Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort
| Main Author: | |
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| Publication Date: | 2022 |
| Other Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | http://hdl.handle.net/10451/55653 |
Summary: | Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology |
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Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohortCopyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of NeurologyBackground and objectives: Disease-modifying therapeutic trials for genetic frontotemporal dementia (FTD) are underway, but sensitive cognitive outcome measures are lacking. The aim of this study was to identify such cognitive tests in early stage FTD by investigating cognitive decline in a large cohort of genetic FTD pathogenic variant carriers and by investigating whether gene-specific differences are moderated by disease stage (asymptomatic, prodromal, and symptomatic). Methods: C9orf72, GRN, and MAPT pathogenic variant carriers as well as controls underwent a yearly neuropsychological assessment covering 8 cognitive domains as part of the Genetic FTD Initiative, a prospective multicenter cohort study. Pathogenic variant carriers were stratified according to disease stage using the global Clinical Dementia Rating (CDR) plus National Alzheimer's Coordinating Center (NACC) FTLD score (0, 0.5, or ≥1). Linear mixed-effects models were used to investigate differences between genetic groups and disease stages as well as the 3-way interaction between time, genetic group, and disease stage. Results: A total of 207 C9orf72, 206 GRN, and 86 MAPT pathogenic variant carriers and 255 controls were included. C9orf72 pathogenic variant carriers performed lower on attention, executive function, and verbal fluency from CDR plus NACC FTLD 0 onwards, with relatively minimal decline over time regardless of the CDR plus NACC FTLD score (i.e., disease progression). The cognitive profile in MAPT pathogenic variant carriers was characterized by lower memory performance at CDR plus NACC FTLD 0.5, with decline over time in language from the CDR plus NACC FTLD 0.5 stage onwards, and executive dysfunction rapidly developing at CDR plus NACC FTLD ≥1. GRN pathogenic variant carriers declined on verbal fluency and visuoconstruction in the CDR plus NACC FTLD 0.5 stage, with progressive decline in other cognitive domains starting at CDR plus NACC FTLD ≥1. Discussion: We confirmed cognitive decline in the asymptomatic and prodromal stage of genetic FTD. Specifically, tests for attention, executive function, language, and memory showed clear differences between genetic groups and controls at baseline, but the speed of change over time differed depending on genetic group and disease stage. This confirms the value of neuropsychological assessment in tracking clinical onset and progression and could inform clinical trials in selecting sensitive end points for measuring treatment effects as well as characterizing the best time window for starting treatment.Wolters KluwerRepositório da Universidade de LisboaPoos, Jackie M.MacDougall, Amyvan den Berg, EstherJiskoot, Lize C.Papma, Janne M.van der Ende, Emma L.Seelaar, HarroRussell, Lucy L.Peakman, GeorgiaConvery, RhianPijnenburg, Yolande A. L.Moreno, FerminSanchez-Valle, RaquelBorroni, BarbaraLaforce, RobertDoré, Marie-ClaireMasellis, MarioTartaglia, Maria CarmelaGraff, CarolineGalimberti, DanielaRowe, James B.Finger, ElizabethSynofzik, MatthisVandenberghe, RikDe Mendonça, AlexandreTiraboschi, PietroSantana, IsabelDucharme, SimonButler, ChristopherGerhard, AlexanderLevin, JohannesDanek, AdrianOtto, MarkusLe Ber, IsabellePasquier, Florencevan Swieten, JohnRohrer, Jonathan D.2023-01-05T12:19:55Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/55653engNeurology. 2022 Jul 19;99(3):e281-e2950028-387810.1212/WNL.0000000000200384info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:51:54Zoai:repositorio.ulisboa.pt:10451/55653Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:27:04.616978Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| dc.title.none.fl_str_mv |
Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort |
| title |
Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort |
| spellingShingle |
Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort Poos, Jackie M. |
| title_short |
Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort |
| title_full |
Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort |
| title_fullStr |
Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort |
| title_full_unstemmed |
Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort |
| title_sort |
Longitudinal cognitive changes in genetic frontotemporal dementia within the GENFI cohort |
| author |
Poos, Jackie M. |
| author_facet |
Poos, Jackie M. MacDougall, Amy van den Berg, Esther Jiskoot, Lize C. Papma, Janne M. van der Ende, Emma L. Seelaar, Harro Russell, Lucy L. Peakman, Georgia Convery, Rhian Pijnenburg, Yolande A. L. Moreno, Fermin Sanchez-Valle, Raquel Borroni, Barbara Laforce, Robert Doré, Marie-Claire Masellis, Mario Tartaglia, Maria Carmela Graff, Caroline Galimberti, Daniela Rowe, James B. Finger, Elizabeth Synofzik, Matthis Vandenberghe, Rik De Mendonça, Alexandre Tiraboschi, Pietro Santana, Isabel Ducharme, Simon Butler, Christopher Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Le Ber, Isabelle Pasquier, Florence van Swieten, John Rohrer, Jonathan D. |
| author_role |
author |
| author2 |
MacDougall, Amy van den Berg, Esther Jiskoot, Lize C. Papma, Janne M. van der Ende, Emma L. Seelaar, Harro Russell, Lucy L. Peakman, Georgia Convery, Rhian Pijnenburg, Yolande A. L. Moreno, Fermin Sanchez-Valle, Raquel Borroni, Barbara Laforce, Robert Doré, Marie-Claire Masellis, Mario Tartaglia, Maria Carmela Graff, Caroline Galimberti, Daniela Rowe, James B. Finger, Elizabeth Synofzik, Matthis Vandenberghe, Rik De Mendonça, Alexandre Tiraboschi, Pietro Santana, Isabel Ducharme, Simon Butler, Christopher Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Le Ber, Isabelle Pasquier, Florence van Swieten, John Rohrer, Jonathan D. |
| 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 |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Poos, Jackie M. MacDougall, Amy van den Berg, Esther Jiskoot, Lize C. Papma, Janne M. van der Ende, Emma L. Seelaar, Harro Russell, Lucy L. Peakman, Georgia Convery, Rhian Pijnenburg, Yolande A. L. Moreno, Fermin Sanchez-Valle, Raquel Borroni, Barbara Laforce, Robert Doré, Marie-Claire Masellis, Mario Tartaglia, Maria Carmela Graff, Caroline Galimberti, Daniela Rowe, James B. Finger, Elizabeth Synofzik, Matthis Vandenberghe, Rik De Mendonça, Alexandre Tiraboschi, Pietro Santana, Isabel Ducharme, Simon Butler, Christopher Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Le Ber, Isabelle Pasquier, Florence van Swieten, John Rohrer, Jonathan D. |
| description |
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology |
| publishDate |
2022 |
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2022 2022-01-01T00:00:00Z 2023-01-05T12:19:55Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/55653 |
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http://hdl.handle.net/10451/55653 |
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eng |
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eng |
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Neurology. 2022 Jul 19;99(3):e281-e295 0028-3878 10.1212/WNL.0000000000200384 |
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openAccess |
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application/pdf |
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Wolters Kluwer |
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Wolters Kluwer |
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