Progressive brain structural abnormality in cerebral small vessel disease assessed with MR imaging by using causal network analysis.

ABSTRACT

AIMS: Cerebral small vessel disease (CSVD) is a complex condition characterized by a combination of microcirculation disorders and neurodegenerative processes, CSVD is associated with structural abnormalities in multiple brain regions. However, the progressive pattern of structural changes remains unknown. METHODS: In order to detail the progressive structural changes in CSVD patients according to the degree of cognitive impairment, we recruited 121 CSVD patients and 104 healthy controls (HCs). Voxel-based morphometry was employed to measure the gray matter volume (GMV) of each participant. According to the VICCCS-2 diagnostic criteria, patients were initially divided into three stage groups, then we investigated the GMV changes in each stage and their causal relationships using causal structure covariance network (CaSCN) analysis. RESULTS: Overall, patients with CSVD presented stage-specific GMV alterations compared with HCs. With the worsening of cognitive impairment, the decrease in gray matter volume starts from the right hippocampus and gradually spreads to the cortical-subcortical brain regions. Importantly, the right hippocampus in CSVD patients plays a driving role in the directional network and forms both positive and negative causal effect networks with cortical-subcortical brain regions. CONCLUSIONS: This study reveals the significance of the right hippocampus as an early pathological area in CSVD patients and its causal impact on brain GMV changes with disease progression, shedding light on structural brain damage hierarchy and compensatory mechanisms.