Uncovering the Neural Bases of Cognitive and Affective Empathy Deficits in Alzheimer's Disease and the Behavioral-Variant of Frontotemporal Dementia.
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.
School of Psychology, The University of New South Wales, Sydney, Australia.|Neuroscience Research Australia, Randwick, Sydney, Australia.
Nadene
N
Dermody
Neuroscience Research Australia, Randwick, Sydney, Australia.|Australian Research Council Centre for Excellence in Cognition and its Disorders, Sydney, Australia.
Stephanie
S
Wong
Neuroscience Research Australia, Randwick, Sydney, Australia.|Prince of Wales Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia.
Rebekah
R
Ahmed
Neuroscience Research Australia, Randwick, Sydney, Australia.|School of Medical Science, The University of New South Wales, Sydney, Australia.|Australian Research Council Centre for Excellence in Cognition and its Disorders, Sydney, Australia.
Olivier
O
Piguet
Neuroscience Research Australia, Randwick, Sydney, Australia.|School of Medical Science, The University of New South Wales, Sydney, Australia.|Australian Research Council Centre for Excellence in Cognition and its Disorders, Sydney, Australia.
John R
JR
Hodges
School of Psychology, The University of New South Wales, Sydney, Australia.|Neuroscience Research Australia, Randwick, Sydney, Australia.|Australian Research Council Centre for Excellence in Cognition and its Disorders, Sydney, Australia.
Muireann
M
Irish
D000341:Affective Disorders, Psychotic / Q000209:etiology*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology / Q000523:psychology; D001931:Brain Mapping; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000209:etiology*; D004645:Empathy; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications / Q000473:pathology / Q000523:psychology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007398:Interpersonal Relations; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000209:etiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010555:Personality Inventory; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric
Neurodegenerative diseases; orbitofrontal cortex; right hemisphere; social cognition; theory of mind