Examining empathy deficits across familial forms of frontotemporal dementia within the GENFI cohort

Phoebe H Foster ,Robert Laforce ,Florence Pasquier ,Rik Vandenberghe ,Barbara Borroni ,Matthis Synofzik ,Carmela Tartaglia ,Fermín Moreno ,Fabrizio Tagliavini ,David M Cash ,Johannes Levin ,Lize C Jiskoot ,Mario Masellis ,Markus Otto ,Alexander Gerhard ,Georgia Peakman ,Alexandre De Mendonça ,Rhian S Convery ,Lucy L Russell ,Arabella Bouzigues ,Raquel Sánchez‐Valle ,Daniela Galimberti ,Sandro Sorbi ,Elizabeth Finger ,John C Van Swieten ,Isabelle Le Ber ,Adrian Danek ,Chris Butler ,Isabel Santana ,Simon Ducharme ,James B Rowe ,Caroline Greaves ,Caroline Graff ,Martina Bocchetta ,Jonathan D Rohrer

doi:10.1016/j.cortex.2022.01.012

Abstract

BackgroundReduced 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. MethodsEmpathy 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. ResultsAll 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. ConclusionsSignificant 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.

Highlights

Frontotemporal dementia (FTD) is a heterogenous group of neurodegenerative disorders, characterised by predominant atrophy in the frontal and temporal lobes [1,2,3]
In the present study, we have demonstrated that the modified version of the Interpersonal Reactivity Index (mIRI) detects empathy deficits in fully symptomatic (CDR 1+) familial frontotemporal dementia (FTD), as well as in very mildly symptomatic/prodromal (CDR 0.5) chromosome 9 open reading frame 72 (C9orf72) expansion carriers, it does not distinguish impaired empathy when comparing other prodromal or asymptomatic individuals
Neural correlates of empathy varied between genetic groups: scores were associated with the left orbitofrontal cortex in all three groups, but more widespread cortical and subcortical regions for GRN mutation carriers, and the anteromedial temporal lobe and insula for microtubule associated protein tau (MAPT) mutation carriers

Summary

Introduction

Frontotemporal dementia (FTD) is a heterogenous group of neurodegenerative disorders, characterised by predominant atrophy in the frontal and temporal lobes [1,2,3]. The disease spectrum encompasses a variety of clinical syndromes: behavioural variant FTD (bvFTD), identifiable by altered personality and behavioural change, as well as a number of language variants, collectively referred to as primary progressive aphasia (PPA), distinguished by progressive deficits in word retrieval, comprehension or speech production [2, 4,5,6,7,8,9,10,11]. Overlapping motor syndromes such as FTD with amyotrophic lateral. Conclusions: Significant empathy deficits present in genetic FTD, in symptomatic individuals and those with a bvFTD phenotype, while prodromal deficits are only seen using the mIRI in C9orf expansion carriers

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Discussion

Conclusion