Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes.


Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978

Informations de publication

Date de publication:
06 2021
Historique:
revised: 15 10 2020
received: 03 08 2020
accepted: 03 11 2020
pubmed: 15 12 2020
medline: 16 11 2021
entrez: 14 12 2020
Statut: ppublish

Résumé

Apathy adversely affects prognosis and survival of patients with frontotemporal dementia (FTD). We test whether apathy develops in presymptomatic genetic FTD, and is associated with cognitive decline and brain atrophy. Presymptomatic carriers of MAPT, GRN or C9orf72 mutations (N = 304), and relatives without mutations (N = 296) underwent clinical assessments and MRI at baseline, and annually for 2 years. Longitudinal changes in apathy, cognition, gray matter volumes, and their relationships were analyzed with latent growth curve modeling. Apathy severity increased over time in presymptomatic carriers, but not in non-carriers. In presymptomatic carriers, baseline apathy predicted cognitive decline over two years, but not vice versa. Apathy progression was associated with baseline low gray matter volume in frontal and cingulate regions. Apathy is an early marker of FTD-related changes and predicts a subsequent subclinical deterioration of cognition before dementia onset. Apathy may be a modifiable factor in those at risk of FTD.

Identifiants

pubmed: 33316852
doi: 10.1002/alz.12252
pmc: PMC8247340
mid: EMS108536
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

969-983

Subventions

Organisme : Medical Research Council
ID : MC_UU_00005/12
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M008525/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M023664/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T046015/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009041/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J009482/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 103838
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K010395/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105597119
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

Investigateurs

Sónia Afonso (S)
Maria Rosario Almeida (MR)
Sarah Anderl-Straub (S)
Christin Andersson (C)
Anna Antonell (A)
Silvana Archetti (S)
Andrea Arighi (A)
Mircea Balasa (M)
Myriam Barandiaran (M)
Nuria Bargalló (N)
Robart Bartha (R)
Benjamin Bender (B)
Alberto Benussi (A)
Luisa Benussi (L)
Valentina Bessi (V)
Giuliano Binetti (G)
Sandra Black (S)
Sergi Borrego-Ecija (S)
Jose Bras (J)
Rose Bruffaerts (R)
Marta Cañada (M)
Paola Caroppo (P)
Miguel Castelo-Branco (M)
Thomas Cope (T)
Maura Cosseddu (M)
Giuseppe Di Fede (G)
Alina Díez (A)
Diana Duro (D)
Chiara Fenoglio (C)
Camilla Ferrari (C)
Catarina B Ferreira (CB)
Nick Fox (N)
Morris Freedman (M)
Giorgio Fumagalli (G)
Alazne Gabilondo (A)
Roberto Gasparotti (R)
Serge Gauthier (S)
Stefano Gazzina (S)
Giorgio Giaccone (G)
Ana Gorostidi (A)
Caroline Greaves (C)
Rita Guerreiro (R)
Tobias Hoegen (T)
Begoña Indakoetxea (B)
Vesna Jelic (V)
Lize Jiskoot (L)
Hans-Otto Karnath (HO)
Ron Keren (R)
Tobias Langheinrich (T)
Maria João Leitão (MJ)
Albert Lladó (A)
Gemma Lombardi (G)
Sandra Loosli (S)
Carolina Maruta (C)
Simon Mead (S)
Lieke Meeter (L)
Gabriel Miltenberger (G)
Rick van Minkelen (R)
Sara Mitchell (S)
Benedetta Nacmias (B)
Jennifer Nicholas (J)
Linn Öijerstedt (L)
Jaume Olives (J)
Sebastien Ourselin (S)
Alessandro Padovani (A)
Jessica Panman (J)
Janne Papma (J)
Michela Pievani (M)
Yolande Pijnenburg (Y)
Cristina Polito (C)
Enrico Premi (E)
Sara Prioni (S)
Catharina Prix (C)
Rosa Rademakers (R)
Veronica Redaelli (V)
Ekaterina Rogaeva (E)
Pedro Rosa-Neto (P)
Giacomina Rossi (G)
Martin Rosser (M)
Beatriz Santiago (B)
Elio Scarpini (E)
Sonja Schönecker (S)
Elisa Semler (E)
Rachelle Shafei (R)
Christen Shoesmith (C)
Miguel Tábuas-Pereira (M)
Mikel Tainta (M)
Ricardo Taipa (R)
David Tang-Wai (D)
David L Thomas (DL)
Paul Thompson (P)
Hakan Thonberg (H)
Carolyn Timberlake (C)
Pietro Tiraboschi (P)
Philip Van Damme (P)
Mathieu Vandenbulcke (M)
Michele Veldsman (M)
Ana Verdelho (A)
Jorge Villanua (J)
Jason Warren (J)
Carlo Wilke (C)
Ione Woollacott (I)
Elisabeth Wlasich (E)
Henrik Zetterberg (H)
Miren Zulaica (M)

Informations de copyright

© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

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Auteurs

Maura Malpetti (M)

Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.

P Simon Jones (PS)

Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.

Kamen A Tsvetanov (KA)

Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.

Timothy Rittman (T)

Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.

John C van Swieten (JC)

Department of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands.

Barbara Borroni (B)

Department of Clinical and Experimental Sciences, Centre for Neurodegenerative Disorders, University of Brescia, Brescia, Italy.

Raquel Sanchez-Valle (R)

Alzheimer's disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacións Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.

Fermin Moreno (F)

Department of Neurology, Cognitive Disorders Unit, Donostia Universitary Hospital, San Sebastian, Spain.
Neuroscience Area, Biodonostia Health Research Institute, San Sebastian, Gipuzkoa, Spain.

Robert Laforce (R)

Clinique Interdisciplinaire de Mémoire, Département des Sciences Neurologiques, CHU de Québec, Faculté de Médecine, Université Laval, Québec, Canada.

Caroline Graff (C)

Department of Neurobiology Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Bioclinicum, Karolinska Institutet, Solna, Sweden.
Unit for Hereditary Dementias, Theme Aging, Karolinska University Hospital, Solna, Sweden.

Matthis Synofzik (M)

Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.

Daniela Galimberti (D)

Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.
Centro Dino Ferrari, University of Milan, Milan, Italy.

Mario Masellis (M)

Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.

Maria Carmela Tartaglia (MC)

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.

Elizabeth Finger (E)

Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada.

Rik Vandenberghe (R)

Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium.
Neurology Service, University Hospitals Leuven, Leuven, Belgium.
KU Leuven, Leuven Brain Institute, Leuven, Belgium.

Alexandre de Mendonça (A)

Faculty of Medicine, University of Lisbon, Lisbon, Portugal.

Fabrizio Tagliavini (F)

Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy.

Isabel Santana (I)

University Hospital of Coimbra (HUC), Neurology Service, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

Simon Ducharme (S)

Department of Psychiatry, McGill University Health Centre, McGill University, Montreal, Québec, Canada.
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Québec, Canada.

Chris R Butler (CR)

Nuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK.

Alexander Gerhard (A)

Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.
Departments of Geriatric Medicine and Nuclear Medicine, University of Duisburg- Essen, Duisburg, Germany.

Johannes Levin (J)

Department of Neurology, Ludwig-Maximilians Universität München, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.

Adrian Danek (A)

Department of Neurology, Ludwig-Maximilians Universität München, Munich, Germany.

Markus Otto (M)

Department of Neurology, University of Ulm, Ulm, Germany.

Giovanni B Frisoni (GB)

IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Roberta Ghidoni (R)

Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Sandro Sorbi (S)

Department of Neuroscience Psychology Drug Research and Child Health, University of Florence, Florence, Italy.
IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.

Carolin Heller (C)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.

Emily G Todd (EG)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.

Martina Bocchetta (M)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.

David M Cash (DM)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.

Rhian S Convery (RS)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.

Georgia Peakman (G)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.

Katrina M Moore (KM)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.

Jonathan D Rohrer (JD)

Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, UK.

Rogier A Kievit (RA)

MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
Cognitive Neuroscience Department, Donders Institute for Brain Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands.

James B Rowe (JB)

Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, UK.
MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.

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