Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes
| Autor: | Matthis Synofzik, Alexandre de Mendonça, Giovanni B. Frisoni, Maura Malpetti, Fermin Moreno, Christopher C Butler, Roberta Ghidoni, Daniela Galimberti, Rik Vandenberghe, Elizabeth Finger, Isabel Santana, Alexander Gerhard, Georgia Peakman, Emily Todd, Carolin Heller, Jonathan D. Rohrer, Katrina M. Moore, Kamen A. Tsvetanov, Rhian S Convery, P. Simon Jones, Johannes Levin, James B. Rowe, Caroline Graff, Markus Otto, Barbara Borroni, Raquel Sánchez-Valle, Sandro Sorbi, Fabrizio Tagliavini, John C. van Swieten, Maria Carmela Tartaglia, Rogier A. Kievit, Simon Ducharme, Robert Laforce, Mario Masellis, Timothy Rittman, Adrian Danek, David M. Cash, Martina Bocchetta |
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| Přispěvatelé: | Apollo - University of Cambridge Repository, Repositório da Universidade de Lisboa, Neurology, Malpetti, Maura [0000-0001-8923-9656], Jones, Simon [0000-0001-9695-0702], Tsvetanov, Kamen A. [0000-0002-3178-6363], Rittman, Timothy [0000-0003-1063-6937], Rowe, James [0000-0001-7216-8679] |
| Rok vydání: | 2020 |
| Předmět: |
Male
longitudinal design SYMPTOMS pathology [Cognitive Dysfunction] Epidemiology Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] Medizin apathy DISEASE 0302 clinical medicine pathology [Brain] pathology [Gray Matter] C9orf72 presymptomatic carriers cognitive decline genetic frontotemporal dementia MRI Apathy Gray Matter Cognitive decline genetics [Frontotemporal Dementia] pathology [Atrophy] 0303 health sciences Health Policy Brain Cognition IMPAIRMENT Middle Aged DEPRESSION Magnetic Resonance Imaging Psychiatry and Mental health Frontotemporal Dementia Female IMPULSIVITY medicine.symptom Life Sciences & Biomedicine Clinical psychology Frontotemporal dementia Clinical Neurology FEATURED ARTICLE Prodromal Symptoms PHENOTYPES genetics [Mutation] Impulsivity 03 medical and health sciences Cellular and Molecular Neuroscience All institutes and research themes of the Radboud University Medical Center Atrophy SDG 3 - Good Health and Well-being Developmental Neuroscience mental disorders medicine Humans Dementia Cognitive Dysfunction ddc:610 BEHAVIORAL-VARIANT 030304 developmental biology Science & Technology EXECUTIVE FUNCTION business.industry DIGIT SYMBOL 1103 Clinical Sciences medicine.disease DYSFUNCTION Geriatrics Mutation FEATURED ARTICLES Neurosciences & Neurology Neurology (clinical) Geriatrics and Gerontology 1109 Neurosciences business 030217 neurology & neurosurgery |
| Zdroj: | Alzheimer's & Dementia Alzheimer's and dementia 17(6), 969-983 (2021). doi:10.1002/alz.12252 Alzheimer's and Dementia, 17(6), 969-983. Elsevier Inc. Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Alzheimer's & Dementia, 17, 6, pp. 969-983 Alzheimer's & Dementia, 17, 969-983 |
| ISSN: | 1552-5279 1552-5260 |
| Popis: | © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Introduction: 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. Methods: 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. Results: 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. Discussion: 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. This work is co‐funded by the UK Medical Research Council (MR/M023664/1), the Italian Ministry of Health and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant and the Bluefield Project, as well as a JPND grant “GENFI‐prox” (by DLR/BMBF to MS, joined with JDR, JvS, MO, BB and CG). MM is supported by the Cambridge Trust & Sidney Sussex College Scholarship. PSJ is supported by the Cambridge Centre for Parkinson Plus. KAT is supported by the British Academy Postdoctoral Fellowship (KAT: PF160048) and Guarantors of Brain (KAT: 101149). TR is supported by the Cambridge Centre for Parkinson Plus and Cambridge Biomedical Resource Centre. RAK is supported by Medical Research Council (RAK: SUAG/047/G101400). JBR reports grants from the NIHR Cambridge Biomedical research centre, Wellcome Trust (103838), and Medical Research Council (SUAG051/G101400; MR/T033371/1); personal fees from Asceneuron, WAVE, Astex, and Biogen; and grants from Janssen, AZ Medimmune, and Eli Lilly, outside the submitted work. JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS‐JF‐19a‐004‐517), and by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK. |
| Databáze: | OpenAIRE |
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