Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/45687 |
Resumo: | © 2021 Benussi A et al. JAMA Network Open. This is an open access article distributed under the terms of the CC-BY License. |
| id |
RCAP_9b7eae609c568bcf078ca227986be6f5 |
|---|---|
| oai_identifier_str |
oai:repositorio.ul.pt:10451/45687 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository_id_str |
7160 |
| spelling |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia© 2021 Benussi A et al. JAMA Network Open. This is an open access article distributed under the terms of the CC-BY License.Importance: Behavioral disturbances are core features of frontotemporal dementia (FTD); however, symptom progression across the course of disease is not well characterized in genetic FTD. Objective: To investigate behavioral symptom frequency and severity and their evolution and progression in different forms of genetic FTD. Design, setting, and participants: This longitudinal cohort study, the international Genetic FTD Initiative (GENFI), was conducted from January 30, 2012, to May 31, 2019, at 23 multicenter specialist tertiary FTD research clinics in the United Kingdom, the Netherlands, Belgium, France, Spain, Portugal, Italy, Germany, Sweden, Finland, and Canada. Participants included a consecutive sample of 232 symptomatic FTD gene variation carriers comprising 115 with variations in C9orf72, 78 in GRN, and 39 in MAPT. A total of 101 carriers had at least 1 follow-up evaluation (for a total of 400 assessments). Gene variations were included only if considered pathogenetic. Main outcomes and measures: Behavioral and neuropsychiatric symptoms were assessed across disease duration and evaluated from symptom onset. Hierarchical generalized linear mixed models were used to model behavioral and neuropsychiatric measures as a function of disease duration and variation. Results: Of 232 patients with FTD, 115 (49.6%) had a C9orf72 expansion (median [interquartile range (IQR)] age at evaluation, 64.3 [57.5-69.7] years; 72 men [62.6%]; 115 White patients [100%]), 78 (33.6%) had a GRN variant (median [IQR] age, 63.4 [58.3-68.8] years; 40 women [51.3%]; 77 White patients [98.7%]), and 39 (16.8%) had a MAPT variant (median [IQR] age, 56.3 [49.9-62.4] years; 25 men [64.1%]; 37 White patients [94.9%]). All core behavioral symptoms, including disinhibition, apathy, loss of empathy, perseverative behavior, and hyperorality, were highly expressed in all gene variant carriers (>50% patients), with apathy being one of the most common and severe symptoms throughout the disease course (51.7%-100% of patients). Patients with MAPT variants showed the highest frequency and severity of most behavioral symptoms, particularly disinhibition (79.3%-100% of patients) and compulsive behavior (64.3%-100% of patients), compared with C9orf72 carriers (51.7%-95.8% of patients with disinhibition and 34.5%-75.0% with compulsive behavior) and GRN carriers (38.2%-100% with disinhibition and 20.6%-100% with compulsive behavior). Alongside behavioral symptoms, neuropsychiatric symptoms were very frequently reported in patients with genetic FTD: anxiety and depression were most common in GRN carriers (23.8%-100% of patients) and MAPT carriers (26.1%-77.8% of patients); hallucinations, particularly auditory and visual, were most common in C9orf72 carriers (10.3%-54.5% of patients). Most behavioral and neuropsychiatric symptoms increased in the early-intermediate phases and plateaued in the late stages of disease, except for depression, which steadily declined in C9orf72 carriers, and depression and anxiety, which surged only in the late stages in GRN carriers. Conclusions and relevance: This cohort study suggests that behavioral and neuropsychiatric disturbances differ between the common FTD gene variants and have different trajectories throughout the course of disease. These findings have crucial implications for counseling patients and caregivers and for the design of disease-modifying treatment trials in genetic FTD.This work is supported by the Joint Programme–Neurodegenerative Disease Research grant no. JPND2019-466-090 “GENFI-prox” (Drs Synofzik, van Swieten, Otto, Graff, Rohrer, and Borroni), the Centre d’Investigation Clinique grant no. ANR/DGOS PRTS 2015-2019 PREV-DEMALS (Dr Le Ber), the Centre pour l’Acquisition et le Traitement des Images platform grant no. ANR-10-IAIHU-06 (Dr Le Ber), the UK Medical Research Council grant no. MR/M023664/1 (Dr Rohrer), the Italian Ministry of Health grant no. 733051042 (Dr Galimberti), and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant no. MOP 327387 (Dr Masellis), a Canadian Institutes of Health Research operating grant.American Medical AssociationRepositório da Universidade de LisboaBenussi, AlbertoPremi, EnricoGazzina, StefanoBrattini, ChiaraBonomi, ElisaAlberici, AntonellaJiskoot, Lizevan Swieten, John CSanchez-Valle, RaquelMoreno, FerminLaforce, RobertGraff, CarolineSynofzik, MatthisGalimberti, DanielaMasellis, MarioTartaglia, CarmelaRowe, James BFinger, ElizabethVandenberghe, RikDe Mendonça, AlexandreTagliavini, FabrizioSantana, IsabelDucharme, SimonButler, Chris RGerhard, AlexanderLevin, JohannesDanek, AdrianOtto, MarkusFrisoni, GiovanniGhidoni, RobertaSorbi, SandroLe Ber, IsabellePasquier, FlorencePeakman, GeorgiaTodd, EmilyBocchetta, MartinaRohrer, Jonathan DBorroni, Barbara2021-01-07T11:39:17Z2021-01-042021-01-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/45687engJAMA Netw Open. 2021;4(1):e2030194.10.1001/jamanetworkopen.2020.301942574-3805info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:47:39Zoai:repositorio.ul.pt:10451/45687Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:58:03.063645Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia |
| title |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia |
| spellingShingle |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia Benussi, Alberto |
| title_short |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia |
| title_full |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia |
| title_fullStr |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia |
| title_full_unstemmed |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia |
| title_sort |
Progression of behavioral disturbances and neuropsychiatric symptoms in patients with genetic frontotemporal dementia |
| author |
Benussi, Alberto |
| author_facet |
Benussi, Alberto Premi, Enrico Gazzina, Stefano Brattini, Chiara Bonomi, Elisa Alberici, Antonella Jiskoot, Lize van Swieten, John C Sanchez-Valle, Raquel Moreno, Fermin Laforce, Robert Graff, Caroline Synofzik, Matthis Galimberti, Daniela Masellis, Mario Tartaglia, Carmela Rowe, James B Finger, Elizabeth Vandenberghe, Rik De Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Ducharme, Simon Butler, Chris R Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Frisoni, Giovanni Ghidoni, Roberta Sorbi, Sandro Le Ber, Isabelle Pasquier, Florence Peakman, Georgia Todd, Emily Bocchetta, Martina Rohrer, Jonathan D Borroni, Barbara |
| author_role |
author |
| author2 |
Premi, Enrico Gazzina, Stefano Brattini, Chiara Bonomi, Elisa Alberici, Antonella Jiskoot, Lize van Swieten, John C Sanchez-Valle, Raquel Moreno, Fermin Laforce, Robert Graff, Caroline Synofzik, Matthis Galimberti, Daniela Masellis, Mario Tartaglia, Carmela Rowe, James B Finger, Elizabeth Vandenberghe, Rik De Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Ducharme, Simon Butler, Chris R Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Frisoni, Giovanni Ghidoni, Roberta Sorbi, Sandro Le Ber, Isabelle Pasquier, Florence Peakman, Georgia Todd, Emily Bocchetta, Martina Rohrer, Jonathan D Borroni, Barbara |
| 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 |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Benussi, Alberto Premi, Enrico Gazzina, Stefano Brattini, Chiara Bonomi, Elisa Alberici, Antonella Jiskoot, Lize van Swieten, John C Sanchez-Valle, Raquel Moreno, Fermin Laforce, Robert Graff, Caroline Synofzik, Matthis Galimberti, Daniela Masellis, Mario Tartaglia, Carmela Rowe, James B Finger, Elizabeth Vandenberghe, Rik De Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Ducharme, Simon Butler, Chris R Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Frisoni, Giovanni Ghidoni, Roberta Sorbi, Sandro Le Ber, Isabelle Pasquier, Florence Peakman, Georgia Todd, Emily Bocchetta, Martina Rohrer, Jonathan D Borroni, Barbara |
| description |
© 2021 Benussi A et al. JAMA Network Open. This is an open access article distributed under the terms of the CC-BY License. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-01-07T11:39:17Z 2021-01-04 2021-01-04T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/45687 |
| url |
http://hdl.handle.net/10451/45687 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
JAMA Netw Open. 2021;4(1):e2030194. 10.1001/jamanetworkopen.2020.30194 2574-3805 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
American Medical Association |
| publisher.none.fl_str_mv |
American Medical Association |
| dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
| instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| repository.mail.fl_str_mv |
|
| _version_ |
1799134525784064000 |