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

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.974114

DOI=10.3389/fnagi.2022.974114

ISSN=1663-4365

ABSTRACT=<p><bold>Background and objective:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> The ALPS-index of VCI patients was significantly lower than that of NC subjects (<italic>P</italic> &lt; 0.001). Multiple linear regression analysis showed that ALPS-index affects cognitive function independently (<italic>β</italic> = 0.411, <italic>P</italic> &lt; 0.001). The results of correlation analysis showed that the ALPS-index was correlated with overall vascular risk factor burden (<italic>r</italic> = −0.263, <italic>P</italic> = 0.001) and multiple cerebrovascular pathologies (<italic>P</italic> &lt; 0.05). In addition, global efficiency (Eg) of network was correlated with ALPS-index in both SVCI (<italic>r</italic> = 0.348, <italic>P</italic> = 0.028) and PSCI (<italic>r</italic> = 0.732, <italic>P</italic> &lt; 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).</p><p><bold>Conclusion:</bold> 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.</p>