Associations among MRI-derived glymphatic system impairment, gray matter reserve and white matter integrity in cerebral small-vessel disease patients.

The aim of this study was to analyze glymphatic system function and its relationship with white/gray matter (WM/GM) abnormalities and structural network efficiency in patients with cerebral small vessel disease (CSVD) by structural magnetic resonance imaging (MRI) scanning and diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index. We retrospectively enrolled 42 clinically confirmed patients with CSVD, including 22 with normal cognition (CSVD_CN), 20 with mild cognitive impairment (CSVD_CI), and 20 matched healthy control (HC) volunteers. All the subjects underwent 3.0 Tesla high-resolution structural MRI scanning and diffusion tensor imaging. Subcortical volumetric analysis was performed using an automated Computational Anatomy Toolbox (CAT12) toolbox, and glymphatic system function was estimated via the DTI-ALPS index. We also calculated the main WM DTI parameters (fractional anisotropy, FA) and performed graph theoretical network analysis to measure global structural connectivity. Correlation and mediation analyses were also conducted to examine the relationships between glymphatic function and its related abnormalities. There were significant differences in the DTI-ALPS index (1.47 vs. 1.34, p = 0.029) between the HC and CSVD_CI groups. No significant changes in DTI-ALPS were found in the CSVD_CN group. Moreover, statistically significant associations were discovered between the DTI-ALPS index and the volume of the hippocampus (left: r = 0.364, p = 0.004; right: r = 0.342, p = 0.007) and the volume of the amygdala (left: r = 0.287, p = 0.024; right: r = 0.342, p = 0.006); there was also a significant correlation between the DTI-ALPS index and structural network efficiency, including the area under curve(AUC) of the clustering coefficient (Cp,r = 0.366, p = 0.003), the AUC of the shortest path length (Lp,r=-0.308, p = 0.015), the AUC of the global efficiency (Eg ,r = 0.311, p = 0.014), and the AUC of the local efficiency (Eloc,r = 0.351, p = 0.005). Mediation analysis also suggested that GM reserve and WM integrity may mediate the relationship between glymphatic dysfunction and structural network efficiency in CSVD. Our results revealed distinct relationships between glymphatic dysfunction and related abnormalities, suggesting that the DTI-ALPS index is a potential marker for early recognition of CI in patients with CSVD. GM reserve and WM integrity may mediate the relationship between glymphatic dysfunction and structural network efficiency. These findings may provide new evidence for the influence of glymphatic system function (as reflected in the DTI-ALPS index) on cognitive decline in patients with CSVD in clinical practice.