Sensitivity of the Social Behavior Observer Checklist to Early Symptoms of Patients With Frontotemporal Dementia

Background and Objectives Changes in social behavior are common symptoms of frontotemporal lobar degeneration (FTLD) and Alzheimer disease syndromes. For early identification of individual patients and differential diagnosis, sensitive clinical measures are required that are able to assess patterns of behaviors and detect syndromic differences in both asymptomatic and symptomatic stages. We investigated whether the examiner-based Social Behavior Observer Checklist (SBOCL) is sensitive to early behavior changes and reflects disease severity within and between neurodegenerative syndromes. Methods Asymptomatic individuals and patients with neurodegenerative disease were selected from the multisite ALLFTD cohort study. In a sample of participants with at least 1 time point of SBOCL data, we investigated whether the Disorganized, Reactive, and Insensitive subscales of the SBOCL change as a function of disease stage within and between these syndromes. In a longitudinal subsample with both SBOCL and neuroimaging data, we examined whether change over time on each subscale corresponds to progressive gray matter atrophy. Results A total of 1,082 FTLD pathogenic variant carriers and noncarriers were enrolled (282 asymptomatic, 341 behavioral variant frontotemporal dementia, 114 semantic and 95 nonfluent variant primary progressive aphasia, 137 progressive supranuclear palsy, and 113 Alzheimer disease syndrome). The Disorganized score increased between asymptomatic to very mild (p = 0.016, estimate = −1.10, 95% CI = −1.99 to −0.22), very mild to mild (p = 0.013, estimate = −1.17, 95% CI = −2.08 to −0.26), and mild to moderate/severe (p < 0.001, estimate = −2.00, 95% CI = −2.55 to −1.45) disease stages in behavioral variant frontotemporal dementia regardless of pathogenic variant status. Asymptomatic GRN pathogenic gene variant carriers showed more reactive behaviors (preoccupation with time: p = 0.001, estimate = 1.11, 95% CI = 1.06 to 1.16; self-consciousness: p = 0.003, estimate = 1.77, 95% CI = 1.52 to 2.01) than asymptomatic noncarriers (estimate = 1.01, 95% CI = 0.98 to 1.03; estimate = 1.31, 95% CI = 1.20 to 1.41). The Insensitive score increased to a clinically abnormal level in advanced stages of behavioral variant frontotemporal dementia (p = 0.003, estimate = −0.73, 95% CI = −1.18 to −0.29). Higher scores on each subscale corresponded with higher caregiver burden (p < 0.001). Greater change over time corresponded to greater fronto-subcortical atrophy in the semantic-appraisal and fronto-parietal intrinsically connected networks. Discussion The SBOCL is sensitive to early symptoms and reflects disease severity, with some evidence for progression across asymptomatic and symptomatic stages of FTLD syndromes; thus, it may hold promise for early measurement and monitoring of behavioral symptoms in clinical practice and treatment trials. Classification of Evidence This study provides Class II evidence that the SBOCL is sensitive to early behavioral changes in FTLD pathogenic variants and early symptomatic individuals in a highly educated patient cohort.

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