Publicação
Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
| Resumo: | 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. |
|---|---|
| Autores principais: | Bussy, Aurélie |
| Outros Autores: | Levy, Jake P.; Best, Tristin; Patel, Raihaan; Cupo, Lani; Van Langenhove, Tim; Nielsen, Jørgen E.; Pijnenburg, Yolande; Waldö, Maria Landqvist; Remes, Anne M.; Schroeter, Matthias L.; Santana, Isabel; Pasquier, Florence; Otto, Markus; Danek, Adrian; Levin, Johannes; Le Ber, Isabelle; Vandenberghe, Rik; Synofzik, Matthis; Moreno, Fermin; De Mendonça, Alexandre; Sanchez‐Valle, Raquel; Laforce, Robert; Langheinrich, Tobias; Gerhard, Alexander; Graff, Caroline; Butler, Chris R.; Sorbi, Sandro; Jiskoot, Lize; Seelaar, Harro; van Swieten, John C.; Finger, Elizabeth; Tartaglia, Maria Carmela; Masellis, Mario; Tiraboschi, Pietro; Galimberti, Daniela; Borroni, Barbara; Rowe, James B.; Bocchetta, Martina; Rohrer, Jonathan D.; Devenyi, Gabriel A.; Chakravarty, M. Mallar; Ducharme, Simon |
| Assunto: | Frontotemporal dementia Genetics Magnetic resonance imaging Neuropsychiatry |
| Ano: | 2023 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866810929245585408 |
|---|---|
| author | Bussy, Aurélie |
| author2 | Levy, Jake P. Best, Tristin Patel, Raihaan Cupo, Lani Van Langenhove, Tim Nielsen, Jørgen E. Pijnenburg, Yolande Waldö, Maria Landqvist Remes, Anne M. Schroeter, Matthias L. Santana, Isabel Pasquier, Florence Otto, Markus Danek, Adrian Levin, Johannes Le Ber, Isabelle Vandenberghe, Rik Synofzik, Matthis Moreno, Fermin De Mendonça, Alexandre Sanchez‐Valle, Raquel Laforce, Robert Langheinrich, Tobias Gerhard, Alexander Graff, Caroline Butler, Chris R. Sorbi, Sandro Jiskoot, Lize Seelaar, Harro van Swieten, John C. Finger, Elizabeth Tartaglia, Maria Carmela Masellis, Mario Tiraboschi, Pietro Galimberti, Daniela Borroni, Barbara Rowe, James B. Bocchetta, Martina Rohrer, Jonathan D. Devenyi, Gabriel A. Chakravarty, M. Mallar Ducharme, Simon |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_facet | Bussy, Aurélie Levy, Jake P. Best, Tristin Patel, Raihaan Cupo, Lani Van Langenhove, Tim Nielsen, Jørgen E. Pijnenburg, Yolande Waldö, Maria Landqvist Remes, Anne M. Schroeter, Matthias L. Santana, Isabel Pasquier, Florence Otto, Markus Danek, Adrian Levin, Johannes Le Ber, Isabelle Vandenberghe, Rik Synofzik, Matthis Moreno, Fermin De Mendonça, Alexandre Sanchez‐Valle, Raquel Laforce, Robert Langheinrich, Tobias Gerhard, Alexander Graff, Caroline Butler, Chris R. Sorbi, Sandro Jiskoot, Lize Seelaar, Harro van Swieten, John C. Finger, Elizabeth Tartaglia, Maria Carmela Masellis, Mario Tiraboschi, Pietro Galimberti, Daniela Borroni, Barbara Rowe, James B. Bocchetta, Martina Rohrer, Jonathan D. Devenyi, Gabriel A. Chakravarty, M. Mallar Ducharme, Simon |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Bussy, Aurélie\"},{\"Person.name\":\"Levy, Jake P.\"},{\"Person.name\":\"Best, Tristin\"},{\"Person.name\":\"Patel, Raihaan\"},{\"Person.name\":\"Cupo, Lani\"},{\"Person.name\":\"Van Langenhove, Tim\"},{\"Person.name\":\"Nielsen, Jørgen E.\"},{\"Person.name\":\"Pijnenburg, Yolande\"},{\"Person.name\":\"Waldö, Maria Landqvist\"},{\"Person.name\":\"Remes, Anne M.\"},{\"Person.name\":\"Schroeter, Matthias L.\"},{\"Person.name\":\"Santana, Isabel\"},{\"Person.name\":\"Pasquier, Florence\"},{\"Person.name\":\"Otto, Markus\"},{\"Person.name\":\"Danek, Adrian\"},{\"Person.name\":\"Levin, Johannes\"},{\"Person.name\":\"Le Ber, Isabelle\"},{\"Person.name\":\"Vandenberghe, Rik\"},{\"Person.name\":\"Synofzik, Matthis\"},{\"Person.name\":\"Moreno, Fermin\"},{\"Person.name\":\"De Mendonça, Alexandre\",\"Person.identifier.orcid\":\"0000-0002-0488-1453\"},{\"Person.name\":\"Sanchez‐Valle, Raquel\"},{\"Person.name\":\"Laforce, Robert\"},{\"Person.name\":\"Langheinrich, Tobias\"},{\"Person.name\":\"Gerhard, Alexander\"},{\"Person.name\":\"Graff, Caroline\"},{\"Person.name\":\"Butler, Chris R.\"},{\"Person.name\":\"Sorbi, Sandro\"},{\"Person.name\":\"Jiskoot, Lize\"},{\"Person.name\":\"Seelaar, Harro\"},{\"Person.name\":\"van Swieten, John C.\"},{\"Person.name\":\"Finger, Elizabeth\"},{\"Person.name\":\"Tartaglia, Maria Carmela\"},{\"Person.name\":\"Masellis, Mario\"},{\"Person.name\":\"Tiraboschi, Pietro\"},{\"Person.name\":\"Galimberti, Daniela\"},{\"Person.name\":\"Borroni, Barbara\"},{\"Person.name\":\"Rowe, James B.\"},{\"Person.name\":\"Bocchetta, Martina\"},{\"Person.name\":\"Rohrer, Jonathan D.\"},{\"Person.name\":\"Devenyi, Gabriel A.\"},{\"Person.name\":\"Chakravarty, M. Mallar\"},{\"Person.name\":\"Ducharme, Simon\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Bussy, Aurélie Levy, Jake P. Best, Tristin Patel, Raihaan Cupo, Lani Van Langenhove, Tim Nielsen, Jørgen E. Pijnenburg, Yolande Waldö, Maria Landqvist Remes, Anne M. Schroeter, Matthias L. Santana, Isabel Pasquier, Florence Otto, Markus Danek, Adrian Levin, Johannes Le Ber, Isabelle Vandenberghe, Rik Synofzik, Matthis Moreno, Fermin De Mendonça, Alexandre Sanchez‐Valle, Raquel Laforce, Robert Langheinrich, Tobias Gerhard, Alexander Graff, Caroline Butler, Chris R. Sorbi, Sandro Jiskoot, Lize Seelaar, Harro van Swieten, John C. Finger, Elizabeth Tartaglia, Maria Carmela Masellis, Mario Tiraboschi, Pietro Galimberti, Daniela Borroni, Barbara Rowe, James B. Bocchetta, Martina Rohrer, Jonathan D. Devenyi, Gabriel A. Chakravarty, M. Mallar Ducharme, Simon |
| datacite.date.Accepted.fl_str_mv | 2023-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2023-03-14T14:21:30Z |
| datacite.date.embargoed.fl_str_mv | 2023-03-14T14:21:30Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Frontotemporal dementia Genetics Magnetic resonance imaging Neuropsychiatry |
| datacite.titles.title.fl_str_mv | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Bussy, Aurélie Levy, Jake P. Best, Tristin Patel, Raihaan Cupo, Lani Van Langenhove, Tim Nielsen, Jørgen E. Pijnenburg, Yolande Waldö, Maria Landqvist Remes, Anne M. Schroeter, Matthias L. Santana, Isabel Pasquier, Florence Otto, Markus Danek, Adrian Levin, Johannes Le Ber, Isabelle Vandenberghe, Rik Synofzik, Matthis Moreno, Fermin De Mendonça, Alexandre Sanchez‐Valle, Raquel Laforce, Robert Langheinrich, Tobias Gerhard, Alexander Graff, Caroline Butler, Chris R. Sorbi, Sandro Jiskoot, Lize Seelaar, Harro van Swieten, John C. Finger, Elizabeth Tartaglia, Maria Carmela Masellis, Mario Tiraboschi, Pietro Galimberti, Daniela Borroni, Barbara Rowe, James B. Bocchetta, Martina Rohrer, Jonathan D. Devenyi, Gabriel A. Chakravarty, M. Mallar Ducharme, Simon |
| dc.date.Accepted.fl_str_mv | 2023-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2023-03-14T14:21:30Z |
| dc.date.embargoed.fl_str_mv | 2023-03-14T14:21:30Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/56655 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Wiley |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Frontotemporal dementia Genetics Magnetic resonance imaging Neuropsychiatry |
| dc.title.fl_str_mv | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/f762bb27-9c47-4cb4-9ffd-a2287a7d0e93/download |
| id | ul_e155df86747ebd2a367d6033a862ff6c |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/56655 |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/56655 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Bussy, Aurélie Levy, Jake P. Best, Tristin Patel, Raihaan Cupo, Lani Van Langenhove, Tim Nielsen, Jørgen E. Pijnenburg, Yolande Waldö, Maria Landqvist Remes, Anne M. Schroeter, Matthias L. Santana, Isabel Pasquier, Florence Otto, Markus Danek, Adrian Levin, Johannes Le Ber, Isabelle Vandenberghe, Rik Synofzik, Matthis Moreno, Fermin De Mendonça, Alexandre De Mendonça, Alexandre https://www.ciencia-id.pt/1615-41B4-0848 1615-41B4-0848 http://orcid.org/0000-0002-0488-1453 0000-0002-0488-1453 Sanchez‐Valle, Raquel Laforce, Robert Langheinrich, Tobias Gerhard, Alexander Graff, Caroline Butler, Chris R. Sorbi, Sandro Jiskoot, Lize Seelaar, Harro van Swieten, John C. Finger, Elizabeth Tartaglia, Maria Carmela Masellis, Mario Tiraboschi, Pietro Galimberti, Daniela Borroni, Barbara Rowe, James B. Bocchetta, Martina Rohrer, Jonathan D. Devenyi, Gabriel A. Chakravarty, M. Mallar Ducharme, Simon |
| publishDate | 2023 |
| publisher.none.fl_str_mv | Wiley |
| reponame_str | Repositório da Universidade de Lisboa |
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| spelling | engWileypt_PTRecent 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.application/pdfpt_PTCerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementiaBussy, AurélieLevy, Jake P.Best, TristinPatel, RaihaanCupo, LaniVan Langenhove, TimNielsen, Jørgen E.Pijnenburg, YolandeWaldö, Maria LandqvistRemes, Anne M.Schroeter, Matthias L.Santana, IsabelPasquier, FlorenceOtto, MarkusDanek, AdrianLevin, JohannesLe Ber, IsabelleVandenberghe, RikSynofzik, MatthisMoreno, FerminPersonalDe Mendonça, AlexandreDSpacehttp://dspace.org/items/53ca3547-99ce-4b68-9330-7879a54c47b7DSpacehttp://dspace.org/items/53ca3547-99ce-4b68-9330-7879a54c47b7de MendonçaAlexandreCiência IDhttps://www.ciencia-id.pt1615-41B4-0848ORCIDhttp://orcid.org0000-0002-0488-1453Scopus Author IDhttps://www.scopus.com7003320823Scopus Author IDhttps://www.scopus.com55307490700Sanchez‐Valle, RaquelLaforce, RobertLangheinrich, TobiasGerhard, AlexanderGraff, CarolineButler, Chris R.Sorbi, SandroJiskoot, LizeSeelaar, Harrovan Swieten, John C.Finger, ElizabethTartaglia, Maria CarmelaMasellis, MarioTiraboschi, PietroGalimberti, DanielaBorroni, BarbaraRowe, James B.Bocchetta, MartinaRohrer, Jonathan D.Devenyi, Gabriel A.Chakravarty, M. MallarDucharme, SimonHostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptISSNIsPartOf1065-9471DOIIsPartOf10.1002/hbm.262202023-03-14T14:21:30Z20232023-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/56655http://purl.org/coar/access_right/c_abf2open accessFrontotemporal dementiaGeneticsMagnetic resonance imagingNeuropsychiatry11069069 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2023http://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/f762bb27-9c47-4cb4-9ffd-a2287a7d0e93/downloadHuman Brain Mapping |
| spellingShingle | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia Bussy, Aurélie Frontotemporal dementia Genetics Magnetic resonance imaging Neuropsychiatry |
| status | SINGLETON |
| subject.fl_str_mv | Frontotemporal dementia Genetics Magnetic resonance imaging Neuropsychiatry |
| title | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia |
| title_full | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia |
| title_fullStr | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia |
| title_full_unstemmed | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia |
| title_short | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia |
| title_sort | Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia |
| topic | Frontotemporal dementia Genetics Magnetic resonance imaging Neuropsychiatry |
| topic_facet | Frontotemporal dementia Genetics Magnetic resonance imaging Neuropsychiatry |
| url | http://hdl.handle.net/10451/56655 |
| visible | 1 |