White matter microstructural alterations are associated with cognitive decline in benzodiazepine use disorders: a multi-shell diffusion magnetic resonance imaging study.

Abstract

Background: Benzodiazepine use disorders (BUDs) have become a public health issue that cannot be ignored. We aimed to demonstrate that patients with BUDs might undergo changes in white matter (WM) integrity, which are related to impaired cognitive function.

Methods: We used diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator (MAP) to observe changes in WM structure from 29 patients with sleep disorders with BUD (SDBUD), 33 patients with sleep disorders with non-BUD (SDNBUD), and 25 healthy participants. We also compared the diagnostic performance of the diffusion metrics and models in predicting the status of BUDs and evaluated the relationship between WM changes and cognitive impairment.

Results: BUD was closely associated with WM damage in the corpus callosum (CC) and pontine crossing tract (PCT). There were 14 main diffusion metrics that could be used to predict BUD status (P=0.001-0.023). DTI, DKI, NODDI, and MAP had similar satisfactory performance for predicting BUD status (P=0.001-0.021). Pearson correlation analysis showed a close relationship between the Trail Making Test B (TMT-B) and DTI/NODDI metrics in the splenium of the CC and PCT and between the Montreal Cognitive Assessment (MoCA) and MAP metrics in the splenium of the CC in the SDBUD group (P=0.008-0.040).

Conclusions: Our findings provide evidence for the neurobiological mechanism of benzodiazepine addiction and a novel method for the clinical diagnosis of BUDs.