TY - JOUR
T1 - Examining empathy deficits across familial forms of frontotemporal dementia within the GENFI cohort
AU - The Genetic FTD Initiative (GENFI)
AU - Foster, Phoebe H.
AU - Russell, Lucy L.
AU - Peakman, Georgia
AU - Convery, Rhian S.
AU - Bouzigues, Arabella
AU - Greaves, Caroline V.
AU - Bocchetta, Martina
AU - Cash, David M.
AU - van Swieten, John C.
AU - Jiskoot, Lize C.
AU - Moreno, Fermin
AU - Sanchez-Valle, Raquel
AU - Laforce, Robert
AU - Graff, Caroline
AU - Masellis, Mario
AU - Tartaglia, Carmela
AU - Rowe, James B.
AU - Borroni, Barbara
AU - Finger, Elizabeth
AU - Synofzik, Matthis
AU - Galimberti, Daniela
AU - Vandenberghe, Rik
AU - de Mendonça, Alexandre
AU - Butler, Chris R.
AU - Gerhard, Alex
AU - Ducharme, Simon
AU - Le Ber, Isabelle
AU - Tagliavini, Fabrizio
AU - Santana, Isabel
AU - Pasquier, Florence
AU - Levin, Johannes
AU - Danek, Adrian
AU - Otto, Markus
AU - Sorbi, Sandro
AU - Rohrer, Jonathan D.
AU - Afonso, Sónia
AU - Almeida, Maria Rosario
AU - Anderl-Straub, Sarah
AU - Andersson, Christin
AU - Antonell, Anna
AU - Archetti, Silvana
AU - Arighi, Andrea
AU - Balasa, Mircea
AU - Barandiaran, Myriam
AU - Bargalló, Nuria
AU - Bartha, Robart
AU - Bender, Benjamin
AU - Benussi, Alberto
AU - Bertoux, Maxime
AU - Maruta, Carolina
N1 - Funding Information:
We thank the research participants for their contribution to the study. The Dementia Research Centre is supported by Alzheimer’s Research UK , Alzheimer's Society , Brain Research UK , and The Wolfson Foundation . This work was supported by the NIHR UCL/H Biomedical Research Centre , the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute , which receives its funding from UK DRI Ltd , funded by the UK Medical Research Council , Alzheimer's Society and Alzheimer's Research UK . 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 ). This work was also supported by the MRC UK GENFI grant ( MR/M023664/1 ), the Bluefield Project and the JPND GENFI-PROX grant ( 2019-02248 ). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510 . RC/CG are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal ( RCN 290173 ). MB is supported by a Fellowship award from the Alzheimer's Society , UK ( AS-JF-19a-004-517 ). MB's work is also supported 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 . JCVS was supported by the Dioraphte Foundation grant 09-02-03-00 , the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organisation for Scientific Research grant HCMI 056-13-018 , ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042 ), Alzheimer Nederland and the Bluefield project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED) . RS-V is supported by an Alzheimer’s Research UK Clinical Research Training Fellowship ( ARUK-CRF2017B-2 ), and has received funding from Fundació Marató de TV3 , Spain (grant no. 20143810 ). CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504 , VR 2015-02926 and 2018-02754 , the Swedish FTD Inititative-Schörling Foundation , Alzheimer Foundation , Brain Foundation and Stockholm County Council ALF . MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute . JBR has received funding from the Wellcome Trust ( 103838 ) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council ( SUAG/051 G101400 ) and the National Institute for Health Research Cambridge Biomedical Research Centre ( BRC-1215-20014 ). EF has received funding from a CIHR grant # 327387 . DG received support from the EU Joint Programme – Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042 . RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. MO has received funding from BMBF (FTLDc).
Funding Information:
We thank the research participants for their contribution to the study. The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. 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). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510. RC/CG are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal (RCN 290173). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004-517). MB's work is also supported 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. JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organisation for Scientific Research grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). RS-V is supported by an Alzheimer's Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2), and has received funding from Fundaci? Marat? de TV3, Spain (grant no. 20143810). CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Inititative-Sch?rling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. JBR has received funding from the Wellcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). EF has received funding from a CIHR grant #327387. DG received support from the EU Joint Programme ? Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. MO has received funding from BMBF (FTLDc).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Background: Reduced empathy is a common symptom in frontotemporal dementia (FTD). Although empathy deficits have been extensively researched in sporadic cases, few studies have explored the differences in familial forms of FTD. Methods: Empathy was examined using a modified version of the Interpersonal Reactivity Index (mIRI) in 676 participants from the Genetic FTD Initiative: 216 mutation-negative controls, 192 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. Using global scores from the CDR® plus NACC FTLD, mutation carriers were divided into three groups, asymptomatic (0), very mildly symptomatic/prodromal (.5), or fully symptomatic (1 or more). The mIRI Total score, as well as the subscores of Empathic Concern (EC) and Perspective Taking (PT) were assessed. Linear regression models with bootstrapping were used to assess empathy ratings across genetic groups, as well as across phenotypes in the symptomatic carriers. Neural correlates of empathy deficits were examined using a voxel-based morphometry (VBM) analysis. Results: All fully symptomatic groups scored lower on the mIRI Total, EC, and PT when compared to controls and their asymptomatic or prodromal counterparts (all p <.001). Prodromal C9orf72 expansion carriers also scored significantly lower than controls on the mIRI Total score (p =.046). In the phenotype analysis, all groups (behavioural variant FTD, primary progressive aphasia and FTD with amyotrophic lateral sclerosis) scored significantly lower than controls (all p <.007). VBM revealed an overlapping neural correlate of the mIRI Total score across genetic groups in the orbitofrontal lobe but with additional involvement in the temporal lobe, insula and basal ganglia in both the GRN and MAPT groups, and uniquely more posterior regions such as the parietal lobe and thalamus in the GRN group, and medial temporal structures in the MAPT group. Conclusions: Significant empathy deficits present in genetic FTD, particularly in symptomatic individuals and those with a bvFTD phenotype, while prodromal deficits are only seen using the mIRI in C9orf72 expansion carriers.
AB - Background: Reduced empathy is a common symptom in frontotemporal dementia (FTD). Although empathy deficits have been extensively researched in sporadic cases, few studies have explored the differences in familial forms of FTD. Methods: Empathy was examined using a modified version of the Interpersonal Reactivity Index (mIRI) in 676 participants from the Genetic FTD Initiative: 216 mutation-negative controls, 192 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. Using global scores from the CDR® plus NACC FTLD, mutation carriers were divided into three groups, asymptomatic (0), very mildly symptomatic/prodromal (.5), or fully symptomatic (1 or more). The mIRI Total score, as well as the subscores of Empathic Concern (EC) and Perspective Taking (PT) were assessed. Linear regression models with bootstrapping were used to assess empathy ratings across genetic groups, as well as across phenotypes in the symptomatic carriers. Neural correlates of empathy deficits were examined using a voxel-based morphometry (VBM) analysis. Results: All fully symptomatic groups scored lower on the mIRI Total, EC, and PT when compared to controls and their asymptomatic or prodromal counterparts (all p <.001). Prodromal C9orf72 expansion carriers also scored significantly lower than controls on the mIRI Total score (p =.046). In the phenotype analysis, all groups (behavioural variant FTD, primary progressive aphasia and FTD with amyotrophic lateral sclerosis) scored significantly lower than controls (all p <.007). VBM revealed an overlapping neural correlate of the mIRI Total score across genetic groups in the orbitofrontal lobe but with additional involvement in the temporal lobe, insula and basal ganglia in both the GRN and MAPT groups, and uniquely more posterior regions such as the parietal lobe and thalamus in the GRN group, and medial temporal structures in the MAPT group. Conclusions: Significant empathy deficits present in genetic FTD, particularly in symptomatic individuals and those with a bvFTD phenotype, while prodromal deficits are only seen using the mIRI in C9orf72 expansion carriers.
KW - Empathic concern
KW - Empathy
KW - Frontotemporal dementia
KW - Interpersonal Reactivity Index
KW - Perspective taking
UR - http://www.scopus.com/inward/record.url?scp=85127879169&partnerID=8YFLogxK
U2 - 10.1016/j.cortex.2022.01.012
DO - 10.1016/j.cortex.2022.01.012
M3 - Article
C2 - 35325762
AN - SCOPUS:85127879169
SN - 0010-9452
VL - 150
SP - 12
EP - 28
JO - Cortex
JF - Cortex
ER -