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Associations between volumes of grey matter regions and white matter hyperintensities with cognitive empathy in oldest-old adults

Chander, R. J.; Grainger, S. A.; Crawford, J. D.; Jiang, J.; Kochan, N. A.; Numbers, K.; Brodaty, H.; Henry, J. D.; Wen, W.; Sachdev, P. S.

2025-10-17 neuroscience
10.1101/2025.10.16.682959 bioRxiv
Show abstract

OBJECTIVESTo study the differential associations of regional volumes of grey matter (GM) and white matter hyperintensities (WMH) with behavioural and informant-reported measures of cognitive empathy (CE), especially in brain regions understood to have functional connectivity involvement with CE abilities. METHODSCommunity-dwelling participants from the Sydney Memory and Ageing Study (Sydney MAS) underwent whole brain MRI. Regional cortical GM volumes were derived using FreeSurfer v7.1 for, and WMH volumes were derived using UBO Detector. On follow-up four years later, CE was indexed via the Reading the Mind in the Eyes Test (RMET; a behavioural task) and Interpersonal Reactivity Index - Perspective Taking subscale (IRI-PT; an informant-reported measure). RESULTSIn 129 participants (mean age 87.01 years), Structural equation modelling (SEM) showed associations between insula GM volumes and RMET scores (p=0.001), and between supramarginal gyrus (SMG) GM volumes and IRI-PT scores (p=0.016). Associations remained significant after inclusion of covariates accounting for age, global cognition, affective symptoms, and social networks. DISCUSSIONCE abilities assessed with RMET (a behavioural task) were positively associated with insula GM volumes. CE abilities on the IRI-PT (an informant-reported measure) were positively associated with SMG GM volumes. No associations between WMH volumes and CE measures were found. These findings may inform clinical workflows that use structural MRI investigations looking at social cognitive disturbances in older adults and provide further evidence of the divergent nature of behavioural and self-report measures of CE.

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