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274 results on '"Seelaar, H"'

1. The behavioral variant of Alzheimer’s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

Author: Singleton, EH, Pijnenburg, YAL, Gami-Patel, P, Boon, BDC, Bouwman, F, Papma, JM, Seelaar, H, Scheltens, P, Grinberg, LT, Spina, S, Nana, AL, Rabinovici, GD, Seeley, WW, Ossenkoppele, R, and Dijkstra, AA
Subjects: Biomedical and Clinical Sciences, Acquired Cognitive Impairment, Brain Disorders, Dementia, Neurosciences, Neurodegenerative, Frontotemporal Dementia (FTD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer Disease, Frontotemporal Dementia, Frontotemporal Lobar Degeneration, Gyrus Cinguli, Humans, Neurons, Alzheimer's disease, Behavior, Frontotemporal dementia, Pathology, Von Economo Neurons, Alzheimer’s disease, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract: BackgroundThe neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer's disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD.MethodsVENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss.ResultsThe number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5.DiscussionVENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.
Published: 2022

2. Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia.

Author: van den Berg, E, Dijkzeul, J, Poos, J, Eikelboom, W, van Hemmen, J, Franzen, S, de Jong, F, Dopper, E, Papma, J, Satoer, D, Jiskoot, L, Seelaar, H, and Vonk, Jet
Subjects: Aphasia, assessment, cognitive, language, neurodegenerative
Abstract: Frontotemporal dementia (FTD) is an early-onset neurodegenerative disorder with a heterogeneous clinical presentation. Verbal fluency is regularly used as a sensitive measure of language ability, semantic memory, and executive functioning, but qualitative changes in verbal fluency in FTD are currently overlooked. This retrospective study examined qualitative, linguistic features of verbal fluency in 137 patients with behavioral variant (bv)FTD (n = 50), or primary progressive aphasia (PPA) [25 non-fluent variant (nfvPPA), 27 semantic variant (svPPA), and 34 logopenic variant (lvPPA)] and 25 control participants. Between-group differences in clustering, switching, lexical frequency (LF), age of acquisition (AoA), neighborhood density (ND), and word length (WL) were examined in the category and letter fluency with analysis of variance adjusted for age, sex, and the total number of words. Associations with other cognitive functions were explored with linear regression analysis. The results showed that the verbal fluency performance of patients with svPPA could be distinguished from controls and other patient groups by fewer and smaller clusters, more switches, higher LF, and lower AoA (all p
Published: 2022

3. Plasma proteome profiling identifies changes associated to AD but not to FTD

Author: Mofrad, R. Babapour, del Campo, M., Peeters, C. F. W., Meeter, L. H. H., Seelaar, H., Koel-Simmelink, M., Ramakers, I. H. G. B., Middelkoop, H. A. M., De Deyn, P. P., Claassen, J. A. H. R., van Swieten, J. C., Bridel, C., Hoozemans, J. J. M., Scheltens, P., van der Flier, W. M., Pijnenburg, Y. A. L., and Teunissen, Charlotte E.
Published: 2022
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4. Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia

Author: Cardiovasculaire Epi Team 5, Circulatory Health, Cardiovasculaire Epi Team 7a, van den Berg, E, Dijkzeul, J C M, Poos, J M, Eikelboom, W S, van Hemmen, J, Franzen, S, de Jong, F J, Dopper, E G P, Vonk, J M J, Papma, J M, Satoer, D, Jiskoot, L C, Seelaar, H, Cardiovasculaire Epi Team 5, Circulatory Health, Cardiovasculaire Epi Team 7a, van den Berg, E, Dijkzeul, J C M, Poos, J M, Eikelboom, W S, van Hemmen, J, Franzen, S, de Jong, F J, Dopper, E G P, Vonk, J M J, Papma, J M, Satoer, D, Jiskoot, L C, and Seelaar, H
Published: 2024

5. Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results

Author: Pasternak, M., Mirza, S., Luciw, N., Mutsaerts, H., (0000-0002-3201-6002) Petr, J., Thomas, D., Cash, D., Bocchetta, M., Tartaglia, C., Mitchell, S., Black, S., Freedman, M., Tang-Wai, D., Rogaeva, E., Russell, L., Bouzigues, A., Swieten, J., Jiskoot, L., Seelaar, H., Laforce Jr., R., Tiraboschi, P., Borroni, B., Galimberti, D., Rowe, J., Graff, C., Finger, E., Sandro, S., Mendonça, A., Butler, C., Gerhard, A., Sánchez-Valle, R., Moreno, F., Synofzik, M., Vandenberghe, R., Ducharme, S., Levin, J., Otto, M., Santana, I., Strafella, A., Macintosh, B., Rohrer, J., Masellis, M., Pasternak, M., Mirza, S., Luciw, N., Mutsaerts, H., (0000-0002-3201-6002) Petr, J., Thomas, D., Cash, D., Bocchetta, M., Tartaglia, C., Mitchell, S., Black, S., Freedman, M., Tang-Wai, D., Rogaeva, E., Russell, L., Bouzigues, A., Swieten, J., Jiskoot, L., Seelaar, H., Laforce Jr., R., Tiraboschi, P., Borroni, B., Galimberti, D., Rowe, J., Graff, C., Finger, E., Sandro, S., Mendonça, A., Butler, C., Gerhard, A., Sánchez-Valle, R., Moreno, F., Synofzik, M., Vandenberghe, R., Ducharme, S., Levin, J., Otto, M., Santana, I., Strafella, A., Macintosh, B., Rohrer, J., and Masellis, M.
Abstract: Genetic frontotemporal dementia is most commonly attributable to mutations in the C9orf72, GRN, or MAPT genes. The disease has near-complete penetrance, making presymptomatic carriers an ideal population for ascertaining the earliest changes in disease progression and the identification of suitable biomarkers for designing therapeutic trials when minimal neuronal loss has occurred. Cerebral perfusion, as measured by arterial spin labelling (ASL) MRI, has shown promise in being one such biomarker. However, longitudinal profiles of change in perfusion over time in presymptomatic carriers across all three genetic subgroups are lacking. Using data from the multicenter GENetic Frontotemporal dementia Initiative, we investigated longitudinal profiles of cerebral perfusion using ASL-MRI in C9orf72 (n = 42), GRN (n = 70), and MAPT (n = 31) presymptomatic mutation carriers and non-carrier controls (n = 158). ASL and T1w scans were processed with the ExploreASL pipeline to produce partial volume corrected perfusion images, which were parcellated to extract mean perfusion values from whole brain grey matter and regions defined by the second version of the automated anatomical atlas (AAL2). Linear mixed effects models were used to assess longitudinal perfusion change. Mutation carrier groups and non-carriers were statistically indistinguishable by baseline demographic and clinical measures. Decline in whole brain grey matter perfusion over time was more pronounced in all three carrier subgroups relative to controls, with changes most pronounced in GRN, followed by C9orf72 and MAPT variants. Additionally, GRN and MAPT groups featured global grey matter hypoperfusion relative to non-carrier controls as early as one year after baseline measurement, with C9orf72 featuring significant hypoperfusion after two years. Region of interest analysis demonstrated that each genetic subgroup had its own regional profile in terms of longitudinal perfusion decline. Perfusion decline in C9orf72
Published: 2024

6. Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia.

Author: van den Berg, E., Dijkzeul, J. C. M., Poos, J. M., Eikelboom, W. S., van Hemmen, J., Franzen, S., de Jong, F. J., Dopper, E. G. P., Vonk, J. M. J., Papma, J. M., Satoer, D., Jiskoot, L. C., and Seelaar, H.
Subjects: EXECUTIVE function, SEMANTIC memory, FRONTOTEMPORAL dementia, LANGUAGE ability, REGRESSION analysis, FRONTOTEMPORAL lobar degeneration
Abstract: Frontotemporal dementia (FTD) is an early-onset neurodegenerative disorder with a heterogeneous clinical presentation. Verbal fluency is regularly used as a sensitive measure of language ability, semantic memory, and executive functioning, but qualitative changes in verbal fluency in FTD are currently overlooked. This retrospective study examined qualitative, linguistic features of verbal fluency in 137 patients with behavioral variant (bv)FTD (n = 50), or primary progressive aphasia (PPA) [25 non-fluent variant (nfvPPA), 27 semantic variant (svPPA), and 34 logopenic variant (lvPPA)] and 25 control participants. Between-group differences in clustering, switching, lexical frequency (LF), age of acquisition (AoA), neighborhood density (ND), and word length (WL) were examined in the category and letter fluency with analysis of variance adjusted for age, sex, and the total number of words. Associations with other cognitive functions were explored with linear regression analysis. The results showed that the verbal fluency performance of patients with svPPA could be distinguished from controls and other patient groups by fewer and smaller clusters, more switches, higher LF, and lower AoA (all p < 0.05). Patients with lvPPA specifically produced words with higher ND than the other patient groups (p < 0.05). Patients with bvFTD produced longer words than the PPA groups (p < 0.05). Clustering, switching, LF, AoA, and ND—but not WL—were differentially predicted by measures of language, memory, and executive functioning (range standardized regression coefficient 0.25–0.41). In addition to the total number of words, qualitative linguistic features differ between subtypes of FTD. These features provide additional information on lexical processing and semantic memory that may aid the differential diagnosis of FTD. [ABSTRACT FROM AUTHOR]
Published: 2024
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7. Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

Author: Poos, J. M., Jiskoot, L. C., Leijdesdorff, S. M. J., Seelaar, H., Panman, J. L., van der Ende, E. L., Mol, M. O., Meeter, L. H. H., Pijnenburg, Y. A. L., Donker Kaat, L., de Jong, F. J., van Swieten, J. C., Papma, J. M., and van den Berg, E.
Published: 2020
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8. 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
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9. 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
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10. Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort

Author: Samra, K, MacDougall, AM, Bouzigues, A, Bocchetta, M, Cash, DM, Greaves, CV, Convery, RS, van Swieten, JC, Jiskoot, L, Seelaar, H, Moreno, F, Sanchez-Valle, R, Laforce, R, Graff, C, Masellis, M, Tartaglia, MC, Rowe, JB, Borroni, B, Finger, E, Synofzik, M, Galimberti, D, Vandenberghe, R, de Mendonça, A, Butler, CR, Gerhard, A, Ducharme, S, Le Ber, I, Tiraboschi, P, Santana, I, Pasquier, F, Levin, J, Otto, M, Sorbi, S, Rohrer, JD, Russell, LL, and Print-Electronic
Subjects: language, C9orf72, progranulin, MAPT, genetic, frontotemporal dementia
Abstract: Data availability: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S0022510X23001727?via%3Dihub#s0100 . Copyright © 2023 The Authors. Objective To identify whether language impairment exists presymptomatically in genetic frontotemporal dementia (FTD), and if so, the key differences between the main genetic mutation groups. Methods 682 participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 290 asymptomatic and 82 prodromal mutation carriers (with C9orf72, GRN, and MAPT mutations) as well as 310 mutation-negative controls. Language was assessed using items from the Progressive Aphasia Severity Scale, as well as the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency task. Participants also underwent a 3 T volumetric T1-weighted MRI from which regional brain volumes within the language network were derived and compared between the groups. Results 3% of asymptomatic (4% C9orf72, 4% GRN, 2% MAPT) and 48% of prodromal (46% C9orf72, 42% GRN, 64% MAPT) mutation carriers had impairment in at least one language symptom compared with 13% of controls. In prodromal mutation carriers significantly impaired word retrieval was seen in all three genetic groups whilst significantly impaired grammar/syntax and decreased fluency was seen only in C9orf72 and GRN mutation carriers, and impaired articulation only in the C9orf72 group. Prodromal MAPT mutation carriers had significant impairment on the category fluency task and the BNT whilst prodromal C9orf72 mutation carriers were impaired on the category fluency task only. Atrophy in the dominant perisylvian language regions differed between groups, with earlier, more widespread volume loss in C9orf72, and later focal atrophy in the temporal lobe in MAPT mutation carriers. Conclusions Language deficits exist in the prodromal but not asymptomatic stages of genetic FTD across all three genetic groups. Improved understanding of the language phenotype prior to phenoconversion to fully symptomatic FTD will help develop outcome measures for future presymptomatic trials. 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) 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. This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant, the Alzheimer's Society grant (AS-PG-16-007), the Bluefield Project and the JPND GENFI-PROX grant (2019–02248). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004-517). JDR 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). JBR is funded by the Wellcome Trust (103838) and the National Institute for Health Research Cambridge Biomedical Research Centre. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). RV's work is supported by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie. Several authors of this publication (JCvS, MS, RSV, AD, MO, RV, JDR) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) - Project ID No 739510.
Published: 2023

11. Correction to: Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

Author: Poos, J. M., Jiskoot, L. C., Leijdesdorff, S. M. J., Seelaar, H., Panman, J. L., van der Ende, E. L., Mol, M. O., Meeter, L. H. H., Pijnenburg, Y. A. L., Donker Kaat, L., de Jong, F. J., van Swieten, J. C., Papma, J. M., and van den Berg, E.
Published: 2020
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12. Protein network analysis reveals selectively vulnerable regions and biological processes in FTD

Author: Bonham, Luke W., Steele, Natasha Z.R., Karch, Celeste M., Manzoni, Claudia, Geier, Ethan G., Wen, Natalie, Ofori-Kuragu, Aaron, Momeni, Parastoo, Hardy, John, Miller, Zachary A., Hess, Christopher P., Lewis, Patrick, Miller, Bruce L., Seeley, William W., Baranzini, Sergio E., Desikan, Rahul S., Ferrari, Raffaele, Yokoyama, Jennifer S., Ferrari, R, Hernandez, D G, Nalls, M A, Rohrer, J D, Ramasamy, A, Kwok, J B J, Dobson-Stone, C, Schofield, P R, Halliday, G M, Hodges, J R, Piguet, O, Bartley, L, Thompson, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, N J, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, M Landqvist, Nilsson, K, Nilsson, C, Mackenzie, I R A, Hsiung, G-Y R, Mann, D, Grafman, J, Morris, C M, Attems, J, Griffiths, T D, McKeith, I G, Thomas, A J, Pietrini, P, Huey, E D, Wassermann, E M, Baborie, A, Jaros, E, Tierney, M C, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Albani, D., Rowe, J B, Schlachetzki, J C M, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, V M, Grossman, M, Trojanowski, J Q, van der Zee, J, Van Broeckhoven, C, Cappa, S F, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, J E, Hjermind, L E, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, M N, Fox, N C, Warren, J D, Spillantini, M G, Morris, H R, Rizzu, P, Heutink, P, Snowden, J S, Rollinson, S, Richardson, A, Gerhard, A, Bruni, A C, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, M E, Smirne, N, Rademakers, R, Baker, M, Dickson, D W, Graff-Radford, N R, Petersen, R C, Knopman, D, Josephs, K A, Boeve, B F, Parisi, J E, Seeley, W W, Miller, B L, Karydas, A M, Rosen, H, van Swieten, J C, Dopper, E G P, Seelaar, H, Pijnenburg, Y A L, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, A A, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, H-H, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, A B, Hardy, J, and Momeni, P
Published: 2018
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13. 19 Frontotemporale dementie (FTD)

Author: Seelaar, H., Pijnenburg, Y.A.L., van Swieten, J.C., Jonker, C., editor, Slaets, J.P.J., editor, and Verhey, F.R.J., editor
Published: 2009
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14. Impaired knowledge of social norms in dementia and psychiatric disorders: Validation of the Social Norms Questionnaire-Dutch Version (SNQ-NL)

Author: Berg, E. van den, Poos, J.M., Jiskoot, L.C., Montagne, B., Kessels, R.P.C., Franzen, S., Hemmen, J. van, Eikelboom, W.S., Heijboer, E.G.C., Kriek, J. de, Vlist, A. van der, Jong, F.J. de, Swieten, J.C. van, Seelaar, H., Papma, J.M., Berg, E. van den, Poos, J.M., Jiskoot, L.C., Montagne, B., Kessels, R.P.C., Franzen, S., Hemmen, J. van, Eikelboom, W.S., Heijboer, E.G.C., Kriek, J. de, Vlist, A. van der, Jong, F.J. de, Swieten, J.C. van, Seelaar, H., and Papma, J.M.
Abstract: Contains fulltext : 232053.pdf (Publisher’s version ) (Open Access), The Social Norms Questionnaire-Dutch version (SNQ-NL) measures the ability to understand and identify social boundaries. We examined the psychometric characteristics of the SNQ-NL and its ability to differentiate between patients with behavioral variant frontotemporal dementia (bvFTD; n = 23), Alzheimer's dementia (AD; n = 26), chronic psychiatric disorders (n = 27), and control participants (n = 92). Between-group differences in the Total score, Break errors, and Overadhere errors were examined and associations with demographic variables and other cognitive functions were explored. Results showed that the SNQ-NL Total Score and Break errors differed between patients with AD and bvFTD, but not between patients with bvFTD and psychiatric disorders. Modest correlations with age, sex, and education were observed. The SNQ-NL Total score and Break errors correlated significantly with emotion recognition and verbal fluency but not with processing speed or mental flexibility. In conclusion, the SNQ-NL has sufficient construct validity and can be used to investigate knowledge of social norms in clinical populations.
Published: 2022

15. Plasma proteome profiling identifies changes associated to AD but not to FTD

Author: Babapour Mofrad, R., Campo, M. del, Peeters, Carel F.W., Meeter, L.H.H., Seelaar, H., Koel-Simmelink, M., Claassen, J.A.H.R., Pijnenburg, Yolande A. L., Teunissen, Charlotte E., Babapour Mofrad, R., Campo, M. del, Peeters, Carel F.W., Meeter, L.H.H., Seelaar, H., Koel-Simmelink, M., Claassen, J.A.H.R., Pijnenburg, Yolande A. L., and Teunissen, Charlotte E.
Abstract: Contains fulltext : 283875.pdf (Publisher’s version ) (Open Access)
Published: 2022

16. Data-driven staging of genetic frontotemporal dementia using multi-modal MRI

Author: McCarthy, J., Borroni, B., Sanchez-Valle, R., Moreno, F., Laforce, R., Graff, C., Synofzik, M., Galimberti, D., Rowe, J. B., Masellis, M., Tartaglia, M. C., Finger, E., Vandenberghe, R., de Mendonça, A., Tagliavini, F., Santana, I., Butler, C., Gerhard, A., Danek, A., Levin, J., Otto, M., Frisoni, G., Ghidoni, R., Sorbi, S., Jiskoot, L. C., Seelaar, H., van Swieten, J. C., Rohrer, J. D., Iturria-Medina, Y., Ducharme, S., Anderl-Straub, S., Andersson, C., Antonell, A., McCarthy, J., Borroni, B., Sanchez-Valle, R., Moreno, F., Laforce, R., Graff, C., Synofzik, M., Galimberti, D., Rowe, J. B., Masellis, M., Tartaglia, M. C., Finger, E., Vandenberghe, R., de Mendonça, A., Tagliavini, F., Santana, I., Butler, C., Gerhard, A., Danek, A., Levin, J., Otto, M., Frisoni, G., Ghidoni, R., Sorbi, S., Jiskoot, L. C., Seelaar, H., van Swieten, J. C., Rohrer, J. D., Iturria-Medina, Y., Ducharme, S., Anderl-Straub, S., Andersson, C., and Antonell, A.
Abstract: Frontotemporal dementia in genetic forms is highly heterogeneous and begins many years to prior symptom onset, complicating disease understanding and treatment development. Unifying methods to stage the disease during both the presymptomatic and symptomatic phases are needed for the development of clinical trials outcomes. Here we used the contrastive trajectory inference (cTI), an unsupervised machine learning algorithm that analyzes temporal patterns in high-dimensional large-scale population datasets to obtain individual scores of disease stage. We used cross-sectional MRI data (gray matter density, T1/T2 ratio as a proxy for myelin content, resting-state functional amplitude, gray matter fractional anisotropy, and mean diffusivity) from 383 gene carriers (269 presymptomatic and 115 symptomatic) and a control group of 253 noncarriers in the Genetic Frontotemporal Dementia Initiative. We compared the cTI-obtained disease scores to the estimated years to onset (age—mean age of onset in relatives), clinical, and neuropsychological test scores. The cTI based disease scores were correlated with all clinical and neuropsychological tests (measuring behavioral symptoms, attention, memory, language, and executive functions), with the highest contribution coming from mean diffusivity. Mean cTI scores were higher in the presymptomatic carriers than controls, indicating that the method may capture subtle pre-dementia cerebral changes, although this change was not replicated in a subset of subjects with complete data. This study provides a proof of concept that cTI can identify data-driven disease stages in a heterogeneous sample combining different mutations and disease stages of genetic FTD using only MRI metrics. © 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
Published: 2022

17. Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia

Author: van den Berg, E., Dijkzeul, J. C. M., Poos, J. M., Eikelboom, W. S., van Hemmen, J., Franzen, S., de Jong, F. J., Dopper, E. G. P., Vonk, J. M. J., Papma, J. M., Satoer, D., Jiskoot, L. C., Seelaar, H., van den Berg, E., Dijkzeul, J. C. M., Poos, J. M., Eikelboom, W. S., van Hemmen, J., Franzen, S., de Jong, F. J., Dopper, E. G. P., Vonk, J. M. J., Papma, J. M., Satoer, D., Jiskoot, L. C., and Seelaar, H.
Abstract: Frontotemporal dementia (FTD) is an early-onset neurodegenerative disorder with a heterogeneous clinical presentation. Verbal fluency is regularly used as a sensitive measure of language ability, semantic memory, and executive functioning, but qualitative changes in verbal fluency in FTD are currently overlooked. This retrospective study examined qualitative, linguistic features of verbal fluency in 137 patients with behavioral variant (bv)FTD (n = 50), or primary progressive aphasia (PPA) [25 non-fluent variant (nfvPPA), 27 semantic variant (svPPA), and 34 logopenic variant (lvPPA)] and 25 control participants. Between-group differences in clustering, switching, lexical frequency (LF), age of acquisition (AoA), neighborhood density (ND), and word length (WL) were examined in the category and letter fluency with analysis of variance adjusted for age, sex, and the total number of words. Associations with other cognitive functions were explored with linear regression analysis. The results showed that the verbal fluency performance of patients with svPPA could be distinguished from controls and other patient groups by fewer and smaller clusters, more switches, higher LF, and lower AoA (all p < 0.05). Patients with lvPPA specifically produced words with higher ND than the other patient groups (p < 0.05). Patients with bvFTD produced longer words than the PPA groups (p < 0.05). Clustering, switching, LF, AoA, and ND-but not WL-were differentially predicted by measures of language, memory, and executive functioning (range standardized regression coefficient 0.25-0.41). In addition to the total number of words, qualitative linguistic features differ between subtypes of FTD. These features provide additional information on lexical processing and semantic memory that may aid the differential diagnosis of FTD.
Published: 2022

18. Impaired Knowledge of Social Norms in Dementia and Psychiatric Disorders:Validation of the Social Norms Questionnaire–Dutch Version (SNQ-NL)

Author: van den Berg, E., Poos, J. M., Jiskoot, L. C., Montagne, B., Kessels, R. P.C., Franzen, S., van Hemmen, J., Eikelboom, W. S., Heijboer, E. G.C., de Kriek, J., van der Vlist, A., de Jong, F. J., van Swieten, J. C., Seelaar, H., Papma, J. M., van den Berg, E., Poos, J. M., Jiskoot, L. C., Montagne, B., Kessels, R. P.C., Franzen, S., van Hemmen, J., Eikelboom, W. S., Heijboer, E. G.C., de Kriek, J., van der Vlist, A., de Jong, F. J., van Swieten, J. C., Seelaar, H., and Papma, J. M.
Abstract: The Social Norms Questionnaire–Dutch version (SNQ-NL) measures the ability to understand and identify social boundaries. We examined the psychometric characteristics of the SNQ-NL and its ability to differentiate between patients with behavioral variant frontotemporal dementia (bvFTD; n = 23), Alzheimer’s dementia (AD; n = 26), chronic psychiatric disorders (n = 27), and control participants (n = 92). Between-group differences in the Total score, Break errors, and Overadhere errors were examined and associations with demographic variables and other cognitive functions were explored. Results showed that the SNQ-NL Total Score and Break errors differed between patients with AD and bvFTD, but not between patients with bvFTD and psychiatric disorders. Modest correlations with age, sex, and education were observed. The SNQ-NL Total score and Break errors correlated significantly with emotion recognition and verbal fluency but not with processing speed or mental flexibility. In conclusion, the SNQ-NL has sufficient construct validity and can be used to investigate knowledge of social norms in clinical populations.
Published: 2022

19. The behavioral variant of Alzheimer’s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

Author: Singleton, E. H., Pijnenburg, Y. A.L., Gami-Patel, P., Boon, B.D.C., Bouwman, F., Papma, J. M., Seelaar, H., Scheltens, P., Grinberg, L. T., Spina, S., Nana, A. L., Rabinovici, G. D., Seeley, W. W., Ossenkoppele, R., Dijkstra, A. A., Singleton, E. H., Pijnenburg, Y. A.L., Gami-Patel, P., Boon, B.D.C., Bouwman, F., Papma, J. M., Seelaar, H., Scheltens, P., Grinberg, L. T., Spina, S., Nana, A. L., Rabinovici, G. D., Seeley, W. W., Ossenkoppele, R., and Dijkstra, A. A.
Abstract: Background: The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer’s disease (bvAD) remain unclear. A selective loss of Von Economo neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD. Methods: VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n = 9) and compared to typical AD (tAD, n = 6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n = 18) and controls (n = 13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss. Results: The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0 ± 15.3, GABRQ-ir pyramidal: 260.4 ± 87.1) and tAD (VENs: 32.0 ± 18.1, p = 1.00, GABRQ-ir pyramidal: 349.8 ± 109.6, p = 0.38) and controls (VENs: 33.5 ± 20.3, p = 1.00, GABRQ-ir pyramidal: 339.4 ± 95.9, p = 0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.5 ± 82.658, p = 0.01) and no significant differences in number of VENs (bvFTD: 10.9 ± 13.8, p = 0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5. Discussion: VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.
Published: 2022

20. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimerʼs and Parkinsonʼs diseases

Author: Ferrari, Raffaele, Wang, Yunpeng, Vandrovcova, Jana, Guelfi, Sebastian, Witeolar, Aree, Karch, Celeste M, Schork, Andrew J, Fan, Chun C, Brewer, James B, Momeni, Parastoo, Schellenberg, Gerard D, Dillon, William P, Sugrue, Leo P, Hess, Christopher P, Yokoyama, Jennifer S, Bonham, Luke W, Rabinovici, Gil D, Miller, Bruce L, Andreassen, Ole A, Dale, Anders M, Hardy, John, Desikan, Rahul S, Hernandez, D G, Nalls, M A, Rohrer, J D, Ramasamy, A, Kwok, J B J, Dobson-Stone, C, Schofield, P R, Halliday, G M, Hodges, J R, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, N J, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Landqvist Waldö, M, Nilsson, K, Nilsson, C, Mackenzie, I R A, Hsiung, G-Y R, Mann, D M A, Grafman, J, Morris, C M, Attems, J, Griffiths, T D, McKeith, I G, Thomas, A J, Pietrini, P, Huey, E D, Wassermann, E M, Baborie, A, Jaros, E, Tierney, M C, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, J B, Schlachetzki, J C M, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, V M, Grossman, M, Trojanowski, J Q, van der Zee, J, Cruts, M, Van Broeckhoven, C, Cappa, S F, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, J E, Hjermind, L E, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, M N, Fox, N C, Warren, J D, Spillantini, M G, Morris, H R, Rizzu, P, Heutink, P, Snowden, J S, Rollinson, S, Richardson, A, Gerhard, A, Bruni, A C, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, M E, Smirne, N, Rademakers, R, Baker, M, Dickson, D W, Graff-Radford, N R, Petersen, R C, Knopman, D, Josephs, K A, Boeve, B F, Parisi, J E, Seeley, W W, Karydas, A M, Rosen, H, van Swieten, J C, Dopper, E G P, Seelaar, H, Pijnenburg, Y A L, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, A A, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, H-H, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, and Singleton, A B
Published: 2017
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21. Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia

Author: van den Berg, E., primary, Dijkzeul, J. C. M., additional, Poos, J. M., additional, Eikelboom, W. S., additional, van Hemmen, J., additional, Franzen, S., additional, de Jong, F. J., additional, Dopper, E. G. P., additional, Vonk, J. M. J., additional, Papma, J. M., additional, Satoer, D., additional, Jiskoot, L. C., additional, and Seelaar, H., additional
Published: 2022
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22. Additional file 1 of The behavioral variant of Alzheimer��s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

Author: Singleton, E. H., Pijnenburg, Y. A. L., Gami-Patel, P., Boon, B. D. C., Bouwman, F., Papma, J. M., Seelaar, H., Scheltens, P., Grinberg, L. T., Spina, S., Nana, A. L., Rabinovici, G. D., Seeley, W. W., Ossenkoppele, R., and Dijkstra, A. A.
Subjects: Data_FILES
Abstract: Additional file 1.
Published: 2022
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23. Additional file 2 of Plasma proteome profiling identifies changes associated to AD but not to FTD

Author: Mofrad, R. Babapour, del Campo, M., Peeters, C. F. W., Meeter, L. H. H., Seelaar, H., Koel-Simmelink, M., Ramakers, I. H. G. B., Middelkoop, H. A. M., De Deyn, P. P., Claassen, J. A. H. R., van Swieten, J. C., Bridel, C., Hoozemans, J. J. M., Scheltens, P., van der Flier, W. M., Pijnenburg, Y. A. L., and Teunissen, Charlotte E.
Abstract: Additional file 2.
Published: 2022
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24. Additional file 1 of Plasma proteome profiling identifies changes associated to AD but not to FTD

Author: Mofrad, R. Babapour, del Campo, M., Peeters, C. F. W., Meeter, L. H. H., Seelaar, H., Koel-Simmelink, M., Ramakers, I. H. G. B., Middelkoop, H. A. M., De Deyn, P. P., Claassen, J. A. H. R., van Swieten, J. C., Bridel, C., Hoozemans, J. J. M., Scheltens, P., van der Flier, W. M., Pijnenburg, Y. A. L., and Teunissen, Charlotte E.
Abstract: Additional file 1. Table S1. Distribution of diagnoses over the different centers.
Published: 2022
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25. Social Norms Questionnaire--Dutch Version

Author: van den Berg, E., primary, Poos, J. M., additional, Jiskoot, L. C., additional, Montagne, B., additional, Kessels, R. P. C., additional, Franzen, S., additional, van Hemmen, J., additional, Eikelboom, W. S., additional, Heijboer, E. G. C., additional, de Kriek, J., additional, van der Vlist, A., additional, de Jong, F. J., additional, van Swieten, J. C., additional, Seelaar, H., additional, and Papma, J. M., additional
Published: 2022
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26. A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers

Author: Zhang M1, 2 3, Ferrari R4, Tartaglia MC3, 5 6, Keith J7, Surace EI8, Wolf U9, Sato C3, Grinberg M3, Liang Y3, Xi Z3, Dupont K3, McGoldrick P3, Weichert A3, McKeever PM3, Schneider R3, 6 7, McCorkindale MD4, Manzoni C10, Rademakers R11, Graff-Radford NR12, Dickson DW11, Parisi JE13, Boeve BF14, Petersen RC14, Miller BL15, Seeley WW16, van Swieten JC17, van Rooij J17, Pijnenburg Y18, van der Zee J19, Van Broeckhoven C19, Le Ber I21, Van Deerlin V23, Suh E23, Rohrer JD24, Mead S25, Graff C26, Öijerstedt L26, Pickering-Brown S28, Rollinson S28, Rossi G29, Tagliavini F30, Brooks WS31, Dobson-Stone C32, Halliday GM32, Hodges JR32, Piguet O34, Binetti G36, Benussi L37, Ghidoni R37, Nacmias B38, Sorbi S38, Bruni AC40, Galimberti D41, Scarpini E41, Rainero I42, Rubino E42, Clarimon J43, Lleó A43, Ruiz A45, Hernández I45, Pastor P46, Diez-Fairen M46, Borroni B48, Pasquier F49, Deramecourt V49, Lebouvier T49, Perneczky R50, 51 52, Diehl-Schmid J50, Grafman J53, Huey ED55, Mayeux R55, Nalls MA57, Hernandez D57, Singleton A57, Momeni P58, Zeng Z59, Hardy J4, Robertson J3, Zinman L6, 7, Rogaeva E3, 6, International FTD-Genomics Consortium (IFGC), Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JBJ, Dobson-Stone C, Brooks WS, Schofield PR, Halliday GM, Hodges JR, Piguet O, Bartley L, Thompson E, Hernández I, Ruiz A, Boada M, Borroni B, Padovani A, Cruchaga C, Cairns NJ, Benussi L, Binetti G, Ghidoni R, Forloni G, Albani D, Galimberti D, Fenoglio C, Serpente M, Scarpini E, Clarimón J, Lleó A, Blesa R, Wald Ouml ML, Nilsson K, Nilsson C, Mackenzie IRA, Hsiung GR, Mann DMA, Grafman J, Morris CM, Attems J, Griffiths TD, McKeith IG, Thomas AJ, Pietrini P, Huey ED, Wassermann EM, Baborie A, Jaros E, Tierney MC, Pastor P, Razquin C, Ortega-Cubero S, Alonso E, Perneczky R, Diehl-Schmid J, Alexopoulos P, Kurz A, Rainero I, Rubino E, Pinessi L, Rogaeva E, St George-Hyslop P, Rossi G, Tagliavini F, Giaccone G, Rowe JB, Schlachetzki JCM, Uphill J, Collinge J, Mead S, Danek A, Van Deerlin VM, Grossman M, Trojanowski JQ, van der Zee J, Van Broeckhoven C, Cappa SF, Leber I, Hannequin D, Golfier V, Vercelletto M, Brice A, Nacmias B, Sorbi S, Bagnoli S, Piaceri I, Nielsen JE, Hjermind LE, Riemenschneider M, Mayhaus M, Ibach B, Gasparoni G, Pichler S, Gu W, Rossor MN, Fox NC, Warren JD, Grazia Spillantini M, Morris HR, Rizzu P, Heutink P, Snowden JS, Rollinson S, Richardson A, Gerhard A, Bruni AC, Maletta R, Frangipane F, Cupidi C, Bernardi L, Anfossi M, Gallo M, Elena Conidi M, Smirne N, Rademakers R, Baker M, Dickson DW, Graff-Radford NR, Petersen RC, Knopman D, Josephs KA, Boeve BF, Parisi JE, Seeley WW, Miller BL, Karydas AM, Rosen H, van Swieten JC, Dopper EGP, Seelaar H, Pijnenburg YAL, Scheltens P, Logroscino G, Capozzo R, Novelli V, Puca AA, Franceschi M, Postiglione A, Milan G, Sorrentino P, Kristiansen M, Chiang HH, Graff C, Pasquier F, Rollin A, Deramecourt V, Lebouvier T, Kapogiannis D, Ferrucci L, Pickering-Brown S, Singleton AB, Hardy J, Momeni P, Human genetics, Amsterdam Neuroscience - Neurodegeneration, Neurology, Divisions, Zhang, M1, 2, 3, Ferrari, R4, Tartaglia, Mc3, 5, 6, Keith, J7, Surace, Ei8, Wolf, U9, Sato, C3, Grinberg, M3, Liang, Y3, Xi, Z3, Dupont, K3, Mcgoldrick, P3, Weichert, A3, Mckeever, Pm3, Schneider, R3, 6, 7, Mccorkindale, Md4, Manzoni, C10, Rademakers, R11, Graff-Radford, Nr12, Dickson, Dw11, Parisi, Je13, Boeve, Bf14, Petersen, Rc14, Miller, Bl15, Seeley, Ww16, van Swieten, Jc17, van Rooij, J17, Pijnenburg, Y18, van der Zee, J19, Van Broeckhoven, C19, Le Ber, I21, Van Deerlin, V23, Suh, E23, Rohrer, Jd24, Mead, S25, Graff, C26, Öijerstedt, L26, Pickering-Brown, S28, Rollinson, S28, Rossi, G29, Tagliavini, F30, Brooks, Ws31, Dobson-Stone, C32, Halliday, Gm32, Hodges, Jr32, Piguet, O34, Binetti, G36, Benussi, L37, Ghidoni, R37, Nacmias, B38, Sorbi, S38, Bruni, Ac40, Galimberti, D41, Scarpini, E41, Rainero, I42, Rubino, E42, Clarimon, J43, Lleó, A43, Ruiz, A45, Hernández, I45, Pastor, P46, Diez-Fairen, M46, Borroni, B48, Pasquier, F49, Deramecourt, V49, Lebouvier, T49, Perneczky, R50, 51, 52, Diehl-Schmid, J50, Grafman, J53, Huey, Ed55, Mayeux, R55, Nalls, Ma57, Hernandez, D57, Singleton, A57, Momeni, P58, Zeng, Z59, Hardy, J4, Robertson, J3, Zinman, L6, Rogaeva, E3, International FTD-Genomics Consortium, (IFGC), Ferrari, R, Hernandez, Dg, Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Brooks, W, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Wald Ouml, Ml, Nilsson, K, Nilsson, C, Mackenzie, Ira, Hsiung, Gr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, Vm, Grossman, M, Trojanowski, Jq, van der Zee, J, Van Broeckhoven, C, Cappa, Sf, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Grazia Spillantini, M, Morris, Hr, Rizzu, P, Heutink, P, Snowden, J, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Elena Conidi, M, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten, Jc, Dopper, Egp, Seelaar, H, Pijnenburg, Yal, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, Ab, Hardy, J, Momeni, P, and Int FTD-Genomics Consortium IFGC
Subjects: Male, Heterozygote, amyotrophic lateral sclerosis, Genotype, genetic association, Age of onset, Polymorphism, Single Nucleotide, frontotemporal dementia, age of onset, C9orf72, Humans, amyotrophic lateral sclerosi, Aged, C9orf72 Protein, Original Articles, DNA Methylation, Middle Aged, Amyotrophic lateral sclerosis, Gene Expression Regulation, Genetic association, CpG Islands, Female, Human medicine, Neurology (clinical), Frontotemporal dementia
Abstract: Discovery of disease age-of-onset modifiers is important for clinical trials and drug design. Zhang et al. perform a genome-wide analysis of epigenetic functional polymorphisms and identify an association between the C6orf10/LOC101929163 locus and age of FTD/ALS onset. The risk allele may be associated with a pro-inflammatory state in the brain., The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.
Published: 2018
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27. Practice effects in genetic frontotemporal dementia and at-risk individuals: a GENFI study

Author: Öijerstedt, L, Andersson, C, Jelic, V, van Swieten, JC, Jiskoot, LC, Seelaar, H, Borroni, B, Sanchez-Valle, R, Moreno, F, Laforce Jr, R, Synofzik, M, Galimberti, D, Rowe, JB, Masellis, M, Tartaglia, MC, Finger, E, Vandenberghe, R, de Mendonca, A, Tagliavini, F, Santana, I, Ducharme, S, Butler, CR, Gerhard, A, Levin, J, Danek, A, Otto, M, Frisoni, G, Ghidoni, R, Sorbi, S, Rohrer, JD, Graff, C, Genetic Frontotemporal Dementia Initiative (GENFI), Bocchetta, M, and Genetic Frontotemporal Dementia Initiative (GENFI)
Abstract: Supplemental material is available at https://jnnp.bmj.com/content/jnnp/93/3/336/DC1/embed/inline-supplementary-material-1.pdf?download=true . This work was supported by grants from SRC/VR 529-2014-7504, VR 2015-02926, VR 2018-02754, VR 2019-02248: JPND GENFI-PROX, the Swedish FTD Initiative-Schörling Foundation, Swedish Alzheimer Foundation, Swedish Brain Foundation, Demensfonden, Stohnes foundation, Gamla Tjänarinnor, Karolinska Institutet Doctoral funding and ALF-Region Stockholm. 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 (grant HCMI 056-13-018); ZonMw Memorabel (Deltaplan Dementie, project numbers 733 050 103 and 733 050 813); and JPND PreFrontAls consortium (project number 733051042). JDR was supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and 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).
Published: 2021

28. The behavioral variant of Alzheimer’s disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

Author: Singleton, E.H., primary, Pijnenburg, Y.A.L, additional, Gami-Patel, P., additional, Boon, B.D.C., additional, Bouwman, F., additional, Papma, J., additional, Seelaar, H., additional, Scheltens, P., additional, Grinberg, L.T., additional, Spina, S., additional, Nana, A.L., additional, Rabinovici, G.D., additional, Seeley, W.W., additional, Ossenkoppele, R., additional, and Dijkstra, A.A., additional
Published: 2021
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29. Impaired Knowledge of Social Norms in Dementia and Psychiatric Disorders: Validation of the Social Norms Questionnaire–Dutch Version (SNQ-NL).

Author: van den Berg, E., Poos, J. M., Jiskoot, L. C., Montagne, B., Kessels, R. P. C., Franzen, S., van Hemmen, J., Eikelboom, W. S., Heijboer, E. G. C., de Kriek, J., van der Vlist, A., de Jong, F. J., van Swieten, J. C., Seelaar, H., and Papma, J. M.
Subjects: STATISTICS, ALZHEIMER'S disease, SOCIAL perception, RESEARCH evaluation, ANALYSIS of variance, SOCIAL norms, RESEARCH methodology evaluation, AGE distribution, RESEARCH methodology, CASE-control method, COGNITION, PSYCHOMETRICS, HEALTH literacy, SEX distribution, MULTITRAIT multimethod techniques, PEARSON correlation (Statistics), QUESTIONNAIRES, DEMENTIA, DESCRIPTIVE statistics, DATA analysis, DATA analysis software, MENTAL illness, FRONTOTEMPORAL dementia, EDUCATIONAL attainment
Abstract: The Social Norms Questionnaire–Dutch version (SNQ-NL) measures the ability to understand and identify social boundaries. We examined the psychometric characteristics of the SNQ-NL and its ability to differentiate between patients with behavioral variant frontotemporal dementia (bvFTD; n = 23), Alzheimer's dementia (AD; n = 26), chronic psychiatric disorders (n = 27), and control participants (n = 92). Between-group differences in the Total score, Break errors, and Overadhere errors were examined and associations with demographic variables and other cognitive functions were explored. Results showed that the SNQ-NL Total Score and Break errors differed between patients with AD and bvFTD, but not between patients with bvFTD and psychiatric disorders. Modest correlations with age, sex, and education were observed. The SNQ-NL Total score and Break errors correlated significantly with emotion recognition and verbal fluency but not with processing speed or mental flexibility. In conclusion, the SNQ-NL has sufficient construct validity and can be used to investigate knowledge of social norms in clinical populations. [ABSTRACT FROM AUTHOR]
Published: 2022
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30. FRONTotemporal dementia Incidence European Research Study—FRONTIERS:rationale and design

Author: Borroni, B. (Barbara), Graff, C. (Caroline), Hardiman, O. (Orla), Ludolph, A. C. (Albert C.), Moreno, F. (Fermin), Otto, M. (Markus), Piccininni, M. (Marco), Remes, A. M. (Anne M), Rowe, J. B. (James B), Seelaar, H. (Harro), Stefanova, E. (Elka), Traykov, L. (Latchezar), Logroscino, G. (Giancarlo), and F. (FRONTIERS)
Subjects: frontotemporal lobar degeneration, incidence, rare diseases, epidemiology, registry, frontotemporal dementia
Abstract: Introduction: The incidence of Frontotemporal Lobar Degeneration (FTLD)–related disorders and their characteristics are not well known. The “FRONTotemporal dementia Incidence European Research Study” (FRONTIERS) is designed to fill this gap. Methods: FRONTIERS is a European prospective, observational population study based on multinational registries. FRONTIERS comprises 11 tertiary referral centers across Europe with long-lasting experience in FTLD-related disorders and comprehensive regional referral networks, enabling incidence estimation over well-defined geographical areas. Endpoints: The primary endpoints are (1) the incidence of FTLD-related disorders across Europe; (2) geographic trends of FTLD-related disorders; (3) the distribution of FTLD phenotypes in different populations and ethnicities in Europe; (4) inheritance of FTLD-related disorders, including the frequencies of monogenic FTLD as compared to overall disease burden; and (5) implementation of data banking for clinical and biological material. Expected impacts: FRONTIERS will improve the understanding of FTLD-related disorders and their epidemiology, promoting appropriate public health service policies and treatment strategies.
Published: 2021

31. Impaired knowledge of social norms in dementia and psychiatric disorders: Validation of the Social Norms Questionnaire-Dutch Version (SNQ-NL)

Author: Berg, E. van den, Poos, J.M., Jiskoot, L.C., Montagne, B., Kessels, R.P.C., Franzen, S., Hemmen, J. van, Eikelboom, W.S., Heijboer, E.G.C., Kriek, J. de, Vlist, A. van der, Jong, F.J. de, Swieten, J.C. van, Seelaar, H., Papma, J.M., Berg, E. van den, Poos, J.M., Jiskoot, L.C., Montagne, B., Kessels, R.P.C., Franzen, S., Hemmen, J. van, Eikelboom, W.S., Heijboer, E.G.C., Kriek, J. de, Vlist, A. van der, Jong, F.J. de, Swieten, J.C. van, Seelaar, H., and Papma, J.M.
Abstract: 15 april 2021, Contains fulltext : 232053.pdf (Publisher’s version ) (Open Access), The Social Norms Questionnaire-Dutch version (SNQ-NL) measures the ability to understand and identify social boundaries. We examined the psychometric characteristics of the SNQ-NL and its ability to differentiate between patients with behavioral variant frontotemporal dementia (bvFTD; n = 23), Alzheimer's dementia (AD; n = 26), chronic psychiatric disorders (n = 27), and control participants (n = 92). Between-group differences in the Total score, Break errors, and Overadhere errors were examined and associations with demographic variables and other cognitive functions were explored. Results showed that the SNQ-NL Total Score and Break errors differed between patients with AD and bvFTD, but not between patients with bvFTD and psychiatric disorders. Modest correlations with age, sex, and education were observed. The SNQ-NL Total score and Break errors correlated significantly with emotion recognition and verbal fluency but not with processing speed or mental flexibility. In conclusion, the SNQ-NL has sufficient construct validity and can be used to investigate knowledge of social norms in clinical populations.
Published: 2021

32. Impaired Knowledge of Social Norms in Dementia and Psychiatric Disorders: Validation of the Social Norms Questionnaire–Dutch Version (SNQ-NL)

Author: van den Berg, E., primary, Poos, J. M., additional, Jiskoot, L. C., additional, Montagne, B., additional, Kessels, R. P. C., additional, Franzen, S., additional, van Hemmen, J., additional, Eikelboom, W. S., additional, Heijboer, E. G. C., additional, de Kriek, J., additional, van der Vlist, A., additional, de Jong, F. J., additional, van Swieten, J. C., additional, Seelaar, H., additional, and Papma, J. M., additional
Published: 2021
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33. Exploring Abstract Semantic Associations in the Frontotemporal Dementia Spectrum in a Dutch Population

Author: Poos, J M, primary, van den Berg, E, additional, Visch-Brink, E, additional, Eikelboom, W S, additional, Franzen, S, additional, van Hemmen, J, additional, Pijnenburg, Y A L, additional, Satoer, D, additional, Dopper, E G P, additional, van Swieten, J C, additional, Papma, J M, additional, Seelaar, H, additional, and Jiskoot, L C, additional
Published: 2021
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34. Correction to:A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity (Acta Neuropathologica, (2019), 138, 2, (237-250), 10.1007/s00401-019-02026-8)

Author: van der Lee, Sven J., Conway, Olivia J., Jansen, Iris, Carrasquillo, Minerva M., Kleineidam, Luca, van den Akker, Erik, Hernández, Isabel, van Eijk, Kristel R., Stringa, Najada, Chen, Jason A., Zettergren, Anna, Andlauer, Till F.M., Diez-Fairen, Monica, Simon-Sanchez, Javier, Lleó, Alberto, Zetterberg, Henrik, Nygaard, Marianne, Blauwendraat, Cornelis, Savage, Jeanne E., Mengel-From, Jonas, Moreno-Grau, Sonia, Wagner, Michael, Fortea, Juan, Keogh, Michael J., Blennow, Kaj, Skoog, Ingmar, Friese, Manuel A., Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Tesi, Niccolo, Morris, Christopher M., Indakoetxea, Begoña, Collij, Lyduine E., Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W., van Berckel, Bart N.M., Alcolea, Daniel, Wiendl, Heinz, Strickland, Samantha L., Pastor, Pau, Rodríguez Rodríguez, Eloy, Mead, S., Synofzik, M., van Swieten, J. C., Leber, I., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B.J., Dobson-Stone, C., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Blesa, R., Landqvist Waldö, M., Nilsson, K., Nilsson, C., Mackenzie, I. R.A., Hsiung, G. Y.R., Mann, D. M.A., Grafman, J., Morris, C. M., Attems, J., Griffiths, T. D., McKeith, I. G., Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C.M., Uphill, J., Collinge, J., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., van der Zee, J., Van Broeckhoven, C., Cappa, S. F., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Baker, M., Josephs, K. A., Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., Dopper, E. G.P., Seelaar, H., Logroscino, G., Capozzo, R., Novelli, V., Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H. H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Boeve, Bradley F., Petersen, Ronald C., Ferman, Tanis J., van Gerpen, Jay A., Reinders, Marcel J.T., Uitti, Ryan J., Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, Boada, Mercè, Zettl, Uwe K., van Schoor, Natasja M., Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K., Ross, Owen A., Dickson, Dennis W., Graff-Radford, Neill R., Knopman, David, Rademakers, Rosa, Lemstra, Afina W., Pijnenburg, Yolande A.L., Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F., Hemmer, Bernhard, Huisman, Martijn A., Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A., Sørensen, Thorkild I.A., Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, Coppola, G., Varpetian, A., Foroud, T. M., Levey, A. I., Kukull, W. A., Mendez, M. F., Ringman, J., Chui, H., Cotman, C., DeCarli, C., Geschwind, D. H., Clarimón, Jordi, Christensen, Kaare, Ertekin-Taner, Nilüfer, Scholz, Sonja W., Ramirez, Alfredo, Ruiz, Agustín, Slagboom, Eline, van der Flier, Wiesje M., and Holstege, Henne
Abstract: The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.
Published: 2020
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35. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity (Acta Neuropathologica, (2019), 138, 2, (237-250), 10.1007/s00401-019-02026-8)

Author: van der Lee, S. J., Conway, O. J., Jansen, I., Carrasquillo, M. M., Kleineidam, L., van den Akker, E., Hernandez, I., van Eijk, K. R., Stringa, N., Chen, J. A., Zettergren, A., Andlauer, T. F. M., Diez-Fairen, M., Simon-Sanchez, J., Lleo, A., Zetterberg, H., Nygaard, M., Blauwendraat, C., Savage, J. E., Mengel-From, J., Moreno-Grau, S., Wagner, M., Fortea, J., Keogh, M. J., Blennow, K., Skoog, I., Friese, M. A., Pletnikova, O., Zulaica, M., Lage, C., de Rojas, I., Riedel-Heller, S., Illan-Gala, I., Wei, W., Jeune, B., Orellana, A., Then Bergh, F., Wang, X., Hulsman, M., Beker, N., Tesi, N., Morris, C. M., Indakoetxea, B., Collij, L. E., Scherer, M., Morenas-Rodriguez, E., Ironside, J. W., van Berckel, B. N. M., Alcolea, D., Wiendl, H., Strickland, S. L., Pastor, P., Rodriguez Rodriguez, E., Mead, S., Synofzik, M., van Swieten, J. C., Leber, I., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Schofield, P. R., Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Blesa, R., Landqvist Waldo, M., Nilsson, K., Nilsson, C., Mackenzie, I. R. A., Hsiung, G. -Y. R., Mann, D. M. A., Grafman, J., Attems, J., Griffiths, T. D., Mckeith, I. G., Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Razquin, C., Ortega-Cubero, S., Alonso, E., Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C. M., Uphill, J., Collinge, J., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., van der Zee, J., Van Broeckhoven, C., Cappa, S. F., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Baker, M., Josephs, K. A., Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., Dopper, E. G. P., Seelaar, H., Logroscino, G., Capozzo, R., Novelli, V., Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H. -H., Graff, C., Pasquier, F., Rollin, A., Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Boeve, B. F., Petersen, R. C., Ferman, T. J., van Gerpen, J. A., Reinders, M. J. T., Uitti, R. J., Tarraga, L., Maier, W., Dols-Icardo, O., Kawalia, A., Dalmasso, M. C., Boada, M., Zettl, U. K., van Schoor, N. M., Beekman, M., Allen, M., Masliah, E., de Munain, A. L., Pantelyat, A., Wszolek, Z. K., Ross, O. A., Dickson, D. W., Graff-Radford, N. R., Knopman, D., Rademakers, R., Lemstra, A. W., Pijnenburg, Y. A. L., Scheltens, P., Gasser, T., Chinnery, P. F., Hemmer, B., Huisman, M. A., Troncoso, J., Moreno, F., Nohr, E. A., Sorensen, T. I. A., Heutink, P., Sanchez-Juan, P., Posthuma, D., Coppola, G., Varpetian, A., Foroud, T. M., Levey, A. I., Kukull, W. A., Mendez, M. F., Ringman, J., Chui, H., Cotman, C., Decarli, C., Geschwind, D. H., Clarimon, J., Christensen, K., Ertekin-Taner, N., Scholz, S. W., Ramirez, A., Ruiz, A., Slagboom, E., van der Flier, W. M., Holstege, H., Neurology, Epidemiology and Data Science, Human genetics, APH - Societal Participation & Health, APH - Aging & Later Life, Amsterdam Neuroscience - Complex Trait Genetics, APH - Personalized Medicine, and APH - Methodology
Subjects: education
Abstract: The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.
Published: 2020

36. 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

37. Primary Dementia Syndromes and Parkinsonism

Author: Lemstra, A.W., primary, Seelaar, H., additional, and van Swieten, J.C., additional
Published: 2013
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38. Underlying genetic variation in familial frontotemporal dementia: sequencing of 198 patients

Author: Mol, M.O., Rooij, J.G.J. (Jeroen) van, Wong, T.H. (Tsz Hang), Melhem, S. (Shamiram), Verkerk, A., Kievit, A.J.A. (Anneke J.A.), Thornton, A.S. (Andrew), Rademakers, S. (Suzanne), Pottier, C. (Cyril), Donker Kaat, L. (Laura), Seelaar, H. (Harro), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Mol, M.O., Rooij, J.G.J. (Jeroen) van, Wong, T.H. (Tsz Hang), Melhem, S. (Shamiram), Verkerk, A., Kievit, A.J.A. (Anneke J.A.), Thornton, A.S. (Andrew), Rademakers, S. (Suzanne), Pottier, C. (Cyril), Donker Kaat, L. (Laura), Seelaar, H. (Harro), Swieten, J.C. (John) van, and Dopper, E.G.P. (Elise)
Abstract: Frontotemporal dementia (FTD) presents with a wide variability in clinical syndromes, genetic etiologies, and underlying pathologies. Despite the discovery of pathogenic variants in several genes, many familial cases remain unsolved. In a large FTD cohort of 198 familial patients, we aimed to determine the types and frequencies of variants in genes related to FTD. Pathogenic or likely pathogenic variants were revealed in 74 (37%) patients, including 4 novel variants. The repeat expansion in C9orf72 was most common (21%), followed by variants in MAPT (6%), GRN (4.5%), and TARDBP (3.5%). Other pathogenic variants were found in VCP, TBK1, PSEN1, and a novel homozygous variant in OPTN. Furthermore, we identified 15 variants of uncertain significance, including a promising variant in TUBA4A and a frameshift in VCP, for which additional research is needed to confirm pathogenicity. The patients without identified genetic cause demonstrated a wide clinical and pathological variety. Our study contributes to the clinical characterization of the genetic subtypes and confirms the value of whole-exome sequencing in identifying novel genetic variants.
Published: 2020
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39. Somatic TARDBP variants as a cause of semantic dementia

Author: Rooij, J.G.J. (Jeroen) van, Mol, M.O., Melhem, S. (Shamiram), van der Wal, P. (Pelle), Arp, P.P. (Pascal), Paron, F. (Francesca), Donker Kaat, L. (Laura), Seelaar, H. (Harro), Miedema, S.S.M. (Suzanne S M), Oshima, T. (Takuya), Eggen, B.J.L. (Bart J L), Uitterlinden, A.G. (André), van Meurs, J. (Joyce), Kesteren, R.E. (Ronald) van, Smit, A.B. (August), Buratti, E. (Emanuele), Swieten, J.C. (John) van, Rooij, J.G.J. (Jeroen) van, Mol, M.O., Melhem, S. (Shamiram), van der Wal, P. (Pelle), Arp, P.P. (Pascal), Paron, F. (Francesca), Donker Kaat, L. (Laura), Seelaar, H. (Harro), Miedema, S.S.M. (Suzanne S M), Oshima, T. (Takuya), Eggen, B.J.L. (Bart J L), Uitterlinden, A.G. (André), van Meurs, J. (Joyce), Kesteren, R.E. (Ronald) van, Smit, A.B. (August), Buratti, E. (Emanuele), and Swieten, J.C. (John) van
Abstract: The aetiology of late-onset neurodegenerative diseases is largely unknown. Here we investigated whether de novo somatic variants for semantic dementia can be detected, thereby arguing for a more general role of somatic variants in
Published: 2020
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40. Unravelling the clinical spectrum and the role of repeat length in C9ORF72 repeat expansions

Author: Ende, E.L. (Emma) van der, Jackson, J.L. (Jazmyne L.), White, A. (Adrianna), Seelaar, H. (Harro), Van Blitterswijk, M. (Marka), Swieten, J.C. (John) van, Ende, E.L. (Emma) van der, Jackson, J.L. (Jazmyne L.), White, A. (Adrianna), Seelaar, H. (Harro), Van Blitterswijk, M. (Marka), and Swieten, J.C. (John) van
Abstract: Since the discovery of the C9orf72 repeat expansion as the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis, it has increasingly been associated with a wider spectrum of phenotypes, including other types of dementia, movement disorders, psychiatric symptoms and slowly progressive FTD. Prompt recognition of patients with C9orf72-associated diseases is essential in light of upcoming clinical trials. The striking clinical heterogeneity associated with C9orf72 repeat expansions remains largely unexplained. In contrast to other repeat expansion disorders, evidence for an effect of repeat length on phenotype is inconclusive. Patients with C9orf72-associated diseases typically have very long repeat expansions, containing hundreds to thousands of GGGGCC-repeats, but smaller expansions might also have clinical significance. The exact threshold at which repeat expansions lead to neurodegeneration is unknown, and discordant cut-offs between laboratories pose a challenge for genetic counselling. Accurate and large-scale measurement of repeat expansions has been severely hindered by technical difficulties in sizing long expansions and by variable repeat lengths across and within tissues. Novel long-read sequencing approaches have produced promising results and open up avenues to further investigate this enthralling repeat expansion, elucidating whether its length, purity, and methylation pattern might modulate clinical features of C9orf72-related diseases.
Published: 2020
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41. Distinctive pattern of temporal atrophy in patients with frontotemporal dementia and the I383V variant in TARDBP

Author: Mol, M.O., Nijmeijer, S.W.R. (Sebastiaan W.R.), Rooij, J.G.J. (Jeroen) van, Van Spaendonk, R.M.L. (Resie M. L.), Pijnenburg, Y.A.L. (Yolande), Lee, S.J. (Sven) van der, Thornton, A.S. (Andrew), Donker Kaat, L. (Laura), Rozemuller, A.J.M. (Annemieke), Janse Van Mantgem, M.R. (Mark R.), Rheenen, W. (Wouter) van, Estrada Gil, K. (Karol), Veldink, J.H. (Jan), Hennekam, R.C.M. (Raoul), Vernooij, M.W. (Meike), Swieten, J.C. (John) van, Cohn-Hokke, P.E. (P.), Seelaar, H. (Harro), Dopper, E.G.P. (Elise), Mol, M.O., Nijmeijer, S.W.R. (Sebastiaan W.R.), Rooij, J.G.J. (Jeroen) van, Van Spaendonk, R.M.L. (Resie M. L.), Pijnenburg, Y.A.L. (Yolande), Lee, S.J. (Sven) van der, Thornton, A.S. (Andrew), Donker Kaat, L. (Laura), Rozemuller, A.J.M. (Annemieke), Janse Van Mantgem, M.R. (Mark R.), Rheenen, W. (Wouter) van, Estrada Gil, K. (Karol), Veldink, J.H. (Jan), Hennekam, R.C.M. (Raoul), Vernooij, M.W. (Meike), Swieten, J.C. (John) van, Cohn-Hokke, P.E. (P.), Seelaar, H. (Harro), and Dopper, E.G.P. (Elise)
Abstract: Introduction Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are closely related disorders, linked pathologically and ge
Published: 2020
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42. Differences in Discriminability and Response Bias on Rey Auditory Verbal Learning Test Delayed Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease

Author: Berg, E. (Esther) van den, Poos, J.M. (Jackie), Jiskoot, L.C. (Lize), Heijnen, L.M., Franzen, S. (Sanne), Steketee, R.M.E., Meijboom, R., Jong, F.J. (Fransina) de, Seelaar, H. (Harro), Swieten, J.C. (John) van, Papma, J.M. (Janne), Berg, E. (Esther) van den, Poos, J.M. (Jackie), Jiskoot, L.C. (Lize), Heijnen, L.M., Franzen, S. (Sanne), Steketee, R.M.E., Meijboom, R., Jong, F.J. (Fransina) de, Seelaar, H. (Harro), Swieten, J.C. (John) van, and Papma, J.M. (Janne)
Abstract: Objective: Episodic memory is impaired in Alzheimer’s disease (AD) dementia but thought to be relatively spared in behavioral variant frontotemporal dementia (bvFTD). This view is challenged by evidence of memory impairment in bvFTD. This study investigated differences in recognition memory performance between bvFTD and AD. Method: We performed a retrospective analysis on the recognition trial of the Rey Auditory Verbal Learning Test in patients with bvFTD (n = 85), AD (n = 55), and control participants (n = 59). Age- and education-adjusted betweengroup analysis was performed on the total score and indices of discriminative ability and response bias. Correlations between recognition and measures of memory, language, executive functioning, and construction were examined. Results: Patients with AD had a significantly lower total recognition score than patients with bvFTD (control 28.8 ± 1.5; bvFTD 24.8 ± 4.5; AD 23.4 ± 3.6, p < .01). Both bvFTD and AD had worse discriminative ability than controls (A’ control 0.96 ± 0.03; bvFTD 0.87 ± 0.03; AD 0.84 ± 0.10, p < .01), but there was no difference in response
Published: 2020
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43. Frontotemporal Dementia: Correlations Between Psychiatric Symptoms and Pathology

Author: Scarioni, M., Gami-Patel, P., Timar, Y., Seelaar, H. (Harro), Swieten, J.C. (John) van, Rozemuller, AJ, Dols, A., Scarpini, E. (Elio), Galimberti, D. (Daniela), Bank, N.B., Hoozemans, J.J., Pijnenburg, YA, Dijkstra, A.A. (Anke), Scarioni, M., Gami-Patel, P., Timar, Y., Seelaar, H. (Harro), Swieten, J.C. (John) van, Rozemuller, AJ, Dols, A., Scarpini, E. (Elio), Galimberti, D. (Daniela), Bank, N.B., Hoozemans, J.J., Pijnenburg, YA, and Dijkstra, A.A. (Anke)
Abstract: Objective: The pathology of frontotemporal dementia, termed frontotemporal lobar degeneration (FTLD), is characterized by distinct molecular classes of aggregated proteins, the most common being TAR DNA-binding protein-43 (TDP43), tau, and fused in sarcoma (FUS). With a few exceptions, it is currently not possible to predict the underlying pathology based on the clinical syndrome. In this study, we set out to investigate the relationship between pathological and clinical presentation at single symptom level, including neuropsychiatric features. Methods: The presence or absence of symptoms from the current clinical guidelines, together with neuropsychiatric features, such as hallucinations and delusions, were scored and compared across pathological groups in a cohort of 150 brain donors. Results: Our cohort consisted of 68.6% FTLD donors (35.3% TDP-43, 28% tau, and 5.3% FUS) and 31.3% non-FTLD donors with a clinical diagnosis of frontotemporal dementia and a different pathological substrate, such as Alzheimer’s disease (23%). The presence of hyperorality points to FTLD rather than non-FTLD pathology (p < 0.001). Within the FTLD group, hallucinations in the initial years of the disease were related to TDP-43 pathology (p = 0.02), including but not limited to chromosome 9 open reading frame 72 (C9orf72) repeat expansion carriers. The presence of perseverative or compulsive behavior was more common in the TDP-B and TDP-C histotypes (p = 0.002). Interpretation: Our findings indicate that neuropsychiatric features are common in FTLD and form an important indicator of underlying pathology. In order to allow better inclusion of patients in targeted molecular trials, the routine ev
Published: 2020
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44. Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

Author: Gao, Y. (Yixin), Wang, T. (Ting), Yu, X. (Xinghao), Ferrari, R. (Raffaele), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Brooks, W.S. (William S.), Schofield, P.R. (Peter R.), Halliday, G.M. (Glenda Margaret), Hodges, J.R. (John R.), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (Elizabeth), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (A.), Boada, M. (Mercè), Borroni, B. (Barbara), Padovani, A. (Alessandro), Crane, L.M.A., Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (Roberta), Forloni, G. (Gianluigi), Albani, D. (Diego), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (Elio), Clarimón, J. (Jordi), Lleo, A. (Alberto), Blesa, R. (Rafael), Waldö, M.L. (Maria Landqvist), Nilsson, K. (Karin), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.-Y.R. (Ging-Yuek R.), Mann, D.M.A. (David M. A.), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.J. (Alan J.), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (Michael C.), Pastor, P. (Pau), Razquin, C. (Cristina), Ortega-Cubero, S. (Sara), Alonso, E. (Elena), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), George-Hyslop, P.S. (Peter St), Rossi, G. (Giacomina), Tagliavini, F. (Fabrizio), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (John), Mead, S. (Simon), Danek, A. (Adrian), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (John Q.), Zee, J. (Jill) van der, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Leber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A. (Alexis), Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (Jørgen E.), Hjermind, L.E. (Lena), Riemenschneider, M. (Matthias), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (Wei), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H.R. (Huw R.), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (Ronald C.), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley F.), Parisi, J.E. (Joseph), Seeley, W.W. (William W.), Miller, B.L. (Bruce L.), Karydas, A.M. (Anna M.), Rosen, H. (Howard), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (Harro), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, M. (Massimo), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, C. (Caroline), Pasquier, F. (Florence), Rollin, A. (Adeline), Deramecourt, V. (Vincent), Lebouvier, T. (Thibaud), Kapogiannis, D. (Dimitrios), Ferrucci, L. (Luigi), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Hardy, J. (John), Momeni, P. (Parastoo), Zhao, H. (Huashuo), Zeng, P. (Ping), Gao, Y. (Yixin), Wang, T. (Ting), Yu, X. (Xinghao), Ferrari, R. (Raffaele), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Brooks, W.S. (William S.), Schofield, P.R. (Peter R.), Halliday, G.M. (Glenda Margaret), Hodges, J.R. (John R.), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (Elizabeth), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (A.), Boada, M. (Mercè), Borroni, B. (Barbara), Padovani, A. (Alessandro), Crane, L.M.A., Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (Roberta), Forloni, G. (Gianluigi), Albani, D. (Diego), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (Elio), Clarimón, J. (Jordi), Lleo, A. (Alberto), Blesa, R. (Rafael), Waldö, M.L. (Maria Landqvist), Nilsson, K. (Karin), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.-Y.R. (Ging-Yuek R.), Mann, D.M.A. (David M. A.), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.J. (Alan J.), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (Michael C.), Pastor, P. (Pau), Razquin, C. (Cristina), Ortega-Cubero, S. (Sara), Alonso, E. (Elena), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), George-Hyslop, P.S. (Peter St), Rossi, G. (Giacomina), Tagliavini, F. (Fabrizio), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (John), Mead, S. (Simon), Danek, A. (Adrian), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (John Q.), Zee, J. (Jill) van der, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Leber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A. (Alexis), Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (Jørgen E.), Hjermind, L.E. (Lena), Riemenschneider, M. (Matthias), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (Wei), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H.R. (Huw R.), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (Ronald C.), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley F.), Parisi, J.E. (Joseph), Seeley, W.W. (William W.), Miller, B.L. (Bruce L.), Karydas, A.M. (Anna M.), Rosen, H. (Howard), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (Harro), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, M. (Massimo), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, C. (Caroline), Pasquier, F. (Florence), Rollin, A. (Adeline), Deramecourt, V. (Vincent), Lebouvier, T. (Thibaud), Kapogiannis, D. (Dimitrios), Ferrucci, L. (Luigi), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Hardy, J. (John), Momeni, P. (Parastoo), Zhao, H. (Huashuo), and Zeng, P. (Ping)
Abstract: We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population.
Published: 2020
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45. Correction to: Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

Author: Poos, J.M. (Jackie), Jiskoot, L.C. (Lize), Leijdersdorff, S.M.J. (Sophie), Seelaar, H. (Harro), Panman, J.L. (Jessica), Ende, E.L. (Emma) van der, Mol, M.O., Meeter, L.H.H. (Lieke), Pijnenburg, Y.A.L. (Yolande), Donker Kaat, L. (Laura), De Jong, F.J. (Frank J.), Swieten, J.C. (John) van, Papma, J.M. (Janne), Berg, E. (Esther) van den, Poos, J.M. (Jackie), Jiskoot, L.C. (Lize), Leijdersdorff, S.M.J. (Sophie), Seelaar, H. (Harro), Panman, J.L. (Jessica), Ende, E.L. (Emma) van der, Mol, M.O., Meeter, L.H.H. (Lieke), Pijnenburg, Y.A.L. (Yolande), Donker Kaat, L. (Laura), De Jong, F.J. (Frank J.), Swieten, J.C. (John) van, Papma, J.M. (Janne), and Berg, E. (Esther) van den
Abstract: The original version of this article unfortunately contained a mistake. The presentation of Table 1 was incorrect. The original article has been corrected. The corrected Table 1 is given below. (Table presented.).
Published: 2020
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46. Cognitive profiles discriminate between genetic variants of behavioral frontotemporal dementia

Author: Poos, J.M. (Jackie), Jiskoot, L.C. (Lize), Leijdersdorff, S.M.J. (Sophie), Seelaar, H. (Harro), Panman, J.L. (Jessica), Ende, E.L. (Emma) van der, Mol, M.O., Meeter, L.H.H. (Lieke), Pijnenburg, Y.A.L. (Yolande), Donker Kaat, L. (Laura), De Jong, F.J. (Frank J.), Swieten, J.C. (John) van, Papma, J.M. (Janne), Berg, E. (Esther) van den, Poos, J.M. (Jackie), Jiskoot, L.C. (Lize), Leijdersdorff, S.M.J. (Sophie), Seelaar, H. (Harro), Panman, J.L. (Jessica), Ende, E.L. (Emma) van der, Mol, M.O., Meeter, L.H.H. (Lieke), Pijnenburg, Y.A.L. (Yolande), Donker Kaat, L. (Laura), De Jong, F.J. (Frank J.), Swieten, J.C. (John) van, Papma, J.M. (Janne), and Berg, E. (Esther) van den
Abstract: Introduction: Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations. Methods: We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described
Published: 2020
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47. 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

48. Differences in Discriminability and Response Bias on Rey Auditory Verbal Learning Test Delayed Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer’s Disease

Author: van den Berg, E., primary, Poos, J.M., additional, Jiskoot, L.C., additional, Heijnen, L.M., additional, Franzen, S., additional, Steketee, R.M.E., additional, Meijboom, R., additional, de Jong, F.J., additional, Seelaar, H., additional, van Swieten, J.C., additional, and Papma, J.M., additional
Published: 2020
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49. Exploring Abstract Semantic Associations in the Frontotemporal Dementia Spectrum in a Dutch Population.

Author: Poos, J M, Berg, E van den, Visch-Brink, E, Eikelboom, W S, Franzen, S, Hemmen, J van, Pijnenburg, Y A L, Satoer, D, Dopper, E G P, Swieten, J C van, Papma, J M, Seelaar, H, and Jiskoot, L C
Subjects: FRONTOTEMPORAL dementia, NEUROPSYCHOLOGICAL tests, CONCRETE testing, LANGUAGE ability testing, DIFFERENTIAL diagnosis
Abstract: Objective To investigate the differential ability of the "Test Relaties Abstracte Concepten" (TRACE), a Dutch test for abstract semantic knowledge, in frontotemporal dementia (FTD). Methods The TRACE was administered in patients with behavioral variant FTD (bvFTD; n = 16), nonfluent variant (nfvPPA; n = 10), logopenic variant (lvPPA; n = 10), and semantic variant primary progressive aphasia (svPPA; n = 9), and controls (n = 59). We examined group differences, performed correlational analyses with other neuropsychological tests and investigated discriminative ability. We compared the TRACE with a semantic association test for concrete stimuli (SAT). Results All patient groups, except nfvPPA, performed worse on the TRACE than controls (p < .01). svPPA patients performed worse than the other patient groups (p < .05). The TRACE discriminated well between patient groups, except nfvPPA, versus controls (all p < .01) and between svPPA versus other patient groups with high sensitivity (75–100%) and specificity (86%–92%). In bvFTD and nfvPPA the TRACE correlated with language tests (ρ > 0.6), whereas in svPPA the concrete task correlated (ρ ≥ 0.75) with language tests. Patients with bvFTD, nfvPPA and lvPPA performed lower on the TRACE than the SAT (p < .05), whereas patients with svPPA were equally impaired on both tasks (p = .2). Discussion We demonstrated impaired abstract semantic knowledge in patients with bvFTD, lvPPA, and svPPA, but not nfvPPA, with svPPA patients performing worse than the other subtypes. The TRACE was a good classifier between each patient group versus controls and between svPPA versus other patient groups. This highlights the value of incorporating semantic tests with abstract stimuli into standard neuropsychological assessment for early differential diagnosis of FTD subtypes. [ABSTRACT FROM AUTHOR]
Published: 2022
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50. Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

Author: van der Lee, Sven J, Conway, Olivia J, Zettergren, Anna, Christensen, Kaare, Ertekin-Taner, Nilüfer, Scholz, Sonja W, Ramirez, Alfredo, Ruiz, Agustín, Slagboom, Eline, van der Flier, Wiesje M, Holstege, Henne, Mead, S., Synofzik, M., Andlauer, Till F M, van Swieten, J. C., Leber, I., Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Schofield, P. R., Diez-Fairen, Monica, Halliday, G. M., Hodges, J. R., Piguet, O., Bartley, L., Thompson, E., Borroni, B., Padovani, A., Cruchaga, C., Cairns, N. J., Benussi, L., Simon-Sanchez, Javier, Binetti, G., Ghidoni, R., Forloni, G., Albani, D., Galimberti, D., Fenoglio, C., Serpente, M., Scarpini, E., Blesa, R., Landqvist Waldö, M., Lleó, Alberto, Nilsson, K., Nilsson, C., Mackenzie, I. R. A., Hsiung, G-Y R, Mann, D. M. A., Grafman, J., Morris, C. M., Attems, J., Griffiths, T. D., McKeith, I. G., Zetterberg, Henrik, Thomas, A. J., Pietrini, P., Huey, E. D., Wassermann, E. M., Baborie, A., Jaros, E., Tierney, M. C., Razquin, C., Ortega-Cubero, S., Alonso, E., Nygaard, Marianne, Perneczky, R., Diehl-Schmid, J., Alexopoulos, P., Kurz, A., Rainero, I., Rubino, E., Pinessi, L., Rogaeva, E., St George-Hyslop, P., Rossi, G., Blauwendraat, Cornelis, Tagliavini, F., Giaccone, G., Rowe, J. B., Schlachetzki, J. C. M., Uphill, J., Collinge, J., Danek, A., Van Deerlin, V. M., Grossman, M., Trojanowski, J. Q., Savage, Jeanne E, van der Zee, J., Van Broeckhoven, C., Cappa, S. F., Hannequin, D., Golfier, V., Vercelletto, M., Brice, A., Nacmias, B., Sorbi, S., Bagnoli, S., Mengel-From, Jonas, Piaceri, I., Nielsen, J. E., Hjermind, L. E., Riemenschneider, M., Mayhaus, M., Ibach, B., Gasparoni, G., Pichler, S., Gu, W., Rossor, M. N., Jansen, Iris, Moreno-Grau, Sonia, Fox, N. C., Warren, J. D., Spillantini, M. G., Morris, H. R., Rizzu, P., Snowden, J. S., Rollinson, S., Richardson, A., Gerhard, A., Bruni, A. C., Wagner, Michael, Maletta, R., Frangipane, F., Cupidi, C., Bernardi, L., Anfossi, M., Gallo, M., Conidi, M. E., Smirne, N., Baker, M., Josephs, K. A., Fortea, Juan, Parisi, J. E., Seeley, W. W., Miller, B. L., Karydas, A. M., Rosen, H., Dopper, E. G. P., Seelaar, H., Logroscino, G., Capozzo, R., Novelli, V., Keogh, Michael J, Puca, A. A., Franceschi, M., Postiglione, A., Milan, G., Sorrentino, P., Kristiansen, M., Chiang, H-H, Graff, C., Pasquier, F., Rollin, A., Blennow, Kaj, Deramecourt, V., Lebouvier, T., Kapogiannis, D., Ferrucci, L., Pickering-Brown, S., Singleton, A. B., Hardy, J., Momeni, P., Coppola, G., Skoog, Ingmar, Varpetian, A., Foroud, T. M., Levey, A. I., Kukull, W. A., Mendez, M. F., Ringman, J., Chui, H., Cotman, C., DeCarli, C., Friese, Manuel A, Geschwind, D. H., Pletnikova, Olga, Zulaica, Miren, Lage, Carmen, Carrasquillo, Minerva M, de Rojas, Itziar, Riedel-Heller, Steffi, Illán-Gala, Ignacio, Wei, Wei, Jeune, Bernard, Orellana, Adelina, Then Bergh, Florian, Wang, Xue, Hulsman, Marc, Beker, Nina, Kleineidam, Luca, Tesi, Niccolo, Morris, Christopher M, Indakoetxea, Begoña, Collij, Lyduine E, Scherer, Martin, Morenas-Rodríguez, Estrella, Ironside, James W, van Berckel, Bart N M, Alcolea, Daniel, Wiendl, Heinz, van den Akker, Erik, Strickland, Samantha L, Pastor, Pau, Rodríguez Rodríguez, Eloy, DESGESCO, EADB, IFGC, IPDGC, RiMod-FTD, Bank, Netherlands Brain, Boeve, Bradley F, Hernández, Isabel, Petersen, Ronald C, Ferman, Tanis J, van Gerpen, Jay A, Reinders, Marcel J T, Uitti, Ryan J, Tárraga, Lluís, Maier, Wolfgang, Dols-Icardo, Oriol, Kawalia, Amit, Dalmasso, Maria Carolina, van Eijk, Kristel R, Boada, Mercè, Zettl, Uwe K, van Schoor, Natasja M, Beekman, Marian, Allen, Mariet, Masliah, Eliezer, de Munain, Adolfo López, Pantelyat, Alexander, Wszolek, Zbigniew K, Ross, Owen A, Stringa, Najada, Dickson, Dennis W, Graff-Radford, Neill R, Knopman, David, Rademakers, Rosa, Lemstra, Afina W, Pijnenburg, Yolande A L, Scheltens, Philip, Gasser, Thomas, Chinnery, Patrick F, Hemmer, Bernhard, Chen, Jason A, Huisman, Martijn A, Troncoso, Juan, Moreno, Fermin, Nohr, Ellen A, Sørensen, Thorkild I A, Heutink, Peter, Sánchez-Juan, Pascual, Posthuma, Danielle, GIFT, and Clarimón, Jordi
Subjects: 0301 basic medicine, Dementia with Lewy bodies, Disease, Bioinformatics, Neurodegenerative disease, 0302 clinical medicine, Missense mutation, media_common, 2. Zero hunger, Longevity, Brain, Parkinson Disease, Phospholipase C Gamma 2, Biobank, 3. Good health, ddc, Frontotemporal Dementia, Microglia, Alzheimer's disease, Alzheimer’s disease, Amyotrophic lateral sclerosis, Frontotemporal dementia, Multiple sclerosis, PLCG2, Parkinson’s disease, Progressive supranuclear palsy, Lewy Body Disease, Risk, Multiple Sclerosis, media_common.quotation_subject, education, Neuroimaging, Genomics, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Alzheimer Disease, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Alleles, Phospholipase C gamma, business.industry, Amyotrophic Lateral Sclerosis, Correction, medicine.disease, 030104 developmental biology, Mutation, Dementia, Neurology (clinical), business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target. The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.
Published: 2019
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