Mild Behavioral Impairment as a Clinical Correlate of Early Neurodegeneration
Authors: Leow Yi Jin , Saffari Seyed Ehsan , Vipin Ashwati , Tanoto Pricilia , Binte Shaik Mohamed Salim Rasyiqah , Qiu Bocheng , Ismail Zahinoor , Kandiah Nagaendran 
Published: January 2025

Importance

Mild Behavioral Impairment(MBI), characterized by neuropsychiatric symptoms(NPS) that precede cognitive decline, may reflect early neurodegenerative changes. Identifying structural brain changes associated with MBI could enhance early risk stratification and intervention.

Objective

To investigate the association between MBI symptoms and cortical thinning as a structural marker of neurodegeneration in a Southeast Asian cohort.

Design, Setting, and Participants

This cross-sectional study analyzed baseline data from the Biomarkers and Cognition Study, Singapore(BIOCIS), a 5-year longitudinal study initiated in 2023 that recruits community participants across Singapore. Cross-sectional data from 1,145 participants(mean age: 62±13.5 years; 53% female) with normal cognition, subjective cognitive decline(SCD), or mild cognitive impairment(MCI) were included.

Main Outcomes and Measures

Behavioral symptoms were assessed using the Mild Behavioral Impairment Checklist(MBI-C), which captures NPS across five domains: decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/false beliefs. Cortical thickness was measured using T1-weighted MRI, processed through FreeSurfer. The primary outcome was the relationship between MBI-C total and subdomain scores, and cortical thinning.

Results

Higher MBI-C Belief scores were associated with cortical thinning in the right hemisphere(β=- 0.0177;95% CI:-0.0342 to −0.0012;P=.035). Significant thinning was observed in specific regions - posterior banks of the superior temporal sulcus(β=-0.020;95% CI:-0.037 to −0.004;P=.013), fusiform gyrus(β=-0.021;95% CI:-0.037 to −0.005;P=.009), superior temporal gyrus(β=-0.020;95% CI:-0.037 to −0.002;P=.025), temporal pole(β=-0.018;95% CI:-0.034 to −0.003;P=.021), and transverse temporal gyrus(β=-0.020;95% CI:-0.036 to −0.004;P=.014). After false discovery rate(FDR) correction, the associations in the posterior banks of the superior temporal sulcus, fusiform gyrus, superior temporal gyrus, and transverse temporal gyrus remained significant(FDR P=.042–.045).

In addition to these temporal regions, higher MBI-C Belief scores were significantly associated with cortical thinning in the right postcentral gyrus(β=-0.020;P=.012) and right supramarginal gyrus(β=- 0.021;P=.013), which remained significant post-FDR correction(FDR P=.039). The right insula(β=- 0.0174;P=.034) showed significant thinning, confirmed by FDR correction(FDR P=.037).

Conclusions and Relevance

Higher MBI-C scores are linked to cortical thinning in brain regions essential for memory, spatial orientation, and emotional regulation. These findings support the use of MBI as an early marker of neurodegeneration, helping identify individuals at risk of cognitive decline. Incorporating MBI assessments into clinical practice could guide triaging of neuroimaging orders, optimizing healthcare resource use.