Mild behavioral impairment as an indicator of early dementia neurodegeneration: Evidence from structural neuroimaging

Abstract Background Mild behavioral impairment (MBI) refers to the de novo emergence of persistent neuropsychiatric symptoms in older adults and has been associated with cognitive decline and incident dementia. The purpose of this study was to identify the structural neural correlates of MBI using a hypothesis‐driven region‐of‐interest (ROI) approach. Method The study cohort consisted of 744 participants (60.3% female; mean and SD of age = 71.0 ± 9.7 years; mean and SD of education: 15.8 ± 5.3 years) without dementia from the National Alzheimer’s Coordinating Centre dataset. Structural T1‐weighted images for each participant were processed and segmented using FreeSurfer and then normalized by age, sex, intracranial volume, scanner characteristics, and image quality to generate adjusted measures of grey matter volume (GMV) for each ROI. Our primary ROIs included five regions, each representing one Braak stage: entorhinal cortex (stage I), hippocampus (stage II), fusiform gyrus (stage III), inferior temporal cortex (stage IV), and frontal pole (stage V). We also included three hippocampal subfields (CA1, CA3, CA4) and four ROIs commonly associated with various psychiatric disorders (amygdala, insula, anterior cingulate, prefrontal cortex) as a secondary analysis. All ROIs are anatomically highlighted in Figure 1. Participants were classified as MBI+ if they presented with MBI symptoms derived from the Neuropsychiatric Inventory Questionnaire for two consecutive visits one year apart. Logistic regressions adjusting for cognitive diagnosis (cognitively normal, n = 568; mild cognitive impairment, n = 176) were used to model the relationship between ROI GMV (predictor) and MBI status (outcome). Result As shown in Table 1, lower GMV in early Braak stage ROIs (entorhinal cortex and hippocampus) was associated with MBI+ status. This trend was maintained for all hippocampal subfield ROIs. However, mid‐late Braak stage ROI (fusiform gyrus, inferior temporal cortex, frontal pole) GMVs were not associated with MBI status. For psychiatric disorder ROIs, lower GMV in only the amygdala was associated with MBI+ status. Conclusion Our findings demonstrate that the presence of MBI may implicate neurodegeneration in regions linked to early‐stage dementia. Furthermore, this explicitly identifies MBI as a neurodegenerative marker sharing few neuroanatomical correlates with psychiatric disorders, despite their clinical manifestations. aging after age 90.