Dissociations in Socioemotional Test Performance Predict Neurodegeneration in Intrinsic Connectivity Networks (P5.191)

OBJECTIVE: To evaluate the additive benefit of testing dissociable (emotional and non-emotional) social functions to predict structural damage and diagnostic syndrome in neurodegenerative patients. BACKGROUND: Distinct atrophy patterns emerge in neurodegenerative diseases, targeting intrinsic connectivity networks (ICNs). Although the correlation between ICNs and atrophic patterns is established, it remains unclear whether identification of specific cross-test patterns of performance on socioemotional measures can better predict ICN involvement, improving diagnostic prediction. DESIGN/METHODS: We evaluated 402 participants, 316 with neurodegenerative disease [behavioral variant FTD (n=77); nonfluent variant PPA (n=36); semantic variant PPA (n=54); AD (n=102); progressive supranuclear palsy (n=47)] and 86 older healthy controls [NC] on video-based tasks measuring emotion naming (TASIT-Emotion Evaluation Task) and non-emotional social perspective taking (UCSF Cognitive Theory Of Mind (cTOM)). SPM8 Dartel preprocessing was performed with structural MRIs, and covariates-only voxel-based morphometry analyses were performed. Region of interest analysis and multivariate modeling were performed to identify test-specific atrophy patterns corresponding to key ICNs (default mode (DMN), salience (SN), frontoparietal (FPN), and semantic appraisal (SAN)). RESULTS: When atrophy predicting reduced cTOM scores was segregated into sets of network-specific ROIs, networks independently predicting non-emotional social cognition were DMN (precuneus, posterior cingulate, dorsomedial prefrontal ROIs), FPN (dorsolateral parietal/frontal), and SAN (anterior temporal, subgenual PFC) (R2=0.45, p<0.001). Only SN (anterior insula, anterior cingulate) independently predicted TASIT-EET emotion reading in the model (R2=0.48, p<0.001). CONCLUSIONS: Atrophy in distinct ICNs contributes to differential performance deficits on emotional versus non-emotional aspects social function in neurodegenerative disease patients. Poor non-emotional social cognition appearing in isolation predicts damage to dorsal networks (DMN, FPN) (e.g., suggestive of AD, nfvPPA), while additional emotion reading deficits predict inclusion of more ventral networks (SN) (e.g., suggestive of bvFTD). Sociocognitive assessments can provide important neuroanatomic and diagnostic information to clinicians even when MRI is unavailable. STUDY SUPPORTED BY: R01AG029577-06, P01AG019724-11, P01AG019724-04, K23AG021606-02