Abstract
| Original language | English |
|---|---|
| Journal | Alzheimer's Dementia |
| DOIs | |
| Publication status | E-pub ahead of print - Dec 14 2020 |
Keywords
- apathy
- cognitive decline
- genetic frontotemporal dementia
- longitudinal design
- MRI
- presymptomatic carriers
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Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes : Alzheimer's and Dementia. / Malpetti, M.; Jones, P.S.; Tsvetanov, K.A.; Rittman, T.; van Swieten, J.C.; Borroni, B.; Sanchez-Valle, R.; Moreno, F.; Laforce, R.; Graff, C.; Synofzik, M.; Galimberti, D.; Masellis, M.; Tartaglia, M.C.; Finger, E.; Vandenberghe, R.; de Mendonça, A.; Tagliavini, F.; Santana, I.; Ducharme, S.; Butler, C.R.; Gerhard, A.; Levin, J.; Danek, A.; Otto, M.; Frisoni, G.B.; Ghidoni, R.; Sorbi, S.; Heller, C.; Todd, E.G.; Bocchetta, M.; Cash, D.M.; Convery, R.S.; Peakman, G.; Moore, K.M.; Rohrer, J.D.; Kievit, R.A.; Rowe, J.B.; (GENFI), on behalf of the Genetic FTD Initiative.
In: Alzheimer's Dementia, 14.12.2020.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Apathy in presymptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes
T2 - Alzheimer's and Dementia
AU - Malpetti, M.
AU - Jones, P.S.
AU - Tsvetanov, K.A.
AU - Rittman, T.
AU - van Swieten, J.C.
AU - Borroni, B.
AU - Sanchez-Valle, R.
AU - Moreno, F.
AU - Laforce, R.
AU - Graff, C.
AU - Synofzik, M.
AU - Galimberti, D.
AU - Masellis, M.
AU - Tartaglia, M.C.
AU - Finger, E.
AU - Vandenberghe, R.
AU - de Mendonça, A.
AU - Tagliavini, F.
AU - Santana, I.
AU - Ducharme, S.
AU - Butler, C.R.
AU - Gerhard, A.
AU - Levin, J.
AU - Danek, A.
AU - Otto, M.
AU - Frisoni, G.B.
AU - Ghidoni, R.
AU - Sorbi, S.
AU - Heller, C.
AU - Todd, E.G.
AU - Bocchetta, M.
AU - Cash, D.M.
AU - Convery, R.S.
AU - Peakman, G.
AU - Moore, K.M.
AU - Rohrer, J.D.
AU - Kievit, R.A.
AU - Rowe, J.B.
AU - (GENFI), on behalf of the Genetic FTD Initiative
N1 - Export Date: 22 February 2021 Correspondence Address: Rowe, J.B.; Department of Clinical Neurosciences, United Kingdom; email: james.rowe@mrc-cbu.cam.ac.uk Correspondence Address: Rowe, J.B.; MRC Cognition and Brain Sciences Unit, United Kingdom; email: james.rowe@mrc-cbu.cam.ac.uk Funding details: Wellcome Trust, WT, MR/T033371/1, SUAG051/G101400, 103838 Funding details: Alzheimer's Society, AS‐JF‐19a‐004‐517 Funding details: Medical Research Council, MRC, MR/M008525/1 Funding details: EU Joint Programme – Neurodegenerative Disease Research, JPND Funding details: UK Dementia Research Institute, UK DRI Funding details: Sidney Sussex College, University of Cambridge Funding details: Eli Lilly and Company Funding details: NIHR Cambridge Biomedical Research Centre Funding details: British Academy, PF160048, 101149 Funding details: Biogen Funding details: BRC149/NS/MH Funding details: National Institute for Health Research, NIHR Funding details: Janssen Biotech Funding details: Canadian Institutes of Health Research, CIHR Funding details: Medical Research Council, MRC, SUAG/047/G101400 Funding details: MR/M023664/1 Funding text 1: 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. 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PY - 2020/12/14
Y1 - 2020/12/14
N2 - 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. © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association
AB - 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. © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association
KW - apathy
KW - cognitive decline
KW - genetic frontotemporal dementia
KW - longitudinal design
KW - MRI
KW - presymptomatic carriers
U2 - 10.1002/alz.12252
DO - 10.1002/alz.12252
M3 - Article
JO - Alzheimer's Dementia
JF - Alzheimer's Dementia
SN - 1552-5260
ER -