Mild Behavioral Impairment and Cortical Thinning: Biomarkers of Early Neurodegeneration.

Background: Mild behavioral impairment (MBI) is increasingly recognized as an early phenotypic marker of neurodegeneration characterized by neuropsychiatric symptoms (NPSs) emerging prior to overt cognitive decline. While structural neuroimaging studies have linked cortical thinning with NPSs, the relationship between MBI and cortical morphology remains underexplored in diverse, community-based cohorts. In this study, we investigated whether early behavioral alterations, assessed via the Mild Behavioral Impairment Checklist (MBI-C), correlate with region-specific cortical thinning in a Southeast Asian cohort.

Methods: A cross-sectional analysis was conducted on 969 participants (mean age 58.59 ± 10.64 years; 39.8% male; 87.4% Chinese) from the BIOCIS (Biomarkers and Cognition Study, Singapore), including cognitively normal individuals and individuals with subjective cognitive decline (SCD) or with mild cognitive impairment. MBI was assessed using the self-report MBI-C. Cortical thickness was measured using T1-weighted magnetic resonance imaging scans processed with FreeSurfer. Associations between cortical thinning and MBI-C total and subdomain scores were evaluated.

Results: Higher scores on the MBI-C Belief subdomain were significantly associated with cortical thinning in the right hemisphere (β = -0.0177; 95% CI, -0.0342 to -0.0012; p = .035). Region-specific analyses showed temporal lobe thinning in the posterior superior temporal sulcus, fusiform gyrus, superior temporal gyrus, temporal pole, and transverse temporal gyrus, and associations remained significant after false discovery rate (FDR) correction (p = .042-.045). Additional cortical thinning was observed in the right postcentral gyrus, supramarginal gyrus, and insula (p_FDR ≤ .039).

Conclusions: Elevated MBI, particularly abnormal beliefs, is linked to cortical thinning in regions subserving memory, sensory integration, and emotion regulation predominantly in the right hemisphere. These findings highlight the potential of the MBI-C as an early neurodegenerative marker. Further longitudinal studies are needed to clarify temporal dynamics and mechanisms underlying behavioral symptoms and neurodegenerative processes.