Mild behavioral impairment and functional connectivity in dementia‐free elderly

Abstract

BackgroundMild Behavioral Impairment (MBI), characterized by de novo emergent and persistent neuropsychiatric symptoms in later life, may be used to improve early detection of neurodegenerative disease. While alterations in resting‐state networks have been demonstrated in early‐stage Alzheimer’s disease (AD), few studies have explored these networks in MBI. Here, we assessed activity in the default mode network (DMN) and the salience network (SN), using resting‐state functional magnetic resonance imaging (fMRI), in association with MBI. We hypothesized that the strength of functional connectivity (FC) within the DMN and SN would be reduced in dementia‐free persons with MBI (MBI+), relative to those without (MBI‐).MethodsData from dementia‐free participants in three prospective cohort studies were pooled. MBI+ status was determined using the MBI‐checklist. Imaging data were acquired using 3T MRI. Seed‐based connectivity analyses were performed using the CONN toolbox. The DMN included the posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC), and lateral parietal (LP) regions, with the PCC as the seed. The SN included the anterior cingulate cortex (ACC), anterior insula (AI), rostral prefrontal cortex (RPFC), and supramarginal gyrus (SMG), with the ACC as the seed. FC maps of the DMN and SN were computed for each MBI group; difference maps were extracted to identify regions with significantly different connectivity across MBI groups. A threshold of p<0.05 was used with false discovery rate correction for multiple comparisons at the cluster level; a p<0.001 uncorrected for voxel level was used for group comparisons. All analyses were covaried for age, sex, years of education, and Montreal Cognitive Assessment scores.ResultsOf the 95 participants, 32 were MBI+ and 63 MBI‐ (mean age 71.7; 54.7% female). Within the DMN, MBI+ individuals had lower functional connectivity between the PCC and MPFC, compared to MBI‐ (β=‐0.15, p=0.004). Within the SN, MBI+ was associated with lower functional connectivity between the ACC and left AI (β=‐0.12, p=0.028).ConclusionOur findings suggest that in dementia‐free individuals, MBI is associated with decreased functional connectivity in networks disrupted in AD. This result lends additional support to MBI as a potential early marker of disease.