Glymphatic dysfunction assessed by DTI-ALPS index predicts early cognitive impairment in acute subcortical infarcts: a prospective clinical cohort study

BackgroundThe glymphatic system (GS), responsible for clearing neurotoxic proteins (such as β-amyloid and tau protein), is critical in stroke pathophysiology. However, its role in acute post-stroke cognitive impairment (PSCI) remains unclear. We investigated GS dysfunction via the DTI-ALPS index in...

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Main Authors: Yirong Wang, Mei Yang, Xingmao Zeng, Shuai Wang, Wenmin Zhang, Weidong Wang, Yang Du, Jurong Ding, Xin Ding
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1605889/full
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author Yirong Wang
Mei Yang
Xingmao Zeng
Shuai Wang
Wenmin Zhang
Weidong Wang
Yang Du
Jurong Ding
Xin Ding
author_facet Yirong Wang
Mei Yang
Xingmao Zeng
Shuai Wang
Wenmin Zhang
Weidong Wang
Yang Du
Jurong Ding
Xin Ding
author_sort Yirong Wang
collection DOAJ
description BackgroundThe glymphatic system (GS), responsible for clearing neurotoxic proteins (such as β-amyloid and tau protein), is critical in stroke pathophysiology. However, its role in acute post-stroke cognitive impairment (PSCI) remains unclear. We investigated GS dysfunction via the DTI-ALPS index in acute subcortical infarct patients and its association with early cognitive decline.MethodsThis prospective cohort included 29 subcortical infarct patients and 25 healthy controls (HC). Participants underwent 3.0 T MRI (DTI/structural sequences) and Montreal Cognitive Assessment (MoCA) at 7 and 90 days post-stroke. Bilateral DTI-ALPS indices were calculated. Group comparisons and Spearman correlations were analyzed.ResultsThe DTI-ALPS index of the lesion (1.371 ± 0.170) and non-lesion side (1.310 ± 0.198) in the SI group were significantly lower than that in HC group (1.568 ± 0.115) (both of p < 0.001, respectively). While, the DTI-ALPS index of the lesion side was no significant difference than that of the non-lesion side in subcortical infarct group (p = 0.214). The scores of MoCA in 7 days and 90 days after stroke were significantly lower than those in HC group (p < 0.001). In patients with subcortical infarct, MoCA scores at 7 days showed significant correlation with lesion-side DTI-ALPS index (r = 0.510, p = 0.005) but not with non-lesion DTI-ALPS values (r = 0.174, p = 0.259). Notably, we observed significant correlations between MoCA scores at 90 days post-stroke and DTI-ALPS index, which were consistently demonstrated in the lesion, non-lesion, and mean bilateral measurements. The ROC analysis demonstrated that the DTI-ALPS index showed moderate discriminative ability (AUC = 0.868) in differentiating patients with cognitive impairment from those with normal cognition following subcortical infarction, exhibiting excellent sensitivity (96.0%) but suboptimal specificity (65.5%).ConclusionIschemic stroke leads to glymphatic dysfunction, which is associated with early post-stroke cognitive impairment.
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spelling doaj-art-4575b0cc8a3c47c4ab05d8bb0f0bb8232025-08-20T02:36:19ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-07-011610.3389/fneur.2025.16058891605889Glymphatic dysfunction assessed by DTI-ALPS index predicts early cognitive impairment in acute subcortical infarcts: a prospective clinical cohort studyYirong Wang0Mei Yang1Xingmao Zeng2Shuai Wang3Wenmin Zhang4Weidong Wang5Yang Du6Jurong Ding7Xin Ding8Department of Neurology, Chengdu Second People’s Hospital, Chengdu, ChinaSchool of Automation and Information Engineering, Sichuan University of Science and Engineering, Zigong, ChinaDepartment of Neurology, Chengdu Fifth People's Hospital, Chengdu, Sichuan, ChinaDepartment of Outpatient, General Hospital of Western Theater Command, Chengdu, Sichuan, ChinaDepartment of Neurology, Chengdu Second People’s Hospital, Chengdu, ChinaDepartment of Neurology, Chengdu Second People’s Hospital, Chengdu, ChinaDepartment of Neurology, Chengdu Second People’s Hospital, Chengdu, ChinaSchool of Automation and Information Engineering, Sichuan University of Science and Engineering, Zigong, ChinaDepartment of Neurology, Chengdu Second People’s Hospital, Chengdu, ChinaBackgroundThe glymphatic system (GS), responsible for clearing neurotoxic proteins (such as β-amyloid and tau protein), is critical in stroke pathophysiology. However, its role in acute post-stroke cognitive impairment (PSCI) remains unclear. We investigated GS dysfunction via the DTI-ALPS index in acute subcortical infarct patients and its association with early cognitive decline.MethodsThis prospective cohort included 29 subcortical infarct patients and 25 healthy controls (HC). Participants underwent 3.0 T MRI (DTI/structural sequences) and Montreal Cognitive Assessment (MoCA) at 7 and 90 days post-stroke. Bilateral DTI-ALPS indices were calculated. Group comparisons and Spearman correlations were analyzed.ResultsThe DTI-ALPS index of the lesion (1.371 ± 0.170) and non-lesion side (1.310 ± 0.198) in the SI group were significantly lower than that in HC group (1.568 ± 0.115) (both of p < 0.001, respectively). While, the DTI-ALPS index of the lesion side was no significant difference than that of the non-lesion side in subcortical infarct group (p = 0.214). The scores of MoCA in 7 days and 90 days after stroke were significantly lower than those in HC group (p < 0.001). In patients with subcortical infarct, MoCA scores at 7 days showed significant correlation with lesion-side DTI-ALPS index (r = 0.510, p = 0.005) but not with non-lesion DTI-ALPS values (r = 0.174, p = 0.259). Notably, we observed significant correlations between MoCA scores at 90 days post-stroke and DTI-ALPS index, which were consistently demonstrated in the lesion, non-lesion, and mean bilateral measurements. The ROC analysis demonstrated that the DTI-ALPS index showed moderate discriminative ability (AUC = 0.868) in differentiating patients with cognitive impairment from those with normal cognition following subcortical infarction, exhibiting excellent sensitivity (96.0%) but suboptimal specificity (65.5%).ConclusionIschemic stroke leads to glymphatic dysfunction, which is associated with early post-stroke cognitive impairment.https://www.frontiersin.org/articles/10.3389/fneur.2025.1605889/fullglymphatic systemDTI-ALPSsubcortical infarctioncognitive impairmentdiffusion tensor imaging
spellingShingle Yirong Wang
Mei Yang
Xingmao Zeng
Shuai Wang
Wenmin Zhang
Weidong Wang
Yang Du
Jurong Ding
Xin Ding
Glymphatic dysfunction assessed by DTI-ALPS index predicts early cognitive impairment in acute subcortical infarcts: a prospective clinical cohort study
Frontiers in Neurology
glymphatic system
DTI-ALPS
subcortical infarction
cognitive impairment
diffusion tensor imaging
title Glymphatic dysfunction assessed by DTI-ALPS index predicts early cognitive impairment in acute subcortical infarcts: a prospective clinical cohort study
title_full Glymphatic dysfunction assessed by DTI-ALPS index predicts early cognitive impairment in acute subcortical infarcts: a prospective clinical cohort study
title_fullStr Glymphatic dysfunction assessed by DTI-ALPS index predicts early cognitive impairment in acute subcortical infarcts: a prospective clinical cohort study
title_full_unstemmed Glymphatic dysfunction assessed by DTI-ALPS index predicts early cognitive impairment in acute subcortical infarcts: a prospective clinical cohort study
title_short Glymphatic dysfunction assessed by DTI-ALPS index predicts early cognitive impairment in acute subcortical infarcts: a prospective clinical cohort study
title_sort glymphatic dysfunction assessed by dti alps index predicts early cognitive impairment in acute subcortical infarcts a prospective clinical cohort study
topic glymphatic system
DTI-ALPS
subcortical infarction
cognitive impairment
diffusion tensor imaging
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1605889/full
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