Disrupted Brain Structure and Function in Alzheimer's Disease Patients With Behavioral and Psychological Symptoms

ABSTRACT Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in Alzheimer's disease (AD), but the underlying mechanisms are unclear. This study aims to elucidate the neuropathological mechanisms underlying BPSD by investigating gray matter volume (GMV) and brain connectivity in AD patients with and without BPSD. Amnestic mild cognitive impairment (aMCI)/AD patients with BPSD ( n = 52) and without BPSD ( n = 45) were analyzed using voxel‐based morphometry to assess GMV and seed‐to‐voxel resting‐state functional connectivity to further analyze the disturbed brain regions and the large‐scale networks associated with BPSD. Significant reductions in GMV were identified in the left middle temporal gyrus, right angular gyrus, right supramarginal gyrus, right cerebellar Crus II, and left cerebellar Crus I in patients with BPSD. Aberrant functional connectivity was primarily observed between the right angular gyrus and the bilateral postcentral cortex, as well as between the right cerebellar Crus II and left cerebellar Lobule VIII. Our findings reveal that abnormal brain structure and connectivity exist not only in the cerebrum but also in the cerebellum, with structural and functional disruptions across multiple crucial brain regions and large‐scale networks. This suggests that these abnormalities might underpin the neuropathological mechanisms contributing to BPSD in AD.