Uncovering the Neural Bases of Cognitive and Affective Empathy Deficits in Alzheimer's Disease and the Behavioral-Variant of Frontotemporal Dementia

Nadene Dermody, Stephanie Wong, Rebekah Ahmed, Olivier Piguet, John R. Hodges, Muireann Irish*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

122 Citations (Scopus)


Loss of empathy is a core presenting feature of the behavioral-variant of frontotemporal dementia (bvFTD), resulting in socioemotional difficulties and behavioral transgressions. In contrast, interpersonal functioning remains relatively intact in Alzheimer's disease (AD), despite marked cognitive decline. The neural substrates mediating these patterns of loss and sparing in social functioning remain unclear, yet are relevant for our understanding of the social brain. We investigated cognitive versus affective aspects of empathy using the Interpersonal Reactivity Index (IRI) in 25 AD and 24 bvFTD patients and contrasted their performance with 22 age- and education-matched controls. Cognitive empathy was comparably compromised in AD and bvFTD, whereas affective empathy was impaired exclusively in bvFTD. While controlling for overall cognitive dysfunction ameliorated perspective-taking deficits in AD, empathy loss persisted across cognitive and affective domains in bvFTD. Voxel-based morphometry analyses revealed divergent neural substrates of empathy loss in each patient group. Perspective-taking deficits correlated with predominantly left-sided temporoparietal atrophy in AD, whereas widespread bilateral frontoinsular, temporal, parietal, and occipital atrophy was implicated in bvFTD. Reduced empathic concern in bvFTD was associated with atrophy in the left orbitofrontal, inferior frontal, and insular cortices, and the bilateral mid-cingulate gyrus. Our findings suggest that social cognitive deficits in AD arise largely as a consequence of global cognitive dysfunction, rather than a loss of empathy per se. In contrast, loss of empathy in bvFTD reflects the deterioration of a distributed network of frontoinsular and temporal structures that appear crucial for monitoring and processing social information.

Original languageEnglish
Pages (from-to)801-816
Number of pages16
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - 30 May 2016
Externally publishedYes


  • Neurodegenerative diseases
  • orbitofrontal cortex
  • right hemisphere
  • social cognition
  • theory of mind


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