ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
This article is part of the Research TopicThe Role of Neurogenesis in Cognitive Decline During AgingView all 5 articles
Glymphatic system impairment in cerebral small vessel disease: associations with perivascular space volume and cognition
Provisionally accepted
- 1First Affiliated Hospital of Anhui Medical University, Hefei, China
- 2Third Affiliated Hospital of Sun Yat-Sen University Center for Psychiatric and Neurological Diseases, Guangzhou, China
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Objective: While emerging evidence links glymphatic dysfunction to cerebral small vessel disease (CSVD), its clinical relevance remains poorly defined. This study aimed to investigate the relationships among glymphatic function, perivascular space (PVS), and cognitive performance in CSVD. Methods: We enrolled 120 CSVD patients [52 with no cognitive impairment (CSVD-NCI) and 68 with mild cognitive impairment (CSVD-MCI)] and 40 healthy controls (HCs). Glymphatic function was assessed using the left ALPS index, derived from diffusion tensor imaging analysis along the perivascular space (DTI-ALPS). Group comparisons in the ALPS index and PVS volume fraction (VF), and correlations among glymphatic function, PVS burden, and cognition were analyzed. Results: Compared to HCs, CSVD patients showed decreased ALPS index and increased PVS VF in basal ganglia (BG), caudate, putamen, and hippocampus, with more pronounced alterations in the left hemisphere. The ALPS index was inversely correlated with PVS VF in the BG (r = –0.232, p = 0.014), thalamus (r = –0.213, p = 0.024), caudate (r = –0.221, p = 0.019), and putamen (r = –0.210, p = 0.026) in CSVD. Furthermore, a lower ALPS index was associated with poorer performance in global cognition (r = 0.312, p = 0.001), executive function (r = 0.242, p = 0.012), processing speed (r = 0.264, p = 0.006), and visuospatial function (r = 0.272, p = 0.004). Finally, ALPS index partially mediated the association between putamen-PVS VF and global cognitive function, especially in the left hemisphere. Conclusion: Our findings demonstrate that impaired glymphatic function was associated with enlarged BG-PVS, especially in putamen, and worse cognitive performance, highlighting its potential role in disease progression and cognitive decline in CSVD.
Keywords: Cerebral small vessel disease, cognitive impairment, diffusion tensor image analysis along the perivascular space, glymphatic function, Subcortical perivascular space
Received: 05 Aug 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Ai, Li, Huang, Huang, Chen, Zhou, Zhu and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaoqun Zhu, zxq_ayfy@163.com
Zhongwu Sun, sunzhwu@126.com
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