Clinical effects of frontal behavioral impairment: Cortical thickness and cognitive decline in individuals with subjective cognitive decline and amnestic mild cognitive impairment

Background: Frontal behavioral impairment (FrBI) is commonly observed in various degenerative diseases and refers to various behavioral symptoms. Objective: We investigated the effects of the presence of FrBI on cortical thickness, and the longitudinal neuropsychological changes in people in the predementia stage. Methods: A total of 794 individuals completed neuropsychological tests and the Frontal Behavioral Inventory (FBI) Questionnaire, and underwent magnetic resonance (MR) scanning. Participants were analyzed and grouped into non-FrBI (FBI=0) or FrBI (FBI≥1). Cortical thickness was measured on MR images using a surface-based method. Results: In total, 281 people with subjective cognitive decline (SCD) and 513 with amnestic mild cognitive impairment (aMCI) were assessed for FrBI. Relative to people without FrBI, those with FrBI presented reduced cortical thickness in the frontal, anterior temporal and lateral parietal regions (p<0.05, FDR corrected). People with FrBI developed Alzheimer's disease, rather than behavioral variant frontotemporal dementia, as observed over seven years. Mixed effects models reported that people with FrBI have greater cognitive decline than those with non-FrBI in multiple domains, including language, memory, and executive functions (p<0.05, FDR corrected). Furthermore, while negative FrBI symptoms (e.g., deficit behaviors) were associated with greater declines in multiple domains, positive FrBI symptoms (e.g., disinhibition symptoms) were related to declines in visuospatial function and verbal memory. Finally, the occurrence of both types of symptoms correlated with multi-domain cognitive decline. Conclusions: FrBI predicted worse clinical outcomes, including reduced cortical thickness and cognitive decline, which are not necessarily specific to frontal dysfunction.