Mild behavioral impairment (MBI) is a neurobehavioral prodrome to dementia with multiple phenotypic characteristics. To investigate the complex neurobiological substrate underlying MBI, we evaluated its association with a composite magnetic resonance imaging (MRI)-based measure of concomitant cerebrovascular disease (CeVD) and neurodegeneration; and the interaction effects of MBI and MRI scores on cognitive and clinical trajectory.

253 dementia-free participants (mean age=71.9, follow-up period=49.89 months) from 2 memory clinics were included in this study. 37 (14.6%) participants met clinical diagnostic criteria for MBI, ascertained by repeated neuropsychiatric inventory assessments. MRI scores were computed using a validated weighted sum of white matter hyperintensities volume, presence of infarct, hippocampal volume, and cortical thickness of known Alzheimer’s disease-associated regions. Clinical and cognitive outcomes were evaluated annually using the Clinical Dementia Rating sum-of-boxes (CDR-SB) and standardized global cognitive scores of a comprehensive neuropsychological battery respectively.

Lower MRI scores, indicating greater burden of comorbid CeVD and neurodegeneration, yielded a 3.8-fold likelihood of MBI compared to 1.5-fold with larger WMH volume or lower cortical thickness individually. Interaction analyses showed that MBI participants with low MRI scores had greater increase in CDR-SB (B=0.05, SE=0.01, p<0.001) over time. All models involving the composite MRI measure yielded a better fit compared to reduced models with either pathology alone.

MBI is associated with a composite MRI measure that reflects mixed pathologies of dementia and their co-evaluation may improve risk profiling and identification of memory clinic patients without dementia who are at the highest risk of experiencing clinical decline.