Structural network efficiency mediates the association between glymphatic function and cognition in mild VCI: a DTI-ALPS study

Hao Song; Zhao Ruan; Lei Gao; Dongwei Lv; Dong Sun; Zeng Li; Ran Zhang; Xiaoli Zhou; Haibo Xu; Junjian Zhang

doi:10.3389/fnagi.2022.974114

Structural network efficiency mediates the association between glymphatic function and cognition in mild VCI: a DTI-ALPS study

Front Aging Neurosci. 2022 Nov 16:14:974114. doi: 10.3389/fnagi.2022.974114. eCollection 2022.

Authors

Hao Song¹, Zhao Ruan², Lei Gao², Dongwei Lv¹, Dong Sun¹, Zeng Li¹, Ran Zhang¹, Xiaoli Zhou², Haibo Xu², Junjian Zhang¹

Affiliations

¹ Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, China.
² Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Abstract

Background and objective: Vascular cognitive impairment (VCI) can be caused by multiple types of cerebrovascular pathology and is considered a network disconnection disorder. The heterogeneity hinders research progress in VCI. Glymphatic failure has been considered as a key common pathway to dementia recently. The emergence of a new method, Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), makes it possible to investigate the changes of the glymphatic function in humans non-invasively. We aimed to investigate alterations of glymphatic function in VCI and its potential impact on network connectivity. Methods: We recruited 79 patients with mild VCI, including 40 with cerebral small vessel disease cognitive impairment (SVCI) and 39 with post-stroke cognitive impairment (PSCI); and, 77 normal cognitive (NC) subjects were recruited. All subjects received neuropsychological assessments and multimodal magnetic resonance imaging scans. ALPS-index was calculated and structural networks were constructed by deterministic tractography, and then, the topological metrics of these structural connectivity were evaluated. Results: The ALPS-index of VCI patients was significantly lower than that of NC subjects (P < 0.001). Multiple linear regression analysis showed that ALPS-index affects cognitive function independently (β = 0.411, P < 0.001). The results of correlation analysis showed that the ALPS-index was correlated with overall vascular risk factor burden (r = -0.263, P = 0.001) and multiple cerebrovascular pathologies (P < 0.05). In addition, global efficiency (Eg) of network was correlated with ALPS-index in both SVCI (r = 0.348, P = 0.028) and PSCI (r = 0.732, P < 0.001) patients. Finally, the results of mediation analysis showed that Eg partially mediated in the impact of glymphatic dysfunction on cognitive impairment (indirect effect = 7.46, 95% CI 4.08-11.48). Conclusion: In both major subtypes of VCI, the ALPS-index was decreased, indicating impaired glymphatic function in VCI. Glymphatic dysfunction may affect cognitive function in VCI by disrupting network connectivity, and, may be a potential common pathological mechanism of VCI. ALPS-index is expected to become an emerging imaging marker for VCI.

Keywords: cerebral small vessel disease; global efficiency; glymphatic system; post stroke cognitive impairment; structural network; vascular cognitive impairment.