Voxel‐based morphometry and resting state fMRI as predictors of neuropsychiatric symptoms in Alzheimer's disease

Background Neuropsychiatric symptoms (NPS) affect most people with Alzheimer’s disease (AD) and have previously been associated with structural and functional brain changes. This study aimed to establish whether there were structural and functional neural correlates that predicted NPS at 3‐year follow‐up. Method 75 (M=40, F=35) patients who met the diagnostic criteria for AD (N=29), MCI (N=39) and subjective cognitive decline (SCD, N=7) were followed up at 3 years and assessed with Neuropsychiatric Inventory (NPI). T1 and T2*‐weighted EPI MR images were obtained at baseline using the Siemens Avanto 1.5 T scanner for volumetric and resting‐state functional MRI (rs‐fMRI) analysis. Pre‐processing was performed with SPM12 voxel‐based morphometry (VBM) pipeline for the structural imaging and FMRIB software library (FSL) package for the rs‐fMRI. The correlation analysis was performed between the NPS as measured by NPI and the regional brain volume and activity in resting state networks. Result Mean age of cohort at baseline was 77 (52‐89). 22 MCI patients converted to AD at 3‐year follow‐up. VBM analysis shows negative correlation with regional brain volume at baseline and presence of neuropsychiatric symptoms (psychosis and affective) at 3 year follow up in people with AD (Figure 1). Brain volumes that correlated negatively with anxiety include anterior/middle cingulate cortex, which has previously been implicated in affective processing and links to default mode network (DMN). Orbitofrontal cortex and cerebellum volumes correlated negatively with high scores in psychosis factor at 3 year f/u. Brain connectivity analysis in participants with AD at f/u (N=41) showed positive correlation of various NPS in default mode (DMN), salience, executive as well as left and right frontoparietal networks( Figure 2 & Figure 3). There was a negative correlation between activity in DMN and appetite. Conclusion NPS in AD measured at 3‐year f/u appear to be inversely correlated with regional brain volume and positively correlated with activity in resting state brain networks. Increased activity in DMN and salience networks has previously been associated with psychosis and affective symptoms in other populations.