To investigate the effects of muscle health on ischemic stroke and the glymphatic system (GS), and to analyze the mediating role of the GS between the two.

Based on data from the UK Biobank, patients diagnosed with ischemic stroke [International Classification of Diseases, Tenth Revision (ICD-10) codes G45 and/or I63] at the time of first imaging acquisition were included in the analysis. Muscle health measures (walking pace and grip strength) were collected for all participants. The diffusion tensor imaging along the perivascular space (DTI-ALPS) index was derived from diffusion-weighted magnetic resonance imaging, including anterior (aALPS), middle (mALPS), posterior (pALPS), and total (tALPS) indices. Walking pace was self-reported and categorized into slow, steady, and fast pace groups. Grip strength was divided into tertiles based on absolute and relative values, resulting in low, medium, and high grip strength groups. Logistic regression was used to analyze the association of walking pace and grip strength with ischemic stroke risk, while multivariate linear regression assessed their association with the DTI-ALPS index. A causal mediation analysis framework was applied to examine the mediating effect of the DTI-ALPS index.

This study included a total of 37 370 ischemic stroke patients with data on grip strength, walking pace, and DTI-ALPS index. Slow walking pace was a risk factor for ischemic stroke (OR=1.577, 95%CI: 1.186 – 2.070, P=0.001), while high absolute grip strength was a protective factor (OR=0.774, 95%CI: 0.628 – 0.952, P=0.016). In contrast, relative grip strength showed no significant effect on the risk of ischemic stroke (OR=0.819 – 0.871, both P＞0.05). Compared with the steady pace group, the slow pace group showed a decrease in all DTI-ALPS indices (β: -0.037 – -0.025, all P＜0.001), while the fast pace group showed an increase in all DTI-ALPS indices (β: 0.009 – 0.012, all P＜0.001). Relative to the low absolute grip strength group, the medium absolute grip strength group exhibited increased DTI-ALPS indices (β: 0.010 – 0.013, all P＜0.001), and the high absolute grip strength group demonstrated even greater increases (β: 0.015 – 0.020, all P＜0.001). Logistic regression analysis revealed that higher DTI-ALPS indices were associated with significantly lower risk of ischemic stroke (aALPS: OR=0.577, P=0.011; mALPS: OR=0.631, P=0.015; pALPS: OR=0.574, P=0.016; tALPS: OR=0.526, P=0.006), with the tALPS index being the most significant. Mediation analysis revealed that all DTI-ALPS indices partially mediated the association of ischemic stroke with slow walking pace (mediation proportion: 2.19% – 3.11%) and high absolute grip strength (mediation proportion: 3.60% – 4.80%) with ischemic stroke.

Individuals with better muscle function, characterized by faster walking pace and stronger grip strength, exhibited improved GS function and a lower risk of ischemic stroke. Improving muscle health in patients with ischemic stroke may help regulate GS function, thereby reducing the risk of stroke occurrence.