Associations of Mild Behavioral Impairment Domains with Brain Volumes: Cross-sectional Analysis of Atherosclerosis Risk in Community (ARIC) Study.

Background: Mild behavioral impairment (MBI) has been associated with global brain atrophy, but the regional neural correlates of MBI symptoms are less clear, particularly among community-dwelling older individuals without dementia.

Objective: Our objective was to examine the associations of MBI domains with gray matter (GM) volumes in a large population-based sample of older adults without dementia.

Methods: We performed a cross-sectional study of 1445 community-dwelling older adults in the Atherosclerosis Risk in Communities Study who underwent detailed neurocognitive assessment and brain magnetic resonance imaging in 2011-2013. MBI domains were defined using an established algorithm that maps data collected from informants on the Neuropsychiatric Inventory Questionnaire to the 5 MBI domains of decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content. We performed voxel-based morphometry analyses to investigate associations of any MBI domain symptoms with GM volumes. We additionally performed region-of-interest analyses using adjusted linear regression models to examine associations between individual MBI domains with a priori-hypothesized regional GM volumes.

Results: Overall, the mean age of participants was 76.5 years; 59% were female, 21% were of Black race, and 26% had symptoms in at least one MBI domain. Participants with normal cognition comprised 60% of the population, and 40% had mild cognitive impairment. Compared to individuals without any MBI domain symptoms, voxel-based morphometry analyses showed that participants with symptoms in at least one MBI domain had consistently lower GM volumes in the cerebellum and bilateral temporal lobes, particularly involving the hippocampus. In adjusted region-of-interest models, affective dysregulation domain symptoms were associated with lower GM volume in the inferior temporal lobe (β = -0.34; 95% confidence interval = -0.64, -0.04), and impulse dyscontrol domain symptoms were associated with lower GM volume in the parahippocampal gyrus (β = -0.06; 95% confidence interval = -0.11, 0.00).

Conclusions: In this community-dwelling population of older adults without dementia, MBI symptoms were associated with lower GM volumes in regions commonly implicated in early Alzheimer's disease pathology. These findings lend support to the notion that MBI symptoms may be useful in identifying individuals at risk for future dementia.