Abstract
Background: Although social cognitive dysfunction is a major feature of frontotemporal dementia (FTD), it has been poorly studied in familial forms. A key goal of studies is to detect early cognitive impairment using validated measures in large patient cohorts. Methods: We used the Revised Self-Monitoring Scale (RSMS) as a measure of socioemotional sensitivity in 730 participants from the genetic FTD initiative (GENFI) observational study: 269 mutation-negative healthy controls, 193 C9orf72 expansion carriers, 193 GRN mutation carriers and 75 MAPT mutation carriers. All participants underwent the standardised GENFI clinical assessment including the ‘CDR® plus NACC FTLD’ scale and RSMS. The RSMS total score and its two subscores, socioemotional expressiveness (EX score) and modification of self-presentation (SP score) were measured. Volumetric T1-weighted magnetic resonance imaging was available from 377 mutation carriers for voxel-based morphometry (VBM) analysis. Results: The RSMS was decreased in symptomatic mutation carriers in all genetic groups but at a prodromal stage only in the C9orf72 (for the total score and both subscores) and GRN (for the modification of self-presentation subscore) groups. RSMS score correlated with disease severity in all groups. The VBM analysis implicated an overlapping network of regions including the orbitofrontal cortex, insula, temporal pole, medial temporal lobe and striatum. Conclusions: The RSMS indexes socioemotional impairment at an early stage of genetic FTD and may be a suitable outcome measure in forthcoming trials.
| Original language | English |
|---|---|
| Article number | 127 |
| Journal | Alzheimer's Research and Therapy |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 12 Jul 2021 |
Bibliographical note
Funding Information:The Dementia Research Centre is supported by Alzheimer’s Research UK, Brain Research Trust and The Wolfson Foundation. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility as well as an Alzheimer’s Society grant [AS-PG-16-007]. This work was also supported by the MRC UK GENFI grant [MR/M023664/1], the Italian Ministry of Health (CoEN015 and Ricerca Corrente) 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, The Bluefield Project and the JPND GENFI-PROX grant [2019-02248]. 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], the Bluefield Project and the Association for Frontotemporal Degeneration. MB is supported by a Fellowship award from the Alzheimer’s Society, UK [AS-JF-19a-004-517]. JBR is supported by the Wellcome Trust [103838], the Medical Research Council and NIHR Cambridge Biomedical Research Centre. This work was also funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology [EXC 2145 SyNergy – ID 390857198]. Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases - Project ID No 739510.
Funding Information:
We thank all participants and their family members for taking part in the GENFI study. GENFI Consortium Authors ? S?nia Afonso - Instituto Ciencias Nucleares Aplicadas a Saude, Universidade de Coimbra, Coimbra, Portugal; ? Maria Rosario Almeida - Faculty of Medicine, University of Coimbra, Coimbra, Portugal; ? Sarah Anderl-Straub ? Department of Neurology, University of Ulm, Ulm, Germany; ? Christin Andersson - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; ? Anna Antonell - Alzheimer?s disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl?nic, Barcelona, Spain; ? Silvana Archetti - Biotechnology Laboratory, Department of Diagnostics, ASST Brescia Hospital, Brescia, Italy; ? Andrea Arighi - Fondazione IRCCS Ca? Granda Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy; University of Milan, Centro Dino Ferrari, Milan, Italy; ? Mircea Balasa - Alzheimer?s disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl?nic, Barcelona, Spain; ? Myriam Barandiaran - Cognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain; Neuroscience Area, Biodonostia Health Research Insitute, San Sebastian, Gipuzkoa, Spain; ? Nuria Bargall? - Imaging Diagnostic Center, Hospital Cl?nic, Barcelona, Spain.
Publisher Copyright:
© 2021, The Author(s).