0000-0002-4458-8390], Van Swieten, John [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, Neurology, and Repositório da Universidade de Lisboa

Subjects
Male, diagnostic imaging [Corpus Striatum], Medizin, Somatosensory system, physiopathology [Frontotemporal Dementia], frontotemporal dementia, Cohort Studies, genetics [Progranulins], 0302 clinical medicine, Progranulins, Thalamus, C9orf72, Cerebellum, diagnostic imaging [Cerebral Cortex], pathology [Cerebellum], Medicine, pain, genetics [Frontotemporal Dementia], Cerebral Cortex, 0303 health sciences, DNA Repeat Expansion, Pain Perception, Middle Aged, Magnetic Resonance Imaging, Temporal Lobe, Psychiatry and Mental health, Cohort, diagnostic imaging [Prefrontal Cortex], Female, Frontotemporal dementia, genetics [Atrophy], Adult, medicine.medical_specialty, pathology [Corpus Striatum], Pain, Prefrontal Cortex, genetics [Perceptual Disorders], MAPT protein, human, tau Proteins, diagnostic imaging [Frontotemporal Dementia], Temporal lobe, Perceptual Disorders, 03 medical and health sciences, Atrophy, pathology [Thalamus], Internal medicine, Humans, ddc:610, genetics [C9orf72 Protein], 030304 developmental biology, diagnostic imaging [Perceptual Disorders], Aged, diagnostic imaging [Thalamus], C9orf72 Protein, business.industry, pathology [Temporal Lobe], diagnostic imaging [Atrophy], physiopathology [Atrophy], medicine.disease, diagnostic imaging [Cerebellum], pathology [Prefrontal Cortex], Corpus Striatum, physiopathology [Perceptual Disorders], genetics [tau Proteins], diagnostic imaging [Temporal Lobe], Logistic Models, Asymptomatic Diseases, Mutation, GRN protein, human, Surgery, Orbitofrontal cortex, pathology [Cerebral Cortex], Neurology (clinical), C9orf72 protein, human, business, 030217 neurology & neurosurgery
Abstract

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. published by BMJ., Objective: Frontotemporal dementia (FTD) is typically associated with changes in behaviour, language and movement. However, recent studies have shown that patients can also develop an abnormal response to pain, either heightened or diminished. We aimed to investigate this symptom in mutation carriers within the Genetic FTD Initiative (GENFI). Methods: Abnormal responsiveness to pain was measured in 462 GENFI participants: 281 mutation carriers and 181 mutation-negative controls. Changes in responsiveness to pain were scored as absent (0), questionable or very mild (0.5), mild (1), moderate (2) or severe (3). Mutation carriers were classified into C9orf72 (104), GRN (128) and MAPT (49) groups, and into presymptomatic and symptomatic stages. An ordinal logistic regression model was used to compare groups, adjusting for age and sex. Voxel-based morphometry was performed to identify neuroanatomical correlates of abnormal pain perception. Results: Altered responsiveness to pain was present to a significantly greater extent in symptomatic C9orf72 expansion carriers than in controls: mean score 0.40 (SD 0.71) vs 0.00 (0.04), reported in 29% vs 1%. No significant differences were seen between the other symptomatic groups and controls, or any of the presymptomatic mutation carriers and controls. Neural correlates of altered pain perception in C9orf72 expansion carriers were the bilateral thalamus and striatum as well as a predominantly right-sided network of regions involving the orbitofrontal cortex, inferomedial temporal lobe and cerebellum. Conclusion: Changes in pain perception are a feature of C9orf72 expansion carriers, likely representing a disruption in somatosensory, homeostatic and semantic processing, underpinned by atrophy in a thalamo-cortico-striatal network.

Published
2020
Full Text
View/download PDF

5. Disease-related cortical thinning in presymptomatic granulin mutation carriers

Author

Borrego-Écija, S. (Sergi), Sala-Llonch, R. (Roser), Swieten, J.C. (John) van, Borroni, B. (Barbara), Moreno, F. (Fermin), Masellis, M. (Mario), Tartaglia, C. (Carmela), Graff, C. (Caroline), Galimberti, D. (Daniela), Laforce, R. (Robert), Rowe, J.B. (James), Finger, E. (Elizabeth), Vandenberghe, R. (Rik), Tagliavini, F. (Fabrizio), De Mendonça, A. (Alexandre), Santana, I. (Isabel), Synofzik, M. (Matthis), Ducharme, S. (Simon), Levin, J. (Johannes), Danek, A. (Adrian), Gerhard, A. (Alex), Otto, M. (Markus), Butler, C. (Chris), Frisoni, G.B. (Giovanni B.), Sorbi, S. (Sandro), Heller, C. (Carolin), Bocchetta, M. (Martina), Cash, D.M. (David M), Convery, R.S. (Rhian S), Moore, K.M. (Katrina M), Rohrer, J.D. (Jonathan), Sánchez-Valle, R. (Raquel), Rossor, M.N. (Martin N.), Fox, N.C. (Nick), Woollacott, I.O.C. (Ione O.C.), Shafei, R. (Rachelle), Greaves, C. (Caroline), Neason, M. (Mollie), Guerreiro, R. (Rita), Bras, J. (Jose), Thomas, D.L. (David L), Nicholas, J. (Jennifer), Mead, S. (Simon), Meeter, L.H.H. (Lieke), Panman, J.L. (Jessica), Papma, J.M. (Janne), Thornton, A.S. (Andrew), Pijnenburg, Y.A.L. (Yolande), Indakoetxea, B. (Begoña), Gabilondo, A. (Alazne), TaintaMD, M. (Mikel), de Arriba, M. (Maria), Gorostidi, A. (Ana), Zulaica, M. (Miren), Villanua, J. (Jorge), Diaz, Z. (Zigor), Olives, J. (Jaume), Lladó, A. (Albert), Balasa, M. (Mircea), Antonell, A. (Anna), Bargallo, N. (Nuria), Premi, E. (Enrico), Cosseddu, M. (Maura), Gazzina, S. (Stefano), Padovani, A. (Alessandro), Gasparotti, R. (Roberto), Archetti, S. (Silvana), Black, S. (Sandra), Mitchell, S. (Sara), Rogaeva, E. (Ekaterina), Freedman, M. (Morris), Keren, R. (Ron), Tang-Wai, D. (David), Öijerstedt, L. (Linn), Andersson, C. (Christin), Jelic, S. (Svetislav Svetislav), Thonberg, H. (Håkan), Arighi, A. (Andrea), Fenoglio, C. (Chiara), Scarpini MD, E. (Elio), Fumagalli, G. (Giorgio), Cope, T. (Thomas), Timberlake, C. (Carolyn), Rittman, T. (Timothy), Shoesmith, C. (Christen), Bartha, R. (Robart), Rademakers, S. (Suzanne), Wilke, C. (Carlo), Bender, B. (Benjamin), Bruffaerts, R. (Rose), Vandamme, P. (Philip), Vandenbulcke, M. (Mathieu), Maruta, C. (Carolina), Ferreira, C.B. (Catarina B.), Miltenberger, G. (Gabriel), Verdelho, A. (Ana), Afonso, S. (Sónia), Taipa, R. (Ricardo), Caroppo, P. (Paola), Di Fede, G. (Giuseppe), Giaccone, G. (Giorgio), Prioni, S. (Sara), Redaelli, V. (Veronica), Rossi, G. (Giacomina), Tiraboschi, P. (Pietro), Duro, D. (Diana), Rosario Almeida, M. (Maria), Castelo-Branco, M. (Miguel), João Leitão, M. (Maria), Tabuas-Pereira, M. (Miguel), Santiago, B. (Beatriz), Gauthier, S. (Serge), Rosa-Neto, P. (Pedro), Veldsman, M. (Michele), Flanagan, T. (Toby), Prix, C. (Catharina), Hoegen, T. (Tobias), Wlasich, E. (Elisabeth), Loosli, S. (Sandra), Schonecker, S. (Sonja), Semler, E. (Elisa), Anderl-Straub, S. (Sarah), Borrego-Écija, S. (Sergi), Sala-Llonch, R. (Roser), Swieten, J.C. (John) van, Borroni, B. (Barbara), Moreno, F. (Fermin), Masellis, M. (Mario), Tartaglia, C. (Carmela), Graff, C. (Caroline), Galimberti, D. (Daniela), Laforce, R. (Robert), Rowe, J.B. (James), Finger, E. (Elizabeth), Vandenberghe, R. (Rik), Tagliavini, F. (Fabrizio), De Mendonça, A. (Alexandre), Santana, I. (Isabel), Synofzik, M. (Matthis), Ducharme, S. (Simon), Levin, J. (Johannes), Danek, A. (Adrian), Gerhard, A. (Alex), Otto, M. (Markus), Butler, C. (Chris), Frisoni, G.B. (Giovanni B.), Sorbi, S. (Sandro), Heller, C. (Carolin), Bocchetta, M. (Martina), Cash, D.M. (David M), Convery, R.S. (Rhian S), Moore, K.M. (Katrina M), Rohrer, J.D. (Jonathan), Sánchez-Valle, R. (Raquel), Rossor, M.N. (Martin N.), Fox, N.C. (Nick), Woollacott, I.O.C. (Ione O.C.), Shafei, R. (Rachelle), Greaves, C. (Caroline), Neason, M. (Mollie), Guerreiro, R. (Rita), Bras, J. (Jose), Thomas, D.L. (David L), Nicholas, J. (Jennifer), Mead, S. (Simon), Meeter, L.H.H. (Lieke), Panman, J.L. (Jessica), Papma, J.M. (Janne), Thornton, A.S. (Andrew), Pijnenburg, Y.A.L. (Yolande), Indakoetxea, B. (Begoña), Gabilondo, A. (Alazne), TaintaMD, M. (Mikel), de Arriba, M. (Maria), Gorostidi, A. (Ana), Zulaica, M. (Miren), Villanua, J. (Jorge), Diaz, Z. (Zigor), Olives, J. (Jaume), Lladó, A. (Albert), Balasa, M. (Mircea), Antonell, A. (Anna), Bargallo, N. (Nuria), Premi, E. (Enrico), Cosseddu, M. (Maura), Gazzina, S. (Stefano), Padovani, A. (Alessandro), Gasparotti, R. (Roberto), Archetti, S. (Silvana), Black, S. (Sandra), Mitchell, S. (Sara), Rogaeva, E. (Ekaterina), Freedman, M. (Morris), Keren, R. (Ron), Tang-Wai, D. (David), Öijerstedt, L. (Linn), Andersson, C. (Christin), Jelic, S. (Svetislav Svetislav), Thonberg, H. (Håkan), Arighi, A. (Andrea), Fenoglio, C. (Chiara), Scarpini MD, E. (Elio), Fumagalli, G. (Giorgio), Cope, T. (Thomas), Timberlake, C. (Carolyn), Rittman, T. (Timothy), Shoesmith, C. (Christen), Bartha, R. (Robart), Rademakers, S. (Suzanne), Wilke, C. (Carlo), Bender, B. (Benjamin), Bruffaerts, R. (Rose), Vandamme, P. (Philip), Vandenbulcke, M. (Mathieu), Maruta, C. (Carolina), Ferreira, C.B. (Catarina B.), Miltenberger, G. (Gabriel), Verdelho, A. (Ana), Afonso, S. (Sónia), Taipa, R. (Ricardo), Caroppo, P. (Paola), Di Fede, G. (Giuseppe), Giaccone, G. (Giorgio), Prioni, S. (Sara), Redaelli, V. (Veronica), Rossi, G. (Giacomina), Tiraboschi, P. (Pietro), Duro, D. (Diana), Rosario Almeida, M. (Maria), Castelo-Branco, M. (Miguel), João Leitão, M. (Maria), Tabuas-Pereira, M. (Miguel), Santiago, B. (Beatriz), Gauthier, S. (Serge), Rosa-Neto, P. (Pedro), Veldsman, M. (Michele), Flanagan, T. (Toby), Prix, C. (Catharina), Hoegen, T. (Tobias), Wlasich, E. (Elisabeth), Loosli, S. (Sandra), Schonecker, S. (Sonja), Semler, E. (Elisa), and Anderl-Straub, S. (Sarah)

Abstract

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an

Published
2021
Full Text
View/download PDF

6. Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia

Author

Altmann, A., Cash, D. M., Bocchetta, M., Heller, C., Reynolds, R., Moore, K., Convery, R. S., Thomas, D. L., Van Swieten, J. C., Moreno, F., Sanchez-Valle, R., Borroni, B., Laforce, R., Masellis, M., Tartaglia, M. C., Graff, C., Galimberti, D., Rowe, J. B., Finger, E., Synofzik, M., Vandenberghe, R., De Mendonca, A., Tagliavini, F., Santana, I., Ducharme, S., Butler, C. R., Gerhard, A., Levin, J., Danek, A., Frisoni, G., Ghidoni, R., Sorbi, S., Otto, M., Ryten, M., Rohrer, J. D., Greaves, C., Peakman, G., Shafei, R., Todd, E., Rossor, M. N., Warren, J. D., Fox, N. C., Zetterberg, H., Guerreiro, R., Bras, J., Nicholas, J., Mead, S., Jiskoot, L., Meeter, L., Panman, J., Papma, J. M., Van Minkelen, R., Pijnenburg, Y., Barandiaran, M., Indakoetxea, B., Gabilondo, A., Tainta, M., De Arriba, M., Gorostidi, A., Zulaica, M., Villanua, J., Diaz, Z., Borrego-Ecija, S., Olives, J., Llado, A., Balasa, M., Antonell, A., Bargallo, N., Premi, E., Cosseddu, M., Gazzina, S., Padovani, A., Gasparotti, R., Archetti, S., Black, S., Mitchell, S., Rogaeva, E., Freedman, M., Keren, R., Tang-Wai, D., Oijerstedt, L., Andersson, C., Jelic, V., Thonberg, H., Arighi, A., Fenoglio, C., Scarpini, E., Fumagalli, G., Cope, T., Timberlake, C., Rittman, T., Shoesmith, C., Bartha, R., Rademakers, R., Wilke, C., Karnarth, H. -O., Bender, B., Bruffaerts, R., Van Damme, P., Vandenbulcke, M., Ferreira, C. B., Miltenberger, G., Maruta, C., Verdelho, A., Afonso, S., Taipa, R., Caroppo, P., Di Fede, G., Giaccone, G., Prioni, S., Redaelli, V., Rossi, G., Tiraboschi, P., Duro, D., Almeida, M. R., Castelo-Branco, M., Leitao, M. J., Tabuas-Pereira, M., Santiago, B., Gauthier, S., Rosa-Neto, P., Veldsman, M., Thompson, P., Langheinrich, T., Prix, C., Hoegen, T., Wlasich, E., Loosli, S., Schonecker, S., Semler, E., Anderl-Straub, S., Benussi, L., Binetti, G., Pievani, M., Lombardi, G., Nacmias, B., Ferrari, C., Bessi, V., Polito, C., Rowe, James [0000-0001-7216-8679], Apollo - University of Cambridge Repository, Medical Research Council, and Genetic FTD Initiative, GENFI

Subjects
0301 basic medicine, Cell type, Imaging genetics, Clinical Neurology, Medizin, Biology, Article, DISEASE, 03 medical and health sciences, 0302 clinical medicine, Atrophy, atrophy, C9orf72, Gene expression, medicine, Astrocytes, Frontotemporal dementia, ddc:610, 10. No inequality, Gene, 030304 developmental biology, Genetics, 0303 health sciences, Science & Technology, TREM2, AcademicSubjects/SCI01870, Neurodegeneration, General Engineering, C9orf72 Gene, Neurosciences, astrocytes, Genetic FTD Initiative, GENFI, medicine.disease, C9orf72 Protein, 030104 developmental biology, gene expression, imaging genetics, Original Article, AcademicSubjects/MED00310, Human medicine, Neurosciences & Neurology, Life Sciences & Biomedicine, 030217 neurology & neurosurgery
Abstract

Frontotemporal dementia is a heterogeneous neurodegenerative disorder characterized by neuronal loss in the frontal and temporal lobes. Despite progress in understanding which genes are associated with the aetiology of frontotemporal dementia, the biological basis of how mutations in these genes lead to cell loss in specific cortical regions remains unclear. In this work, we combined gene expression data for 16 772 genes from the Allen Institute for Brain Science atlas with brain maps of grey matter atrophy in symptomatic C9orf72, GRN and MAPT mutation carriers obtained from the Genetic Frontotemporal dementia Initiative study. No significant association was seen between C9orf72, GRN and MAPT expression and the atrophy patterns in the respective genetic groups. After adjusting for spatial autocorrelation, between 1000 and 5000 genes showed a negative or positive association with the atrophy pattern within each individual genetic group, with the most significantly associated genes being TREM2, SSBP3 and GPR158 (negative association in C9Orf72, GRN and MAPT respectively) and RELN, MXRA8 and LPA (positive association in C9Orf72, GRN and MAPT respectively). An overrepresentation analysis identified a negative association with genes involved in mitochondrial function, and a positive association with genes involved in vascular and glial cell function in each of the genetic groups. A set of 423 and 700 genes showed significant positive and negative association, respectively, with atrophy patterns in all three maps. The gene set with increased expression in spared cortical regions was enriched for neuronal and microglial genes, while the gene set with increased expression in atrophied regions was enriched for astrocyte and endothelial cell genes. Our analysis suggests that these cell types may play a more active role in the onset of neurodegeneration in frontotemporal dementia than previously assumed, and in the case of the positively associated cell marker genes, potentially through emergence of neurotoxic astrocytes and alteration in the blood–brain barrier, respectively., Altmann et al. investigated the concordance between spatial cortical gene expression in healthy subjects and atrophy patterns in genetic frontotemporal dementia. They found that elevated gene expression of endothelial cell and astrocyte-related genes in regions with atrophy, suggesting a role of these cell types in the aetiology of frontotemporal dementia., Graphical Abstract Graphical Abstract

Published
2020
Full Text
View/download PDF

7. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study

Author

Moore, K.M. Nicholas, J. Grossman, M. McMillan, C.T. Irwin, D.J. Massimo, L. Van Deerlin, V.M. Warren, J.D. Fox, N.C. Rossor, M.N. Mead, S. Bocchetta, M. Boeve, B.F. Knopman, D.S. Graff-Radford, N.R. Forsberg, L.K. Rademakers, R. Wszolek, Z.K. van Swieten, J.C. Jiskoot, L.C. Meeter, L.H. Dopper, E.G. Papma, J.M. Snowden, J.S. Saxon, J. Jones, M. Pickering-Brown, S. Le Ber, I. Camuzat, A. Brice, A. Caroppo, P. Ghidoni, R. Pievani, M. Benussi, L. Binetti, G. Dickerson, B.C. Lucente, D. Krivensky, S. Graff, C. Öijerstedt, L. Fallström, M. Thonberg, H. Ghoshal, N. Morris, J.C. Borroni, B. Benussi, A. Padovani, A. Galimberti, D. Scarpini, E. Fumagalli, G.G. Mackenzie, I.R. Hsiung, G.-Y.R. Sengdy, P. Boxer, A.L. Rosen, H. Taylor, J.B. Synofzik, M. Wilke, C. Sulzer, P. Hodges, J.R. Halliday, G. Kwok, J. Sanchez-Valle, R. Lladó, A. Borrego-Ecija, S. Santana, I. Almeida, M.R. Tábuas-Pereira, M. Moreno, F. Barandiaran, M. Indakoetxea, B. Levin, J. Danek, A. Rowe, J.B. Cope, T.E. Otto, M. Anderl-Straub, S. de Mendonça, A. Maruta, C. Masellis, M. Black, S.E. Couratier, P. Lautrette, G. Huey, E.D. Sorbi, S. Nacmias, B. Laforce, R., Jr Tremblay, M.-P.L. Vandenberghe, R. Damme, P.V. Rogalski, E.J. Weintraub, S. Gerhard, A. Onyike, C.U. Ducharme, S. Papageorgiou, S.G. Ng, A.S.L. Brodtmann, A. Finger, E. Guerreiro, R. Bras, J. Rohrer, J.D. Heller, C. Convery, R.S. Woollacott, I.O. Shafei, R.M. Graff-Radford, J. Jones, D.T. Dheel, C.M. Savica, R. Lapid, M.I. Baker, M. Fields, J.A. Gavrilova, R. Domoto-Reilly, K. Poos, J.M. Van der Ende, E.L. Panman, J.L. Donker Kaat, L. Seelaar, H. Richardson, A. Frisoni, G. Mega, A. Fostinelli, S. Chiang, H.-H. Alberici, A. Arighi, A. Fenoglio, C. Heuer, H. Miller, B. Karydas, A. Fong, J. João Leitão, M. Santiago, B. Duro, D. Ferreira, C. Gabilondo, A. De Arriba, M. Tainta, M. Zulaica, M. Ferreira, C. Semler, E. Ludolph, A. Landwehrmeyer, B. Volk, A.E. Miltenberger, G. Verdelho, A. Afonso, S. Tartaglia, M.C. Freedman, M. Rogaeva, E. Ferrari, C. Piaceri, I. Bessi, V. Lombardi, G. St-Onge, F. Doré, M.-C. Bruffaerts, R. Vandenbulcke, M. Van den Stock, J. Mesulam, M.M. Bigio, E. Koros, C. Papatriantafyllou, J. Kroupis, C. Stefanis, L. Shoesmith, C. Robertson, E. Coppola, G. Da Silva Ramos, E.M. Geschwind, D.

Abstract

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49·5 years (SD 10·0; onset) and 58·5 years (11·3; death) in the MAPT group, 58·2 years (9·8; onset) and 65·3 years (10·9; death) in the C9orf72 group, and 61·3 years (8·8; onset) and 68·8 years (9·7; death) in the GRN group. Mean disease duration was 6·4 years (SD 4·9) in the C9orf72 group, 7·1 years (3·9) in the GRN group, and 9·3 years (6·4) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0·45 between individual and parental age at onset, r=0·63 between individual and mean family age at onset, r=0·58 between individual and parental age at death, and r=0·69 between individual and mean family age at death) than in either the C9orf72 group (r=0·32 individual and parental age at onset, r=0·36 individual and mean family age at onset, r=0·38 individual and parental age at death, and r=0·40 individual and mean family age at death) or the GRN group (r=0·22 individual and parental age at onset, r=0·18 individual and mean family age at onset, r=0·22 individual and parental age at death, and r=0·32 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35–62, for age at onset; 61%, 47–73, for age at death), and even more by family membership (66%, 56–75, for age at onset; 74%, 65–82, for age at death). In the GRN group, only 2% (0–10) of the variability of age at onset and 9% (3–21) of that of age of death was explained by the specific mutation, whereas 14% (9–22) of the variability of age at onset and 20% (12–30) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11–26) of the variability of age at onset and 19% (12–29) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society. © 2020 Elsevier Ltd

Published
2020

9. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study

Author

Moore, K.M. Nicholas, J. Grossman, M. McMillan, C.T. Irwin, D.J. Massimo, L. Van Deerlin, V.M. Warren, J.D. Fox, N.C. Rossor, M.N. Mead, S. Bocchetta, M. Boeve, B.F. Knopman, D.S. Graff-Radford, N.R. Forsberg, L.K. Rademakers, R. Wszolek, Z.K. van Swieten, J.C. Jiskoot, L.C. Meeter, L.H. Dopper, E.G. Papma, J.M. Snowden, J.S. Saxon, J. Jones, M. Pickering-Brown, S. Le Ber, I. Camuzat, A. Brice, A. Caroppo, P. Ghidoni, R. Pievani, M. Benussi, L. Binetti, G. Dickerson, B.C. Lucente, D. Krivensky, S. Graff, C. Öijerstedt, L. Fallström, M. Thonberg, H. Ghoshal, N. Morris, J.C. Borroni, B. Benussi, A. Padovani, A. Galimberti, D. Scarpini, E. Fumagalli, G.G. Mackenzie, I.R. Hsiung, G.-Y.R. Sengdy, P. Boxer, A.L. Rosen, H. Taylor, J.B. Synofzik, M. Wilke, C. Sulzer, P. Hodges, J.R. Halliday, G. Kwok, J. Sanchez-Valle, R. Lladó, A. Borrego-Ecija, S. Santana, I. Almeida, M.R. Tábuas-Pereira, M. Moreno, F. Barandiaran, M. Indakoetxea, B. Levin, J. Danek, A. Rowe, J.B. Cope, T.E. Otto, M. Anderl-Straub, S. de Mendonça, A. Maruta, C. Masellis, M. Black, S.E. Couratier, P. Lautrette, G. Huey, E.D. Sorbi, S. Nacmias, B. Laforce, R., Jr Tremblay, M.-P.L. Vandenberghe, R. Damme, P.V. Rogalski, E.J. Weintraub, S. Gerhard, A. Onyike, C.U. Ducharme, S. Papageorgiou, S.G. Ng, A.S.L. Brodtmann, A. Finger, E. Guerreiro, R. Bras, J. Rohrer, J.D. Heller, C. Convery, R.S. Woollacott, I.O. Shafei, R.M. Graff-Radford, J. Jones, D.T. Dheel, C.M. Savica, R. Lapid, M.I. Baker, M. Fields, J.A. Gavrilova, R. Domoto-Reilly, K. Poos, J.M. Van der Ende, E.L. Panman, J.L. Donker Kaat, L. Seelaar, H. Richardson, A. Frisoni, G. Mega, A. Fostinelli, S. Chiang, H.-H. Alberici, A. Arighi, A. Fenoglio, C. Heuer, H. Miller, B. Karydas, A. Fong, J. João Leitão, M. Santiago, B. Duro, D. Ferreira, C. Gabilondo, A. De Arriba, M. Tainta, M. Zulaica, M. Ferreira, C. Semler, E. Ludolph, A. Landwehrmeyer, B. Volk, A.E. Miltenberger, G. Verdelho, A. Afonso, S. Tartaglia, M.C. Freedman, M. Rogaeva, E. Ferrari, C. Piac and Moore, K.M. Nicholas, J. Grossman, M. McMillan, C.T. Irwin, D.J. Massimo, L. Van Deerlin, V.M. Warren, J.D. Fox, N.C. Rossor, M.N. Mead, S. Bocchetta, M. Boeve, B.F. Knopman, D.S. Graff-Radford, N.R. Forsberg, L.K. Rademakers, R. Wszolek, Z.K. van Swieten, J.C. Jiskoot, L.C. Meeter, L.H. Dopper, E.G. Papma, J.M. Snowden, J.S. Saxon, J. Jones, M. Pickering-Brown, S. Le Ber, I. Camuzat, A. Brice, A. Caroppo, P. Ghidoni, R. Pievani, M. Benussi, L. Binetti, G. Dickerson, B.C. Lucente, D. Krivensky, S. Graff, C. Öijerstedt, L. Fallström, M. Thonberg, H. Ghoshal, N. Morris, J.C. Borroni, B. Benussi, A. Padovani, A. Galimberti, D. Scarpini, E. Fumagalli, G.G. Mackenzie, I.R. Hsiung, G.-Y.R. Sengdy, P. Boxer, A.L. Rosen, H. Taylor, J.B. Synofzik, M. Wilke, C. Sulzer, P. Hodges, J.R. Halliday, G. Kwok, J. Sanchez-Valle, R. Lladó, A. Borrego-Ecija, S. Santana, I. Almeida, M.R. Tábuas-Pereira, M. Moreno, F. Barandiaran, M. Indakoetxea, B. Levin, J. Danek, A. Rowe, J.B. Cope, T.E. Otto, M. Anderl-Straub, S. de Mendonça, A. Maruta, C. Masellis, M. Black, S.E. Couratier, P. Lautrette, G. Huey, E.D. Sorbi, S. Nacmias, B. Laforce, R., Jr Tremblay, M.-P.L. Vandenberghe, R. Damme, P.V. Rogalski, E.J. Weintraub, S. Gerhard, A. Onyike, C.U. Ducharme, S. Papageorgiou, S.G. Ng, A.S.L. Brodtmann, A. Finger, E. Guerreiro, R. Bras, J. Rohrer, J.D. Heller, C. Convery, R.S. Woollacott, I.O. Shafei, R.M. Graff-Radford, J. Jones, D.T. Dheel, C.M. Savica, R. Lapid, M.I. Baker, M. Fields, J.A. Gavrilova, R. Domoto-Reilly, K. Poos, J.M. Van der Ende, E.L. Panman, J.L. Donker Kaat, L. Seelaar, H. Richardson, A. Frisoni, G. Mega, A. Fostinelli, S. Chiang, H.-H. Alberici, A. Arighi, A. Fenoglio, C. Heuer, H. Miller, B. Karydas, A. Fong, J. João Leitão, M. Santiago, B. Duro, D. Ferreira, C. Gabilondo, A. De Arriba, M. Tainta, M. Zulaica, M. Ferreira, C. Semler, E. Ludolph, A. Landwehrmeyer, B. Volk, A.E. Miltenberger, G. Verdelho, A. Afonso, S. Tartaglia, M.C. Freedman, M. Rogaeva, E. Ferrari, C. Piac

Abstract

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49·5 years (SD 10·0; onset) and 58·5 years (11·3; death) in the MAPT group, 58·2 years (9·8; onset) and 65·3 years (10·9; death) in the C9orf72 group, and 61·3 years (8·8; onset) and 68·8 years (9·7; death) in the GRN group. Mean disease duration was 6·4 years (SD 4·9) in the C9orf72 group, 7·1 years (3·9) in the GRN group, and 9·3 years (6·4) in the MAPT group. Individual age at onset and at

Published
2020

10. Social cognition impairment in genetic frontotemporal dementia within the GENFI cohort

Author

Russell, L.L. (Lucy L.), Greaves, C.V. (Caroline V.), Bocchetta, M. (Martina), Nicholas, J.M. (Jennifer), Convery, R.S. (Rhian S.), Moore, K. (Katrina), Cash, D.M. (David M.), Swieten, J.C. (John) van, Jiskoot, L.C. (Lize), Moreno, F. (Fermin), Sánchez-Valle, R. (Raquel), Borroni, B. (Barbara), Laforce, R. (Robert), Masellis, M. (Mario), Tartaglia, M.C. (Maria Carmela), Graff, C. (Caroline), Rotondo, E. (Emanuela), Galimberti, D. (Daniela), Rowe, J.B. (James), Finger, E. (Elizabeth), Synofzik, M. (Matthis), Vandenberghe, R. (Rik), De Mendonça, A. (Alexandre), Tagliavini, F. (Fabrizio), Santana, I. (Isabel), Ducharme, S. (Simon), Butler, C. (Chris), Gerhard, A. (Alex), Levin, J. (Johannes), Danek, A. (Adrian), Otto, M. (Markus), Warren, J.D. (Jason), Rohrer, J.D. (Jonathan), Rossor, M. (Martin), Fox, N.C. (Nick), Woollacott, I.O.C. (Ione O.C.), Shafei, R. (Rachelle), Heller, C. (Carolin), Guerreiro, R. (Rita), Bras, J. (Jose), Thomas, D.L. (David L), Mead, S. (Simon), Meeter, L.H.H. (Lieke), Panman, J.L. (Jessica), Papma, J.M. (Janne), Poos, J.M. (Jackie), Thornton, A.S. (Andrew), Pijnenburg, Y. (Yolanda), Barandiaran, M. (Myriam), Indakoetxea, B. (Begoña), Gabilondo, A. (Alazne), Tainta, M. (Mikel), de Arriba, M. (Maria), Gorostidi, A. (Ana), Zulaica, M. (Miren), Villanua, J. (Jorge), Diaz, Z. (Zigor), Borrego-Ecija, S. (Sergi), Olives, J. (Jaume), Lladó, A. (Albert), Balasa, M. (Mircea), Antonell, A. (Anna), Bargallo, N. (Nuria), Premi, E. (Enrico), Cosseddu MPsych, M. (Maura), Gazzina, S. (Stefano), Padovani, A. (Alessandro), Gasparotti, R. (Roberto), Archetti, S. (Silvana), Black, S.E. (Sandra), Mitchell, S. (Sara), Rogaeva, E. (Ekaterina), Freedman, M. (Morris), Keren, R. (Ron), Tang-Wai, D. (Daid), Öijerstedt, L. (Linn), Andersson, C. (Christin), Jelic, S. (Svetislav Svetislav), Thonberg, H. (Håkan), Arighi, A. (Andrea), Fenoglio, C. (Chiara), Scarpini, E. (Elio), Fumagalli, G. (Giorgio), Cope, T. (Thomas), Timberlake, C. (Carolyn), Rittman, T. (Timothy), Shoesmith, C. (Christen), Bartha, R. (Robart), Rademakers, S. (Suzanne), Wilke, C. (Carlo), Karnarth, H.-O. (Hans-Otto), Bender, B. (Benjamin), Bruffaerts, R. (Rose), Vandamme, P. (Philip), Vandenbulcke, M. (Mathieu), Ferreira, C.B. (Catarina B.), Miltenberger, G. (Gabriel), Maruta MPsych, C. (Carolina), Verdelho, A. (Ana), Afonso, S. (Sónia), Taipa, R. (Ricardo), Caroppo, P. (Paola), Di Fede, G. (Giuseppe), Giaccone, G. (Giuseppe), Muscio, C. (Cristina), Prioni, S. (Sara), Redaelli, V. (Veronica), Rossi, G. (Giacomina), Tiraboschi, P. (Pietro), Duro NPsych, D. (Diana), Almeida, M.R. (Maria R.), Castelo-Branco, M. (Miguel), Leitão, M.J. (Maria J.), Tabuas-Pereira, M. (Miguel), Santiago, B. (Beatriz), Gauthier, S. (Serge), Rosa-Neto, P. (Pedro), Veldsman, M. (Michele), Thompson, P.M. (Paul), Langheinrich, T. (Tobias), Prix, C. (Catharina), Hoegen, T. (Tobias), Wlasich, E. (Elisabeth), Loosli, S. (Sandra), Schonecker, S. (Sonja), Semler, E. (Elisa), Anderl-Straub, S. (Sarah), Russell, L.L. (Lucy L.), Greaves, C.V. (Caroline V.), Bocchetta, M. (Martina), Nicholas, J.M. (Jennifer), Convery, R.S. (Rhian S.), Moore, K. (Katrina), Cash, D.M. (David M.), Swieten, J.C. (John) van, Jiskoot, L.C. (Lize), Moreno, F. (Fermin), Sánchez-Valle, R. (Raquel), Borroni, B. (Barbara), Laforce, R. (Robert), Masellis, M. (Mario), Tartaglia, M.C. (Maria Carmela), Graff, C. (Caroline), Rotondo, E. (Emanuela), Galimberti, D. (Daniela), Rowe, J.B. (James), Finger, E. (Elizabeth), Synofzik, M. (Matthis), Vandenberghe, R. (Rik), De Mendonça, A. (Alexandre), Tagliavini, F. (Fabrizio), Santana, I. (Isabel), Ducharme, S. (Simon), Butler, C. (Chris), Gerhard, A. (Alex), Levin, J. (Johannes), Danek, A. (Adrian), Otto, M. (Markus), Warren, J.D. (Jason), Rohrer, J.D. (Jonathan), Rossor, M. (Martin), Fox, N.C. (Nick), Woollacott, I.O.C. (Ione O.C.), Shafei, R. (Rachelle), Heller, C. (Carolin), Guerreiro, R. (Rita), Bras, J. (Jose), Thomas, D.L. (David L), Mead, S. (Simon), Meeter, L.H.H. (Lieke), Panman, J.L. (Jessica), Papma, J.M. (Janne), Poos, J.M. (Jackie), Thornton, A.S. (Andrew), Pijnenburg, Y. (Yolanda), Barandiaran, M. (Myriam), Indakoetxea, B. (Begoña), Gabilondo, A. (Alazne), Tainta, M. (Mikel), de Arriba, M. (Maria), Gorostidi, A. (Ana), Zulaica, M. (Miren), Villanua, J. (Jorge), Diaz, Z. (Zigor), Borrego-Ecija, S. (Sergi), Olives, J. (Jaume), Lladó, A. (Albert), Balasa, M. (Mircea), Antonell, A. (Anna), Bargallo, N. (Nuria), Premi, E. (Enrico), Cosseddu MPsych, M. (Maura), Gazzina, S. (Stefano), Padovani, A. (Alessandro), Gasparotti, R. (Roberto), Archetti, S. (Silvana), Black, S.E. (Sandra), Mitchell, S. (Sara), Rogaeva, E. (Ekaterina), Freedman, M. (Morris), Keren, R. (Ron), Tang-Wai, D. (Daid), Öijerstedt, L. (Linn), Andersson, C. (Christin), Jelic, S. (Svetislav Svetislav), Thonberg, H. (Håkan), Arighi, A. (Andrea), Fenoglio, C. (Chiara), Scarpini, E. (Elio), Fumagalli, G. (Giorgio), Cope, T. (Thomas), Timberlake, C. (Carolyn), Rittman, T. (Timothy), Shoesmith, C. (Christen), Bartha, R. (Robart), Rademakers, S. (Suzanne), Wilke, C. (Carlo), Karnarth, H.-O. (Hans-Otto), Bender, B. (Benjamin), Bruffaerts, R. (Rose), Vandamme, P. (Philip), Vandenbulcke, M. (Mathieu), Ferreira, C.B. (Catarina B.), Miltenberger, G. (Gabriel), Maruta MPsych, C. (Carolina), Verdelho, A. (Ana), Afonso, S. (Sónia), Taipa, R. (Ricardo), Caroppo, P. (Paola), Di Fede, G. (Giuseppe), Giaccone, G. (Giuseppe), Muscio, C. (Cristina), Prioni, S. (Sara), Redaelli, V. (Veronica), Rossi, G. (Giacomina), Tiraboschi, P. (Pietro), Duro NPsych, D. (Diana), Almeida, M.R. (Maria R.), Castelo-Branco, M. (Miguel), Leitão, M.J. (Maria J.), Tabuas-Pereira, M. (Miguel), Santiago, B. (Beatriz), Gauthier, S. (Serge), Rosa-Neto, P. (Pedro), Veldsman, M. (Michele), Thompson, P.M. (Paul), Langheinrich, T. (Tobias), Prix, C. (Catharina), Hoegen, T. (Tobias), Wlasich, E. (Elisabeth), Loosli, S. (Sandra), Schonecker, S. (Sonja), Semler, E. (Elisa), and Anderl-Straub, S. (Sarah)

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

Published
2020
Full Text
View/download PDF

11. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: an international retrospective cohort study

Author

Moore, KM, Nicholas, J, Grossman, M, McMillan, CT, Irwin, DJ, Massimo, L, Van Deerlin, VM, Warren, JD, Fox, NC, Rossor, MN, Mead, S, Bocchetta, M, Boeve, BF, Knopman, DS, Graff-Radford, NR, Forsberg, LK, Rademakers, R, Wszolek, ZK, van Swieten, JC, Jiskoot, LC, Meeter, LH, Dopper, EGP, Papma, JM, Snowden, JS, Saxon, J, Jones, M, Pickering-Brown, S, Le Ber, I, Camuzat, A, Brice, A, Caroppo, P, Ghidoni, R, Pievani, M, Benussi, L, Binetti, G, Dickerson, BC, Lucente, D, Krivensky, S, Graff, C, Oijerstedt, L, Fallstrom, M, Thonberg, H, Ghoshal, N, Morris, JC, Borroni, B, Benussi, A, Padovani, A, Galimberti, D, Scarpini, E, Fumagalli, GG, Mackenzie, IR, Hsiung, G-YR, Sengdy, P, Boxer, AL, Rosen, H, Taylor, JB, Synofzik, M, Wilke, C, Sulzer, P, Hodges, JR, Halliday, G, Kwok, J, Sanchez-Valle, R, Llado, A, Borrego-Ecija, S, Santana, I, Almeida, MR, Tabuas-Pereira, M, Moreno, F, Barandiaran, M, Indakoetxea, B, Levin, J, Danek, A, Rowe, JB, Cope, TE, Otto, M, Anderl-Straub, S, de Mendonca, A, Maruta, C, Masellis, M, Black, SE, Couratier, P, Lautrette, G, Huey, ED, Sorbi, S, Nacmias, B, Laforce, R, Tremblay, M-PL, Vandenberghe, R, Van Damme, P, Rogalski, EJ, Weintraub, S, Gerhard, A, Onyike, CU, Ducharme, S, Papageorgiou, SG, Ng, ASL, Brodtmann, A, Finger, E, Guerreiro, R, Bras, J, Rohrer, JD, Heller, C, Convery, R, Woollacott, IOC, Shafei, R, Graff-Radford, J, Jones, DT, Dheel, CM, Savica, R, Lapid, MI, Baker, M, Fields, JA, Gavrilova, R, Domoto-Reilly, K, Poos, JM, van der Ende, EL, Panman, JL, Kaat, LD, Seelaar, H, Richardson, A, Frisoni, G, Mega, A, Fostinelli, S, Chiang, H-H, Alberici, A, Arighi, A, Fenoglio, C, Heuer, H, Miller, B, Karydas, A, Fong, J, Leitao, MJ, Santiago, B, Duro, D, Ferreira, C, Gabilondo, A, de Arriba, M, Tainta, M, Zulaica, M, Ferreira, CB, Semler, E, Ludolph, A, Landwehrmeyer, B, Volk, AE, Miltenberger, G, Verdelho, A, Afonso, S, Tartaglia, MC, Freedman, M, Rogaeva, E, Ferrari, C, Piaceri, I, Bessi, V, Lombardi, G, St-Onge, F, Dore, M-C, Bruffaerts, R, Vandenbulcke, M, Van den Stock, J, Mesulam, MM, Bigio, E, Koros, C, Papatriantafyllou, J, Kroupis, C, Stefanis, L, Shoesmith, C, Roberson, E, Coppola, G, Ramos, EMDS, Geschwind, D, Moore, KM, Nicholas, J, Grossman, M, McMillan, CT, Irwin, DJ, Massimo, L, Van Deerlin, VM, Warren, JD, Fox, NC, Rossor, MN, Mead, S, Bocchetta, M, Boeve, BF, Knopman, DS, Graff-Radford, NR, Forsberg, LK, Rademakers, R, Wszolek, ZK, van Swieten, JC, Jiskoot, LC, Meeter, LH, Dopper, EGP, Papma, JM, Snowden, JS, Saxon, J, Jones, M, Pickering-Brown, S, Le Ber, I, Camuzat, A, Brice, A, Caroppo, P, Ghidoni, R, Pievani, M, Benussi, L, Binetti, G, Dickerson, BC, Lucente, D, Krivensky, S, Graff, C, Oijerstedt, L, Fallstrom, M, Thonberg, H, Ghoshal, N, Morris, JC, Borroni, B, Benussi, A, Padovani, A, Galimberti, D, Scarpini, E, Fumagalli, GG, Mackenzie, IR, Hsiung, G-YR, Sengdy, P, Boxer, AL, Rosen, H, Taylor, JB, Synofzik, M, Wilke, C, Sulzer, P, Hodges, JR, Halliday, G, Kwok, J, Sanchez-Valle, R, Llado, A, Borrego-Ecija, S, Santana, I, Almeida, MR, Tabuas-Pereira, M, Moreno, F, Barandiaran, M, Indakoetxea, B, Levin, J, Danek, A, Rowe, JB, Cope, TE, Otto, M, Anderl-Straub, S, de Mendonca, A, Maruta, C, Masellis, M, Black, SE, Couratier, P, Lautrette, G, Huey, ED, Sorbi, S, Nacmias, B, Laforce, R, Tremblay, M-PL, Vandenberghe, R, Van Damme, P, Rogalski, EJ, Weintraub, S, Gerhard, A, Onyike, CU, Ducharme, S, Papageorgiou, SG, Ng, ASL, Brodtmann, A, Finger, E, Guerreiro, R, Bras, J, Rohrer, JD, Heller, C, Convery, R, Woollacott, IOC, Shafei, R, Graff-Radford, J, Jones, DT, Dheel, CM, Savica, R, Lapid, MI, Baker, M, Fields, JA, Gavrilova, R, Domoto-Reilly, K, Poos, JM, van der Ende, EL, Panman, JL, Kaat, LD, Seelaar, H, Richardson, A, Frisoni, G, Mega, A, Fostinelli, S, Chiang, H-H, Alberici, A, Arighi, A, Fenoglio, C, Heuer, H, Miller, B, Karydas, A, Fong, J, Leitao, MJ, Santiago, B, Duro, D, Ferreira, C, Gabilondo, A, de Arriba, M, Tainta, M, Zulaica, M, Ferreira, CB, Semler, E, Ludolph, A, Landwehrmeyer, B, Volk, AE, Miltenberger, G, Verdelho, A, Afonso, S, Tartaglia, MC, Freedman, M, Rogaeva, E, Ferrari, C, Piaceri, I, Bessi, V, Lombardi, G, St-Onge, F, Dore, M-C, Bruffaerts, R, Vandenbulcke, M, Van den Stock, J, Mesulam, MM, Bigio, E, Koros, C, Papatriantafyllou, J, Kroupis, C, Stefanis, L, Shoesmith, C, Roberson, E, Coppola, G, Ramos, EMDS, and Geschwind, D

Abstract

BACKGROUND: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. METHODS: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. FINDINGS: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49·5 years (SD 10·0; onset) and 58·5 years (11·3; death) in the MAPT group, 58·2 years (9·8; onset) and 65·3 years (10·9; death) in the C9orf72 group, and 61·3 years (8·8; onset) and 68·8 years (9·7; death) in the GRN group. Mean disease duration was 6·4 years (SD 4·9) in the C9orf72 group, 7·1 years (3·9) in the GRN group, and 9·3 years (6·4) in the MAPT group. Individual age at onset and at

Published
2020

12. Social cognition impairment in genetic frontotemporal dementia within the GENFI cohort

Author

Russell, LL, Greaves, CV, Bocchetta, M, Nicholas, J, Convery, RS, Moore, K, Cash, DM, van Swieten, J.C., Jiskoot, Lize, Moreno, F, Sanchez-Valle, R, Borroni, B, Laforce, R, Jr, Masellis, M, Tartaglia, MC, Graff, C, Rotondo, E, Galimberti, D, Rowe, JB, Finger, E, Synofzik, M, Vandenberghe, R, Mendonça, A, Tagliavini, F, Santana, I, Ducharme, S, Butler, C, Gerhard, A, Levin, J, Danek, A, Otto, M, Warren, JD, Rohrer, JD, Rossor, MN, Fox, NC, Woollacott, IOC, Shafei, R, Heller, C, Guerreiro, R, Bras, J, Thomas, DL, Mead, S, Meeter, Lieke, Panman, J, Papma, J, Poos, J, van Minkelen, Rick, Al Pijnenburg, Y, Barandiaran, M, Indakoetxea, B, Gabilondo, A, Tainta, M, de Arriba, M, Gorostidi, A, Zulaica, M, Villanua, J, Diaz, Z, Borrego-Ecija, S, Olives, J, Lladó, A, Balasa, M, Antonell, A, Bargallo, N, Premi, E, Cosseddu Mpsych, M, Gazzina, S, Padovani, A, Gasparotti, R, Archetti, S, Black, S, Mitchell, S, Rogaeva, E, Freedman, M, Keren, R, Tang-Wai, D, Öijerstedt, L, Andersson, C, Jelic, V, Thonberg, H, Arighi, A, Fenoglio, C, Scarpini, E, Fumagalli, G, Cope, T, Timberlake, C, Rittman, T, Shoesmith, C, Bartha, R, Rademakers, R, Wilke, C, Karnarth, HO, Bender, B, Bruffaerts, R, Vandamme, P, Vandenbulcke, M, Ferreira, CB, Miltenberger, G, Maruta Mpsych, C, Verdelho, A, Afonso, S, Taipa, R, Caroppo, P, Di Fede, G, Giaccone, G, Muscio, C, Prioni, S, Redaelli, V, Rossi, G, Tiraboschi, P, Duro Npsych, D, Almeida, M R, Castelo-Branco, M, Leitão, MJ, Tabuas-Pereira, M, Santiago, B, Gauthier, S, Rosa-Neto, P, Veldsman, M, Thompson, P, Langheinrich, T, Prix, C, Hoegen, T, Wlasich, E, Loosli, S, Schonecker, S, Semler, E, Anderl-Straub, S, Russell, LL, Greaves, CV, Bocchetta, M, Nicholas, J, Convery, RS, Moore, K, Cash, DM, van Swieten, J.C., Jiskoot, Lize, Moreno, F, Sanchez-Valle, R, Borroni, B, Laforce, R, Jr, Masellis, M, Tartaglia, MC, Graff, C, Rotondo, E, Galimberti, D, Rowe, JB, Finger, E, Synofzik, M, Vandenberghe, R, Mendonça, A, Tagliavini, F, Santana, I, Ducharme, S, Butler, C, Gerhard, A, Levin, J, Danek, A, Otto, M, Warren, JD, Rohrer, JD, Rossor, MN, Fox, NC, Woollacott, IOC, Shafei, R, Heller, C, Guerreiro, R, Bras, J, Thomas, DL, Mead, S, Meeter, Lieke, Panman, J, Papma, J, Poos, J, van Minkelen, Rick, Al Pijnenburg, Y, Barandiaran, M, Indakoetxea, B, Gabilondo, A, Tainta, M, de Arriba, M, Gorostidi, A, Zulaica, M, Villanua, J, Diaz, Z, Borrego-Ecija, S, Olives, J, Lladó, A, Balasa, M, Antonell, A, Bargallo, N, Premi, E, Cosseddu Mpsych, M, Gazzina, S, Padovani, A, Gasparotti, R, Archetti, S, Black, S, Mitchell, S, Rogaeva, E, Freedman, M, Keren, R, Tang-Wai, D, Öijerstedt, L, Andersson, C, Jelic, V, Thonberg, H, Arighi, A, Fenoglio, C, Scarpini, E, Fumagalli, G, Cope, T, Timberlake, C, Rittman, T, Shoesmith, C, Bartha, R, Rademakers, R, Wilke, C, Karnarth, HO, Bender, B, Bruffaerts, R, Vandamme, P, Vandenbulcke, M, Ferreira, CB, Miltenberger, G, Maruta Mpsych, C, Verdelho, A, Afonso, S, Taipa, R, Caroppo, P, Di Fede, G, Giaccone, G, Muscio, C, Prioni, S, Redaelli, V, Rossi, G, Tiraboschi, P, Duro Npsych, D, Almeida, M R, Castelo-Branco, M, Leitão, MJ, Tabuas-Pereira, M, Santiago, B, Gauthier, S, Rosa-Neto, P, Veldsman, M, Thompson, P, Langheinrich, T, Prix, C, Hoegen, T, Wlasich, E, Loosli, S, Schonecker, S, Semler, E, and Anderl-Straub, S

Published
2020

15. Otologic and otoneurologic injuries in divers: Clinical Studies On Nine Commercial and Two Sport Divers.

Author

Caruso, V. G., Winkelmann, P. E., Correia, M. J., Miltenberger, G. E., and Love, J. T.

Abstract

In the past two decades, we have seen a great increase in the number of injuries from commercial and sport diving. During this time, our knowledge of the physiology and pathophysiology of diving has also increased. As a result, we now can accurately diagnose and successfully treat many of these injuries. Of the commercial and sport divers examined as patients in the Department of Otolaryngology at the University of Texas Medical Branch in Galveston, Tex., between September, 1974, and May, 1975, 11 showed positive otologic and otoneurologic findings which are reported herein. One patient was surgically explored for an oval window fistula. In localizing and classifying these injuries, we have utilized extensive and broad-based test batteries, which include complete history, otologic and otoneurologic physical examination, audiometry, a central auditory test battery, and a vestibular test battery. These tests are described. The findings in each of the divers are illustrated and analyzed. This article further describes the use of these test batteries, which were employed to localize otoneurologic pathology in this sample of injured divers. Based on these cases, we have expanded and modified Edmonds' classification of the etiology of vertigo related to diving. We feel that the test batteries which we describe, or similar tests, should be part of the otologic and otoneurologic workup of injured divers. Index terms are: 1. central auditory tests; -2. oval window rupture; 3. diving injuries; and 4. vestibular test battery [ABSTRACT FROM AUTHOR]

Published
1977
Full Text
View/download PDF

18. Phenotypic variability in chorea-acanthocytosis associated with novel VPS13A mutations.

Author

Niemelä V, Salih A, Solea D, Lindvall B, Weinberg J, Miltenberger G, Granberg T, Tzovla A, Nordin L, Danfors T, Savitcheva I, Dahl N, and Paucar M

Abstract

Objective: To perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden., Methods: Clinical assessments, targeted genetic studies, neuroimaging with MRI, [ 18 F]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with 123 I FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectroscopy (MRS)., Results: Four patients living in Sweden but with different ethnical backgrounds were included. Their clinical features were variable. Biallelic VPS13A mutations were confirmed in all patients, including 3 novel mutations. All tested patients had either low or absent chorein levels. One patient had progressive caudate atrophy. Investigation using FDG-PET revealed severe bilateral striatal hypometabolism, and DaTscan SPECT displayed presynaptic dopaminergic deficiency in 3 patients. MRS demonstrated reduced N-acetylaspartate/creatine (Cr) ratio and mild elevation of both choline/Cr and combined glutamate and glutamine/Cr in the striatum in 1 case. One patient died during sleep, and another was treated with deep brain stimulation, which transiently attenuated feeding dystonia but not his gait disorder or chorea., Conclusions: Larger longitudinal neuroimaging studies with different modalities, particularly MRS, are needed to determine their potential role as biomarkers for ChAc., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Published
2020
Full Text
View/download PDF

19. Rapidly progressive frontotemporal dementia and bulbar amyotrophic lateral sclerosis in Portuguese patients with C9orf72 mutation.

Author

Chester C, de Carvalho M, Miltenberger G, Pereira S, Dillen L, van der Zee J, van Broeckhoven C, and de Mendonça A

Subjects
Adult, Female, Genetic Testing, Humans, Male, Middle Aged, Mutation genetics, Polymorphism, Single Nucleotide genetics, Portugal, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis genetics, Frontotemporal Dementia diagnosis, Frontotemporal Dementia genetics, Genetic Predisposition to Disease genetics, Muscular Disorders, Atrophic diagnosis, Muscular Disorders, Atrophic genetics
Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) form a spectrum of clinically, pathologically, and genetically overlapping disorders, as confirmed by the recent report that it can be caused by a hexanucleotide repeat expansion in C9orf72. One hundred and fourteen Portuguese cases diagnosed as probable or possible familial FTLD, as part of the EOD consortium study, and nine further Portuguese cases with familial ALS were tested for the presence of this mutation. Results showed that six Portuguese patients from unrelated families had the mutation, five (4.4%) patients from the FTLD group and one (11.1%) from the ALS sample. Of these, three patients had FTLD and rapidly progressive bulbar ALS. Electromyography confirmed diffuse loss of motor units with marked bulbar involvement. In conclusion, the cases now reported showed a very rapid progression, suggesting bulbar ALS could be particularly common and aggressive in patients with the C9orf72 hexanucleotide repeat expansion, in the Portuguese population.

Published
2013
Full Text
View/download PDF

20. The effect of the bis-(2-pyridil-1-oxide)-disulfide adduct with Mg SO4 on the scalp and hair lipids.

Author

Gloor M, Mildenberger KH, and Miltenberger G

Subjects
Adolescent, Animals, Cricetinae, Cyclic N-Oxides pharmacology, Fatty Acids, Nonesterified metabolism, Hair metabolism, Humans, Male, Mesocricetus, Scalp metabolism, Time Factors, Triglycerides metabolism, Hair drug effects, Hair Preparations pharmacology, Lipid Metabolism, Pyridines pharmacology, Scalp drug effects
Abstract

Animal experiments demonstrate that the topical application of the bis-(2-pyridyl-l-oxide)- disulfide adduct with MgSO4(Omadine MDS) increases the mitosis rate and also the size of the sebaceous glands in the Syrian hamster ear. Corresponding results have been obtained in human subjects in whom the secretion of the sebaceous glands was shown to increase after application of the compound. The studies also demonstrate that it decreases the fatty acid content of the scalp lipids. In this way a seborrhoea oleosa is transformed into a seborrhoea sicca. The undesired side effect of a stimulation of the sebaceous gland secretion is thus in part compensated for the patient's subjective feeling.

Published
1979

21. Central auditory testing with peripheral hearing loss.

Author

Miltenberger GE, Dawson GJ, and Raica AN

Subjects
Adolescent, Adult, Aged, Auditory Threshold, Hearing Tests, Humans, Middle Aged, Hearing Disorders diagnosis
Abstract

Seventy subjects with sensorineural hearing losses participated in this study. The goal of the study was to examine the effect of peripheral hearing loss on auditory tasks that are used to assess dysfunction within the central auditory pathways. Each subject received a central auditory processing (CAP) test battery that consisted of: (1) a dichotic sentence listening task; (2) a monosyllabic filtered word task; (3) a spondaic word binaural fusion task; and (4) a rapidly alternating speech task. All of these tasks were affected by certain degrees/configurations of sensorineural hearing loss, with the monosyllabic filtered word task being the most seriously affected. From the results of this study, it was concluded that while the CAP test battery can be administered to certain persons with sensorineural hearing losses, all results must be interpreted with caution and in view of the basic audiological assessment.

Published
1978
Full Text
View/download PDF

22. Utilization of a central auditory processing test battery in evaluating residual effects of decompression sickness.

Author

Miltenberger GE, Caruso VG, Correia MJ, Love JT, and Winkelmann P

Subjects
Adult, Central Nervous System Diseases etiology, Diving, Humans, Male, Middle Aged, Vestibulocochlear Nerve Diseases diagnosis, Vestibulocochlear Nerve Diseases etiology, Central Nervous System Diseases diagnosis, Decompression Sickness complications, Hearing Tests, Vestibular Nerve
Abstract

Six professional divers were examined as patients who presented peripheral auditory, vestibular, or central symptoms attributed to incidents which occurred while diving. Each diver received a central auditory processing (CAP) test battery consisting of: (1) a dichotic sentence listening task, (2) a monotic filtered word task, (3) a binaural fusion task, and (4) an alternating speech task. The CAP test results, in all cases substantiated other neurological/vestibular test battery results which we have reported in detail previously.

Published
1979
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results